Contents

Search

HMG CoA reductase inhibitor (statin)

Classification: - high-intensity statin [323] - atorvastatin 40-80 mg daily, rosuvastatin 20-40 mg daily - medium intensity statin - atorvastatin 20 mg daily, pravastatin 40-80 mg daily rosuvastatin 5-10 mg daily, simvastatin 20-40 mg daily [314] - low intensity statin - atorvastatin 10 mg daily - fluvastatin 20-40 mg daily, lovastatin 20 mg daily, pitavastatin 1 mg daily, pravastatin 10-20 mg daily, simvastatin 10 mg daily [323] Epidemiology: - 25% of people > 45 years of age are on a statin [99] Indications: - treatment of hypercholesterolemia* - LDL cholesterol >= 190 mg/dL [124] - may be coadministered with ezetimibe; - effects on LDL cholesterol additive, but clinical benefit does not correlate - may not be useful in patients > 80 year of age [45] - *treatment of proteinuria in conjunction with ACE inhibitors - Kidney Disease Improving Global Outcomes Lipid Work Group recommends statins for all patients with chronic kidney disease >= 50 years of age [151] - may reduce all-cause mortality (RR=0.81) & cardiovascular mortality (RR=0.78) in patients with chronic renal failure [141, 249] - no benefit for dialysis patients [141,250] - may reduce risk of contrast nephropathy in patients undergoing coronary angiography (relative risk = 0.58) [248] - may reduce risk of liver disease, hepatocellular carcinoma & liver-related mortality - especially benificial in men with diabetes mellitus & high Fibrosis-4 index [320] === primary prevention of cardiovascular disease === - meta-analysis used to promote statins for primary prevention [300] - primary prevention in low-risk patients may constitute low-value care [289] - low-to-moderate-dose statins for adults aged 40-75 without known cardiovascular disease with at least one risk factor (dyslipidemia, diabetes, hypertension, smoking) & a 10-year risk of >=10% (USPSTF) [200 241,242] - AHA/ACC recommends moderate dose statin for adults 40-75 years with diabetes mellitus type 2 regardless of calculated ASCVD risk [1] - atorvastatin, rosuvastatin & simvastatin best statins for lowering non-HDL cholesterol in patients with diabetes mellitus [307] - estimated 10-year cardiovascular risk >= 7.5% (AHA/ACC) [124] - benefits less likely with risk of 7.5-10% [242] - benefits only begin to outweigh the risks when CVD risk is 14% for men age 40-49 years, 21% for men age 70-75 years, & 17-22% for women [272] - USPSTF concludes statins of benefit for primary prevention in adults 40-75 years with at least on major risk factor (dyslipidemia, diabetes, hypertension, smoking) & a 10 year cardiovascular risk > 10% [304, 312] - benefit is small if 10 year cardiovascular risk is < 10% [304, 312] - evidence is insufficient to determine the balance of benefits & harms of statin use for the primary prevention of CVD events & mortality in adults >75 years [312] - USPSTF recommendations of 10-year risk of >=10% would lead to 9 million fewer U.S. patients prescribed statins than AHA/ACC recommendations of 10-year risk of >=7.5% [244] - 2021 European Society of Cardiology recommends statin for primary prevention if >= 7.5% 10-year cardiovascular risk & age 40-49 years & >= 10% 10-year cardiovascular risk & age 50-69 years [311] - calculating 30 year risk of cardiovascular disease rather than 10 year risk would result in even more statin eligible persons (American College of Cardiology) [271] - benefit for primary prevention confirmed [101], including primary prevention in the elderly (73 +/- 3 years) [121] - no evidence of benefit for primary prevention in patients > 80 years of age [233] - no benefit for primary prevention of cardiovascular disease or all-cause mortality among healthy adults over age 75 years [269] - initiating statin therapy in elderly > 75 years without cardiovascular disease lowers 7 year cardiovascular mortality (RR=0.80) & all cause mortality (RR-0.75); retrospective study [292] - no benefit of pravastatin 40 mg/day for primary prevention in patients > 65 years of age [247] - diabetes mellitus in patients 40-75 years of age with LDL cholesterol > 70 mg/dL [124] - no mortality benefit demonstrated in clinical trials [196] - may reduce risk of diabetic retinopathy (11 v 12%) [275] - benefit for primary prevention absent in patients without hypertension (see Jupiter study) - benefit for primary prevention in terms of mortality (RR=0.86), MI (RR= 0.75), stroke (RR=0.78) [185]; Cochrane review of 18 trials, 14 of which recruited participants with hyperlipidemia, diabetes mellitus, hypertension &/or microalbuminuria [185] - in analyses adjusted substantially, risk for stroke reduced in elderly (>= 70 years) without known cardiovascular disease (RR=0.7) [186] - no mortality benefit for primary prevention [76,121] - harms exceed small benefit for primary prevention in elderly > 75 years of age [165] - evidence is insufficient to weigh benefits vs harms in elderly > 75 years of age [242,279] - discontinuation of statin associated with 33% increased risk of hospitalization for cardiovascular event in 75-year-old treated for primary prevention [285] (French study) - no reduction in mortality [121] - no benefit of statin for primary prevention in elderly >65-70 years of age in SPRINT trial [260] - use for primary prevention controversial [1] - benefits in patients with low cardiovascular risk (5 year risk < 10%) similar to benefits in high-risk patients [101] - ~ 1/2 of patients taking statins don't experience a substantial lowering of LDL cholesterol [281] - 5 year cardiovascular death reduction of 1.2% in elderly > 75 years, including elderly > 85 years, NNT=20 to avert 1 cardiovascular death [327] - A meta-analysis of 28 randomized controlled treals did not find strong evidence of benefit in primary prevention among epderly > 75 years [276,327] - suggestion is made that everyone over 50 years of age should take a statin: allegedly, benefits of statins outweigh risks, even in the healthiest patients [101] - nearly all of 19 randomized controlled trials reviewed for guidelines were industry-sponsored - a global statin market of roughly US $20 billion annually drives much of the research & interest in statins for primary prevention [254] === secondary prevention of cardiovascular disease === - clinical atherosclerotic cardiovascular disease [124] - cardiovascular risk reduction [67,75,76] {4-year}; (secondary prevention) - mortality risks decrease as statin doses increase [240] - lowers risk for vascular events in adults > 70 years of age, - benefit only in those with history of vascular disease [276] - coronary artery disease - preferential benefit for patients at high genetic risk [159] - history of myocardial infarction - no significant benefit for patients > 80 years of age [233] - peripheral arterial disease [30] - may reduce arterial inflammation - reduces carotid inflammation [123] - reduces progression of arterial stiffness in Chinese as assessed by brachial-ankle pulse wave velocity [310] - ischemic cerebrovascular disease - history of transient ischemic attack or ischemic stroke - conflicting data on benefit/risk for hemorrhagic stroke [168-173,322] - may attenuate risk associated with elevated CRP - *after acute myocardial infarction [3] - *in prevention of unstable angina & myocardial infarction [6, 15,36] - *even in those patients with low LDL cholesterol* [17] - serum CRP does NOT predict response to statins [82] - may reduce risk of severe or fatal COVID-19 (30%) [293] - questionable benefit for patients with rheumatologic disease [274] - may or may not benefit elderly with heart failure [45,46,71] - statin initiation in patients in HFpEF reduces major cardiovascular events, hospitalizations & all cause mortality in veterans without prevalent atherosclerotic cadiovascular disease [328] - cardiovascular benefits may be independent of LDL cholesterol [10], or total cholesterol [19,27] - target for statin therapy may be non-HDL cholesterol [98] - benefit of secondary prevention for women with coronary artery disease may not extend to stroke or all-cause mortality [105] - long-term statin use associated with greater myocardial salvage in patients with STEMI after PCI [201] * ACC/AHA cardiovascular risk calculator overestimates risk [194] * may reduce non arterial inflammation * may reduce risk of inflammatory bowel disease [206] * may diminish inflammatory-associated demyelination in multiple sclerosis [23] * may reduce inflammatory gum disease (periodontal disease) * may prevent sepsis in elderly with atherosclerosis [44] * may provide benefit for osteoporosis [2,40] * may diminish risk of fractures [42] * may diminish risk of macular degeneration [8,40] * may diminish risk of glaucoma [40,282] & cataracts* [50] * might be associated with reduction in cancer risk [55-57] - statins reduce cancer risk in patients with heart failure (RR=0.84) [298] - statins reduce risk of cancer deaths in patients with heart failure (RR=0.64) [298] * may diminish risk of prostate cancer & colon cancer [39] * may diminish risk of metastatic, but not localized prostate cancer * post-diagnosis statin may diminish risk of prostate cancer-specific mortality (RR=0.81) & all-cause mortality (RR=0.85) [256] - benefit may be restricted to men on androgen-deprivation therapy [256] * may reduce risk of liver cancer [111] * lipophilic statins (atorvastatin, simvastatin) may reduce risk of hepatocellular carcinoma (3% vs 8%) in patients with chronic viral hepatitis [286] * 15% reductions observed in risk for 13 types of cancer with similar reduction in all-cause mortality [111] * no reduction in cancer risk [43,157] * may reduce mortality from ischemic stroke [48] * may diminish risk of stroke in women > 55 years of age * may reduce cardiovascular mortality (RR=0.8) & all-cause mortality in women (RR=0.9) [56,157] * may reduce mortality in nursing home residents with or without dementia [324] * equally effective in men & women [157] * may diminish perioperative mortality [52] * may reduce risk of postoperative acute renal failure (RR = 0.81) [114] * rosuvastatin & other statins may reduce risk of venous thromboembolism [66] * may reduce risk of venous thromboembolism in women on hormone replacement therapy [144] - no plausible mechanism is apparent [144] * may diminish risk of mortality associated with pneumonia [83] * may slow brain atrophy in patients with secondary progressive multiple sclerosis [130] * statin use after concussion may be associated with a lower risk for dementia the elderly (37 vs 43 cases per 1000 annually) [284] * may be of benefit in treatment of venous stasis ulcers [133] * statins may reduce risk of osteoarthritis [326] * statin therapy may be ineffective in the setting of untreated hypothyroidism, diabetes mellitus, biliary disease, or nephrotic syndrome [1] Contraindications: - hemorrhagic stroke (data are conflicting) [168-173] - liver disease - rhabdomyolysis - pregnancy - lactation - myositis - patients on renal dialysis - limited prognosis - stopping statins in patients with limited prognosis is not associated with increased risk of cardiovascular events or increased mortality & may improve quality of life, reduce use of other useless medications & lower overall costs [167] * data are conflicting on use of statins after hemorrhagic stroke [81,168-173,182,322] - caution recommended in use of statins in patients with previous haemorrhagic stroke & in patients with poorly controlled hypertension [169] * not a contraindication for hormone replacement therapy in post-menopausal women [166] * probably does not diminish risk of dementia * not useful for treatment of dementia [88] (see Statins & the risk of dementia ..) [4,40,202] * may not benefit patients > 80 years of age [45,154]# * does not lower risk of infection [87] * no benefit to starting statin within 14 days of MI [164] * peroperative statin does not prevent postoperative delirium [234] * no benefit of statins in patients with aneurysmal subarachnoid hemorrhage [183] * no benefit for COPD [138] * no benefit for ARDS [138,146] * as an alternative to exercise to reduce cardiovascular risk through improving physical fitness [113] * as an alternative to a heart healthy diet - 4 of 5 MIs in men are preventable through healthy diet & lifetyle [155] - this translates to a number needed to treat of 1.25 * no study has has compared statins with beneficial lifestyle changes & found that statins had a superior or additive effect on clinical outcomes [152,153] # benefits in elderly (see PROSPER study, [44]) # benefits in elderly shown in meta-analysis [41] # insufficient evidence to assess net harms & benefits of initiating statins in adults >=76 years, regardless of estimated 10-year cardiovascular risk [312] # benefits in elderly with coronary artery disease > 80 years [93] # no reduction in mortality after MI in the elderly (> 80) [45] # insufficient data to recommend initiation or continuation of statins in patients with known cardiovascular disease >= 80 years of age [154] # discontinuation of statin in palliative care patients may improve quality of life [167]. Pregnancy category: X - potentially teratogenic, risk may be small [117] - statin use during the first trimester of pregnancy is not associated with increased risk for congenital malformations [160] - FDA is removing contraindication against using statins in all pregnant patients [299] Benefit/risk: - subjects without known cardiovascular disease - number needed to treat (NNT) - 104 for 5 years to prevent 1 MI* [162] - 154 for 5 years to prevent 1 stroke [162] - 144 for 9 years to prevent 1 stroke (elderly >= 70 years) [186] - 50-200 for 5 years prevent 1 major cardiovascular event [254] - 145 for 5 years to prevent 1 MI & 88 to prevent 1 cardiovascular event (elderly 70-79 years with moderate intensity statin) [294] - 80 for 5 years to prevent 1 MI & 42 to prevent 1 cardiovascular event (elderly 80-100 years with moderate intensity statin) [294] - no mortality benefit [162] - 66 for 10 years to prevent 1 cardiovascular event in subjects at low genetic risk (Jupiter trial) [159] - industry-sponsored study stopped early after median follow-up of 1.9 years (Jupiter trial) [159] - 25 for 10 years to prevent 1 cardiovascular event in subjects at high genetic risk [159] - eligibility for guideline-directed statin use between 1987 & 2016 in Ireland increased eligible patients from 8% to 61%, resulting in number needed to treat to prevent one major cardiovascular event from 40 to 400 [289] - may reduce cardiac events for some adults aged 50-75 years with life expectancy >=2.5 years; no data suggest a mortality benefit [295] - subjects with known heart disease [41,147,148,149] - number needed to treat (NNT) - 39 for 5 years for prevent 1 non-fatal MI [163] - 24 for 1 year to prevent 1 MI (pravastatin in Prosper trial [25,147] - 125 for 5 years for prevent 1 stroke [163] - 83 for 5 years to prevent 1 death [163] - number needed to harm (5 years of treatment) [41,147,148,149,162,258] - diabetes mellitus = 50 - mypopathy = 10, ranges of 5-minimal risk [258] - according to the American Heart Association [273] - primary prevention in 5% of patients treated for 5 years (who achieve a 77-mg/dL reduction in LDL) - secondary prevention in 10% of those treated - risk of myopathy, including rhabdomyolysis < 0.1% [273] - absolute risk reductions for all-cause mortality, myocardial infarction, & stroke of treatment with statins are modest compared with the relative risk reductions [305] - significant heterogeneity further reduces the certainty of the evidence [305] - conclusive association between absolute reductions in LDL-C levels & individual clinical outcomes is not established [305] * compare to diet & lifestyle behaviors - can prevent 4 out of 5 MIs [155] * compare to a Mediterranean diet: - NNT = 61 for 5 years to prevent 1 stroke, MI or death in subjects without known heart disease - 30 for 5 years to prevent 1 death or 1 cancer after MI * nearly all of 19 randomized controlled trials used to establish guidelines for statin use were industry-sponsored [258] - raw data from these trials has not been made available for peer review [258] * global market of US $20 billion annually fuels guidelines for statin use & further research [258] Dosage: 1) QD or QOD dosing may be equivalent [21] 2) most of benefit obtained at usual starting dose [26] 3) combination of low-dose statin plus either a bile acid sequestrant or ezetimibe reduces LDL cholesterol more than high-dose statin monotherapy [128] - long-term clinical benefits uncertain 4) high-intensity statin - atorvastatin 40-80 mg QD, rosuvastatin 20-40 mg QD - indications - known cardiovascular disease - LDL cholesterol > 190 mg/dL - diabetes mellitus & 10 year cardiovascular risk >= 7.5% [1,124] - treat-to-target LDL cholesterol 50-70 mg/dL non-inferior to high-intensity statins for patients with coronary artery disease [318] 5) moderate dose statins [1] - atorvastatin 10-20 mg QD, rosuvastatin 5-10 mg QD, simvastatin 20-40 mg QD, provastatin 40-80 mg QD, lovastatin 40 mg QD, fluvastatin 40 mg BID - indications - LDL-cholesterol > 70 mg/dL AND - diabetes mellitus OR - 10 year cardiovascular risk >= 7.5% [1] - high-dose statin otherwise indicated, but - age > 75 [88,207] - renal insufficiency - coadministration of drug that interferes with statin metabolism [1] 6) high dose statins might be warranted for patients with ischemic stroke with evidence of atherosclerosis [306] 7) QHS dosing of short-acting statin may have benefit [156] Pharmacokinetics: 1) most statins are metabolized by cyt P450 3A4, except a) pravastatin is isomerized to inactive metabolite b) rosuvastatin (Crestor) & fluvastatin (Lescol) are metabolized by cyt P450 2C9 2) lovastatin bioavailability increased by food -> others may be taken without food [12] 3) most statins cross the blood brain barrier a) the CNS has its own cholesterol metabolism b) pravastatin does not penetrate the blood brain barrier, [54]; rosuvastatin probably doesn't either 4) transcriptional activity of the HMG-CoA reductase gene in the liver peaks in the middle of the night [156] - activity of a gene associated with statin-induced myopathy peaks in the middle of the day [156] Dosage adjustment in renal failure: - not required for atorvastatin, fluvastatin [12] Monitor: 1) liver function tests no longer routinely indicated [80,97,100] a) check LFTs prior to initiation of statin b) check LFTs again only if symptomatic c) slight difference in recommendations for each statin [74] d) discontinue if serum ALT or serum AST > 3x upper limit of normal e) increased liver function tests (< 10-fold normal) NOT associated with increased risk of hepatotoxicity [33] 2) creatine kinase [20] a) baseline levels on ALL patients (former recommendation) - not indicated in the absence of myalgias [1] b) recheck patients who develop myalgias or brown urine c) discontinue if 10x upper limit of normal d) monitor elevated levels < 10x normal weekly e) routine monitoring NOT recommended 3) lipid panel baseline, at 1-3 months, thereafter every 3-12 months* * no reason given except for assessment of medication compliance; no suggestion given how results of testing would change management [1] Adverse effects: 1) adverse effects occur in 17% of patients, mostly myopathy a) widely different reported incidence of adverse effects b) adverse effects occur in 13% of patients after rechallange with a different statin [116] c) simvastatin & pravastatin score best in safety profile [119] 2) statin myopathy [49, 115] a) increase in creatine kinase (mild to rhabdomyolysis) b) myopathy may occur with normal serum creatine kinase [22] c) risk factors [88] - older age - female gender - renal insufficiency - coadministration of fibrates, niacin, macrolides - coadministration of antiarrhythmic agents [315] - hypothyroidism - alcoholism - obesity - exertion - increased risk of exertional rhabdomyolysis (RR=3.0) [243] - LILRB5 variant rs12975366: T > C Asp247Gly may predispose to statin myopathy [264] - genetic variants in SLCO1B1 may predispose to statin myopathy [265] d) statin use attenuates substrate use during maximal exercise, induces muscle fatigue during repeated muscle contractions, & decreases muscle mitochondrial oxidative capacity [263] e) genetic variants in SLCO1B1 gene may predispose to statin myopathy [58] f) uncertain benefit of CoQ supplements [31,53] - CoQ supplements of no benefit [158] g) symptoms usually subside within a month or two after stopping the statin, but they sometimes persist longer [70] h) hydrophilic statins (fluvastatin, pravastatin, & rosuvastatin) less likely to cause statin myopathy than lipophilic statins [1] i) conflicting reports regarding frequency of statin myopathy - atorvastatin 10 mg QD in patients at high cardiovascular risk not associated with myopathy unless patients knew they were taking statin [245] - no overall effect of atorvastatin 20 mg on muscle symptoms compared with placebo [296] - > 90% of muscle symptoms in patients taking statins not due to statin [313] - 31% of new statin users complain of muscle symptoms; 13% discontinue use [316] - vitamin D not helpful [316] j) a statin-associated autoimmune-necrotizing myopathy with autoantibody directed against HMG-CoA reductase, the pharmacologic target of statins [129] - occurs in a minority of patients with statin-induced myopathy k) inflammatory myositis (inclusion body myositis) [268] 3) increased risk of musculoskeletal injuries (19%) - sprains, muscle strain [118] 4) increased risk of musculoskeletal pain (9%) - increased risk of generalized pain in cancer patients > 80 years of age [150] 5) increase risk of osteoarthritis & other arthropathies (7%) - not stastically significant [118] - increased risk of back disorders, including - spondylosis, intervertebral disc disorders, herniated discs spinal stenosis [246] - NNH=17, RR=1.5-1.7 (4 years use) [246] 6) memory impairment is the 2nd most common complaint [14,54] a) reversible cognitive impairment [97,203] b) most statins cross the blood brain barrier 1] the CNS has its own cholesterol metabolism 2] pravastatin does not cross the blood brain barrier - rosuvastatin probably does not either c) no increase in risk of cognitive impairment - no robust association between lipid levels or statin use & cognitive impairment [266] - data limited, especially for high-dose statins [125] - no definitive evidence of benefit or harm [277] d) no adverse affects on memory, cognition, or brain volumes in elderly >= 70 years [291] e) acute memory impairment within 30 days (RR=4.4, all antihyperlipidemic agents) [187] f) no increased risk of dementia or mild cognitive impairment whether lipophilic or hydrophilic statin [297] - risk of Alzheimer's disease may be elevated in persons in lowest quartile of baseline cognitive function [297] - no increased risk for dementia in patients with familial hypercholesterolemia taking high-intesity statins over most if not all of adult life [308] 7) may increase incidence of postoperative delirium [61] 8) hepatotoxicity (rare) [20,29,80] a) increased serum transaminases 3-10 fold 1.4% [40] - up to 3-fold is acceptable to continue statin [319] b) increased liver function tests (> 10-fold) 1% [29,33,40] c) statins reduce cardiovascular events in patients with moderately abnormal liver function tests [LFTs] d) statins more beneficial in patients with abnormal LFTs than with normal LFTs [77] e) patients with abnormal LFTs who receive statins tend to have improvements in LFTs [77,80] f) no particular statin is more or less likely to cause LFT abnormalities [80] g) statins account for 2% of drug-related hepatotoxicity [142] h) 18% of patients with statin-induced hepatotoxicity develop chronic liver disease [142] 9) increased risk of renal failure - acute renal failure (RR=1.3) - chronic renal failure (RR=1.4-1.5) [199] 10) peripheral neuropathy (< 0.1%/year) [16] a) no evidence that CoQ supplements help [18] b) may take 3-12 months for neuropathy to improve after discontinuing statin [18] c) statins do not increase risk of peripheral neuropathy [283] 11) statin use may increase risk of pneumonia [69] 12) intracranial hemorrhage (ICH) - increased risk independent of LDL [81] - no increased risk of intracerebral hemorrhage [175] - decreased risk of intracerebral hemorrhage (RR=0.68) [190] - pre-ICH statin use not associated with improved ICH functional outcome or mortality [191] - post-ICH statin use is not associated with an increased risk of ICH recurrence [191,322] - statins may reduce risk of intracranial hemorrhage [317] - discontinuation of statin after ICH is associated with increased risk of mortality (RR=3.9 within 30 days; RR=1.5 at 3 months [192] 13) statins may increase risk of type 2 diabetes (RR=1.12) a) risk is inherent in inhibition of HMG CoA reductase [145] - mediated by body weight or other modifiable metabolic factors [145] - impaired pancreatic beta-cell function [1] - increased peripheral insulin resistance [1] b) atorvastatin & rosuvastatin (evidence-base) c) risk may be dose-related [84] d) benefits outweigh risks in secondary prevention & high-risk patients [87,108,109] e) overall increase in risk varies dependent on dose, duration & source of data - ~ 10% [119] - risk of type 2 diabetes in statin users is 31% vs 19% in non users after 7 years; NNH=9 [197] f) higher dose statins & rosuvastatin, 10 mg & up; atorvastatin, 20 mg & up; simvastatin, 40 mg & up) with 15% higher rate of new diabetes diagnoses than lower-dose statin users [139] g) increased risk in patients with impaired glucose tolerance [112], (RR=1.5, number needed to harm = 12) [112] h) new-onset diabetes more common in patients with baseline HgbA1c) in the prediabetes range than in patients with lower HgbA1c [325] i) incidence of new-onset diabetes highest in 1st 4 months of statin use [139] j) 46% increase in risk for type 2 diabetes in statin users [193] k) statin use associated with diabetes progression in patients with diabetes [303] l) among patients with known diabetes at baseline, glycemia worsens slightly with statin therapy compared with placebo [325] m) risk may be associated with increased expression of LDL receptor [161] n) unknown if type 2 diabetes resolves when statin is discontinued [197] 14) NO evidence of increased cancer risk within 10 years [37] 15) decreased energy & increased fatigue with exertion, especially among women [103] 16) statin use in older men is associated with a slight reduction in physical activity [140] 17) increased risk of cataracts (9%, 20% without comorbidities) [122] 18) increased caloric intake (10%), including dietary fat (14%) with resultant increase in BMI (1.3 vs 0.4) for non-users [134] 19) statin use may increase risk of Parkinson's disease (RR=1.6-1.7) [239] - statin use associated with worse baseline nigrostriatal dopamine degeneration [302] - statin use prior to diagnosis of Parkinson's disease associated with increased risk of dementia [302] 20) not associated with increased risk of pancreatitis [107] 21) not associated with increased risk of erectile dysfunction [259] 22) accelerated coronary plaque calcification [267] - slower progression of coronary atherosclerosis volume - reduction of high-risk plaque features - no protection against progression of coronary lesions to high-grade stenoses [267] 23) increased risk of gynecomastia (RR=1.4) [241] 24) immune-mediated necrotizing myopathy (IMNM) Drug interactions: 1) inhibitors of cyt P450 3A4 inhibit metabolism of statins a) simvastatin (Zocor), lovastatin (Mevacor) > atorvastatin (Lipitor) b) pravastatin (Pravachol), rosuvastatin (Crestor), fluvastatin (Lescol) are safe to use with cyt P450 3A4 inhibitors c) pravastatin allegedly has least interaction [68] d) cyt P450 3A4 inhibitors that may interact with statins - antibiotics: - erythromycin, clarithromycin, telithromycin, isoniazid - azithromycin ok - antifugals: - itraconazole, ketoconazole - terbinafine ok - Ca+2 channel blockers: diltiazem, nifedipine, verapamil - antiretrovirals: delavirdine, efavirenz, indinavir, ritonavir, saquinavir - others, see cyt P450 3A4 2) increased risk of myopathy when statin is combined with: a) fibrates, cyclosporine, niacin b) use fenofibrate rather than gemfibrozil with statin [68] c) fluvastatin may be safest to use with cyclosporine [68] 3) diminished response to vitamin D [255] 4) statin drug interaction summaries [47,68,72,238] Laboratory: - baseline serum ALT; further monitoring unnecessary if normal [1] - routine serum creatine kinase unnecessary - serum C-reactive protein does not predict response to statins [82] - elevated fasting serum triglyceride in patients on statins is associated with an increased risk of cardiovascular events (when >175 mg/dL, RR=1.6 relative to < 80 mg/dL) [184] Mechanism of action: 1) inhibition of HMG CoA reductase a) inhibition to cholesterol biosynthesis - response to lipid-lowering effects dependent on genotype: apo E2 > apo E3 > apo E4 b) also inhibits biosynthesis of isopentenyl pyrophosphate derivatives, including: 1] ubiquinone CoQ 2] dolichol phosphate 3] prenyl proteins c) inhibition of HMG CoA reductase in the liver stimulates LDL-receptors, which results in an increased clearance of LDL from the bloodstream & a decrease in blood cholesterol & LDL cholesterol levels 2) statin use associated with transformation of coronary atherosclerosis toward high-density calcification but does not slow plaque progression on serial coronary CT angiography [301] 3) anti-inflammatory properties a) reduction of plasma levels of C-reactive protein [7] b) lowers mortality associated with sepsis [11] 1] Gram negative bacteria 2] Staphylococcus aureus - reduces risk of community-acquired sepsis due to S aureus [257] c) improves renal tubule function; reduces proteinuria [20] 4) reduction in autoimmunity [24] a) reduction in MHC class II molecules b) increased production of Th2 cells c) decreased production of Th1 cells 5) anti-platelet effects [13] 6) enhancement of nitric oxide synthase activity [9] 7) inhibition of endothelin-1 [9] 8) inhibits proliferation of endothelial cells - effects observed at somewhat higher level than achieved with clinical dose 9) may have antithrombotic effects & fibrinolytic effects & may enhance the activity of other fibrinolytic agents [81,188,189] - statins inhibit expression of tissue factor which downregulates the coagulation cascade extrinsic pathway [188] - statins increase thrombomodulin expression on endothelial cells, thus may facilitate anticoagulation via protein C - most of the antithrombotic effects of statins are attributed to the inhibition of isoprenylation of signaling proteins [188] 10) reduces risk of myocardial infarction & stroke in diabetics regardless of cholesterol levels [28] 11) continuation of prescribed statin therapy lowers risk for all-cause mortality among patients with & without coronary heart disease (mean age, 58 years; 51% female) [64] 12) pravastatin does not lower blood pressure; it is not likely that other statin do either [73] 13) high doses of rosuvastatin & atorvastatin result in similar atherosclerosis regression, despite greater reductions in LDL cholesterol with rosuvastatin [86] 14) enhancement of osteoblast activity [2] 15) not much of an effect on non-cardiovascular outcomes [270] Notes: - for comparison of different statins (see [80]) - PCSK9 inhibitors may enhance LDL-lowering effect of statins [110] - exercise & improved fitness [7 METS] as adjunct treatment to statins may further diminish risk of mortality in patients with dyslipidemia [112] - advertisements increase statin use only in patients for whom a statin is not indicated [120] - 2013 AHA & ACC guidelines increase number of Americans eligible for statins - most of increase is for primary prevention - 48% of population eligible for statins [131] - 87% of men 60-75 years of age eligible for statins [132] - according to industry-sponsored study, not being offered a statin was the most common reason for non-use [280] - for secondary prevention, not being offered a statin & discontuing use of a statin were equally common [280] - most patients who discontinued statins did so because of adverse effects [280] - 1/3 of elderly (>= 80 years) without vascular disease prescribed statins [195] - generic statins associated with - better medication compliance (77% vs 71%) - slightly better outcomes - 8% fewer cardiovascular events - 1.5 fewer cardiovascular events per 100 patient years - improved affordablility [143] - patients with serious cardiovascular risk least likely to stop statin [204] - stopping statin therapy may be associated with increased cardiovascular risk 13.9% vs 12.2% [251] - a higher medication possession ratio among veterans with cadiovascular disease associated with fewer hospitalizations for ischemic heart disease & stroke & lower mortality [278] - in contrast, a statin controversy in 2013 in France led to discontinuation of statin use for primary prevention by 50% & all-cause mortality & cardiovascular mortality declined rather than increased [253] - nearly all of 19 randomized controlled trials reviewed for guidelines were industry-sponsored - a global statin market of roughly US $20 billion annually drives much of the research & interest in statins for primary prevention [254] - women & men of color are less likely to receive appropriate statin therapy than non-Hispanic white men [321]

