The most recent trials of aspirin for primary prevention didn’t tip the risk-benefit balance for relatively healthy people, according to a meta-analysis.
Aspirin’s antiplatelet effects were tied to a lowering of combined cardiovascular mortality, myocardial infarction (MI), and stroke compared with a control group (57.1 vs 61.4 per 10,000 patient-years, HR 0.89, 95% CI 0.84-0.95), with an absolute risk reduction of 0.38% and a number needed to treat of 265, reported Sean Zheng, BM, BCh, of the London-based King’s College Hospital NHS Foundation Trust, and Alistair Roddick, BSc, of King’s College London.
The benefit was driven by fewer MIs and ischemic strokes, they reported online in JAMA.
An uptick in major bleeding was apparent with aspirin use, however (23.1 vs 16.4 per 10,000 patient-years, HR 1.43, 95% CI 1.30-1.56). The researchers noted an absolute risk increase of 0.47% and a number needed to harm of 210.
“Aspirin use was not associated with a reduction in cardiovascular mortality, and deaths due to bleeding were rare. Consequently, the decision to use aspirin for primary prevention may need to be made on an individual basis, accounting for the patient’s risk of bleeding and their views on the balance of risk vs benefit,” they concluded.
The meta-analysis included the ASCEND, ASPREE, and ARRIVE trials from 2018.
“The best estimates for the effects of aspirin on cardiovascular disease events and bleeding have not materially changed after the results of the 2018 trials,” commented J. Michael Gaziano, MD, MPH, of Brigham and Women’s Hospital in Boston, in an accompanying editorial.
An individualized approach to aspirin in primary prevention rests on the ability to accurately estimate a person’s risk, and that has been a challenge, he cautioned.
“Cardiovascular disease risk calculators tend to overestimate risk for populations in which cardiovascular risk is declining, such as in the United States and Europe. Further, risk is not static. If patients stop smoking, achieve better control of lipids and blood pressure, or adopt healthier lifestyles, the future risk of cardiovascular disease events declines,” according to Gaziano.
“In places of the world in which cardiovascular disease risk is rising or where other preventive strategies, such as statins, are less available, aspirin as a low-cost intervention may have a more important role,” he added.
That said, Gaziano noted that the meta-analysis was well conducted.
There were 13 randomized trials studied (n=164,225) with a median follow-up of 5 years. Trial participants were people with no known cardiovascular disease (baseline 10-year risk for the primary outcome being 9.2%). The median age was 62, and 47% were men. Approximately one in five had diabetes.
Patients were randomized to aspirin or a control (placebo or no treatment), with the former group getting 75-100 mg aspirin daily in most studies.
The ASPREE trial had associated aspirin with an increased risk of cancer mortality, though the meta-analysis showed no difference in either incident cancer or cancer mortality between groups.
Zheng and Roddick acknowledged that their meta-analysis was inherently subject to the limitations of the studies included. Moreover, they were faced with different endpoints and aspirin doses among the trials.
Continued uncertainty over the benefit-risk balance for primary prevention with aspirin is apparent in contradictory guidelines — the European Society of Cardiology does not recommend aspirin in this setting, whereas the U.S. Preventive Services Task Force does, taking into consideration the patient’s longevity, personal preferences, and other factors.
Zheng and Roddick disclosed no relevant relationships with industry.
Gaziano disclosed serving on the executive committee of the ARRIVE trial and relevant relationships with Bayer.