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aspirin (Ecotrin, Empirin, Bayer aspirin, Vazalore, ASA)

Acetylsalicylic acid (ASA). Enteric-coated acetylsalicylic acid (ECASA). Tradenames: Ecotrin, Empirin, Bayer. Indications: 1) temporary relief of minor aches & pains, inflammation & fever - 325 to 650 mg PO every 4-6 hours, max 4 g/day 2) prophylaxis for myocardial infarction, ischemic stroke a) secondary prevention of cardiovascular disease - secondary stroke prevention (relative risk reduction of 13%) - low-dose aspirin reduces risk of all-cause dementia in adults with coronary artery disease [98] b) USPSTF recommends aspirin for primary prevention for: - prevention of cardiovascular disease in adults age 50-59 years of age with a 10-year cardiovascular risk of >= 10% [99] - USPSTF reccommends against low-dose aspirin for primary prevention in adults >= 60 years [99] c) other recommendations for primary prevention 1] prevention of colorectal cancer in adults 50-69 years of age [67,69] - benefit not realized until 10 years after starting aspirin [67,69] 2] no benefit in primary prevention of fatal myocardial infarction [41] 3] aspirin 100 mg QD reduces risk of serious vascular events (RR=0.88) but increases risk of major bleeding (RR=1.3) in patients with diabetes mellitus [78] 4] no benefit for primary prevention in patients with or without diabetes mellitus [57] 5] FDA recommends against use of aspirin for primary prevention [58] 6] reduction in cardiovascular risk at cost of increased risk for major bleed [85] 7] inconclusive evidence on whether discontinuation of aspirin for primary prevention after at age 70 years is associated with benefit or harm [102] 8] individualized benefit-harm analysis may be appropriate [90] d) may only be effective in patients with systolic blood pressure < 130 mm Hg [6] e) 75-150 mg QD as effective as higher doses [9] 75-162 mg recommended by American Heart Association [16] f) no benefit of added dipyridamole [9] g) 10% less effective than clopidogrel or ticlopidine [9] h) stopping aspirin may result in increased risk of heart attack & stroke (increased platelet production) [19] i) 81 mg QD may not reduce atherosclerotic events in adults with type 2 diabetes [24] j) no better than placebo in patients with peripheral arterial disease [29,37] k) no benefit in primary prevention for Japanese men > 60 years of age [60] l) low-dose aspirin does not prevent primary cardiovascular events in black patients [92] m) 100 mg QD of no benefit for primary prevention in non-diabetic men >= 55 years + 2-4 risk factors or women >= 60 years + >= 3 risk factors (increased risk of GI bleed noted) [79] n) no benefit for primary prevention of cardiovascular disease or mortality (100 mg/day) in healthy elderly [80] o) aspirin use >= 3 times per week reduces cardiovascular mortality in elderly (RR=0.7) [91] 3) treatment of acute MI - 160-325 mg PO (chewed, not EC), then 325 mg PO QD 4) percutaneous coronary intervention (used with clopidogrel) 5) management of rheumatoid arthritis, rheumatic fever, osteoarthritis, bursitis -> 325 to 650 mg PO every 4-6 hours, max 4 g/day 6) Kawasaki disease: a) 100 mg/kg/day PO divided every 6 hours until fever resolves, then 8-10 mg/kg PO QD b) monitor serum concentration 7) combined with warfarin (INR of 3) for high-risk patients with artificial heart valves 8) prophylaxis for venous thromboembolism: - safer but less effective than warfarin [47] 9) may diminish risks of cancer, death from cancer, & cancer metastasis [42,44] a) may diminish risk of colon cancer [9] 1] benefit of colorectal cancer prevention is not apparent until 10 years after aspirin therapy is started [69,112] 2] *see aspirin & colorectal polyps & Nurses Health Study 3] does not reduce mortality from colon cancer [28] - USPSTF says evidence inconclusive to recommend for or against aspirin for prevention of colorectal cancer [99] 4] *dose-independent reduction in mortality due to proximal colon cancer & rectal cancer 5] no reduction in mortality due to distal colon cancer [38] 6] aspirin lowers risk of colorectal cancer in patients with wild-tyep BRAF but not mutated BRAF [54] 7] aspirin 100 mg QOD reduces risk of colorectal cancer (RR = 0.80) in middle-aged women - does not reduce total cancer risk or all-cause mortality [55] b) may diminish risk of gastrointestinal cancer (RR=0.85) when used at least twice weekly for > 6 years [68] - reduces risk of colorectal cancer, esophageal cancer, & gastric cancer [59]* - associated with lower cancer mortality, especially for gastrointestinal cancers, regardless of weight [93] c) may reduce risk of prostate cancer [9] d) may reduce risk of ovarian cancer [9,82] e) may reduce risk of breast cancer [12] - may reduce mortality in patients with breast cancer [36] f) may reduce mortality from several adenocarcinomas [39] g) may reduce risk of hepatocellular carcinoma (RR = 0.59) [48,82] h) may reduce risk of melanoma in postmenopausal white women [52] i) modestly reduces risk of lung cancer, breast cancer, & prostate cancer [59] j) low-dose aspirin < 100 mg/day at least twice a week lowers risk for lung cancer 11% after 9 years [87] k) aspirin use >= 3 times per week reduces cancer mortality in elderly (RR=0.9) [91] 10) reduces risk of death from chronic liver disease (RR = 0.55) [48] * risk for nontrivial bleeding roughly equals benefit in primary prevention of nonfatal myocardial infarction [41] * benefit exceeds bleeding risk for myocardial infarction, ischemic stroke, & cancer [59] Contraindications: 1) USPSTF recommends against initiating aspirin for primary prevention of cardiovascular disease in adults >= 60 years [99] - modeling data suggests risk of continuing low-dose aspirin for primary prevention beyond age 75 may exceed benefit. 