Clinical InvestigationPrevention and RehabilitationAspirin for the prevention of cardiovascular events in patients without clinical cardiovascular disease: A meta-analysis of randomized trials
Section snippets
Search strategy
From 1966 to 2005, a computerized search was performed that identified 6 published randomized trials of aspirin in patients without clinical CVD. In the previous meta-analysis of these trials, aspirin therapy significantly reduced the risk of an MCE (nonfatal MI, nonfatal stroke, or cardiovascular death) by 12% in women and 14% in men.18 From 2005 to the present, a subsequent review of the literature (MEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE) identified 3
Results
Nine prospective randomized trials involving 102,621 participants were identified for inclusion. A total of 710,053 person-years of exposure were recorded: 359,709 in the aspirin group and 350,344 in the placebo or control group. All trials included patients without clinical CVD, which was defined as the absence of a cardiovascular event, or clinical symptoms of CVD including angina or transient ischemic attack. Among the 3 new trials,19, 20, 21 2 included only diabetic patients,19, 21 and 2
Discussion
The current meta-analysis included 9 prevention trials in >100,000 subjects without clinical evidence of CVD treated with aspirin versus placebo or control for the prevention of ischemic cardiovascular events. The pooled results found a statistically significant 10% relative reduction in the primary end point of MCE and a statistically significant 62% relative increase in major bleeding events. The absolute benefit versus risk demonstrated that, in 1,000 patients treated for 5 years, there were
Conclusions
This meta-analysis of >100,000 randomized patients (>700,000 person-year follow-up) comparing aspirin versus placebo or control demonstrated that aspirin decreased MCE by approximately 10% among patients without clinical CVD. Major bleeding, however, occurred more frequently with aspirin therapy. The decision to use aspirin for the prevention of a first MI or stroke remains a complex issue. Weighing the overall benefit and risk requires careful consideration by the physician and patient before
Disclosures
Dr Jeffrey Berger reports receiving research support from Astra Zaneca and has received honoraria for advisory board participation from Astra Zaneca. Dr William Hiatt reports receiving research support from Astra Zaneca.
Conflicts of interest: none. Drs Berger and Hiatt had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Acknowledgements
We thank Dr Sanjay Kaul for his insightful comments and editorial assistance.
References (45)
- et al.
Low-dose aspirin in patients with stable cardiovascular disease: a meta-analysis
Am J Med
(2008) - et al.
Antiplatelet drugs: American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition)
Chest
(2008) - et al.
Double-blind trial of aspirin in primary prevention of myocardial infarction in patients with stable chronic angina pectoris. The Swedish Angina Pectoris Aspirin Trial (SAPAT) group
Lancet
(1992) Aspirin (75 mg/day) after an episode of unstable coronary artery disease: long-term effects on the risk for myocardial infarction, occurrence of severe angina and the need for revascularization. Research Group on Instability in Coronary Artery Disease in Southeast Sweden
J Am Coll Cardiol
(1991)- et al.
Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group
Lancet
(1998) - et al.
Screening for cardiovascular risk in asymptomatic patients
J Am Coll Cardiol
(2010) Cilostazol: potential mechanism of action for antithrombotic effects accompanied by a low rate of bleeding
Atheroscler Suppl
(2005)Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients
BMJ (Clin Res ed)
(2002)- 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) - et al.
2007 focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the Canadian Cardiovascular Society endorsed by the American Academy of Family Physicians: 2007 writing group to review new evidence and update the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction, writing on behalf of the 2004 writing committee
Circulation
(2008)
ACC/AHA 2007 guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the 2002 guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction): developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons: endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine
Circulation
Swedish Aspirin Low-Dose Trial (SALT) of 75 mg aspirin as secondary prophylaxis after cerebrovascular ischaemic events
Lancet
The United Kingdom transient ischaemic attack (UK-TIA) aspirin trial: final results
J Neurol Neurosurg Psychiatry
Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2
Lancet
Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. Results of a Veterans Administration Cooperative Study
N Engl J Med
Indications for early aspirin use in acute ischemic stroke : a combined analysis of 40 000 randomized patients from the Chinese acute stroke trial and the international stroke trial. On behalf of the CAST and IST collaborative groups
Stroke
An aspirin a day: are we barking up the wrong willow tree?
Pharmacotherapy
Aspirin as preventive therapy in patients with asymptomatic vascular disease
JAMA
Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials
Lancet
Aspirin for the primary prevention of cardiovascular events in women and men: a sex-specific meta-analysis of randomized controlled trials
JAMA
The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease
BMJ (Clin Res ed.)
Cited by (124)
Peripheral Artery Disease: Overview of Diagnosis and Medical Therapy
2023, Medical Clinics of North AmericaAtherosclerosis: Conventional intake of cardiovascular drugs versus delivery using nanotechnology – A new chance for causative therapy?
2021, Journal of Controlled ReleaseAspirin for Primary Prevention of Cardiovascular Disease in the 21<sup>st</sup> Century: A Review of the Evidence
2021, American Journal of CardiologyAspirin for Primary Prevention of Coronary Artery Disease
2021, Current Problems in Cardiology
Roger S. Blumenthal, MD served as guest editor for this article.
Dr Berger was partially funded by an American Heart Association Fellow to Faculty Award (0775074N). Dr Krantz was partially funded by grant U01 HL079160 from the National Heart, Lung, and Blood Institute.