Interactions

drug interactions drug adverse effects (more general classes) monitor with HMG CoA reductase inhibitors (statins)

Related

cholesterol biosynthesis high-intensity statin therapy HMG CoA reductase inhibitor contraindication (statin contraindication) hydroxymethylglutaryl [HMG] CoA reductase (HMGCR) statin clinical trials statin deprescribing statin intolerance statin myopathy statin therapy in children Statins & the risk of dementia

Specific

hydrophilic statin lipophilic statin statins in the elderly

General

anti-hyperlipidemic agent enzyme inhibitor

Properties

INHIBITS: HMG CoA reductase

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2012, 2015, 2018, 2021.
  2. Journal Watch 20(15): 124, 2000 Wang PS et al, HMG-CoA reductase inhibitors and the risk of hip fractures in elderly patients. JAMA 283:3211, 2000 PMID: 10866868 - Chan KA et al Inhibitors of hydroxymethylglutaryl-coenzyme A reductase and risk of fracture among older women. Lancet 355:2185, 2000 PMID: 10881890 - Edwards CJ et al Oral statins and increased bone-mineral density in postmenopausal women. Lancet 355:2218, 2000 PMID: 10881898 - Cummings SR & Bauer DC Do statins prevent both cardiovascular disease and fracture? JAMA 283:3255, 2000 PMID: 10866875
  3. Journal Watch 21(1):1, 2001 Horne BD et al Statin therapy, lipid levels, C-reactive protein and the survival of patients with angiographically severe coronary artery disease. J Am Coll Cardiol 36:1774, 2000 PMID: 11092643
  4. Journal Watch 21(1):3, 2001 Jick H et al Statins and the risk of dementia. Lancet 356:1627, 2000 PMID: 11089820
  5. Prescriber's Letter 8(2):8 2001
  6. Journal Watch 21(15):122, 2001 Ridker PM et al Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med, 344:1959, 2001 PMID: 11430324
  7. Journal Watch 21(15):121, 2001 Albert MA et al Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study. JAMA 286:64, 2001 PMID: 11434828 - Simpson RJ Placing PRINCE in perspective. JAMA 286:91, 2001 PMID: 11434833
  8. Journal Watch 21(19):157, 2001 Hall NF et al Risk of macular degeneration in users of statins: cross sectional study. BMJ 18:323, 2001 PMID: 11509429
  9. Marx J. Alzheimer's disease. Bad for the heart, bad for the mind? Science 294:508-509, 2001 PMID: 11641483
  10. Prescriber's Letter 8(12):69 2001
  11. Journal Watch 21(23):185, 2001
  12. Prescriber's Letter 9(1):1 2002
  13. Hartmann T. Cholesterol, A beta and Alzheimer's disease. Trends Neurosci. 2001 Nov;24(11 Suppl):S45-8. Review. PMID: 11881745
  14. Prescriber's Letter 9(3):14 2002 Statins and Memory Detail-Document#: 180303 (subscription needed) http://www.prescribersletter.com
  15. Prescriber's Letter 9(4):20 2002
  16. Journal Watch 22(12):91, 2002 Gaist D et al Statins and risk of polyneuropathy: a case-control study. Neurology 58:1333, 2002 PMID: 12011277
  17. Journal Watch 22(12):92, 2002 Ridker PM et al Plasma homocysteine concentration, statin therapy, and the risk of first acute coronary events. Circulation 105:1776, 2002 PMID: 11956118
  18. Prescriber's Letter 9(7):37-38 2002
  19. Journal Watch 22(16):124, 2002 Heart Protection Study Collaborative Group MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360:7, 2002 PMID: 12114036 Heart Protection Study Collaborative Group, MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360:23, 2002 PMID: 12114037
  20. Prescriber's Letter 9(9):49 2002
  21. Prescriber's Letter 9(11):63 2002
  22. Journal Watch 22(23):171, 2002 Phillips PS et al Statin-associated myopathy with normal creatine kinase levels. Ann Intern Med 137:581, 2002 PMID: 12353945
  23. Prescriber's Letter 9(12):71 2002
  24. Journal Watch 23(1):2, 2003 Youssef S et al The HMG-CoA reductase inhibitor, atorvastatin, promotes a Th2 bias and reverses paralysis in central nervous system autoimmune disease. Nature 420:78, 2002 PMID: 12422218
  25. Journal Watch 23(3):23, 2003 Shepherd J et al Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 360:1623, 2002 PMID: 12103306 - Collins R & Armitage J High-risk elderly patients PROSPER from cholesterol-lowering therapy. Lancet 360:1618, 2002 PMID: 12457780 http://www.thelancet.com/journal/vol360/iss9346/full/llan.360.9346.original_research.23196.1
  26. Combination Cholesterol-Lowering Therapy Prescriber's Letter 10(3):14 2003 Detail-Document#: 190304 (subscription needed) http://www.prescribersletter.com
  27. Journal Watch 23(10):77, 2003 Sever PS et al Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 361(Apr 5):1149, 2003 PMID: 12686036 - Lindhol LH & Samuelsson O What are the odds at ASCOT today? Lancet 361:1144, 2003 PMID: 12686031
  28. Statin Therapy for Patients with Diabetes Prescriber's Letter 10(7):38 2003 Detail-Document#: 190702 (subscription needed) http://www.prescribersletter.com
  29. Characteristics of the Various Statins Prescriber's Letter 10(8):43 2003 Detail-Document#: 190801 (subscription needed) http://www.prescribersletter.com
  30. Statins and Peripheral Arterial Disease Prescriber's Letter 10(10):60 2003 Detail-Document#: 191006 (subscription needed) http://www.prescribersletter.com
  31. Lipid Lowering with Statins: How low should LDL go? Prescriber's Letter 11(4):19 2004 Detail-Document#: 200401 (subscription needed) http://www.prescribersletter.com
  32. Lipid Control in Diabetes: Review of Clinical Practice Guidelines Prescriber's Letter 11(6):35 2004 Detail-Document#: 200612 (subscription needed) http://www.prescribersletter.com
  33. Journal Watch 24(12):97, 2004 Chalasani N, Aljadhey H, Kesterson J, Murray MD, Hall SD. Patients with elevated liver enzymes are not at higher risk for statin hepatotoxicity. Gastroenterology. 2004 May;126(5):1287-92. PMID: 15131789
  34. What You Should Know About Statins Prescriber's Letter 11(7):40 2004 Detail-Document#: 200701 (subscription needed) http://www.prescribersletter.com
  35. Do All Statins Need to be Taken in the Evening? Prescriber's Letter 10(12):70 2003 Detail-Document#: 191206 (subscription needed) http://www.prescribersletter.com
  36. Journal Watch 24(14):110, 2004 Spencer FA, Allegrone J, Goldberg RJ, Gore JM, Fox KA, Granger CB, Mehta RH, Brieger D; GRACE Investigators. Association of statin therapy with outcomes of acute coronary syndromes: the GRACE study. Ann Intern Med. 2004 Jun 1;140(11):857-66. PMID: 15172899
  37. Journal Watch 24(19):151, 2004 Strandberg TE, Pyorala K, Cook TJ, Wilhelmsen L, Faergeman O, Thorgeirsson G, Pedersen TR, Kjekshus J; 4S Group. Mortality and incidence of cancer during 10-year follow-up of the Scandinavian Simvastatin Survival Study (4S). Lancet. 2004 Aug 28;364(9436):771-7. PMID: 15337403
  38. Journal Watch 25(2):16, 2005 Graham DJ, Staffa JA, Shatin D, Andrade SE, Schech SD, La Grenade L, Gurwitz JH, Chan KA, Goodman MJ, Platt R. Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA. 2004 Dec 1;292(21):2585-90. Epub 2004 Nov 22. PMID: 15572716
  39. Journal Watch 25(12):95, 2005 Poynter JN, Gruber SB, Higgins PD, Almog R, Bonner JD, Rennert HS, Low M, Greenson JK, Rennert G. Statins and the risk of colorectal cancer. N Engl J Med. 2005 May 26;352(21):2184-92. PMID: 15917383
  40. Journal Watch 25(14):114, 2005 Charles EC, Olson KL, Sandhoff BG, McClure DL, Merenich JA. Evaluation of cases of severe statin-related transaminitis within a large health maintenance organization. Am J Med. 2005 Jun;118(6):618-24. PMID: 15922693
  41. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, Kirby A, Sourjina T, Peto R, Collins R, Simes R; Cholesterol Treatment Trialists' (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005 Oct 8;366(9493):1267-78. Epub 2005 Sep 27. Erratum in: Lancet. 2005 Oct 15-21;366(9494):1358. PMID: 16214597 - Baigent C et al for the Cholesterol Treatment Trialists (CTT) Collaboration Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010 Nov 13;376(9753):1670-81. Epub 2010 Nov 8. PMID: 21067804
  42. Scranton RE et al, Statin use and fracture risk: study of a US Veterans Population Arch Intern Med 2005; 165:2007 PMID: 16186471
  43. Dale KM, Coleman CI, Henyan NN, Kluger J, White CM. Statins and cancer risk: a meta-analysis. JAMA. 2006 Jan 4;295(1):74-80. PMID: 16391219
  44. Hackam DG, Mamdani M, Li P, Redelmeier DA. Statins and sepsis in patients with cardiovascular disease: a population-based cohort analysis. Lancet. 2006 Feb 4;367(9508):413-8. PMID: 16458766
  45. Foody JM et al, Hydroxymethylglutaryl-CoA reductase inhibitors in older persons with acute myocardial infarction: Evidence for age- statin interaction J Am Geriatr Soc 2006; 54:421 PMID: 16551308
  46. Foody JM, Shah R, Galusha D, Masoudi FA, Havranek EP, Krumholz HM. Statins and mortality among elderly patients hospitalized with heart failure. Circulation. 2006 Feb 28;113(8):1086-92. Epub 2006 Feb 20. PMID: 16490817 - Sola S et al, Atorvastatin improves left ventricular systolic function and serum markers of inflammation in nonischemic heart failure. J Am Coll Cardiol 2006, 47:332 PMID: 16412856 - Ramasubbu K and Mann DL The emerging role of statins in the treatment of heart failure. J Am Coll Cardiol 2006, 47:342 PMID: 16412858
  47. Prescriber's Letter 13(4): 2006 Clinically Significant Statin Drug Interactions Detail-Document#: 220404 (subscription needed) http://www.prescribersletter.com
  48. Internal Medicine World Report, 21(3): March 2006
  49. Antons KA et al, Clinical perspectives of statin-induced rhabdomyolysis. Am J Med 2006; 119:400 PMID: 1661050
  50. Klein BEK et al, Statin use and incident nuclear cataract. JAMA 2006; 295:2752 PMID: 16788130
  51. Prescriber's Letter 13(8): 2006 Characteristics of the Various Statins Detail-Document#: 220802 (subscription needed) http://www.prescribersletter.com
  52. Hindler K et al, Improved postoperative outcomes associated with preoperative statin therapy. Anesthesiology 2006, 105:1260 PMID: 17122590
  53. Caso G, Kelly P, McNurlan MA, Lawson WE. Effect of coenzyme q10 on myopathic symptoms in patients treated with statins. Am J Cardiol. 2007 May 15;99(10):1409-12. Epub 2007 Apr 3. PMID: 17493470
  54. Prescriber's Letter 15(4): 2008 Statins and Cognitive Function Detail-Document#: 240411 (subscription needed) http://www.prescribersletter.com - Kuller LH. Statins and dementia. Curr Atheroscler Rep. 2007 Aug;9(2):154-61. Review. PMID: 17877925 - Wagstaff LR, Mitton MW, Arvik BM, Doraiswamy PM. Statin-associated memory loss: analysis of 60 case reports and review of the literature. Pharmacotherapy 2003;23:871-80. PMID: 12885101 - Muldoon MF, Ryan CM, Sereika SM, Flory JD, Manuck SB. Randomized trial of the effects of simvastatin on cognitive functioning in hypercholesterolemic adults. Am J Med. 2004 Dec 1;117(11):823-9. PMID: 15589485
  55. Karp I et al, Statins and cancer risk Am J Med 2008, 121:302 PMID: 18374689
  56. Mizuno K et al. Usefulness of pravastatin in primary prevention of cardiovascular events in women: Analysis of the Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese (MEGA study). Circulation 2008 Jan 29; 117:494. PMID: 18172039
  57. Karp I et al, Statins and cancer risk. Am J Med 2008, 121:202 PMID: 18374689
  58. Link E et al. SLCO1B1 variants and statin-induced myopathy. A genomewide study. N Engl J Med 2008 Aug 21; 359:789. PMID: 18650507 http://dx.doi.org/10.1056/NEJMoa0801936
  59. Buettner C et al. Prevalence of musculoskeletal pain and statin use. J Gen Intern Med 2008 Aug; 23:1182. PMID: 18449611 http://dx.doi.org/10.1007/s11606-008-0636-7
  60. Beck M. Can a drug that helps hearts be harmful to the brain? Wall Street Journal 2008 Feb 12. http://online.wsj.com/article/SB120277403869360595.html
  61. Redelmeier DA et al. Delirium after elective surgery among elderly patients taking statins. CMAJ 2008 Sep 23; 179:645. PMID: 18809895 http://dx.doi.org/10.1503/cmaj.080443
  62. Hindler K et al. Improved postoperative outcomes associated with preoperative statin therapy. Anesthesiology 2006 Dec; 105:1260 PMID: 17122590
  63. Golomb BA et al. Conceptual foundations of the UCSD Statin Study: A randomized controlled trial assessing the impact of statins on cognition, behavior, and biochemistry. Arch Intern Med 2004 Jan 26; 164:153. PMID: 14744838
  64. Shalev V et al, Continuation of Statin Treatment and All-Cause Mortality: A Population-Based Cohort Study Arch Intern Med. 2009;169(3):216 PMID: 19204217
  65. Pletcher MJ et al Comparing impact and cost-effectiveness of primary prevention strategies for lipid lowering. Ann Intern Med 2009 Feb 17; 150:243. PMID: 19221376
  66. Glynn RJ et al A randomized trial of rosuvastatin in the prevention of venous thromboembolism. N Engl J Med 2009 Mar 29 PMID: 19329822 - Prescriber's Letter 16(5) 2000 Statins for Venous Thromboembolism Prevention Detail-Document#: 250503 (subscription needed) http://www.prescribersletter.com
  67. Brugts JJ et al The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials BMJ 2009;338:b2376 PMID: 19567909 http://www.bmj.com/cgi/content/full/338/jun30_1/b2376
  68. Prescriber's Letter 16(8): 2009 Clinically Significant Statin Drug Interactions Detail-Document#: 250812
  69. Dublin S et al. Statin use and risk of community acquired pneumonia in older people: Population based case-control study. BMJ 2009 Jun 16; 338:b2137 PMID: 19531550 http://dx.doi.org/10.1136/bmj.b2137
  70. Prescriber's Letter 16(10): 2009 COMMENTARY: Statin Myopathy CHART: Clinically Significant Statin Drug Interactions GUIDELINES: Use and Safety of Statins (ACC/AHA/NHLBI, 2002) Detail-Document#: 251008 (subscription needed) http://www.prescribersletter.com
  71. GISSI-HF Investigators. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): A randomised, double-blind, placebo-controlled trial. Lancet 2008 Oct 4; 372:1223. PMID: 18757090 - Prescriber's Letter 15(11): 2008 Statins and Fish Oil for Heart Failure Detail-Document#: 241103 (subscription needed) http://www.prescribersletter.com - Kjekshus J et al for the CORONA group Rosuvastatin in older patients with systolic heart failure. N Engl J Med 2007, Nov 5 http://dx.doi.org/10.1056/NEJMoa0706201
