Contents

Search

drug adverse effects of HMG CoA reductase inhibitors

Etiology: - risk factors [73] - older age - female gender - renal insufficiency - coadministration of fibrates, niacin, macrolides - coadministration of antiarrhythmic agents [72] - hypothyroidism - alcoholism - obesity - exertion - increased risk of exertional rhabdomyolysis (RR=3.0) [58] - LILRB5 variant rs12975366: T > C Asp247Gly may predispose to statin myopathy [74] - genetic variants in SLCO1B1 may predispose to statin myopathy [75] Adverse effects: 1) statin myopathy (most common) a) increase in serum creatine kinase (mild to rhabdomyolysis) b) myopathy may occur with normal serum creatine kinase [5] c) statin use attenuates substrate use during maximal exercise, induces muscle fatigue during repeated muscle contractions, & decreases muscle mitochondrial oxidative capacity [60] d) increased risk of exertional rhabdomyolysis (RR=3.0) [58] e) increased risk of hospitalization for acute renal failure with high-dose or potent statin [26] f) stop statin if - serum creatine > 10-fold upper reference value, or severe myalgias [9] f) CoQ10 may or may not help myalgias [9,10] - CoQ10 of no benefit [45] g) symptoms usually subside within a month or two after stopping the statin, but they sometimes persist longer [15] h) hydrophilic statins (fluvastatin, pravastatin, & rosuvastatin) less likely to cause statin myopathy than lipophilic statins [33] i) transcriptional activity of a gene associated with statin-induced myopathy peaks in the middle of the day [44] j) 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 [64] - no overall effect of atorvastatin 20 mg on muscle symptoms compared with placebo [65] - > 90% of muscle symptoms in patients taking statins not due to statin [71] - 31% of new statin users complain of muscle symptoms; 13% discontinue use [316] - vitamin D not helpful [76] k) a statin-associated autoimmune-necrotizing myopathy with autoantibody directed against HMG-CoA reductase, the pharmacologic target of statins [35] - occurs in a minority of patients with statin-induced myopathy 2) increased risk of musculoskeletal injuries (19%) - sprains, muscle strain [29] 3) increased risk of musculoskeletal pain (9%) [29] - increased risk of generalized pain in cancer patients > 80 years of age [43] 4) increase risk of osteoarthrities & other arthropathies (7%) - not stastically significant [29] 5) memory impairment is 2nd most common complaint [1,11] a) reversible cognitive impairment [19] 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 [11]; rosuvastatin probably does not either c) no increase in risk of cognitive impairment - data limited, especially for high-dose statins [32] - no definitive evidence of benefit or harm [62] d) acute memory impairment within 30 days (RR=4.4, all antihyperlipidemic agents) [48] e) no increased risk of dementia or mild cognitive impairment whether lipophilic or hydrophilic statin [66] - risk of Alzheimer's disease may be elevated in persons in lowest quartile of baseline cognitive function [66] - no increased risk for dementia in patients with familial hypercholesterolemia taking high-intesity statins over most if not all of adult life [69] 6) may increase incidence of postoperative delirium [16] 7) hepatotoxicity (rare) [4, 6] a) increased liver function tests 1% [6] b) baseline serum ALT [33] - further monitoring of LFTs no longer routinely required [19] - up to 3 fold elevation in serum ALT acceptable to continue statin [77] c) no particular statin is more or less likely to cause LFT abnormalities [39,40] d) statins account for 2% of drug-related hepatotoxicity [39] e) 18% of patients with statin-induced hepatotoxicity develop chronic liver disease [39] 8) increased risk of renal failure - acute renal failure (RR=1.3) - chronic renal failure (RR=1.4-1.5) [56] 9) peripheral neuropathy (< 0.1%/year) [2] a) no evidence that CoQ* supplements help [3] b) may take 3-12 months for neuropathy to improve