A comparison of contemporary versus older studies of aspirin for primary prevention.

Background: Recent aspirin trials have not shown similar benefits for primary prevention as older studies.

Objective: To compare benefits and harms of aspirin for primary prevention before and after widespread use of statins and colorectal cancer screening.

Methods: We compared studies of aspirin for primary prevention that recruited patients from 2005 onward with previous individual patient data (IPD) meta-analyses that recruited patients from 1978 to 2002. Data for contemporary studies were synthesized using random-effects models. We report vascular [major adverse cardiovascular events (MACE), myocardial infarction (MI) and stroke], bleeding, cancer and mortality outcomes.

Results: The IPD analyses of older studies included 95 456 patients for CV prevention and 25 270 for cancer mortality, while the four newer studies had 61 604 patients. Relative risks for vascular outcomes for older versus newer studies follow: MACE: 0.89 [95% confidence interval (CI) 0.83-0.95] versus 0.93 (0.86-0.99); fatal haemorrhagic stroke: 1.73 (1.11-2.72) versus 1.06 (0.66-1.70); any ischaemic stroke: 0.86 (0.74-1.00) versus 0.86 (0.75-0.98); any MI: 0.84 (0.77-0.92) versus 0.88 (0.77-1.00); and non-fatal MI: 0.79 (0.71-0.88) versus 0.94 (0.83-1.08). Cancer death was not significantly decreased in newer studies (1.11, 0.92-1.34). Major haemorrhage was significantly increased (older studies RR 1.48, 95% CI 1.25-1.76 versus newer studies RR 1.37, 1.24-1.53). There was no effect on all-cause mortality, cardiovascular mortality, fatal stroke or fatal MI.

Conclusions: Per 1200 persons taking aspirin for primary prevention for 5 years, there will be 4 fewer MACEs, 3 fewer ischaemic strokes, 3 more intracranial haemorrhages and 8 more major bleeding events. Aspirin should no longer be recommended for primary prevention.