Data suggest that several million individuals are currently prescribed aspirin as prophylaxis against cardiovascular disease (CVD) events, despite the efficacy and safety of doing so remaining unclear. In fact, emerging evidence indicates that this practice may not be most appropriate and perhaps even harmful, explains Jawahar L. Mehta, MD, PhD. With an “immense need to study this issue in a very sophisticated fashion,” Dr. Mehta, Marwan Saad, MD, PhD, Naga Venkata K. Pothineni, MD, and colleagues sought to examine the clinical outcomes with aspirin for primary prevention of CVD following the then-recent publication of large trials adding more than 45,000 individuals to the published data.

An Extensive Analysis

For a study published in the Journal of the American College of Cardiology, the researchers specifically sought to determine if aspirin is helpful in preventing CVD events without causing significant side effects. The team analyzed results of 15 randomized controlled trials that included 165,502 participants (83,529 on aspirin, 81,973 controls) and that had a follow-up duration of at least 1 year. They used the Cochrane Collaboration tool to assess the risk of bias among included studies and the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) tool to assess quality of evidence for each outcome. Efficacy outcomes included all-cause mortality, CV death, myocardial infarction (MI), stroke, transient ischemic attack, and major adverse CV events. 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.

“Based on our extensive analysis, aspirin use for primary prevention of CVD was associated with similar all-cause mortality (relative risk [RR], 0.97), CV-related mortality (RR, 0.93), and non-CV-related mortality (RR, 0.98) as control, but a lower risk or nonfatal MI (RR, 0.82), transient ischemic attack (RR, 0.79) and ischemic stroke (RR, 0.87,” says Dr. Mehta. Patients on aspirin had a higher risk of major (RR, 1.50), intracranial (RR, 1.32), and major GI bleeding (RR, 1.52), but similar fatal bleeding rates (RR, 1.09), when compared with control subjects. During follow-up, total cancer and cancer-related death rates were similar in both groups.

The risk (mainly bleeding) and benefit (decrease in cardiovascular events and stroke) are summarized in the Figure. “The physician who prescribes it should carefully look at this figure and evaluate the need for aspirin use as prophylaxis,” Dr. Mehta says. “We recommend that the use of aspirin routinely as prophylaxis in primary prevention be discouraged unless the individual is at excess risk. Even then, the individual to whom the drug is to be given and his/her physician should thoroughly discuss the risk-benefit ratio of routine aspirin therapy.”

Looking Ahead

With recent studies suggesting that—even in the setting of acute CV events like stent placement in the coronary artery—prolonged use of aspirin may not be beneficial, Dr. Mehta believes additional research is needed to estimate the risk-benefit ratio in the modern era when lifestyle modifications are being employed in a large percentage of the population and many patients take a variety of cardioprotective medications. In meantime, he says, “We believe that the decision to use aspirin for primary prevention should be tailored to the individual patient based on estimated risk of cardiovascular event and bleeding risk. When aspirin is used for primary prevention, a low dose (<100 mg/day) should be recommended.”