after discontinuing statin [3] c) statins do not increase risk of peripheral neuropathy [63] 10) erectile dysfunction? [7] - not associated with erectile dysfunction [59] 11) aggressive statin therapy in the elderly, resulting in reductions of total cholesterol < 148 mg//dL may result in subtle affective changes. [8] 12) intracranial hemorrhage (ICH) - increased risk independent of LDL [49] - increased risk of non-fatal hemorrhagic stroke, RR = 1.7 - no increased risk of intracerebral hemorrhage [50] - decreased risk of intracerebral hemorrhage (RR=0.68) [51] - pre-ICH statin use not associated with improved ICH functional outcome or mortality [52] - post-ICH statin use is not associated with an increased risk of ICH recurrence [52,78] - discontinuation of statin after ICH is associated with increased risk of mortality (RR=3.9 within 30 days; RR=1.5 at 3 months [53] 13) diabetes mellitus type 2 (RR=1.12) [13,17,18,23,28] a) risk is inherent in inhibition of HMG CoA reductase - mediated by body weight or other modifiable metabolic factors [42] b) overall increase in risk varies dependent on dose, duration & source of data - increase is risk ~ 10% [17] - risk of type 2 diabetes in statin users is 31% vs 19% in non users after 7 years; NNH=9 [55] c) risk of diabetes increases with duration of statin therapy [53] d) statin use associated with diabetes progression in patients with diabetes [68] e) one additional case of diabetes for every 255 patients on statin for 4 years [13,15] f) 498 patients treated with high-dose for 1 year for 1 patient to develop diabetes [18]; compare with 155 high-risk patients treated for one year to prevent 1 cardiovascular event [18] g) increased risk of diabetes with high dose rosuvastatin is 27% [25] h) benefits outweigh risks in secondary prevention & high-risk patients [21,23] i) risk higher for more potent statins (simvastatin, rosuvastatin, atorvastatin) than low potency statins (pravastatin, lovastatin, fluvastatin) [28,38] j) increased risk in patients with impaired glucose tolerance [34], (RR=1.5, number needed to harm = 12) [34] k) new-onset diabetes more common in patients with baseline HgbA1c) in the prediabetes range than in patients with lower HgbA1c [79] l) among patients with known diabetes at baseline, glycemia worsens slightly with statin therapy compared with placebo [79] m) risk may be associated with increased expression of LDL receptor [47] n) unknown if type 2 diabetes resolves when statin is discontinued [55] 14) statin use may increase risk of pneumonia [14] 15) increased risk of acute renal failure [26] a) risk greatest in the 1st 120 days b) risk higher for more potent statins c) relative risk higher in patients without chronic kidney disease d) also see myopathy (above) 16) decreased energy & increased fatigue with exertion, especially among women [20] 17) statin use in older men is associated with a slight reduction in physical activity [37] 18) increased caloric intake (10%), including dietary fat (14%) with resultant increase in BMI (1.3 vs 0.4) for non-users [36] 19) statin use may increase risk of Parkinson's disease (RR=1.6-1.7) [57] - statin use associated with worse baseline nigrostriatal dopamine degeneration [67] - statin use prior to diagnosis of Parkinson's disease associated with increased risk of dementia [67] 20) not associated with increased risk of pancreatitis [22] 21) no consensus on statins & risk of cataracts [24] - increased risk of cataracts (9%, 20% without corbidities) [31] 22) potentially teratogenic, risk may be small [27] - statin use during the first trimester of pregnancy is not associated with increased risk for congenital malformations [41] 23) use of statins before diagnosis of incident diabetes is not associated with an increased risk of microvascular disease [41] 24) increased risk of gynecomastia (RR=1.4) [61] 25) immune-mediated necrotizing myopathy (IMNM) 26) simvastatin & pravastatin score best in safety profile [30]

