Routine Use of Aspirin for Primary Prevention of Cardiovascular Events

The use of aspirin for primary prevention of cardiovascular events was not shown to be beneficial for preventing fatal myocardial infarction (MI), stroke, or death related to cardiovascular disease (CVD) or cancer, according to results of a recent study reported online in Archives of Internal Medicine [doi:10.1001/archinternmed.2011.628]. Significant reductions in nonfatal MI, however, were observed. Evidence has previously indicated a modest benefit for the use of aspirin in primary prevention of CVD, as well as reduction in cancer mortality. Guidelines recommending aspirin prophylaxis for prevention of CVD, however, are based on data compiled from trials before 2005. Researchers conducted a meta-analysis to provide an update on the role of aspirin in primary prevention of cardiovascular events as well as nonvascular disorders. The researchers also sought to examine the risks (bleeding episodes) versus benefits of aspirin treatment. The researchers identified 9 randomized, placebo-controlled primary prevention trials consisting of a total of 102,621 participants with at least 1 year of follow-up. The trials also included information on bleeding events. Most participants were at increased risk of CVD. The pooled weighted mean age was 57 years and 46% were men. Primary efficacy end points were total CVD and total cancer mortality. Secondary efficacy end points were subtypes of vascular disease, total cardiovascular events, cause-specific death, and all-cause mortality. The composite primary safety end point was clinically “nontrivial” bleeding (including fatal bleeding, cerebrovascular or retinal bleeding, bleeding that required hospitalization and/or transfusion, or any major bleeding). Results showed there were 2169 coronary heart disease (CHD) events over a mean follow-up period of 6 years; 1540 events were nonfatal MI and 592 were fatal CHD events. Other major outcomes included stroke (n=1504); total CVD events (n=4278); CVD death (n=1285); nonvascular death (n=2587); cancer death (n=1512); noncancer, nonvascular death (n=983); all-cause mortality (n=3895); total bleeding events (n=40,712); and nontrivial bleeding events (n=10,049). Other findings are shown in the Table. Owing mainly to a 20% risk reduction of nonfatal MI (odds ratio [OR], 0.80; 95% confidence interval [CI], 0.67-0.96), the use of aspirin was associated with a significant 10% reduction in risk of total CVD events (OR, 0.90; 95% CI, 0.85-0.96). The number needed to treat to avoid 1 nonfatal MI and 1 CVD event over a 6-year period was 162 and 120, respectively. There was no beneficial effect on fatal MI (OR, 1.06; 95% CI, 0.83-1.37), stroke (OR, 0.94; 95% CI, 0.84-1.06), or CVD death (OR, 0.99; 95% CI, 0.85-1.15). Nonsignificant reductions were found for total CHD (OR, 0.86; 95% CI, 0.74-1.01), total nonvascular mortality (OR, 0.92; 95% CI, 0.85-1.00), and all-cause mortality (OR, 0.94; 95% CI, 0.88-1.00). CVD event risk tended to be lower among older individuals (above the mean age) taking aspirin (OR, 0.78; 95% CI, 0.59-1.04). No benefit was seen with regard to cancer mortality (OR, 0.93; 95% CI, 0.84-1.03). Results also showed an excess risk of bleeding of 70% (OR, 1.70; 95% CI, 1.17-2.46) and a >30% excess risk of nontrivial bleeding events (OR, 1.31; 95% CI, 1.14-1.50) among those receiving aspirin. The risk of nontrivial bleeding tended to be somewhat higher among younger individuals (below the mean age) and those with higher systolic blood pressure. For every 73 individuals treated with aspirin for approximately 6 years, at least 1 nontrivial bleeding event was caused. Among the study limitations were an inability of the researchers to harmonize outcome definitions across studies and to precisely quantify the effect of aspirin treatment in clinically relevant subgroups.