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

Weighing Benefits and Risks of Aspirin for Primary Cardiovascular Prevention

Medscape: You were the first to demonstrate that taking low-dose aspirin will prevent a first MI. Despite all the debate over the years, your opinion on the use of aspirin in primary CV prevention doesn't seem to have changed.

Dr Hennekens: My position has never wavered: For practicing clinicians, the role of aspirin in primary prevention has to be viewed in light of the totality of evidence. A consistent body of evidence shows conclusively that in the highest-risk people, such as those experiencing an MI, taking an aspirin during or up to 24 hours after the onset of symptoms and continuing it daily will reduce their risk for death by 23%, as well as risks for reinfarction, stroke, and death from CVD.[37] The findings are similar among those who have survived a prior MI or other occlusive CV event. In all such high-risk patients, the absolute risk for an event is so high compared with the absolute risk for side effects of aspirin, that aspirin needs to be routinely used, almost without exception.

In that context, if you look at the data on primary prevention, since the PHS, all of the trials over the years have shown that aspirin prevents a first MI, but virtually all have been conducted in very low-risk men and women. The problem in primary prevention is twofold. Number one is that those same absolute risks associated with aspirin, when given during or after an MI as secondary prevention, are present in primary prevention, but the absolute benefit of aspirin in primary prevention is lower because the absolute risk for an event is lower. So the question for the doctor or healthcare provider in primary prevention is: What to do about primary prevention if the absolute benefit is lower than that seen with use for secondary prevention, because the absolute risk for an event is lower but that absolute hazard of aspirin is the same?

This is complicated by the fact that even though around 100,000 people have been studied in primary prevention trials, over 95% of them were at very low risk, so we don't have data in the population that we probably want to give aspirin to, which is the intermediate-risk people—ie, those who have a 10-year risk for an event of less than 10%. Only about 5000 patients of the 100,000 randomized in trials were in that group, so these data on their own are not reliable. So, in my opinion, it isn't that the quality of the evidence in primary prevention is a concern. Rather, the quantity is less in the population in which we would want to give aspirin. In the previous primary prevention trials, that 10-year risk was around 5%, so it was very low. In contrast, in the ARRIVE trial, 10-year risk for an event is 10%-20%, which corresponds to a mean 10-year CVD risk of approximately 30%.[9] ARRIVE is one of several trials in moderate- and high-risk primary prevention subjects that will provide direct randomized evidence on the risk-benefit ratio of aspirin in primary prevention subjects at intermediate risk.

Medscape: That seems very clear. So why didn't everyone see it like that?

Dr Hennekens: I believe that what happened over the past two decades was that people were initially emphasizing the benefit of aspirin and not considering the risks. Alternatively, there were also people who were emphasizing the risks of aspirin without considering the benefit. If you look at the totality of evidence in primary prevention, the decision to use aspirin should never be a routine, knee-jerk response the way it is in secondary prevention or during an MI. It ought to be an individual clinical judgment that weighs the absolute benefit of aspirin in a particular patient against the absolute risk.


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