2) does NOT block restenosis after coronary angioplasty or carotid endarterectomy 3) of NO benefit in primary stroke prevention for men - see sex differences for aspirin therapy 4) old-age alone not indication for low-dose aspirin [17] 5) no benefit for low-dose (81 mg) ASA in preventing cancer or cardiovascular disease in women [18] 6) no benefit for low-dose (81 mg) ASA in preventing cognitive impairment in middle-age & elderly subjects at moderate cardiovascular risk [23] 7) no evidence that low-dose aspirin (< 300 mg/day prevents cognitive decline or dementia or improves cognitive test scores [72,95] 8) of no benefit in prevention of depression in the elderly [94] 9) routine use of low-dose aspirin for primary prevention of cardiovascular disease in apparently healthy individuals, including those with elevated blood pressure, diabetes or low ankle-brachial index (< 0.95) [33,36] 10) for most patients risks outweigh benefits for primary prevention [88] 11) in older adults (> 70 years) 100 mg of aspirin daily may accelerate progression of cancer [96] 12) of no cardiovascular benefit in patients on hemodialysis [103] 13) low-dose aspirin does not decrease risk of falls in the elderly, but increases risk of serious falls [104] 14) low-dose aspirin result in a 38% increase in intracranial bleeding among healthy older adult without any reduced risk of ischemic stroke [107] Caution: 1) aspirin may cause severe asthma - clopidogrel if aspirin would be indicated but patient intolerant 2) a triad of asthma, nasal polyposis & aspirin sensitivity 3) control hypertension before starting aspirin [21] 4) uncertain net value; reduction in cardiovascular events needs to be weighed against risk of major bleed [30] Benefit/risk: - number needed to treat (NNT) (primary prevention) [62] - 1667 for 1 year to prevent 1 cardiovascular event - 146 for patients already taking aspirin for primary prevention [75] - 2000 for 1 year to prevent 1 non-fatal MI - 3000 for 1 year to preccent 1 non-fatal stroke - no mortality benefit [62] - number needed to harm* - 3300 for 1 year to precipitate 1 major bleeding event - number needed to treat (NNT) (secondary prevention) [63] - 50 for 2 years to prevent 1 cardiovascular event - 36 for 1 year to prevent 1 cardiovascular event in patient already taking aspirin for secondary prevention [75] - 333 for 2 years to prevent 1 death - 77 for 2 years to prevent 1 non-fatal MI - 200 for 2 years to prevent 1 stroke - number needed to harm* - 400 for 2 years to induce 1 major hemorrhage [63] - number needed to treat immediately following STEMI [64] - 42 to save 1 life - 167 to result in non-dangerous bleeding - number needed to treat with 160-600 mg QD within 48 hours following ischemic stroke [65] - 79 for mortality, dependency - 143 to prevent recurrent stroke - number needed to harm - 245 for major hemorrhage - 574 for intracranial hemorrhage [65] * likely comparing different doses of aspirin or perhaps different patient population with different comorbidities Dosage: - prevention of stroke, heart attack: - 75-81 mg PO QD sufficient [45,97] - no significant benefit of low-dose aspirin for patients > 70 kg [77] - 300-500 mg QD may be necessary for patients > 70 kg - no difference in safety or efficacy for secondary prevention of cardiovascular events of 81 mg vs 325 mg QD (male or female) [111] - lifetime therapy for secondary prevention [40] - add proton pump inhibitor to aspirin for elderly [73] - headache, myalgia, arthralgia: 325-650 mg every 4 hours or 325-975 mg every 6 hours Tabs: 81, 325, 500, 650, 975 mg. Suppository: 120, 200, 300, 600 mg. Enteric-coated as effective as plain aspirin in prevention of cardiovascular disease [11]; may be less effective [49]; effectiveness & safety in patients with cardiovascular disease similar [109] Quick-release form: 325 mg, 500 mg (Bayer) Vazalore with a special complex within the capsule allows for targeted release of aspirin minimizing direct contact with the stomach. [101] - Capsules 81 mg, 325 mg Pharmacokinetics: 1) hydrolyzes to salicylate by esterases in the GI mucosa, erythrocytes, synovial fluid & blood 2) salicylate is metabolized by the liver 3) 1/2 life of parent compound is 15-20 minutes 4) 1/2 life of salicylate is 3-10 hours 5) onset of analgesia is 30 minutes 6) duration of action is 3-4 hours Adverse effects: 1) nausea/vomiting 2) dyspepsia/heartburn* 3) risk of GI bleeding - risk of GI bleeding increases with age (with or without aspirin) - older age & male sex are important risk factors for GI bleeding (USPSTF) [112,113,114] 4) increased risk