Properties

DRUGS: HMG CoA reductase inhibitor FORM: drug adverse effects hmg coa reductase inhibitor

References

  1. Prescriber's Letter 9(3):14 2002
  2. Journal Watch 22(12):91, 2002 Gaist D et al, Neurology 58:1333, 2002
  3. Prescriber's Letter 9(7):37-38 2002
  4. Prescriber's Letter 9(9):49 2002
  5. 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
  6. Prescriber's Letter 10(8):43 2003
  7. Prescriber's Letter 11(12): 2004 Does Statin Use Decrease Libido and Erectile Function? Detail-Document#: 201202 (subscription needed) http://www.prescribersletter.com
  8. Morales K et al, Simvastatin causes changes in affective processes in elderly volunteers. J Am Geriatr Soc 2006; 54:70 PMID: 164202002
  9. Prescriber's Letter 13(3): 2006 Statin-Associated Myopathy Detail-Document#: 220310 (subscription needed) http://www.prescribersletter.com
  10. 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
  11. 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
  12. Goldstein LB et al. Hemorrhagic stroke in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels study. Neurology 2008 Jun 10; 70:2364. PMID: 18077795 - Jacobs BS and Greenberg SM. Statins, low cholesterol, and hemorrhagic stroke: An uncertain triangle. Neurology 2008 Jun 10; 70:2355. PMID: 18541869
  13. Prescriber's Letter 16(1): 2009 Do Statins Cause Diabetes? Detail-Document#: 250110 (subscription needed) http://www.prescribersletter.com
  14. 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
  15. 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
  16. 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
  17. Sattar N et al Statins and risk of incident diabetes: A collaborative meta-analysis of randomised statin trials. Lancet 2010 Feb 27; 375:735. PMID: 20167359
  18. Preiss D et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: A meta-analysis. JAMA 2011 Jun 22/29; 305:2556. PMID: 21693744
  19. FDA MedWatch: 02/28/2012 Statin Drugs - Drug Safety Communication: Class Labeling Change http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm293670.htm
  20. 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
  21. Wang KL et al Statins, Risk of Diabetes, and Implications on Outcomes in the General Population ONLINE FIRST J Am Coll Cardiol. 2012;():. doi:10.1016, August 2012 PMID: 22884288 http://content.onlinejacc.org/article.aspx?articleID=1309632
  22. Preiss D et al. Lipid-modifying therapies and risk of pancreatitis: A meta-analysis. JAMA 2012 Aug 22/29; 308:804 PMID: 22910758
  23. 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
  24. Prescriber's Letter 19(10): 2012 Cataract Risk with Statins Detail-Document#: 281015 (subscription needed) http://www.prescribersletter.com
  25. Miller R Medscape: Feb 28, 2012 FDA Adds Warnings to Statin Label http://www.medscape.com/viewarticle/759335?src=top10 - FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drugs. Feb 28, 2012 http://www.fda.gov/Drugs/DrugSafety/ucm293101.htm
  26. Dormuth CR et al Use of high potency statins and rates of admission for acute kidney injury: multicenter, retrospective observational analysis of administrative databases. BMJ 2013;346:f880 PMID: 23511950 http://www.bmj.com/content/346/bmj.f880
  27. 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
  28. Carter AA et al. Risk of incident diabetes among patients treated with statins: Population based study. BMJ 2013 May 23; 346:f2610. PMID: 23704171 - Huupponen R and Viikari J. Statins and the risk of developing diabetes. BMJ 2013 May 23; 346:f3156 PMID: 23709567
  29. Mansi I et al. Statins and musculoskeletal conditions, arthropathies, and injuries. JAMA Intern Med 2013 PMID: 23877079 http://archinte.jamanetwork.com/article.aspx?articleid=1691918
  30. 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
  31. Leuschen J et al Association of Statin Use With Cataracts. A Propensity Score- Matched Analysis. JAMA Ophthalmol. Published online September 19, 2013 PMID: 24052188 http://archopht.jamanetwork.com/article.aspx?articleid=1739520
  32. 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
  33. Medical Knowledge Self Assessment Program (MKSAP) 16, 17, 18. American College of Physicians, Philadelphia 2012, 2015, 2018.
  34. Shen L et al. Role of diuretics, beta-blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: Reanalysis of data from the NAVIGATOR study. BMJ 2013 Dec 9; 347:f6745 PMID: 24322398 http://www.bmj.com/content/347/bmj.f6745
  35. 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
  36. 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: 24763439 http://archinte.jamanetwork.com/article.aspx?articleid=1861768
  37. 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
  38. 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
  39. Russo MW et al. Spectrum of statin hepatotoxicity: Experience of the drug- induced liver injury network. Hepatology 2014 Aug; 60:679 PMID: 24700436
  40. 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
  41. Nielsen SF and Nordestgaard BG Statin use before diabetes diagnosis and risk of microvascular disease: a nationwide nested matched study. The Lancet Diabetes & Endocrinology, September 10, 2014 PMID: 25217178 http://www.thelancet.com/journals/landia/article/PIIS2213-8587%2814%2970173-1/abstract
  42. 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
  43. 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
  44. 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
  45. 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
  46. Bateman BT et al Statins and congenital malformations: cohort study. BMJ 2015;350:h1035 PMID: 25784688 http://www.bmj.com/content/350/bmj.h1035
  47. 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
  48. Strom BL et al Statin Therapy and Risk of Acute Memory Impairment. JAMA Intern Med. Published online June 08, 2015 http://archinte.jamanetwork.com/article.aspx?articleID=2301148
  49. 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
  50. 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
  51. Asberg S, Eriksson M Statin therapy and the risk of intracerebral haemorrhage: a nationwide observational study. Int J Stroke. 2015 Jun 4 PMID: 26043664
  52. 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
  53. 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
  54. 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
  55. 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
  56. 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 Dec 2. pii: S0002-9149(15)02315-2 PMID: 26742473 http://www.ajconline.org/article/S0002-9149%2815%2902315-2/abstract
  57. Melville NA Statin Use Linked to Increased Parkinson's Risk. Medscape. Oct 26, 2016 http://www.medscape.com/viewarticle/870996
  58. 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
  59. Harding A Meta-analysis Finds No Link Between Statins, Erectile Dysfunction Medscape - Dec 01, 2017. https://www.medscape.com/viewarticle/889463
  60. 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
  61. 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
  62. 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
  63. Warendorf JK, Vrancken AFJE, van Eijk RPA et al. Statins do not increase risk of polyneuropathy. Neurology 2019 Apr 30; 92:e2136. PMID: 30737334
  64. 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
  65. 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
  66. 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
  67. 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
  68. 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
  69. 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
  70. 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
  71. 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
  72. Windle ML Rapid Rx Quiz: Statin Intolerance and Related Concerns Medscape. September 01, 2022 https://reference.medscape.com/viewarticle/979515
  73. 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
  74. 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
  75. 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
  76. 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
  77. NEJM Knowledge+ Gastroenterology
  78. 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
  79. 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