  72. Prescriber's Letter 17(4): 2010 CHART: Clinically Significant Statin Drug Interactions Detail-Document#: 260409 (subscription needed) http://www.prescribersletter.com
  73. Mancia G et al. Statins, antihypertensive treatment, and blood pressure control in clinic and over 24 hours: Evidence from PHYLLIS randomised double blind trial. BMJ 2010 Mar 25; 340:c1197 PMID: 20339154 http://dx.doi.org/10.1136/bmj.c1197
  74. Prescriber's Letter 17(6): 2010 CHART: Characteristics of the Various Statins CHART: Clinically Significant Statin Drug Interactions Detail-Document#: 260611 (subscription needed) http://www.prescribersletter.com
  75. Ray KK et al, Statins and All-Cause Mortality in High-Risk Primary Prevention A Meta-analysis of 11 Randomized Controlled Trials Involving 65 229 Participants Arch Intern Med. 2010;170(12):1024-1031 PMID: 20585067 http://archinte.ama-assn.org/cgi/content/full/170/12/1024 - de Logeril M et al Cholesterol Lowering, Cardiovascular Diseases, and the Rosuvastatin-JUPITER Controversy Arch Intern Med. 2010;170(12):1032-1036 PMID: 20585068 http://archinte.ama-assn.org/cgi/content/short/170/12/1032 - Kaul S et al. By Jove! What is a clinician to make of JUPITER? Arch Intern Med 2010 Jun 28; 170:1073. PMID: 20585074 - Green LA. Cholesterol-lowering therapy for primary prevention: Still much we don't know. Arch Intern Med 2010 Jun 28; 170:1007 PMID: 20585062
  76. Prescriber's Letter 17(8): 2010 Statins for Primary Prevention Detail-Document#: 260814 (subscription needed) http://www.prescribersletter.com
  77. Athyros VG et al Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post-hoc analysis Lancet 2010 Dec 4; 376:1916 PMID: 21109302 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961272-X/fulltext
  78. Geriatrics at your Fingertips, 13th edition, 2011 Reuben DB et al (eds) American Geriatric Society
  79. Medical Knowledge Self Assessment Program (MKSAP) 15, American College of Physicians, Philadelphia 2009
  80. Prescriber's Letter 18(1): 2011 COMMENTARY: Statins and the Liver CHART: Characteristics of the Various Statins Detail-Document#: 270104 (subscription needed) http://www.prescribersletter.com
  81. Westover MB et al Statin Use Following Intracerebral Hemorrhage: A decision analysis. Archives of Neurology Jan 10, 2011 PMID: 21220650 http://archneur.ama-assn.org/cgi/content/full/archneurol.2010.356 - Goldstein LB Statins After Intracerebral Hemorrhage: To Treat or Not to Treat Archives of Neurology Jan 11, 2011 PMID: 21220651 http://archneur.ama-assn.org/cgi/content/full/archneurol.2010.349
  82. Heart Protection Study Collaborative Group C-reactive protein concentration and the vascular benefits of statin therapy: an analysis of 20,536 patients in the Heart Protection Study The Lancet, Early Online Publication, 28 January 2011 PMID: 21277016 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62174-5/fulltext
  83. Douglas I et al. Effect of statin treatment on short term mortality after pneumonia episode: Cohort study. BMJ 2011 Apr 6; 342:d1642. PMID: 21471172
  84. Prescriber's Letter 18(8): 2011 Do Statins Cause Diabetes? Detail-Document#: 270804 (subscription needed) http://www.prescribersletter.com
  85. Prescriber's Letter 18(9): 2011 CHART: Statin Dose Comparison CHART: Clinically Significant Statin Drug Interactions Detail-Document#: 270902 (subscription needed) http://www.prescribersletter.com
  86. Nicholls SJ et al. Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med 2011 Nov 15 PMID: 22085316 http://www.nejm.org/doi/full/10.1056/NEJMoa1110874
  87. van den Hoek HL et al. Statins and prevention of infections: Systematic review and meta-analysis of data from large randomised placebo controlled trials. BMJ 2011 Nov 29; 343:d7281 PMID: 22127443
  88. Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010 - Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013 - Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016 - Geriatric Review Syllabus, 10th edition () Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019
  89. Prescriber's Letter 19(2): 2012 COMMENTARY: Do Benefits of Statins Outweigh Risks in the Elderly? Detail-Document#: 280225 (subscription needed) http://www.prescribersletter.com - Strandberg TE et al Statin treatment is associated with clearly reduced mortality risk of cardiovascular patients aged 75 years and older. J Gerontol A Biol Sci Med Sci 2008;63:213-4 PMID: 18314461
  90. Diamond GA, Kaul S. Prevention and treatment: a tale of two strategies. J Am Coll Cardiol 2008;51:46-8. PMID: 18174035
  91. Morley JE. The cholesterol conundrum. J Am Geriatr Soc 2011;59:1955-6. PMID: 22091506
  92. Newson RS, Felix JF, Heeringa J, et al. Association between serum cholesterol and noncardiovascular mortality in older age. J Am Geriatr Soc 2011;59:1779-85 PMID: 22091490
  93. Allen Maycock CA et al. Statin therapy is associated with reduced mortality across all age groups of individuals with significant coronary disease, including very elderly patients. J Am Coll Cardiol 2002;40:1777-85. PMID: 12446061
  94. Maroo BP, Lavie CJ, Milani RV. Secondary prevention of coronary heart disease in elderly patients following myocardial infarction: are all HMG-CoA reductase inhibitors alike? Drugs Aging 2008;25:649-64. PMID: 18665658
  95. National Cholesterol Education Program. Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III. Final Report. September 2002.
  96. Afilalo J, Duque G, Steele R, et al. Statins for secondary prevention in elderly patients: a hierarchical bayesian meta-analysis. J Am Coll Cardiol 2008;51:37-45. PMID: 18174034
  97. FDA MedWatch: 02/28/2012 Statin Drugs - Drug Safety Communication: Class Labeling Change http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm293670.htm
  98. Boekholdt SM et al Association of LDL Cholesterol, Non-HDL Cholesterol, and Apolipoprotein B Levels With Risk of Cardiovascular Events Among Patients Treated With Statins JAMA. 2012;307(12):1302-1309 PMID: 22453571 http://jama.ama-assn.org/content/307/12/1302.short
  99. Prescriber's Letter 19(4): 2012 COMMENTARY: Update on Statin Risks PATIENT EDUCATION HANDOUT: What You Should Know About Statins Detail-Document#: 280423 (subscription needed) http://www.prescribersletter.com
  100. Prescriber's Letter 19(5): 2012 CHART: Characteristics of the Various Statins Detail-Document#: 280523 (subscription needed) http://www.prescribersletter.com
  101. Cholesterol Treatment Trialists' (CTT) Collaborators The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials The Lancet, Early Online Publication, 17 May 2012 PMID: 22607822 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60367-5/fulltext - Ebrahim S and Casas JP Statins for all by the age of 50 years? The Lancet, Early Online Publication, 17 May 2012 PMID: 22607823 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60694-1/fulltext
  102. Prescriber's Letter 19(6): 2012 COMMENTARY: Statin-Associated Muscle Symptoms CHART: Clinically Significant Statin Drug Interactions CHART: Characteristics of the Various Statins Detail-Document#: 280616 (subscription needed) http://www.prescribersletter.com
  103. Golomb BA et al Effects of Statins on Energy and Fatigue With Exertion: Results From a Randomized Controlled Trial Arch Intern Med. 2012;():1-2. PMID: 22688574 http://archinte.jamanetwork.com/article.aspx?articleid=1182551
  104. same as 101
  105. Gutierrez J et al Statin Therapy in the Prevention of Recurrent Cardiovascular Events: A Sex-Based Meta-analysis Arch Intern Med. 2012;172(12):909-919 PMID: 22732744 http://archinte.jamanetwork.com/article.aspx?articleid=1195535 - Taylor F and Ebrahim S Statins Work Just as Well in Women as in Men: Comment on "Statin Therapy in the Prevention of Recurrent Cardiovascular Events" Arch Intern Med. 2012 Jun 25;172(12):919-20. PMID: 22732745 - Redberg RF Don't Assume Women Are the Same as Men: Include Them in the Trial: Comment on "Statin Therapy in the Prevention of Recurrent Cardiovascular Events" Arch Intern Med. 2012 Jun 25;172(12):921. PMID: 22732746
  106. Sheppard JP et al. Impact of age and sex on primary preventive treatment for cardiovascular disease in the West Midlands, UK: Cross sectional study. BMJ 2012 Jul 12; 345:e4535 PMID: 22791787
  107. Preiss D et al. Lipid-modifying therapies and risk of pancreatitis: A meta-analysis. JAMA 2012 Aug 22/29; 308:804 PMID: 22910758
  108. Wang KL et al. Statins, risk of diabetes, and implications on outcomes in the general population. J Am Coll Cardiol 2012 Aug 2; PMID: 22884288 http://www.sciencedirect.com/science/article/pii/S0735109712020694
  109. Ridker PM et al. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: An analysis from the JUPITER trial. Lancet 2012 Aug 11; 380:565 PMID: 22883507
  110. Roth EM et al Atorvastatin with or without an Antibody to PCSK9 in Primary Hypercholesterolemia. N Engl J Med. Oct 31, 2012 PMID: 23113833 http://www.nejm.org/doi/full/10.1056/NEJMoa1201832 - Giugliano RP et al Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study The Lancet, Early Online Publication, 6 November 2012 PMID: 23141813 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61770-X/abstract - Tonkin AM and Watts GF Into the future: diversifying lipid management The Lancet, Early Online Publication, 6 November 2012 PMID: 23141812 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61888-1/fulltext
  111. Nielsen SF et al Statin Use and Reduced Cancer-Related Mortality N Engl J Med 2012; 367:1792-1802 PMID: 23134381 http://www.nejm.org/doi/full/10.1056/NEJMoa1201735 - Caporaso NE Statins and Cancer-Related Mortality - Let's Work Together. N Engl J Med 2012; 367:1848-1850 PMID: 23134387 - Chiu H-F et al. Statin use and the risk of liver cancer: A population-based case-control study. Am J Gastroenterol 2011 May; 106:894. PMID: 21157439
  112. Kokkinos PF Interactive effects of fitness and statin treatment on mortality risk in veterans with dyslipidaemia: a cohort study. The Lancet, Early Online Publication, 28 November 2012 PMID: 23199849 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61426-3/abstract
  113. Kokkinos PF et al. Interactive effects of fitness and statin treatment on mortality risk in veterans with dyslipidaemia: A cohort study. Lancet 2012 Nov 28 PMID: 23199849
  114. Brunelli SM et al. Preoperative statin use and postoperative acute kidney injury. Am J Med 2012 Dec; 125:1195 PMID: 23062398 - Rosner MH. Prevention of postoperative acute kidney injury: One step closer. Am J Med 2012 Dec; 125:1153. PMID: 23084972
  115. Joy TR, Hegele RA. Narrative review: statin-related myopathy. Ann Intern Med. 2009 Jun 16;150(12):858-68. PMID: 19528564
  116. Zhang H et al Discontinuation of Statins in Routine Care Settings: A Cohort Study. Ann Intern Med. 2 April 2013;158(7):526-534 PMID: 23546564 http://annals.org/article.aspx?articleid=1671715 - Grundy SM Statin Discontinuation and Intolerance: The Challenge of Lifelong Therapy. Ann Intern Med. 2 April 2013;158(7):562-563 PMID: 23546569 http://annals.org/article.aspx?articleid=1671720
  117. Kazmin A, Garcia-Bournissen F, Koren G. Risks of statin use during pregnancy: a systematic review. J Obstet Gynaecol Can. 2007 Nov;29(11):906-8. PMID: 17977494
  118. Mansi I, Frei CR, Pugh MJ, Makris U, Mortensen EM. Statins and musculoskeletal conditions, arthropathies, and injuries. JAMA Intern Med 2013 PMID: 23877079 http://archinte.jamanetwork.com/article.aspx?articleid=1691918
  119. Naci H et al Comparative Tolerability and Harms of Individual Statins: A Study-Level Network Meta-Analysis of 246,955 Participants from 135 Randomized Controlled Trials. Circulation. July 9, 2013 PMID: 23838105 http://circoutcomes.ahajournals.org/content/early/2013/07/09/CIRCOUTCOMES.111.000071.full.pdf+html
  120. Niederdeppe J et al. Direct-to-consumer television advertising exposure, diagnosis with high cholesterol, and statin use. J Gen Intern Med 2013 Jul; 28:886 PMID: 23463454 - Ross JS and Kravitz RL. Direct-to-consumer television advertising: Time to turn off the tube? J Gen Intern Med 2013 Jul; 28:862. PMID: 23539285
  121. Savarese G et al Benefits Of Statins In Elderly Subjects Without Established Cardiovascular Disease. A Meta-Analysis. J Am Coll Cardiol. 2013 Dec 3;62(22):2090-9. PMID: 23954343 http://content.onlinejacc.org/article.aspx?articleid=1732396 - Waters DD Meta-analyses of Statin Trials: Clear Benefit for Primary Prevention in the Elderly. J Am Coll Cardiol. 2013 Dec 3;62(22):2100-1 PMID: 23994398 http://content.onlinejacc.org/article.aspx?articleid=1732395
  122. Leuschen J et al Association of Statin Use With Cataracts. A Propensity Score- Matched Analysis. AMA Ophthalmol. Published online September 19, 2013 PMID: 24052188 http://archopht.jamanetwork.com/article.aspx?articleid=1739520
  123. Subramanian S et al High Dose Atorvastatin Reduces Periodontal Inflammation: A Novel Pleiotropic Effect of Statins. Journal of the American College of Cardiology.Sept 24,2013 PMID: 24070911 http://www.sciencedirect.com/science/article/pii/S073510971305314X - Blaha MJ and Martin SS How Do Statins Work? Changing Paradigms with Implications for Statin Allocation. PMID: 24067403 http://www.sciencedirect.com/science/article/pii/S0735109713053138
  124. Stone NJ et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013 Nov 12 PMID: 24222016 http://content.onlinejacc.org/article.aspx?articleid=1770217
  125. Richardson K et al Statins and Cognitive Function: A Systematic Review. Ann Intern Med. 2013;159(10):688-697 PMID: 24247674 http://annals.org/article.aspx?articleid=1770674
  126. Calderon RM, Cubeddu LX, Goldberg RB, Schiff ER. Statins in the treatment of dyslipidemia in the presence of elevated liver aminotransferase levels: a therapeutic dilemma. Mayo Clin Proc. 2010 Apr;85(4):349-56 PMID: 20360293
  127. Hayward RA, Krumholz HM, Zulman DM, Timbie JW, Vijan S. Optimizing statin treatment for primary prevention of coronary artery disease. Ann Intern Med. 2010 Jan 19;152(2):69-77 PMID: 20083825
