Low-Dose Aspirin in Patients with Stable Cardiovascular Disease: A Meta-analysis



      Many recommendations for aspirin in stable cardiovascular disease are based on analyses of all antiplatelet therapies at all dosages and in both stable and unstable patients. Our objective was to evaluate the benefit and risk of low-dose aspirin (50-325 mg/d) in patients with stable cardiovascular disease.


      Secondary prevention trials of low-dose aspirin in patients with stable cardiovascular disease were identified by searches of the MEDLINE database from 1966 to 2006. Six randomized trials were identified that enrolled patients with a prior myocardial infarction (MI) (n=1), stable angina (n=1), or stroke/transient ischemic attack (n=4). A random effects model was used to combine results from individual trials.


      Six studies randomized 9853 patients. Aspirin therapy was associated with a significant 21% reduction in the risk of cardiovascular events (nonfatal MI, nonfatal stroke, and cardiovascular death) (95% confidence interval [CI], 0.72-0.88), 26% reduction in the risk of nonfatal MI (95% CI, 0.60-0.91), 25% reduction in the risk of stroke (95% CI, 0.65-0.87), and 13% reduction in the risk of all-cause mortality (95% CI, 0.76-0.98). Patients treated with aspirin were significantly more likely to experience severe bleeding (odds ratio 2.2, 95% CI, 1.4-3.4). Treatment of 1000 patients for an average of 33 months would prevent 33 cardiovascular events, 12 nonfatal MIs, 25 nonfatal strokes, and 14 deaths, and cause 9 major bleeding events. Among those with ischemic heart disease, aspirin was most effective at reducing the risk of nonfatal MI and all-cause mortality; however, among those with cerebrovascular disease, aspirin was most effective at reducing the risk of stroke.


