Aspirin for Primary Prevention of CV Events

Study Questions:

What is the impact of adding the results of recent clinical trials (>45,000 subjects) to historic trials of aspirin for primary prevention of cardiovascular disease (CVD)?


Randomized controlled trials comparing clinical outcomes with aspirin versus control for primary prevention with follow-up duration of ≥1 year were included. Efficacy outcomes included all-cause death, CV death, myocardial infarction (MI), stroke, transient ischemic attack (TIA), and major adverse cardiovascular events (MACE). Safety outcomes included major bleeding, intracranial bleeding, fatal bleeding, and major gastrointestinal (GI) bleeding. Random effects DerSimonian-Laird risk ratios (RRs) for outcomes were calculated.


A total of 15 randomized controlled trials including 165,502 participants (aspirin n = 83,529, control n = 81,973) were available for analysis. Mean age was 61.6 years and mean follow-up was 6.4 years. The estimated 10-year CV risk was high (≥7.5%) in 11 studies and low-intermediate in four studies. Four trials were limited to diabetes. Using data from six randomized controlled trials, a composite of nonfatal MI, nonfatal stroke, TIA, or CV death was lower with aspirin than control (3.8% vs. 4.24%, RR, 0.90; p = 0.001). Compared with control, aspirin was associated with similar all-cause death (RR, 0.97), CV death (RR, 0.93), and non-CV death (RR, 0.98), but a lower risk of nonfatal MI (RR, 0.82; 95% CI, 0.72-0.94), TIA (RR, 0.79; 95% CI, 0.71-0.89), and ischemic stroke (RR, 0.87; 95% CI, 0.79-0.95). Aspirin was associated with a higher risk of major bleeding (RR, 1.5; 95% CI, 1.33-1.69), intracranial bleeding (RR, 1.32; 95% CI, 1.12-1.55), and major GI bleeding (RR, 1.52; 95% CI, 1.34-1.73), with similar rates of fatal bleeding (RR, 1.09) compared with the control subjects. The number needed to treat (NNT) to prevent a MACE was 263, and NNT harm with intracranial bleeding was 1,000. Total cancer and cancer-related deaths were similar in both groups within the follow-up period of the study.


Aspirin for primary prevention reduces nonfatal ischemic events, but significantly increases nonfatal bleeding events.


Should one use this meta-analysis to decide in favor of low-dose aspirin in persons at low risk for GI bleeding and intracranial hemorrhage? The argument that the three recent trials in which patients were much more likely on statins, have less smokers, better blood pressure control, and a trend to lower 10-year atherosclerotic CVD (ASCVD) risk argues against it. Risk estimates are not very accurate in individuals and most overestimate in the modern era. My take is that persons 50-70 years old with at least a 10% 10-year risk of ASCVD but low risk for GI bleeding, particularly those unwilling or unable to take a statin, smokers, and those with a family history of premature ASCVD should have the discussion of risk/benefit of low-dose aspirin.

Clinical Topics: Dyslipidemia, Prevention, Nonstatins, Novel Agents, Statins, Smoking

Keywords: Aspirin, Atherosclerosis, Blood Pressure, Brain Ischemia, Diabetes Mellitus, Gastrointestinal Tract, Hemorrhage, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Intracranial Hemorrhages, Ischemic Attack, Transient, Myocardial Infarction, Neoplasms, Primary Prevention, Smoking, Stroke, Vascular Diseases

< Back to Listings