  128. Gudzune KA, Monroe AK, Sharma R et al Effectiveness of Combination Therapy With Statin and Another Lipid-Modifying Agent Compared With Intensified Statin Monotherapy: A Systematic Review. Ann Intern Med. Published online 11 February 2014 PMID: 24514899 http://annals.org/article.aspx?articleid=1828554
  129. Mohassel P and Mammen AL The Spectrum of Statin Myopathy. Curr Opin Rheumatol. 2013;25(6):747-752. PMID: 24061077 http://www.medscape.com/viewarticle/814502
  130. Chataway J et al Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial. The Lancet, Early Online Publication, 19 March 2014 PMID: 24655729 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2962242-4/abstract - Palace J and Robertson N Modifying disability in progressive multiple sclerosis The Lancet, Early Online Publication, 19 March 2014 PMID: 24655728 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2962641-0/fulltext
  131. Pencina MJ et al Application of New Cholesterol Guidelines to a Population- Based Sample. N Engl J Med. March 19, 2014 PMID: 24645848 http://www.nejm.org/doi/full/10.1056/NEJMoa1315665
  132. O'Riordan M New Guidelines Extend Statins to 13M More Americans. Medscape. March 19, 2014 http://www.medscape.com/viewarticle/822210
  133. Evangelista MT et al. Simvastatin as a novel therapeutic agent for venous ulcers: A randomized, double-blind, placebo-controlled trial. Br J Dermatol 2014 Feb 7 PMID: 24506834 http://onlinelibrary.wiley.com/doi/10.1111/bjd.12883/abstract
  134. Sugiyama T et al Different Time Trends of Caloric and Fat Intake Between Statin Users and Nonusers Among US AdultsGluttony in the Time of Statins? JAMA Intern Med. Published online April 24, 2014 PMID: 24763487 http://archinte.jamanetwork.com/article.aspx?articleid=1861769 - Redberg RF Statins and Weight Gain. JAMA Intern Med. Published online April 24, 2014 PMID: 24733072 http://archinte.jamanetwork.com/article.aspx?articleid=1861768
  135. Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group1, Armitage J, Bowman L, Wallendszus K et al Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. Lancet. 2010 Nov 13;376(9753):1658-69 PMID: 21067805
  136. D'Agostino RB Sr, Ansell BJ, Mora S, Krumholz HM. Clinical decisions. The guidelines battle on starting statins. N Engl J Med. 2014 Apr 24;370(17):1652-8 PMID: 24758622
  137. Godlee F Adverse effects of statins. BMJ 2014;348:g3306 PMID: 25134141 http://www.bmj.com/content/348/bmj.g3306
  138. Criner GJ et al Simvastatin for the Prevention of Exacerbations in Moderate- to-Severe COPD. N Engl J Med. May 18, 2014 PMID: 24836125 http://www.nejm.org/doi/full/10.1056/NEJMoa1403086 - The National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Rosuvastatin for Sepsis-Associated Acute Respiratory Distress Syndrome. N Engl J Med. May 18, 2014 PMID: 24835849 http://www.nejm.org/doi/full/10.1056/NEJMoa1401520 - Drazen JM and Gelijns AC Statin Strikeout N Engl J Med. May 18, 2014 PMID: 24835850 http://www.nejm.org/doi/full/10.1056/NEJMe1405032
  139. Dormuth CR et al Higher potency statins and the risk of new diabetes: multicentre, observational study of administrative databases. BMJ 2014;348:g3244 PMID: 2487497 http://www.bmj.com/content/348/bmj.g3244
  140. Lee DS, Markwardt S, Goeres L et al Statins and Physical Activity in Older Men. The Osteoporotic Fractures in Men Study. JAMA Intern Med. Published online June 09, 2014 PMID: 24911216 http://archinte.jamanetwork.com/article.aspx?articleid=1878470 - Golomb BA Statins and Activity. Proceed With Caution. JAMA Intern Med. Published online June 09, 2014 PMID: 24912133 http://archinte.jamanetwork.com/article.aspx?articleid=1878466
  141. Palmer SC, Craig JC, Navaneethan SD, et al. Benefits and harms of statin therapy for persons with chronic kidney disease: a systematic review and meta-analysis. Ann Intern Med. 2012;157(4):263-275 PMID: 22910937
  142. Russo MW et al. Spectrum of statin hepatotoxicity: Experience of the drug- induced liver injury network. Hepatology 2014 Aug; 60:679 PMID: 24700436
  143. Gagne JJ et al Comparative Effectiveness of Generic and Brand-Name Statins on Patient Outcomes: A Cohort Study. Ann Intern Med. 2014;161(6):400-407 PMID: 25222387 http://annals.org/article.aspx?articleid=1905128
  144. Fournier JP et al. Concurrent use of statins and hormone therapy and risk of venous thromboembolism in postmenopausal women: a population-based case-control study. Menopause 2014 Sep; 21:1023 PMID: 24937027
  145. Swerdlow DI et al. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: Evidence from genetic analysis and randomised trials. Lancet 2014 Sep 24; PMID: 25262344 - Frayling TM. Statins and type 2 diabetes: Genetic studies on target. Lancet 2014 Sep 24 PMID: 25262342
  146. McAuley DF et al. Simvastatin in the acute respiratory distress syndrome. N Engl J Med 2014 Sep 30 PMID: 25268516
  147. Therapeutics Initiative Statin's benefit for secondary prevention confirmed. What is the optimal dosing strategy? Therapeutics Letter Issue 49 / Jul - Sep 2003 http://www.ti.ubc.ca/newsletter/statins-benefit-secondary-prevention-confirmed-what-optimal-dosing-strategy
  148. The NNT Statins Given for 5 Years for Heart Disease Prevention (With Known Heart Disease) http://www.thennt.com/nnt/statins-for-heart-disease-prevention-with-known-heart-disease/ - Thavendiranathan P. et al Primary prevention of cardiovascular disease with statin therapy. Arch Int Med. 2006; 166: 2307-13. PMID: 17130382
  149. Ridker PM et al. Rosuvastatin to prevent vascular events in men and women with elevated c-reactive protein. NEJM. 2008; 359(21): 2195-2207. PMID: 18997196
  150. Turner JP et al. Statin use and pain in older people with cancer: A cross- sectional study. J Am Geriatr Soc 2014 Oct; 62:1900. PMID: 25284040
  151. Colantonio LD et al Contrasting Cholesterol Management Guidelines for Adults with CKD. J Am Soc of Nephrol. Nov 2014, 25 (11) PMID: 25395432 http://jasn.asnjournals.org/content/early/2014/11/12/ASN.2014040400.abstract
  152. Kostis WJ, Cheng JQ, Dobrzynski JM, Cabrera J, Kostis JB. Meta-analysis of statin effects in women versus men. J Am Coll Cardiol. 2012;59:572-582 PMID: 22300691
  153. Mascitelli L, Pezzetta F. Questioning the "beatification" of statins. Int J Cardiol. 2008;123:197-198 PMID: 17320217 - Jenkins DJ; Kendall CW; Marchie A et al Effects of a dietary portfolio of cholesterol-lowering foods vs lovastatin on serum lipids and C-reactive protein. JAMA. 2003; 290(4):502-10 (ISSN: 1538-3598) PMID: 12876093
  154. Petersen LK, Christensen K, Kragstrup J. Lipid-lowering treatment to the end? A review of observational studies and RCTs on cholesterol and mortality in 80+-year olds. Age Ageing. 2010;39:674-680 PMID: 20952373
  155. Akesson A, Larsson SC, Discacciati A, Wolk A. Low-risk diet and lifestyle habits in the primary prevention of myocardial infarction in men. J Am Coll Cardiol 2014; PMID: 25257629 http://content.onlinejacc.org/article.aspx?articleID=1909605 - Mozaffarian D. The promise of lifestyle for cardiovascular health. J Am Coll Cardiol 2014 PMID: 25257630
  156. Zhang R et al. A circadian gene expression atlas in mammals: Implications for biology and medicine. Proc Natl Acad Sci U S A 2014 Nov 11; 111:16219 PMID: 25349387 http://www.pnas.org/content/111/45/16219
  157. Cholesterol Treatment Trialists' (CTT) Collaboration. Efficacy and safety of LDL-lowering therapy among men and women: Meta-analysis of individual data from 174 000 participants in 27 randomised trials. Lancet 2015 Jan 8; PMID: 25579834 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2961368-4/abstract
  158. Banach M et al. Effects of coenzyme Q10 on statin-induced myopathy: A meta- analysis of randomized controlled trials. Mayo Clin Proc 2015 Jan; 90:24 PMID: 25440725 - Taylor BA et al. A randomized trial of coenzyme Q10 in patients with confirmed statin myopathy. Atherosclerosis 2015 Feb; 238:329. PMID: 25545331
  159. Mega JL et al Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials. Lancet March 3, 2015 PMID: 25748612 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2961730-X/abstract - Schunkert H, Samani NJ Statin treatment: can genetics sharpen the focus? Lancet March 3, 2015 PMID: 25748613 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2961931-0/abstract
  160. Bateman BT et al Statins and congenital malformations: cohort study. BMJ 2015;350:h1035 PMID: 25784688 http://www.bmj.com/content/350/bmj.h1035
  161. Besseling J et al. Association between familial hypercholesterolemia and prevalence of type 2 diabetes mellitus. JAMA 2015 Mar 10; 313:1029. PMID: 25756439 http://jama.jamanetwork.com/article.aspx?articleid=2190985 - Preiss D and Sattar N. Does the LDL receptor play a role in the risk of developing type 2 diabetes? JAMA 2015 Mar 10; 313:1016. PMID: 25756436 http://jama.jamanetwork.com/article.aspx?articleid=2190968
  162. The NNT: Statin Drugs Given for 5 Years for Heart Disease Prevention (Without Known Heart Disease) http://www.thennt.com/nnt/statins-for-heart-disease-prevention-without-prior-heart-disease/
  163. The NNT: Statins Given for 5 Years for Heart Disease Prevention (With Known Heart Disease) http://www.thennt.com/nnt/statins-for-heart-disease-prevention-with-known-heart-disease/
  164. The NNT: Statins for Acute Coronary Syndrome http://www.thennt.com/nnt/statins-for-acute-coronary-syndrome/ - Vale N, Nordmann AJ, Schwartz GG et al Statins for acute coronary syndrome. Cochrane Database Syst Rev. 2011 Jun 15;(6):CD006870. Review. PMID: 21678362
  165. Odden MC et al Cost-Effectiveness and Population Impact of Statins for Primary Prevention in Adults Aged 75 Years or Older in the United States. Ann Intern Med. 2015;162(8):533-541 PMID: 25894023 http://annals.org/article.aspx?articleid=2275384 - Rich MW Cost-Effectiveness of Statins in Older Adults: Further Evidence That Less Is More. Ann Intern Med. 2015;162(8):590-591 PMID: 25894030 http://annals.org/article.aspx?articleid=2275394
  166. Berglind IA et al. Hormone therapy and risk of cardiovascular outcomes and mortality in women treated with statins. Menopause 2015 Apr; 22:369. PMID: 25335101 - Hodis HN and Mack WJ. Hormone therapy and risk of all-cause mortality in women treated with statins. Menopause 2015 Apr; 22:363 PMID: 25756694
  167. Kutner JS et al. Safety and benefit of discontinuing statin therapy in the setting of advanced, life-limiting illness: A randomized clinical trial. JAMA Intern Med 2015 May; 175:691 PMID: 25798575
  168. Kaiser Permanente. Press Release. September 22, 2014 Statin Use Following Hemorrhagic Stroke Associated with Improved Survival. http://share.kaiserpermanente.org/article/statin-use-during-hospitalization-for-hemorrhagic-stroke-strongly-associated-with-improved-post-stroke-survival/
  169. Hu M, Cheung BMY, Tomlinson B Medscape Oncology: Safety of Statins. An Update Ther Adv in Drug Safe. 2012;3(3):133-144. http://www.medscape.com/viewarticle/763800_5
  170. Hackam DG, Woodward M, Newby LK et al Statins and intracerebral hemorrhage. Circulation. 2011;124:2233-2242 PMID: 22007076 - Goldstein LB. Letter by goldstein regarding article, "statins and intracerebral hemorrhage" Circulation. 2012 Jun 12;125(23):e1015 PMID: 22689936
  171. Goldstein LB Hemorrhagic stroke in the stroke prevention by aggressive reduction in cholesterol levels study. Neurology. 2009;72:1447-1448 PMID: 19380708
  172. Goldstein LB Statin Therapy Should be Discontinued in Patients with Hemorrhagic Stroke. Stroke 2013; 44: 2058-2059 PMID: 2376594 http://stroke.ahajournals.org/content/44/7/2058.extract#
  173. Flint AC, Conell C, Rao VA Effect of statin use during hospitalization for intracerebral hemorrhage on mortality and discharge disposition. JAMA Neurol. 2014 Nov;71(11):1364-71 PMID: 25244578
  174. Bogiatzi C, Hackam DG, McLeod AI, Spence JD Secular trends in ischemic stroke subtypes and stroke risk factors. Stroke. 2014 Nov;45(11):3208-13. PMID: 25213343
  175. McKinney JS, Kostis WJ. Statin therapy and the risk of intracerebral hemorrhage: a meta-analysis of 31 randomized controlled trials. Stroke. 2012 Aug;43(8):2149-56 PMID: 22588266
  176. Leker RR, Khoury ST, Rafaeli G et al Prior Use of Statins Improves Outcome in Patients With Intracerebral Hemorrhage. Prospective Data from the National Acute Stroke Israeli Surveys (NASIS). Stroke. 2009; 40: 2581-2584 PMID: 19407227
  177. Westover MB, Bianchi MT, Eckman MH, Greenberg SM. Statin use following intracerebral hemorrhage: a decision analysis. Arch Neurol. 2011 May;68(5):573-9. PMID: 21220650
  178. Gandey A Statins Not Recommended for Patients With Intracerebral Hemorrhage. Medscape Multispecialty. January 11, 2011 http://www.medscape.com/viewarticle/735596
  179. Athyros VG1, Tziomalos K, Karagiannis A et al Aggressive statin treatment, very low serum cholesterol levels and haemorrhagic stroke: is there an association? Curr Opin Cardiol. 2010 Jul;25(4):406-10 PMID: 20375883
  180. Amarenco P, Bogousslavsky J, Callahan A 3rd et al High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006 Aug 10;355(6):549-59. PMID: 16899775
  181. Goldstein LB, Amarenco P, Szarek M et al Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels study. Neurology. 2008 Jun 10;70(24 Pt 2):2364-70 PMID: 18077795
  182. Collins R, Armitage J, Parish S et al Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions. Lancet. 2004 Mar 6;363(9411):757-67 PMID: 15016485
  183. Vergouwen MD, de Haan RJ, Vermeulen M, Roos YB. Effect of statin treatment on vasospasm, delayed cerebral ischemia, and functional outcome in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis update. Stroke. 2010 Jan;41(1):e47-52. PMID: 19875741
  184. Schwartz GG et al Fasting Triglycerides Predict Recurrent Ischemic Events in Patients With Acute Coronary Syndrome Treated With Statins. J Am Coll Cardiol. 2015;65(21):2267-2275 PMID: 26022813 http://content.onlinejacc.org/article.aspx?articleID=2297631 - Joshi PH, Martin SS, Blumenthal RS The Remnants of Residual Risk. J Am Coll Cardiol. 2015;65(21):2276-2278 PMID: 26022814 http://content.onlinejacc.org/article.aspx?articleID=2297630