for major hemorrhage (RR = 1.55) a) RR = 1.55 for low dose aspirin [43] - increased risk for GI bleed when used for primary prevention (100 mg/day) in healthy elderly [80] - elderly > 75 years at highest risk 31/100,000 [110] b) bleeding risk correlates with ischemic risk [61] c) no increase in risk for patients with diabetes mellitus d) risk of serious GI bleeding is 2 times greater in men than in women [112,113,114] e) gastrointestinal ulceration (0.06%/year 75-500 mg daily)* 1] low dose in combination with proton pump inhibitor a] minimizes risk of GI bleed [15,20,25] b] does not reduce risk of upper GI bleed [89] 2] risk of cardiovascular complications after stopping low dose aspirin outweighs risk of GI bleed in patients who take aspirin for secondary prophylaxis [34] 3] clopidogrel alone is more likely to cause recurrent GI bleeding than aspirin combined with a PPI [34] 4] lower GI bleed - continued use of low-dose asprin after lower GI bleed associated with increased risk of bleeding (19% vs 7% for placebo at 5 years) but lower overall mortality (23% vs. 36%) in apparently high-risk patients [70] f) intracranial hemorrhage - increases risk of hemorrhagic stroke [7,8] (0.02%/year), especially with hypertension [21] - doses > 200 mg/day double the risk of bleeding [12] - does NOT increase risk of intracranial hemorrhage with head trauma in the elderly [13] - low dose aspirin 75-300 mg QD does not increase risk of intracranial hemorrhage [76] g) iron-deficiency anemia uncommon with low-dose aspirin [106] h) risk vs benefit calculator [53] 5) rash 6) dyspnea 7) bronchospasm 8) renal impairment (may contribute to anemia) 8) exacerbation of gout a) low-dose aspirin (<= 325 mg/day) blocks uric acid secretion & increases serum uric acic [5,56] b) treatment with hypouricemic agent may lower risk [56] c) high-dose aspirin in uricosuric [56] 10) aspirin primarily affects cochlear function of the inner ear - tinnitus, hearing loss - little or no vertigo [108] 11) allergic reactions (anaphylactoid reactions) a) urticaria b) angioedema c) results from inhibition of cyclooxygenase d) no skin testing is available e) antigen desensitization if NSAIDs are imperitive f) leukotriene & 5-lipoxygenase inhibitors attenuate allergic reaction to aspirin 12) may be associated with nasal polyps & rhinosinusitis - aspirin-exacerbated respiratory disease [81] 13) increased risk of neovascular type late macular degeneration (RR = 1.7) [50,51] - data not strong enough to overturn use of aspirin for evidence-based indications [51] 14) heart failure? - 325 mg QD does not appear to worsen heart failure (all patients taking ACE inhibitor) [74] - risk of heart failure for patients taking daily aspirin for 5 years (RR-1.26) [100] * GI prophylaxis - proton pump inhibitors should be considered for patients on long-term antiplatelet therapy if: [3] a) history of peptic ulcer or gastrointestinal bleeding b) dual antiplatelet therapy or con6co6mitan6t anticoagulation c) additional risk factors (age >6=6 60, steroid use, dyspepsia, or gastroesophageal reflux) - in patients with a history of ulcer histories who are starting chronic antiplatelet therapy, test for & eradicate H pylori [3] - famotidine 20 mg BID prevents peptic ulcers & erosive esophagitis in patients taking low-dose aspirin [32] Toxicity: (management) 1) overdose a) induce emesis with ipecac b) gastric lavage with saline c) follow with activated charcoal 2) dehydration a) IV fluids (normal or 1/2 normal saline) with KCl b) do NOT use D5W 3) metabolic acidosis - sodium bicarbonate 4) hyperthermia - spone baths, fan, cooling blanket 5) coagulopathy/hemorrhage - IV vitamin K 6) hypoglycemia (with coma, seizures, or mental status change) - dextrose 25 g IV 7) seizures: diazepam 5-10 mg IV Drug interactions: 1) corticosteroids increases risk of GI & renal-related toxicity 2) aspirin may antagonize uricosuric effect of probenecid 3) aspirin increases methotrexate levels by binding site displacement & inhibiting renal excretion 4) increased risk of bleeding when coadministered with warfarin 5) may displace valproic acid from binding sites & increase toxicity 6) ibuprofen & other NSAIDs may inhibit antiplatelet activity of aspirin [10] - if coadministered, aspirin should be taken 2 hours before the NSAID (not with, or immediately after NSAID) 7) aspirin does not significantly increase blood pressure when used in combination with antihypertensives [71] - aspirin might inhibit action of ACE inhibitors [74] 8) dichlorphenamide increases aspirin levels (contraindicated) - coadministration of dichlorphenamide with high-dose aspirin can cause anorexia, lethargy, tachypnea, coma [105] Mechanism of action: 1) inhibits prostaglandin synthesis a) cyclo-oxygenase 1 1] GI effects 2] renal effects 3] inhibition of platelet aggregation b) cyclo-oxygenase 2 -> anti-inflammatory properties 2) acts on temperature regulation center in the hypothalamus 3) inhibits formation of thromboxane A2 - irreversibile platelet effects last 10 days 4) inhibits NF-kappa B in macrophages 5) diabetes mellitus does not affect platelet function or response to low-dose aspirin [84] Notes: - risk vs benefit calculator [53]

