A Comparison of Contemporary versus Older Studies of Aspirin for Primary Prevention

Objective This study compares the 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 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], 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 vs newer studies follow: MACE: 0.89 (95% CI 0.83-0.95) vs 0.93 (0.86-0.99); fatal hemorrhagic stroke: 1.73 (1.11-2.72) vs 1.06 (0.66-1.70); any ischemic stroke: 0.86 (0.74-1.00) vs 0.86 (0.75-0.98); any MI: 0.84 (0.77-0.92) vs 0.88 (0.77-1.00); and non-fatal MI: 0.79 (0.71-0.88) vs 0.94 (0.83-1.08). Cancer death was not significantly decreased in newer studies (RR 1.11, 0.92-1.34). Major hemorrhage was significantly increased for both older and newer studies (RR 1.48, 95% CI 1.25-1.76 vs 1.37, 95% CI 1.24-1.53). There was no effect in either group on all-cause mortality, cardiovascular mortality, fatal stroke, or fatal MI. Conclusions In the modern era characterized by widespread statin use and cancer screening, aspirin does not reduce the risk of non-fatal MI or cancer death. There are no mortality benefits and a significant risk of major hemorrhage. Aspirin should no longer be recommended for primary prevention. Summary of current evidence and what this study adds What is already known about this subject? The cumulative evidence for aspirin suggests a role in the primary prevention of cardiovascular disease, and in reducing cancer incidence and mortality. However most of the trials of aspirin for primary prevention were set in Europe and the United States and recruited patients prior to the year 2000. The benefits and harms of aspirin should be considered separately in studies performed in the eras before and after widespread use of statins and colorectal cancer screening. What does this study add? This study provides the most detailed summary to date of cardiac, stroke, bleeding, mortality and cancer outcomes to date in the literature. In trials of aspirin for primary prevention from 2005 onwards, aspirin reduced major adverse cardiovascular events but significantly increased the risk of bleeding, with no benefit for mortality or, Unlike older studies, there was no reduction in cancer mortality and non-fatal myocardial infarction. How does this impact on clinical practice? Our study suggests aspirin should not be recommended for primary prevention in the modern era.