  185. Taylor F, Huffman MD, Macedo AF et al Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013 Jan 31;1:CD004816 PMID: 23440795
  186. Mueller PS Lipid-Lowering Drugs for Primary Prevention in Older Adults NEJM Journal Watch. June 4, 2015 Massachusetts Medical Society (subscription needed) http://www.jwatch.org - Alperovitch A et al. Primary prevention with lipid lowering drugs and long term risk of vascular events in older people: Population based cohort study. BMJ 2015 May 19; 350:h2335 PMID: 25989805
  187. Strom BL et al Statin Therapy and Risk of Acute Memory Impairment. JAMA Intern Med. Published online June 08, 2015 PMID: 2605403 http://archinte.jamanetwork.com/article.aspx?articleID=2301148
  188. Undas A, Brummel-Ziedins KE, Mann KG. Anticoagulant effects of statins and their clinical implications. Thromb Haemost. 2014 Mar 3;111(3):392-400 PMID: 24285296 - Undas A, Brummel-Ziedins KE, Mann KG. Statins and blood coagulation. Arterioscler Thromb Vasc Biol. 2005 Feb;25(2):287-94 PMID: 15569822
  189. Violi F, Calvieri C, Ferro D, Pignatelli P. Statins as antithrombotic drugs. Circulation. 2013 Jan 15;127(2):251-7 PMID: 23319813
  190. Asberg S, Eriksson M Statin therapy and the risk of intracerebral haemorrhage: a nationwide observational study. Int J Stroke. 2015 Jun 4 PMID: 26043664
  191. FitzMaurice E, Wendell L, Snider R et al Effect of statins on intracerebral hemorrhage outcome and recurrence. Stroke. 2008 Jul;39(7):2151-4 PMID: 18436876
  192. Tapia-Perez JH, Zilke R, Schneider T Match-study of statin therapy in spontaneous intracerebral hemorrhage: is the discontinuation reasonable? J Neurosurg Sci. 2014 Dec 11 PMID: 25501007
  193. Davenport L, Vega CP Diabetes Increased by Almost Half Among Statin Users. Medscape Education Briefs. 5/20/2015 http://www.medscape.org/viewarticle/843980
  194. Mittleman MA et al Treatment of Blood Cholesterol to Reduce Risk for Atherosclerotic Cardiovascular Disease: Grand Rounds Discussion From the Beth Israel Deaconess Medical Center. Ann Intern Med. 2015;163(4):280-290. PMID: 26280414 http://annals.org/article.aspx?articleid=2427595
  195. Johansen ME, Green LA Statin Use in Very Elderly Individuals, 1999-2012. JAMA Intern Med. Published online August 24, 2015. PMID: 26301475 http://archinte.jamanetwork.com/article.aspx?articleid=2429533
  196. DuBroff RJ The statin diabetes conundrum: short-term gain, long-term risk or inconvenient truth? Evid Based Med. 2015 Aug;20(4):121-3 PMID: 26180130
  197. Brett AS Another Study of the Statin-Diabetes Relation. Physician's First Watch, Nov 19, 2015 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org - Mansi I, Frei CR, Wang CP, Mortensen EM. Statins and new-onset diabetes mellitus and diabetic complications: A retrospective cohort study of US healthy adults. J Gen Intern Med 2015 Nov; 30:1599 PMID: 25917657 http://link.springer.com/article/10.1007%2Fs11606-015-3335-1
  198. see ref [242] this was USPSTF Draft recommendation replaced by [242]
  199. Acharya T, Huang J, Tringali S, et al. Statin use and the risk of kidney disease with long term follow-up (8.4-years study). Am J Cardiol 2015 PMID: 26742473 http://www.ajconline.org/article/S0002-9149%2815%2902315-2/abstract
  200. Brauser D. Medscape: Task Force Recommends Statins for Adults Under 75 With Risk Factors, Questions Child Screenings. http://www.medscape.com/viewarticle/856986
  201. Marenzi G, Cosentino N, Cortinovis S et al Myocardial Infarct Size in Patients on Long-Term Statin Therapy Undergoing Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction. Am J Cardiol. 2015 Dec 15;116(12):1791-7. PMID: 26602070
  202. McGuinness B, Craig D, Bullock R, Passmore P. Statins for the prevention of dementia. Cochrane Database Syst Rev. 2016;1:CD003160 PMID: 26727124
  203. Suraweera C, de Silva V, Hanwella R. Simvastatin-induced cognitive dysfunction: two case reports. J Med Case Rep. 2016 Apr 5;10(1):83. PMID: 27048383 Free PMC Article
  204. Vinogradova Y, Coupland C, Brindle P, Hippisley-Cox J. Discontinuation and restarting in patients on statin treatment: prospective open cohort study using a primary care database. BMJ 2016;353:i3305 PMID: 27353261 http://www.bmj.com/content/353/bmj.i3305
  205. Paauw DS Dangerous and Deadly Drug Combinations Medscape. June 30, 2016 http://www.medscape.com/features/slideshow/dangerous-drug-combinations
  206. Brooks M Statin Use Tied to Lower Risk of Inflammatory Bowel Disease. Medscape. Jul 04, 2016. http://www.medscape.com/viewarticle/865671
  207. Fleg JL, Forman DE, Berra K et al Secondary prevention of atherosclerotic cardiovascular disease in older adults: a scientific statement from the American Heart Association. Circulation. 2013 Nov 26;128(22):2422-46. PMID: 24166575 Free PMC Article
  208. Chowdhury R, Khan H, Heydon E et al Adherence to cardiovascular therapy: a meta-analysis of prevalence and clinical consequences. Eur Heart J. 2013 Oct;34(38):2940-8. Review. PMID: 23907142 Free Article
  209. Yaffe K, Barrett-Connor E, Lin F, Grady D. Serum lipoprotein levels, statin use, and cognitive function in older women. Arch Neurol. 2002 Mar;59(3):378-84. PMID: 11890840
  210. Bernick C, Katz R, Smith NL Statins and cognitive function in the elderly: the Cardiovascular Health Study. Neurology. 2005 Nov 8;65(9):1388-94. PMID: 16275825
  211. Etminan M, Gill S, Samii A. The role of lipid-lowering drugs in cognitive function: a meta-analysis of observational studies. Pharmacotherapy. 2003 Jun;23(6):726-30. PMID: 12820814
  212. Dufouil C, Richard F, Fievet N et al APOE genotype, cholesterol level, lipid-lowering treatment, and dementia: the Three-City Study. Neurology. 2005 May 10;64(9):1531-8. PMID: 15883313
  213. Sparks DL, Kryscio RJ, Sabbagh MN et al Reduced risk of incident AD with elective statin use in a clinical trial cohort. Curr Alzheimer Res. 2008 Aug;5(4):416-21. PMID: 18690839 - Sparks DL, Kryscio RJ, Connor DJ et al Cholesterol and cognitive performance in normal controls and the influence of elective statin use after conversion to mild cognitive impairment: results in a clinical trial cohort. Neurodegener Dis. 2010;7(1-3):183-6. PMID: 20224282 Free PMC Article - Sparks DL, Connor DJ, Sabbagh MN et al Circulating cholesterol levels, apolipoprotein E genotype and dementia severity influence the benefit of atorvastatin treatment in Alzheimer's disease: results of the Alzheimer's Disease Cholesterol-Lowering Treatment (ADCLT) trial. Acta Neurol Scand Suppl. 2006;185:3-7. PMID: 16866904 - Sparks DL, Lemieux SK, Haut MW et al Hippocampal volume change in the Alzheimer Disease Cholesterol-Lowering Treatment trial. Cleve Clin J Med. 2008 Mar;75 Suppl 2:S87-93. PMID: 18540154
  214. Vuorio A, Kuoppala J, Kovanen PT et al Statins for children with familial hypercholesterolemia. Cochrane Database Syst Rev. 2019 Nov 7;2019(11). PMID: 31696945
  215. Hajjar I, Schumpert J, Hirth V, Wieland D, Eleazer GP. The impact of the use of statins on the prevalence of dementia and the progression of cognitive impairment. J Gerontol A Biol Sci Med Sci. 2002 Jul;57(7):M414-8. PMID: 12084801
  216. Li G, Higdon R, Kukull WA et al Statin therapy and risk of dementia in the elderly: a community- based prospective cohort study. Neurology. 2004 Nov 9;63(9):1624-8. PMID: 15534246
  217. Arvanitakis Z, Schneider JA, Wilson RS Statins, incident Alzheimer disease, change in cognitive function, and neuropathology. Neurology. 2008 May 6;70(19 Pt 2):1795-802.. PMID: 18199831
  218. Zandi PP, Sparks DL, Khachaturian AS et al Do statins reduce risk of incident dementia and Alzheimer disease? The Cache County Study. Arch Gen Psychiatry. 2005 Feb;62(2):217-24. PMID: 15699299
  219. Cutler N, Sramek J, Veroff A Effects of treatment with simvastatin and pravastatin on cognitive function in patients with hypercholesterolaemia. Br J Clin Pharmacol. 1995 Mar;39(3):333-6. PMID: 7619678 Free PMC Article
  220. Szwast SJ, Hendrie HC, Lane KA Association of statin use with cognitive decline in elderly African Americans. Neurology. 2007 Nov 6;69(19):1873-80. PMID: 17984456 Free PMC Article
  221. Agostini JV, Tinetti ME, Han L, et al. Effects of statin use on muscle strength, cognition, and depressive symptoms in older adults. J Am Geriatr Soc 2007;55:420-5. PMID: 17341246
  222. Feldman HH, Doody RS, Kivipelto M et al Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe. Neurology. 2010 Mar 23;74(12):956-64. PMID: 20200346
  223. McGuinness B, Craig D, Bullock R, Malouf R, Passmore P. Statins for the treatment of dementia. Cochrane Database Syst Rev. 2014 Jul 8;(7):CD007514. Review. PMID: 25004278
  224. Trompet S, van Vliet P, de Craen AJ Pravastatin and cognitive function in the elderly. Results of the PROSPER study. J Neurol. 2010 Jan;257(1):85-90. PMID: 19653027
  225. Swiger KJ, Manalac RJ, Blumenthal RS, Blaha MJ, Martin SS Statins and cognition: a systematic review and meta-analysis of short- and long-term cognitive effects. Mayo Clin Proc. 2013 Nov;88(11):1213-21. Review. PMID: 24095248
  226. Ott BR, Daiello LA, Dahabreh IJ et al Do statins impair cognition? A systematic review and meta- analysis of randomized controlled trials. J Gen Intern Med. 2015 Mar;30(3):348-58. Review. PMID: 25575908 Free PMC Article
  227. Rojas-Fernandez CH, Goldstein LB, Levey AI et al An assessment by the Statin Cognitive Safety Task Force: 2014 update. J Clin Lipidol. 2014 May-Jun;8(3 Suppl):S5-16. PMID: 24793442
  228. Doraiswamy PM, Steffens DC, McQuoid DR. Statin use and hippocampal volumes in elderly subjects at risk for Alzheimer's disease: a pilot observational study. Am J Alzheimers Dis Other Demen. 2004 Sep-Oct;19(5):275-8. PMID: 15553983
  229. Locatelli S, Lutjohann D, Schmidt HH Reduction of plasma 24S-hydroxycholesterol (cerebrosterol) levels using high-dosage simvastatin in patients with hypercholesterolemia: evidence that simvastatin affects cholesterol metabolism in the human brain. Arch Neurol. 2002 Feb;59(2):213-6. PMID: 11843691
  230. Simons M, Schwarzler F, Lutjohann D Treatment with simvastatin in normocholesterolemic patients with Alzheimer's disease: A 26-week randomized, placebo- controlled, double-blind trial. Ann Neurol. 2002 Sep;52(3):346-50. PMID: 12205648
  231. Thelen KM, Laaksonen R, Paaiva H, Lehtimaki T, Lutjohann D. High-dose statin treatment does not alter plasma marker for brain cholesterol metabolism in patients with moderately elevated plasma cholesterol levels. J Clin Pharmacol. 2006 Jul;46(7):812-6. PMID: 16809807
  232. McFarland AJ, Anoopkumar-Dukie S, Arora DS et al Molecular mechanisms underlying the effects of statins in the central nervous system. Int J Mol Sci. 2014 Nov 10;15(11):20607-37. Review. PMID: 25391045 Free PMC Article
  233. Brett AS Statins in Patients with Coronary Disease Who Are Older than 80. NEJM Journal Watch. July 28, 2016 Massachusetts Medical Society (subscription needed) http://www.jwatch.org - Rothschild DP, Novak E, Rich MW. Effect of Statin Therapy on Mortality in Older Adults Hospitalized with Coronary Artery Disease: A Propensity- Adjusted Analysis. J Am Geriatr Soc. 2016 Jul;64(7):1475-9. PMID: 27295083
  234. Mariscalco G, Cottini M, Zanobini M et al Preoperative statin therapy is not associated with a decrease in the incidence of delirium after cardiac operations. Ann Thorac Surg. 2012 May;93(5):1439-47. PMID: 22541176
  235. Morandi A, Hughes CG, Thompson JL et al Statins and delirium during critical illness: a multicenter, prospective cohort study. Crit Care Med. 2014 Aug;42(8):1899-909. PMID: 24810528 Free PMC Article
  236. Collins R, Reith C, Emberson J et al Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. Sept 8, 2016. PMID: 27616593 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)31357-5/abstract
  237. Pokharel Y, Gosch K, Nambi V et al Practice-Level Variation in Statin Use Among Patients With Diabetes. Insights From the PINNACLE Registry. J Am Coll Cardiol. 2016;68(12):1368-1369 PMID: 27634128 https://content.onlinejacc.org/article.aspx?articleID=2552333
  238. Wiggins BS, Saseen JJ, Page RL 2nd et al Recommendations for Management of Clinically Significant Drug-Drug Interactions With Statins and Select Agents Used in Patients With Cardiovascular Disease. A Scientific Statement From the American Heart Association. Circulation. 2016;134:00-00 PMID: 27754879 http://circ.ahajournals.org/content/circulationaha/early/2016/10/17/CIR.0000000000000456.full.pdf
  239. Melville NA Statin Use Linked to Increased Parkinson's Risk. Medscape. Oct 26, 2016 http://www.medscape.com/viewarticle/870996
  240. Rodriguez F, Maron DJ, Knowles JW et al Association Between Intensity of Statin Therapy and Mortality in Patients With Atherosclerotic Cardiovascular Disease. JAMA Cardiol. Published online November 9, 2016 PMID: 27829091 - Bonow RO, Yancy CW. High-Intensity Statins for Secondary Prevention. JAMA Cardiol. 2016 Nov 9. PMID: 27829079
  241. Skeldon SC, Carleton B, Brophy JM, Sodhi M, Etminan M. Statin medications and the risk of gynecomastia. Clin Endocrinol (Oxf). 2018 Oct;89(4):470-473. Epub 2018 Jul 15. PMID: 29923212
  242. US Preventive Services Task Force Statin Use for the Primary Prevention of Cardiovascular Disease in Adults. US Preventive Services Task Force Recommendation Statement. JAMA. 2016;316(19):1997-2007. PMID: 27838723 http://jamanetwork.com/journals/jama/fullarticle/2584058 - Chou R, Dana T, Blazina I et al Statins for Prevention of Cardiovascular Disease in Adults. Evidence Report and Systematic Review for the US Preventive Services Task Force. PMID: 27838722 http://jamanetwork.com/journals/jama/fullarticle/2584058 - Greenland P, Bonow RO. Interpretation and use of another statin guideline. JAMA 2016 Nov 15; 316:1977. PMID: 27838703 - Redberg RF, Katz MH. Statins for primary prevention: The debate is intense, but the data are weak. JAMA 2016 Nov 15; 316:1979. PMID: 27838702 - Navar AM, Peterson ED. Evolving approaches for statins in primary prevention: Progress, but questions remain. JAMA 2016 Nov 15; 316:1981 PMID: 27838704