Interactions

drug interactions drug adverse effects (more general classes) monitor with non steroidal anti-inflammatory agents (NSIADs)

Related

sex differences for aspirin therapy

General

antiplatelet agent salicylate

Properties

INHIBITS: cyclooxygenase MISC-INFO: elimination route KIDNEY 1/2life 0.25-0.33 HOURS pregnancy-category D safety in lactation ?

Database Correlations

PUBCHEM correlations

References

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Component-of

acetaminophen/aspirin acetaminophen/aspirin/caffeine (Excedrin Extra, Excedrin migraine) acetaminophen/aspirin/caffeine/codeine/salicylamide acetaminophen/aspirin/caffeine/salicylamide acetaminophen/aspirin/codeine acetaminophen/aspirin/diphenhydramine acetaminophen/aspirin/pseudoephedrine aluminum hydroxide/aspirin/magnesium hydroxide (Ascriptin) aspirin/butalbital/caffeine (Fiorinal) aspirin/butalbital/caffeine/codeine (Fiorinal with Codeine) aspirin/caffeine aspirin/caffeine/citrate/orphenadrine aspirin/caffeine/dihydrocodeine aspirin/caffeine/orphenadrine (Norgesic) aspirin/caffeine/propoxyphene (Darvon Compound) aspirin/caffeine/salicylamide aspirin/calcium carbonate aspirin/camphor/menthol/methyl salicylate aspirin/carisoprodol (Soma Compound) aspirin/carisoprodol/codeine (Soma Compound with Codeine) aspirin/chlorpheniramine/dextromethorphan/phenylephrine aspirin/chlorpheniramine/phenylephrine aspirin/citrate/diphenhydramine/nov protein aspirin/citrate/sodium bicarbonate aspirin/citric acid/sodium bicarbonate (Alka-Seltzer) aspirin/codeine (Empirin with Codeine) aspirin/codeine/phosphate aspirin/dextromethorphan/doxylamine/phenylephrine aspirin/dextromethorphan/phenylephrine aspirin/diphenhydramine aspirin/dipyridamole (Aggrenox) aspirin/HMG CoA reductase inhibitor aspirin/hydrocodone aspirin/menthol aspirin/meprobamate aspirin/methocarbamol (Robaxisal) aspirin/omeprazole aspirin/oxycodone (Percodan) aspirin/pentazocine (Talwin Compound) aspirin/phenyltoloxamine aspirin/pravastatin (Pravigard PAC) polypill (Polycap)