      In patients with stable cardiovascular disease, low-dose aspirin therapy reduces the incidence of adverse cardiovascular events and all-cause mortality, and increases the risk of severe bleeding.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The American Journal of Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Falk E.
        Coronary thrombosis: pathogenesis and clinical manifestations.
        Am J Cardiol. 1991; 68: 28B-35B
        • Fuster V.
        • Stein B.
        • Ambrose J.A.
        • et al.
        Atherosclerotic plaque rupture and thrombosis.
        Circulation. 1990; 82: II47-II59
        • Gawaz M.
        • Langer H.
        • May A.E.
        Platelets in inflammation and atherogenesis.
        J Clin Invest. 2005; 115: 3378-3384
        • Steinhubl S.R.
        • Moliterno D.J.
        The role of the platelet in the pathogenesis of atherothrombosis.
        Am J Cardiovasc Drugs. 2005; 5: 399-408
        • Wagner D.D.
        • Burger P.C.
        Platelets in inflammation and thrombosis.
        Arterioscler Thromb Vasc Biol. 2003; 23: 2131-2137
      1. Collaborative overview of randomised trials of antiplatelet therapy-I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients.
        BMJ. 1994; 308 (Anonymous) ([see comment] [erratum appears in BMJ. 1994;308:1540]): 81-106
        • Antithrombotic Trialists C
        Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.
        BMJ. 2002; 324 ([see comment] [erratum appears in BMJ. 2002;324:141]): 71-86
        • Jackson S.P.
        • Schoenwaelder S.M.
        Antiplatelet therapy: in search of the ‘magic bullet’.
        Nat Rev Drug Discov. 2003; 2: 775-789
        • Patrono C.
        • Bachmann F.
        • Baigent C.
        • et al.
        Expert consensus document on the use of antiplatelet agents.
        Eur Heart J. 2004; 25: 166-181
        • Stein B.
        • Fuster V.
        • Israel D.H.
        • et al.
        Platelet inhibitor agents in cardiovascular disease: an update.
        J Am Coll Cardiol. 1989; 14: 813-836
        • Tendera M.
        • Wojakowski W.
        Role of antiplatelet drugs in the prevention of cardiovascular events.
        Thromb Res. 2003; 110: 355-359
        • Patrono C.
        • Coller B.
        • FitzGerald G.A.
        • et al.
        Platelet-active drugs: the relationships among dose, effectiveness, and side effects: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.
        Chest. 2004; 126: 234S-264S
        • Smith Jr, S.C.
        • Allen J.
        • Blair S.N.
        • et al.
        AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute.
        Circulation. 2006; 113 ([erratum appears in Circulation. 2006;113:e847]): 2363-2372
        • Meade M.O.
        • Richardson W.S.
        Selecting and appraising studies for a systematic review.
        Ann Intern Med. 1997; 127: 531-537
        • Schulz K.F.
        • Chalmers I.
        • Hayes R.J.
        • Altman D.G.
        Empirical evidence of bias.
        JAMA. 1995; 273 ([see comment]): 408-412
        • Diener H.C.
        • Cunha L.
        • Forbes C.
        • et al.
        European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke.
        J Neurol Sci. 1996; 143 ([see comment]): 1-13
        • Farrell B.
        • Godwin J.
        • Richards S.
        • Warlow C.
        The United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: final results.
        J Neurol Neurosurg Psychiatry. 1991; 54: 1044-1054
      2. Swedish Aspirin Low-Dose Trial (SALT) of 75 mg aspirin as secondary prophylaxis after cerebrovascular ischaemic events.
        Lancet. 1991; 338 (anonymous) ([see comment]): 1345-1349
        • Boysen G.
        • Sorensen P.S.
        • Juhler M.
        • et al.
        Danish very-low-dose aspirin after carotid endarterectomy trial.
        Stroke. 1988; 19: 1211-1215
        • Elwood P.C.
        • Cochrane A.L.
        • Burr M.L.
        • et al.
        A randomized controlled trial of acetyl salicylic acid in the secondary prevention of mortality from myocardial infarction.
        Br Med J. 1974; 1: 436-440
        • Juul-Moller S.
        • Edvardsson N.
        • Jahnmatz B.
        • et al.
        Double-blind trial of aspirin in primary prevention of myocardial infarction in patients with stable chronic angina pectoris.
        Lancet. 1992; 340: 1421-1425
        • Ajani U.A.
        • Ford E.S.
        • Greenland K.J.
        • et al.
        Aspirin use among U.S. adults: Behavioral Risk Factor Surveillance System.
        Am J Prev Med. 2006; 30: 74-77
        • Rosamond W.
        • Flegal K.
        • Friday G.
        • et al.
        Heart disease and stroke statistics—2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee.
        Circulation. 2007; 115: e69-e171
        • Baigent C.
        • Keech A.
        • Kearney P.M.
        • et al.
        Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins.
        Lancet. 2005; 366 ([see comment] [erratum appears in Lancet. 2005;366:1358]): 1267-1278
        • Dagenais G.R.
        • Pogue J.
        • Fox K.
        • et al.
        Angiotensin-converting-enzyme inhibitors in stable vascular disease without left ventricular systolic dysfunction or heart failure: a combined analysis of three trials.
        Lancet. 2006; 368 ([see comment]): 581-588
        • Eikelboom J.W.
        • Mehta S.R.
        • Anand S.S.
        • et al.
        Adverse impact of bleeding on prognosis in patients with acute coronary syndromes.
        Circulation. 2006; 114: 774-782
        • Rao S.V.
        • Jollis J.G.
        • Harrington R.A.
        • et al.
        Relationship of blood transfusion and clinical outcomes in patients with acute coronary syndromes.
        JAMA. 2004; 292 ([see comment]): 1555-1562
        • Patrono C.
        • Ciabattoni G.
        • Patrignani P.
        • et al.
        Clinical pharmacology of platelet cyclooxygenase inhibition.
        Circulation. 1985; 72: 1177-1184
        • Roth G.J.
        • Stanford N.
        • Majerus P.W.
        Acetylation of prostaglandin synthase by aspirin.
        Proc Natl Acad Sci U S A. 1975; 72: 3073-3076
        • Mason P.J.
        • Jacobs A.K.
        • Freedman J.E.
        Aspirin resistance and atherothrombotic disease.
        J Am Coll Cardiol. 2005; 46 ([see comment]): 986-993
        • Pamukcu B.
        A review of aspirin resistance; definition, possible mechanisms, detection with platelet function tests, and its clinical outcomes.
        J Thromb Thrombolysis. 2007; 23: 213-222
        • Gurbel P.A.
        • Bliden K.P.
        • DiChiara J.
        • et al.
        Evaluation of dose-related effects of aspirin on platelet function: results from the Aspirin-Induced Platelet Effect (ASPECT) study.
        Circulation. 2007; 115: 3156-3164
        • Campbell C.L.
        • Smyth S.
        • Montalescot G.
        • Steinhubl S.R.
        Aspirin dose for the prevention of cardiovascular disease: a systematic review.
        JAMA. 2007; 297: 2018-2024