Does Aspirin Prevent Cardiovascular Disease and Cancer? Ignore the Guidelines

An Expert Interview With Charles H. Hennekens, MD, DrPH

Linda Brookes, MSc; Charles H. Hennekens, MD, DrPH


October 29, 2014

In This Article

Waiting for the Right Evidence

Medscape: So the clinical trial data cited in support of the overall benefit of aspirin in primary prevention[1,2,3,4,5,6] didn't constitute sufficient evidence to convince you?

Dr Hennekens: Frankly, I don't really understand why there was a regulatory submission for this indication again. Aspirin was first submitted to the FDA for primary prevention in 1989 (I was involved in that submission), and the Cardiorenal Drugs Advisory Committee voted 6-2 in favor of the routine use of aspirin in men without risk factors, though this recommendation was never acted on by FDA. The same reasons apply today: namely that the data are insufficient in the intermediate- and high-risk subjects who will be the population for which aspirin is likely to be prescribed in primary prevention.

At that time, there were only two primary prevention trials—the PHS and the British Doctors' Trial (BDT).[2] Subsequent data from three more trials—the Thrombosis Prevention Trial (TPT),[3] the Hypertension Optimal Treatment (HOT) trial,[4] and the Primary Prevention Project (PPP) trial[5] —were the basis for a similar submission made in 2003, which was rejected by a vote of 11-3.[38] The average risk for a first event in these six trials is less than 5%, whereas the likely cutpoint for aspirin use may be about 10%.[1,2,3,4,5,6] So it's not a question of whether aspirin works in secondary prevention but doesn't work in primary—that's not true. The data are quite consistent, in my view, that aspirin does prevent MIs, and I feel that the accumulating randomized evidence in moderate- and high-risk primary prevention subjects will allow regulatory authorities and clinicians to make more informed decisions about aspirin use in primary prevention.

The main trial that will provide that evidence will be the ARRIVE trial,[9] but there are other trials in the United Kingdom and Europe:

ASCEND (A Study of Cardiovascular Events in Diabetes), where people are defined as being at moderate risk because of having diabetes alone with no prior CV events [10];

ACCEPT-D (Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes) trial [13]; and

The ASPREE (Aspirin in Reducing Events in the Elderly) trial.[11]

When the totality of evidence is incomplete, it is appropriate to remain uncertain. Meanwhile, it is interesting to note that, as a founding member of the Antithrombotic Trialists' Collaboration, the meta-analysis we published in The Lancet a few years ago, which concluded that aspirin is "of uncertain net value in primary prevention,"[39] was not intended to tell people not to use aspirin; rather, it meant to tell them to avoid using it routinely.


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