Updates on Aspirin in Primary Prevention of Cardiovascular Disease Create New Clinical and Policy Challenges

Background: In secondary prevention benefits of aspirin outweigh risks.  In primary prevention the issues are less clear and far more complex. Methods: We conducted the most updated meta-analysis of all major randomised trials of aspirin in primary prevention and used CVD defined as myocardial infarction, stroke, and CVD death. Findings: Primary prevention subjects assigned to aspirin had a statistically significant 13% reduction in CVD events. (Odds ratio=0.87; 95% confidence interval from 0.83 to 0.93). Interpretation: Based on the results of the individual randomised trials and this most updated meta-analysis,in primary prevention, aspirin produces a statistically significant and clinically important reduction in major CVD events. The findings in primary prevention concerning relative reductions in benefits and risks are similar to those in secondary prevention.  The absolute benefits, however, are far lower and absolute risks similar. Adherence is particularly relevant in randomised trials of aspirin as the half-life of platelets is about 8 days so the benefits are acute and of short duration.  While this issue needs further research, in the meanwhile, we believe that the prescription of aspirin should be based on individual clinical judgments and only when the absolute benefits exceed the absolute risks. When the magnitudes of benefits and risks are similar, individual patient preference assumes increasing importance. This may include consideration of whether the prevention of a first myocardial infarction or stroke is more important to an individual patient than the development of a gastrointestinal bleed.  Guidelines for aspirin in primary prevention are premature.  Individual clinical judgements about the prescription of aspirin in primary prevention of CVD will do far more good than harm as well as the most good for the most patients. These findings provide the most recent updates on aspirin in the primary prevention of CVD and create  new clinical and policy challenges. Funding: None to declare. Declaration of Interest: Professor DeMets reports that that he is serves as an independent scientist in an advisory role to the National Institutes of Health, the Food and Drug Administration and the pharmaceutical and medical device industry on the design, monitoring and analysis of trials. He serves on data monitoring committees for Astra Zeneca, Amgen, Action, GSK, Merck, Sanofi, Boehringer Ingelheim, Teva, and Abbvie. He holds no stock in any pharmaceutical or device company. Professor Gaziano reports that he serves as a consultant to Bayer. Professor Pfeffer reports that he receives research support from Novartis. He serves as an independent scientist in an advisory role to AstraZeneca, Corvidia, DalCor, GlaxoSmithKline, Innovative Science Solutions, Jazz, MyoKardia, Novartis, Novo Nordisk, Pharmascience, Sanofi and Takeda; and has equity in DalCor. Professor Hennekens reports that he serves as an independent scientist in an advisory role to investigators and sponsors as Chair of data monitoring committees for Amgen, British Heart Foundation, Cadila, Canadian Institutes of Health Research, DalCor, and Regeneron; to the United States (U.S.) Food and Drug Administration, and UpToDate; receives royalties for authorship or editorship of 3 textbooks and as co-inventor on patents for inflammatory markers and cardiovascular disease that are held by Brigham and Women’s Hospital; has an investment management relationship with the West-Bacon Group within SunTrust Investment Services, which has discretionary investment authority; does not own any common or preferred stock in any pharmaceutical or medical device company. Dean Wood reports that she serves as an independent scientist in an advisory role to investigators and sponsors as member of three data monitoring committees for Amgen. All others have nothing to declare.