AN EXPERT INTERVIEW WITH CHARLES H. HENNEKENS, MD, DRPH
Linda Brookes, MSc, Charles H. Hennekens, MD, DrPH
October 29, 2014
OUR ROLLERCOASTER RELATIONSHIP WITH ASPIRIN
Opinions on the use of aspirin in the prevention of cardiovascular disease (CVD) have varied over the past 25 years since the Physicians’ Health Study (PHS) first demonstrated conclusively that low-dose aspirin (325 mg every other day) prevents a first myocardial infarction (MI) in apparently healthy men.[1]
Governmental and health organizations have consistently endorsed the use of aspirin in secondary prevention. In contrast, despite the accumulation of data from several randomized trials that demonstrate that aspirin reduces the risk for a first MI,[2-6] the US Food and Drug Administration (FDA) has not acted on three applications for the use of aspirin as primary prevention.[7] After the third submission, the FDA announced in May 2014 that the data still did not sufficiently support this indication, although FDA conceded that the results from additional ongoing clinical trials “may provide new evidence that could be the basis for changing the current uses (indications) for aspirin.”[8-13] The FDA position is based primarily on the fact that virtually all of the trials were in such low-risk subjects that reliable evidence is sparse in the moderate- and high-risk primary prevention subjects in whom the benefits of aspirin will clearly outweigh the risks.
Such data are accumulating in ongoing randomized trials such as the Aspirin to Reduce Risk of Initial Vascular Events (ARRIVE) trial in subjects who are at moderate to high risk for a first event.
Despite the lack of regulatory approval, several randomized trials indicate that aspirin provides the same degree of protection against nonfatal MI as a statin.[14] In addition, in secondary prevention, the benefits of aspirin and statins are, at least, additive. Aspirin was proposed as a basic component of a primary prevention polypill.[15]Clinical practice guidelines were initially and cautiously enthusiastic about low-dose aspirin, stating that it might be appropriate in a proportion of healthy adults.[16-20] As a result, support grew for the use of low-dose aspirin to prevent first MI.
Since that time, however, most guidelines have become even more cautious, recommending “a more pragmatic approach.”[21] An exception is the most recent guidelines of the American College of Chest Physicians, suggesting low-dose aspirin (75-100 mg/day) over no aspirin in patients older than 50 years without symptomatic CVD.[22] The current guideline of the US Preventive Services Task Force recommends the use of aspirin for men aged 45-79 years to prevent MI and women aged 55-79 years to prevent ischemic strokes, when the potential benefit outweighs the potential harm due to an increase in gastrointestinal hemorrhage.[23] (This guideline is being updated.)
Recent reports have concluded that patients have been receiving inconsistent[24] or no advice about taking aspirin for primary prevention.[25] One analysis suggested that between 2007 and 2011, despite the fact that enthusiasm waned in clinical guidelines, more people with CVD equivalents used aspirin for primary prevention.[26] This perceived increase has been attributed to generalization from observational studies[1,27]about the clear benefits of aspirin as high-risk primary prevention in patients who have a prior CV event.[27,28] Another reason is the emergence of data indicating that it may stave off colorectal cancer,[29-31] in addition to reducing the risk for a first MI.[26]
Subgroup analyses of randomized trials have suggested that aspirin may help prevent other gastrointestinal cancers as well as breast, lung, and prostate cancers. Although the randomized evidence is strongest for prevention of colorectal cancer, the supporting data for other cancers have, so far, come from retrospective analyses of randomized trials designed to look at the effects on prevention of CVD, and not from randomized trials designed to measure this outcome. Currently, no cancer or other health organization recommends taking aspirin specifically to help prevent cancer. In the meantime, researchers and the guidelines committees of medical societies and governmental agencies are attempting to balance the overall benefits and harms of prophylactic use of aspirin for prevention of CVD and cancer in the general population. Some are awaiting the results of new trials.
Several recently concluded and ongoing trials in CVD and cancer that are expected to conclude by 2019 may clarify the extent to which aspirin diminishes cancer incidence and mortality.[32]Analyses of available data continue, with a recent review stating that “for average-risk individuals aged 50-65 years taking aspirin for 10 years, there would be a relative reduction of between 7% (women) and 9% (men) in the number of cancer, MI or stroke events over a 15-year period and an overall 4% relative reduction in all deaths over a 20-year period.”[33]
At the 2014 Congress of the European Society of Cardiology (ESC) in Barcelona, Spain, Charles Hennekens, MD, DrPH, founding principal investigator of both the PHS and the Women’s Health Study (WHS), reviewed the overall benefits and risks of prophylactic aspirin use.[34-36] After the meeting, Dr Hennekens explained to Linda Brookes, for Medscape, how he views the evidence and how he believes it should be interpreted by healthcare providers.