  243. Asplund CA, O'Connor FG. Challenging Return to Play Decisions: Heat Stroke, Exertional Rhabdomyolysis, and Exertional Collapse Associated With Sickle Cell Trait. Sports Health. 2016 Mar-Apr;8(2):117-25. PMID: 26896216 - Saxena P, Chavarria C, Thurlow J. Rhabdomyolysis in a Sickle Cell Trait Positive Active Duty Male Soldier. US Army Med Dep J. 2016 Jan-Mar:20-3. PMID: 26874092 - Nelson DA, Deuster PA, Carter R 3rd et al., Sickle Cell Trait, Rhabdomyolysis, and Mortality among U.S. Army Soldiers. N Engl J Med. 2016 Aug 4;375(5):435-42. PMID: 27518662
  244. Pagidipati NJ, Navar AM, Mulder H et al Comparison of Recommended Eligibility for Primary Prevention Statin Therapy Based on the US Preventive Services Task Force Recommendations vs the ACC/AHA Guidelines JAMA. 2017;317(15):1563-1567. PMID: 28418481 http://jamanetwork.com/journals/jama/article-abstract/2618621
  245. Gupta A, Thompson D, Whitehouse A et al Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial - Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase. Lancet. May 2, 2017 PMID: 28476288 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)31075-9/fulltext?elsca1=tlpr - Pedro-Botet J, Rubies-Prat J. Statin-associated muscle symptoms: Beware of the nocebo effect. Lancet 2017 May 2 PMID: 28476289 http://www.jwatch.org/na44073/2017/05/25/muscle-symptoms-statin-users-might-be-nocebo-effect
  246. Busko M Statin Use Increases Odds of Back Disorder: Cohort Study Medscape, May 08, 2017. http://www.medscape.com/viewarticle/879387 - Makris UE, Alvarez CA Wei W et al Association of Statin Use With Risk of Back Disorder Diagnoses. JAMA Intern Med. Published online May 1, 2017. PMID: 28459971 http://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2623526
  247. Han BH, Sutin D, Williamson JD et al for the ALLHAT Collaborative Research Group. Effect of Statin Treatment vs Usual Care on Primary Cardiovascular Prevention Among Older Adults. The ALLHAT-LLT Randomized Clinical Trial. JAMA Intern Med. Published online May 22, 2017 PMID: 28531241 http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2628971 - Curfman G Risks of Statin Therapy in Older Adults. JAMA Intern Med. Published online May 22, 2017 PMID: 28531249 http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2628968
  248. Boggs W. Statins Reduce Risk of Contrast-induced Acute Kidney Injury Medscape. May 29, 2017. http://www.medscape.com/viewarticle/880734
  249. Palmer SC, Navaneethan SD, Craig JC et al HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis. Cochrane Database Syst Rev. 2014 May 31;(5):CD007784. Review. PMID: 24880031
  250. Palmer SC, Navaneethan SD, Craig JC et al HMG CoA reductase inhibitors (statins) for dialysis patients. Cochrane Database Syst Rev. 2013 Sep 11;(9):CD004289. Review. PMID: 24022428
  251. Zhang H, Plutzky J, Shubina M, Turchin A Continued Statin Prescriptions After Adverse Reactions and Patient Outcomes: A Cohort Study. Ann Intern Med. 2017 PMID: 28738423 http://annals.org/aim/article/2645552/continued-statin-prescriptions-after-adverse-reactions-patient-outcomes-cohort-study - Nissen SE Statin Denial: An Internet-Driven Cult With Deadly Consequences PMID: 28738422 http://annals.org/aim/article/2645554/statin-denial-internet-driven-cult-deadly-consequences
  252. Rabaeus M, Nguyen PV, de Lorgeril M. Recent Flaws In Evidence-Based Medicine: Statin Effects In Primary Prevention And Consequences Of Suspending The Treatment. J Controversies Biomed Res 2017;3(1):1-10 Not indexed in PubMed http://jcbmr.com/index.php/jcbmr/article/view/18/37
  253. Gurwitz JH, Go AS, Fortmann SP. Statins for Primary Prevention in Older Adults: Uncertainty and the Need for More Evidence. JAMA. 2016 Nov 15;316(19):1971-1972. No abstract available. PMID: 27838724 Free PMC Article
  254. Guideline Watch 2017. jwatch.org
  255. Bischoff-Ferrari HA, Fischer K, Orav EJ Statin Use and 25-Hydroxyvitamin D Blood Level Response to Vitamin D Treatment of Older Adults. J Am Geriatr Soc. 2017 Jun;65(6):1267-1273. Epub 2017 Feb 27. PMID: 28240766
  256. Murtola TJ, Peltomaa AI, Talala K et al Statin Use and Prostate Cancer Survival in the Finnish Randomized Study of Screening for Prostate Cancer. Eur Urol Focus. 2016 Jun 2. pii: S2405-4569(16)30052-9. PMID: 28753762 - Larsen SB, Dehlendorff C, Skriver C Postdiagnosis Statin Use and Mortality in Danish Patients With Prostate Cancer. J Clin Oncol. 2017 Aug 14:JCO2016718981. PMID: 28806117
  257. Brooks M Statins May Help Guard Against S Aureus Bacteremia. Medscape. Oct 26, 2017. https://www.medscape.com/viewarticle/887676
  258. NEJM Guideline Watch 2017 https://secure.jwatch.org/resources/generic_pages/GMAAALLE0917B/display
  259. Harding A Meta-analysis Finds No Link Between Statins, Erectile Dysfunction Medscape. Dec 01, 2017. https://www.medscape.com/viewarticle/889463
  260. Huesch MD. Association of Baseline Statin Use Among Older Adults Without Clinical Cardiovascular Disease in the SPRINT Trial. JAMA Intern Med. Published online January 22, 2018 PMID: 29356825 https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2669904
  261. Mortensen MB , Nordestgaard BG. Comparison of five major guidelines for statin use in primary prevention in a contemporary general population. Ann Intern Med 2018 Jan 16; 168:85. PMID: 29297004 http://annals.org/aim/article-abstract/2667694/comparison-five-major-guidelines-statin-use-primary-prevention-contemporary-general - Mancini GBJ. Comparison shopping: Guidelines for statins for primary prevention of cardiovascular disease. Ann Intern Med 2018 Jan 16; 168:145. PMID: 29297007 http://annals.org/aim/article-abstract/2667697/comparison-shopping-guidelines-statins-primary-prevention-cardiovascular-disease
  262. Mortensen MB, Falk E. Primary Prevention With Statins in the Elderly. J Am Coll Cardiol. 2018 Jan 2;71(1):85-94. Review. PMID: 29301631 Free Article
  263. Allard NAE, Schirris TJJ, Verheggen RJ et al Statins Affect Skeletal Muscle Performance: Evidence for Disturbances in Energy Metabolism. J Clin Endocrinol Metab. 2018 Jan 1;103(1):75-84 PMID: 29040646
  264. Siddiqui MK, Maroteau C, Veluchamy A et al A Common Missense Variant of LILRB5 Is Associated With Statin Intolerance and Myalgia. Eur Heart J. 2017;38(48):3569-3575 Medscape. March 2018 PMID: 29020356 Free PMC Article https://www.medscape.com/viewarticle/891063
  265. Ramsey LB, Johnson SG, Caudle KE et al The Clinical Pharmacogenetics Implementation Consortium guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update. Clin Pharmacol Ther. 2014 Oct;96(4):423-8 PMID: 24918167
  266. Ong KL, Morris MK, McClelland RL et al Relationship of Lipids and Lipid-Lowering Medications With Cognitive Function. Am J Epidemiol. 2018;187(4):767-776. PMID: 29617947 https://www.medscape.com/viewarticle/894973
  267. Baltic S Study Confirms Pro-Calcific Effects of Statins on Coronary Plaques in Low-Risk Patients. Medscape. Jul 05, 2018 https://www.medscape.com/viewarticle/898945
  268. Caughey GE, Gabb GM, Ronson S et al Association of Statin Exposure With Histologically Confirmed Idiopathic Inflammatory Myositis in an Australian Population. JAMA Intern Med. Published online July 30, 2018 PMID: 30073275 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2687990 - Curfman G Statin-Associated Myopathy - An Elusive Clinical Problem. JAMA Intern Med. Published online July 30, 2018 PMID: 30073289 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2687984
  269. Ramos R, Comas-Cufi M, Marti-Lluch R et al Statins for primary prevention of cardiovascular events and mortality in old and very old adults with and without type 2 diabetes: retrospective cohort study. BMJ 2018;362:k3359 PMID: 30185425 https://www.bmj.com/content/362/bmj.k3359 - Ryan A, Heath S, Cook P Primary prevention with statins for older adults. BMJ 2018;362:k3695 PMID: 30185474 https://www.bmj.com/content/362/bmj.k3695
  270. He Y, Li X, Gasevic D et al Statins and Multiple Noncardiovascular Outcomes: Umbrella Review of Meta-analyses of Observational Studies and Randomized Controlled Trials. Ann Intern Med. 2018. Oct 9 PMID: 30304368 http://annals.org/aim/article-abstract/2706169/statins-multiple-noncardiovascular-outcomes-umbrella-review-meta-analyses-observational-studies
  271. Thanassoulis G, Sniderman AD, Pencina MJ. A long-term benefit approach vs. standard risk-based approaches for statin eligibility in primary prevention. JAMA Cardiol 2018 Oct 24 PMID: 30422172 https://jamanetwork.com/journals/jamacardiology/fullarticle/2706611
  272. Yebyo HG, Puhan MA, Aschmann HE Finding the Balance Between Benefits and Harms When Using Statins for Primary Prevention of Cardiovascular Disease: A Modeling Study. Ann Intern Med. 2018. Dec 4, 2018 PMID: 30508425 http://annals.org/aim/article-abstract/2717730/finding-balance-between-benefits-harms-when-using-statins-primary-prevention - Richman IB, Ross JS. Weighing the Harms and Benefits of Using Statins for Primary Prevention: Raising the Risk Threshold. Ann Intern Med. 2018. Dec 4, 2018 PMID: 30508426 http://annals.org/aim/article-abstract/2717122/weighing-harms-benefits-using-statins-primary-prevention-raising-risk-threshold
  273. Newman CB, Preiss D, Tobert JA et al Statin Safety and Associated Adverse Events: A Scientific Statement From the American Heart Association. Arteriosclerosis, Thrombosis, and Vascular Biology. Jan 2018. https://www.ahajournals.org/doi/10.1161/ATV.0000000000000073
  274. Jorge AM, Lu N, Keller SF, Rai SK, Zhang Y, Choi HK. The effect of statin use on mortality in systemic autoimmune rheumatic diseases. J Rheumatol. 2018 Dec;45(12):1689-1695. PMID: 30173155 http://www.jrheum.org/content/45/12/1689
  275. Kang EYC, Chen TH, Garg SJ et al Association of Statin Therapy With Prevention of Vision- Threatening Diabetic Retinopathy. JAMA Ophthalmol. Published online January 10, 2019. PMID: 30629109 https://jamanetwork.com/journals/jamaophthalmology/article-abstract/2720491
  276. Cholesterol Treatment Trialists' Collaboration Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials Lancet. Feb 2, 2019 PMID: 30712900 Free Article https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31942-1/fulltext
  277. Newman CB, Preiss D, Tobert JA et al. Statin safety and associated adverse events: A Scientific Statement from the American Heart Association. Arterioscler Thromb Vasc Biol 2019 Feb; 39:e38. PMID: 30580575 https://www.ahajournals.org/doi/10.1161/ATV.0000000000000073
  278. Rodriguez F, Maron DJ, Knowles JW et al. Association of statin adherence with mortality in patients with atherosclerotic cardiovascular disease. JAMA Cardiol 2019 Feb 13 PMID: 30758506
  279. Skolnik N Reexamining Recommendations for Treatment of Hypercholesterolemia in Older Adults. JAMA. Published online March 11, 2019 PMID: 30855637 https://jamanetwork.com/journals/jama/fullarticle/2728377
  280. Bradley CK, Wang TY, Li S et al Patient-Reported Reasons for Declining or Discontinuing Statin Therapy: Insights From the PALM Registry. Journal of the American Heart Association. 2019; March 27. PMID: 30913959 Free full text https://www.ahajournals.org/doi/full/10.1161/JAHA.118.011765
  281. Akyea RK, Kai J, Qureshi N et al Sub-optimal cholesterol response to initiation of statins and future risk of cardiovascular disease. Heart. Published Online: April 15, 2019 PMID: 30988003 Free Article https://heart.bmj.com/content/early/2019/04/16/heartjnl-2018-314253 - Bittencourt MS, Cesena FHY. Statin dose in primary prevention: aim for the target! Heart. Published Online: April 15, 2019 PMID: 30988002 https://heart.bmj.com/content/early/2019/03/30/heartjnl-2019-314723
  282. Kang JH, Boumenna T, Stein JD et al Association of Statin Use and High Serum Cholesterol Levels With Risk of Primary Open-Angle Glaucoma. JAMA Ophthalmol. Published online May 2, 2019. PMID: 31046067 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2732293 - Liu Y, Klein BE The Role of Statins and Cholesterol in the Primary Prevention of Primary Open-Angle Glaucoma. JAMA Ophthalmol. Published online May 2, 2019 PMID: 31046110 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2732286
  283. Warendorf JK, Vrancken AFJE, van Eijk RPA et al. Statins do not increase risk of polyneuropathy. Neurology 2019 Apr 30; 92:e2136. PMID: 30737334 https://n.neurology.org/content/92/18/e2136
  284. Redelmeier DA, Manzoor F, Thiruchelvam D et al Association Between Statin Use and Risk of Dementia After a Concussion. JAMA Neurol. Published online May 20, 2019. PMID: 31107515 https://jamanetwork.com/journals/jamaneurology/fullarticle/2733673 - Whitmer RA. Concussions and Dementia - Are Statins the Salve in the Wound? JAMA Neurol. Published online May 20, 2019. PMID: 31107521 https://jamanetwork.com/journals/jamaneurology/article-abstract/2733670
  285. Giral P, Neumann A, Weill A, Coste J. Cardiovascular effect of discontinuing statins for primary prevention at the age of 75 years: a nationwide population-based cohort study in France Euro Heart J. [published online July 31, 2019]. PMID: 31362307
  286. Simon TG, Duberg AS, Aleman S et al Lipophilic Statins and Risk for Hepatocellular Carcinoma and Death in Patients With Chronic Viral Hepatitis: Results From a Nationwide Swedish Population. Ann Intern Med. 2019 Aug 20. PMID: 31426090 https://annals.org/aim/article-abstract/2748619/lipophilic-statins-risk-hepatocellular-carcinoma-death-patients-chronic-viral-hepatitis
  287. NEJM Knowledge+ Question of the Week. Oct 1, 2019 https://knowledgeplus.nejm.org/question-of-week/498/ - McKenney JM, Davidson MH, Jacobson TA et al. Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force. Am J Cardiol 2006 Apr 4; 97:89C-94C. PMID: 16581336 - U.S. Food and Drug Administration (FDA). July 2012. FDA drug safety communication: important safety label changes to cholesterol-lowering statin drugs. Rockville, MD. http://www.fda.gov/drugs/drugsafety/ucm293101.htm - Grundy SM, Stone NJ, Bailey AL et al 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019 Jun 18;139(25):e1082-e1143. PMID: 30586774 - Grundy SM, Stone NJ, Bailey AL et al 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019 Jun 18;139(25):e1046-e1081. PMID: 30565953 - Forman DE, Stone NJ, Grundy SM. Treating Hypercholesterolemia in Older Adults. JAMA. 2019 Aug 20;322(7):695. No abstract available. PMID: 31429891
