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Updated systematic review of aspirin primary prevention shows benefits, risks

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Aspirin prophylaxis depends on individual decisions

The three trials published in 2018 that added important new data on primary prevention for cardiovascular disease with aspirin must ideally be interpreted within the context of the totality of evidence on this subject. This was achieved in the analysis reported by Dr. Mehta and his associates, as well as in other more recent publications.

Making a decision about using aspirin for primary prevention in individuals based on trial data is very challenging because it requires weighing a modest potential benefit that people gain from daily aspirin for preventing a first cardiovascular event against the modest risk of an adverse bleeding event. It does not suffice simply to compare the number of cardiovascular and bleeding events, because those two types of events do not have the same immediate or long-term consequences. Each patient must make a personal choice between the risks and benefits.

The greatest potential benefit from aspirin prophylaxis seems to be in people with increased cardiovascular risk but with no increased bleeding risk. In general, this means people aged 50-59 years old, and also possibly those aged 60-69 years old if their estimated 10-year cardiovascular disease risk is more than 10%. It may make more sense to first focus on other risk-reducing steps, such as smoking cessation, blood pressure control, and statin treatment. After that, prophylactic aspirin may be reasonable for people who retain a 10-year cardiovascular disease risk of more than 10% who are also not at increased bleeding risk. That seems to make it prudent to avoid aspirin for primary prevention once people reach the age of 70 years, although people who have been taking aspirin safely for a period of time before reaching 70 might reasonably consider continuing the prophylaxis for a period of time.

This and similar reviews continue to have major limitations. The duration of the trials they reviewed, a mean of 6.4 years, is insufficient to understand the full effect from aspirin prophylaxis. Also, none of the recent reviews used a patient-level meta-analysis, which could better help us understand aspirin’s action in key subgroups, such as women, patients with diabetes, and patients on treatments such as statins that reduce their cardiovascular risk.

Michael Pignone, MD, is professor and chair of medicine at the University of Texas Dell Medical School in Austin. He had no disclosures. He made these comments in an editorial that accompanied the report (J Am Coll Cardiol. 2019 Jun 10. doi: 10.1016/j.jacc.2019.03.502).



Using daily aspirin treatment for the primary prevention of cardiovascular events remains an individualized decision that needs to balance a person’s risks for ischemic events and bleeding, according to results from a new systematic review of 15 randomized, aspirin-prevention trials, including results from 3 major trials that researchers reported during 2018.

“The findings suggest that the decision to use aspirin for primary prevention should be tailored to the individual patients based on estimated atherosclerotic cardiovascular disease risk and perceived bleeding risk, as well as patient preferences regarding the types of event prevented versus potential bleeding caused,” Jawahar L. Mehta, MD, and his associates wrote in an article published on June 10 in the Journal of the American College of Cardiology.

The authors also concluded that if a person decides to use aspirin for primary prevention, then a low dose of 100 mg/day or less is recommended.

This new systematic review follows two reviews published earlier in 2019 that reached roughly similar conclusions after analyzing largely the same randomized trial data, including the same three major trials from 2018. One of these prior reviews included data from 13 trials and a total of 164,225 people (JAMA. 2019 Jan 22;321[3]:277-87). The second review had data from 11 trials with 157,248 people (Eur Heart J. 2019 Feb 14;40[7]:607-17). The newly published review used data collected by 15 trials from 165,502 people.

The three 2018 trials that triggered the updated data assessments were the ARRIVE trial, with 12,546 people randomized (Lancet. 2018 Sep 22;392[10152]:1036-46), the ASPREE trial, with 19,114 people randomized (New Engl J Med. 2018 Oct 18;379[16]:1509-18), and the ASCEND trial, with 15,480 people randomized (New Engl J Med. 2018 Oct 18;379[16]:1529-39).

As stated in the new report from Dr. Mehta, a professor of medicine at the University of Arkansas for Medical Sciences in Little Rock, and his associates, the recent trial results from 2018 added new data from more than 45,000 additional subjects, a development that warranted a reappraisal of the evidence for aspirin’s efficacy and safety for primary prevention in contemporary practice.

The major findings from the analysis by Dr. Mehta and his associates were that in adults without a history of cardiovascular disease, daily aspirin use reduced the incidence of MIs, with a number needed to treat (NNT) of 357; reduced ischemic stroke (NNT, 500), reduced transient ischemic attack (NNT, 370), and reduced the overall, combined rate of all major adverse cardiovascular events (NNT, 263). But on the safety side, daily aspirin led to an increased rate of major bleeding episodes, with a number needed to harm (NNH) of 222, increased intracranial bleeds (NNH, 1,000), and an increase in gastrointestinal bleeds (NNH, 385).

The analysis “demonstrates a potential reduction of net benefit with aspirin in the contemporary era,” the authors concluded. They also noted that the benefits from aspirin prevention were, as expected, “more pronounced” among people with a higher estimated risk from atherosclerotic cardiovascular disease.

The systematic review findings came against the backdrop of a recently released primary prevention guideline from the American College of Cardiology and American Heart Association (J Am Coll Card. 2019 Mar. doi: 10.1016/j.jacc.2019.03.010). The guideline said that aspirin prophylaxis for primary prevention “might be considered” for adults aged 40-70 years, but should not be used for people who are older than 70, and also should not be given to people with an increased risk for bleeding. In general, the experts who produced this guideline said that aspirin prophylaxis should be infrequent.

The new analysis also found no reduction in the incidence of cancer or cancer-related death linked with aspirin use for primary prevention. The systematic review published earlier in 2019 in JAMA also found no link between aspirin use and cancer incidence or mortality. The review from the European Heart Journal did not report on the link between aspirin use and cancer incidence or mortality.

Dr. Mehta has been a consultant to AstraZeneca, Bayer, Boehringer Ingelheim, Medimmune, and Pfizer, and has received grant support from AstraZeneca, Bayer, and Boehringer Ingelheim.

SOURCE: Abdelaziz HK et al. J Am Coll Cardiol. 2019 Jun 10. doi: 10.1016/j.jacc.2019.03.501.

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