  288. Mortensen MB, Nordestgaard BG. Statin Use in Primary Prevention of Atherosclerotic Cardiovascular Disease According to 5 Major Guidelines for Sensitivity, Specificity, and Number Needed to Treat. JAMA Cardiol. Published online October 2, 2019 PMID: 31577339 https://jamanetwork.com/journals/jamacardiology/fullarticle/2752379
  289. Byrne P, Cullinan J, Smith SM, Statins for primary prevention of cardiovascular disease. BMJ 2019;367:l5674 PMID: 31619406 https://www.bmj.com/content/367/bmj.l5674
  290. Hennekens CH, Teng B, Pfeffer MA Statins and Diabetes: Current Perspectives and Implications for Clinicians. Am J Med. 2017 Jan 12 PMID: 28089803 http://www.amjmed.com/article/S0002-9343(17)30014-1/fulltext
  291. Samaras K, Makkar SR, Crawford JD, et al. Effects of statins on memory, cognition, and brain volume in the elderly. J Am Coll Cardiol 2019 Nov 26; 74:2554 PMID: 31753200 https://www.sciencedirect.com/science/article/pii/S073510971937799X
  292. Orkaby AR et al. Association of statin use with all-cause and cardiovascular mortality in US veterans 75 years and older. JAMA 2020 Jul 7; 324:68 https://jamanetwork.com/journals/jama/fullarticle/2767861
  293. Kincaid E COVID-19 Update: Statins and Mortality, Value of Imperfect Tests. Medscape - Aug 28, 2020 https://www.medscape.com/viewarticle/936530
  294. Mortensen MB et al Elevated LDL cholesterol and increased risk of myocardial infarction and atherosclerotic cardiovascular disease in individuals aged 70. Lancet. 2020. Nov 10 PMID: 33186534 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32233-9/fulltext - Gencer B et al Efficacy and safety of lowering LDL cholesterol in older patients: a systematic review and meta-analysis of randomised controlled trials. Lancet. 2020. Nov 10 PMID: 33186535 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32332-1/fulltext - Raal FJ, Mohamed F Never too old to benefit from lipid-lowering treatment. Lancet. 2020. Nov 10 PMID: 33186536 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32333-3/fulltext
  295. Yourman LC, Cenzer IS, Boscardin WJ et al Evaluation of Time to Benefit of Statins for the Primary Prevention of Cardiovascular Events in Adults Aged 50 to 75 YearsA Meta-analysis. JAMA Intern Med. Published online November 16, 2020. PMID: 33196766 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2773065
  296. Herrett E, Williamson E, Brack K et al Statin treatment and muscle symptoms: series of randomised, placebo controlled n-of-1 trials. BMJ. 2021 Feb 24;372:n135 PMID: 33627334
  297. Lou N Statins and Dementia: Are Some Folks More Prone to Harm? ASPREE neurocognition analysis largely neutral for most people. MedPage Today June 21, 2021 https://www.medpagetoday.com/cardiology/prevention/93207 - Zhou Z, Ryan J, Ernst ME et al Effect of statin therapy on cognitive decline and incident dementia in older adults. J Am Coll Cardiol 2021 PMID: 34167639 https://www.jacc.org/doi/10.1016/j.jacc.2021.04.075 - Ballantyne CM, Nambi V Statins and your memory: 'forget' about it? J Am Coll Cardiol 2021 PMID: 34167640 https://www.jacc.org/doi/10.1016/j.jacc.2021.04.076
  298. Hughes S Statins Linked to Lower Cancer Rate in Heart Failure Patients. Medscape June 24, 2021 https://www.medscape.com/viewarticle/953680 - Ren QW, Yu SY, Teng THK et al Statin associated lower cancer risk and related mortality in patients with heart failure. Eur Heart J. ehab325 2021. June 22 PMID: 34157723 https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehab325/6307232
  299. FDA Drug Safety Communication. July 20, 2021 Statins: Drug Safety Communication - FDA Requests Removal of Strongest Warning Against Using Cholesterol-lowering Statins During Pregnancy. https://www.fda.gov/safety/medical-product-safety-information/statins-drug-safety-communication-fda-requests-removal-strongest-warning-against-using-cholesterol
  300. Cai T, Abel L, Lanford O et al. Associations between statins and adverse events in primary prevention of cardiovascular disease: Systematic review with pairwise, network, and dose-response meta-analyses. BMJ 2021 Jul 14; 374:n1537 https://www.bmj.com/content/374/bmj.n1537
  301. Lou N Statin Users See Good Changes in Atherosclerotic Plaques. Plaques undergo metamorphosis toward harder, denser composition. MedPage Today August 18, 2021 https://www.medpagetoday.com/cardiology/prevention/94099 - van Rosendael A, van den Hoogen IJ, Gianni U et al Association of Statin Treatment With Progression of Coronary Atherosclerotic Plaque Composition. JAMA Cardiol. 2021;6(11):1257-1266. PMID: 34406326 PMCID: PMC8374741 (available on 2022-08-18) https://jamanetwork.com/journals/jamacardiology/fullarticle/2783117
  302. Jeong SH, Lee HS, Chung SJ et al. Effects of statins on dopamine loss and prognosis in Parkinson's disease. Brain 2021 Aug 4; [e-pub]. PMID: 34347020 https://academic.oup.com/brain/advance-article-abstract/doi/10.1093/brain/awab292/6339771
  303. Mansi IA, Chansard M, Lingvay I et al. Association of statin therapy initiation with diabetes progression: A retrospective matched-cohort study. JAMA Intern Med 2021 Oct 4 PMID: 34605849 https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2784799
  304. Stiles S USPSTF Tweaks Primary Prevention Statin Recommendations in New Draft Guidance. Medscape. 2022. Feb 22. https://www.medscape.com/viewarticle/968963 - U.S Preventive Services Task Force (USPSTF) Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: Preventive Medication. Draft Evidence Review. Feb 22, 2022 https://www.uspreventiveservicestaskforce.org/uspstf/document/draft-evidence-review/statin-use-primary-prevention-cardiovascular-disease-adults
  305. Byrne P, Demasi M, Jones M, Smith SM, O'Brien KK, DuBroff R Evaluating the Association Between Low-Density Lipoprotein Cholesterol Reduction and Relative and Absolute Effects of Statin Treatment: A Systematic Review and Meta-analysis JAMA Intern Med. 2022 Mar 14. PMID: 35285850 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2790055
  306. Lee M, Cheng CY, Wu YL et al Association Between Intensity of Low-Density Lipoprotein Cholesterol Reduction With Statin-Based Therapies and Secondary Stroke Prevention. A Meta-analysis of Randomized Clinical Trials. JAMA Neurol. 2022;79(4):349-358 PMID: 35188949 PMCID: PMC8861901 Free PMC article https://jamanetwork.com/journals/jamaneurology/fullarticle/2789410
  307. Lowry F The Best Statins to Lower Non-HDL Cholesterol in Diabetes? Medscsape. April 13, 2022 https://www.medscape.com/viewarticle/972109 - Hodkinson A, Tsimpida D, Kontopantelis E et al Comparative effectiveness of statins on non-high density lipoprotein cholesterol in people with diabetes and at risk of cardiovascular disease: systematic review and network meta-analysis. BMJ 2022;376:e067731 PMID: 35331984 PMCID: PMC8943592 Free PMC article https://www.bmj.com/content/376/bmj-2021-067731
  308. Mundal LJ, Igland J, Svendsen K et al Association of Familial Hypercholesterolemia and Statin Use With Risk of Dementia in Norway. JAMA Netw Open. 2022;5(4):e227715. PMID: 35438756 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2791295
  309. Hughes S New National Lipid Association Statement on Statin Intolerance. Medscape. June 15, 2022 https://www.medscape.com/viewarticle/975674 - Cheeley MK et al NLA scientific statement on statin intolerance: a new definition and key considerations for ASCVD risk reduction in the statin intolerant patient. J Clin Lipidology. 2022. June 8 PMID: 35718660 https://www.lipidjournal.com/article/S1933-2874(22)00167-2/fulltext
  310. Zhou YF, Wang Y, Wang G et al Association Between Statin Use and Progression of Arterial Stiffness Among Adults With High Atherosclerotic Risk. JAMA Netw Open. 2022;5(6):e2218323 PMID: 35713899 Free article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2793490
  311. Mortensen MB, Tybjaerg-Hansen A, Nordestgaard BG Statin Eligibility for Primary Prevention of Cardiovascular Disease According to 2021 European Prevention Guidelines Compared With Other International Guideline. JAMA Cardiol. Published online July 6, 2022. PMID: 35793078 https://jamanetwork.com/journals/jamacardiology/fullarticle/2793729
  312. US Preventive Services Task Force Statin Use for the Primary Prevention of Cardiovascular Disease in Adults. US Preventive Services Task Force Recommendation Statement. JAMA. 2022;328(8):746-753 PMID: 35997723 https://jamanetwork.com/journals/jama/fullarticle/2795521 - Habib AR, Katz MH, Redberg RF. Statins for Primary Cardiovascular Disease PreventionTime to Curb Our Enthusiasm. JAMA Intern Med. 2022;182(10):1021-1024. PMID: 35997985 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2795661
  313. Cholesterol Treatment Trialists' Collaboration Effect of statin therapy on muscle symptoms: an individual participant data meta-analysis of large-scale, randomised, double-blind trials. Lancet. 2022. August 29 PMID: 36049498 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)01545-8/fulltext
  314. NEJM Knowledge+ Question of the Week for November 15, 2022 https://knowledgeplus.nejm.org/question-of-week/40/
  315. Windle ML Rapid Rx Quiz: Statin Intolerance and Related Concerns Medscape. September 01, 2022 https://reference.medscape.com/viewarticle/979515
  316. Hlatky MA, Gonzalez PE, Manson JE et al Statin-Associated Muscle Symptoms Among New Statin Users Randomly Assigned to Vitamin D or Placebo. JAMA Cardiol. Published online November 23, 2022. PMID: 36416841 https://jamanetwork.com/journals/jamacardiology/fullarticle/2798958
  317. Hughes S Statins Tied to Lower ICH Risk Regardless of Bleed Location. Medscape Dec 9, 2022 https://www.medscape.com/viewarticle/985340 - Jensen Boe N, Hald SM, Micheelsen Jensen M Association Between Statin Use and Intracerebral Hemorrhage Location: A Nested Case-Control Registry Study Neurology. December 7, 2022, Not indexed in PubMed https://n.neurology.org/content/early/2022/12/07/WNL.0000000000201664
  318. Hong SJ, Lee YJ, Lee SJ et al Treat-to-Target or High-Intensity Statin in Patients With Coronary Artery Disease. A Randomized Clinical Trial. JAMA. 2023;329(13):1078-1087. March 6 PMID: 36877807 PMCID: PMC9989958 (available on 2023-09-06)
  319. NEJM Knowledge+ Gastroenterology
  320. Vell MS, Loomba R, Krishnan A et al Association of Statin Use With Risk of Liver Disease, Hepatocellular Carcinoma, and Liver-Related Mortality. JAMA Netw Open. 2023;6(6):e2320222 PMID: 37358849 PMCID: PMC10293910 Free PMC articl https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2806370
  321. Frank DA et al. Disparities in guideline-recommended statin use for prevention of atherosclerotic cardiovascular disease by race, ethnicity, and gender: A nationally representative cross-sectional analysis of adults in the United States. Ann Intern Med 2023 Jul 25; [e-pub]. PMID: 37487210 https://www.acpjournals.org/doi/10.7326/M23-0720
  322. Gaist D, Garcia Rodriguez LA, Hallas J et al Association of Statin Use With Risk of Stroke Recurrence After Intracerebral Hemorrhage. Neurology. 2023 Aug 30:10.1212/WNL.0000000000207792 PMID: 37648526 https://n.neurology.org/content/early/2023/08/30/WNL.0000000000207792
  323. Chou R, Cantor A, Dana T et al Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: A Systematic Review for the U.S. Preventive Services Task Force [Internet]. Agency for Healthcare Research and Quality (US); 2022 Aug. (Evidence Synthesis, No. 219.) Table 1, Statin Dosing and ACC/AHA Classification of Intensity. https://www.ncbi.nlm.nih.gov/books/NBK583664/table/ch1.tab1/ - Grundy SM, Stone NJ, Bailey AL et al AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019 June 18;139(25):e1046-e1081 PMID: 30565953 Free article
  324. O'Sullivan JL, Kohl R, Lech S, et al. Statin use and all-cause mortality in nursing home residents with and without dementia: A retrospective cohort study using claims data. Neurology 2024 Mar 26; 102:e209189. PMID: 38412394 https://www.neurology.org/doi/10.1212/WNL.0000000000209189
  325. Cholesterol Treatment Trialists' (CTT) Collaboration. Effects of statin therapy on diagnoses of new-onset diabetes and worsening glycaemia in large-scale randomised blinded statin trials: An individual participant data meta-analysis. Lancet Diabetes Endocrinol 2024 May; 12:306. PMID: 38554713 Free article https://www.thelancet.com/journals/landia/article/PIIS2213-8587(24)00040-8/fulltext - Gerstein HC, igeyre M. How clinically relevant is statin-induced diabetes? Lancet Diabetes Endocrinol 2024 May; 12:286. PMID: 38554714 https://www.thelancet.com/journals/landia/article/PIIS2213-8587(24)00059-7/abstract
  326. Zhang L, Sui L, Li J, Zhang R, Pan W, Lv T. Potential Benefits of Statin Therapy in Reducing Osteoarthritis Risk: A Mendelian Randomization Study. Arthritis Care Res (Hoboken). 2024 Apr 3. PMID: 38570925 https://acrjournals.onlinelibrary.wiley.com/doi/abs/10.1002/acr.25343
  327. Xu W et al Benefits and Risks Associated With Statin Therapy for Primary Prevention in Old and Very Old Adults: Real-World Evidence From a Target Trial Emulation Study. Ann Intern Med 2024. May 28. PMID: 38801776 https://www.acpjournals.org/doi/10.7326/M24-0004
  328. Orkaby AR et al Initiation of Statins for Primary Prevention in Heart Failure With Preserved Ejection Fraction. JACC Adv 2024 Apr, 3(4):100869 PMID: 38939680 PMCID: PMC11198708 Free PMC article https://www.jacc.org/doi/10.1016/j.jacadv.2024.100869

Component-of

aspirin/HMG CoA reductase inhibitor calcium channel blocker/HMG CoA reductase inhibitor HMG CoA reductase inhibitor/nicotinic acid polypill (Polycap)