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Chronic aspirin therapy for the prevention of cardiovascular events: a waste of time, or worse?

Nature Clinical Practice Cardiovascular Medicine volume 3, pages 234–235 (2006)Cite this article

Few therapies in cardiovascular medicine have been studied so intently and adopted so widely into clinical practice as aspirin, especially with so little evidence of long-term benefit for people with or at risk of coronary artery disease. A series of studies has shown that long-term aspirin therapy is ineffective, or worse, for the primary, secondary or tertiary prevention of cardiovascular events; however, distorted reporting of these studies, in a way that would not be tolerated for other pharmacologic agents, has led many readers to misinterpret neutral studies as showing benefit with aspirin (see Supplementary Table 1 online for a list of these investigations). To the dismay of some, but fuelled by evidence, debate about the efficacy and safety of aspirin is growing within the cardiology community. Admitting that previous advice could have been wrong is unappealing, but the need to be correct should be stronger than the desire to be consistent. International guidelines have started to recommend withdrawal of aspirin, albeit in specific populations of high-risk patients with heart disease, because of the increase in adverse effects with this drug and its failure to reduce vascular events.1,2 In this Viewpoint, I will discuss why I believe that these recommendations should be extended to many other patients groups with or at risk of cardiovascular disease in whom aspirin has failed to show long-term benefit.

Why is aspirin so popular in the management of cardiovascular disease? Aspirin's popularity is a recent phenomenon—in 1986 the ISIS-1 study randomized patients to a control or intravenous-atenolol-therapy group and reported that at hospital discharge only 5% of patients were receiving antiplatelet therapy.2 Two pieces of information led to a change in attitude towards aspirin. First, the ISIS-2 study—a large, robust double-blind trial—reported that a 5-week course of aspirin after a myocardial infarction reduced the risk of reinfarction and death compared with placebo.4 This study formed the basis for recommending short-term aspirin therapy after myocardial infarction but provided no evidence that treatment should extend beyond 5 weeks. Aspirin withdrawal studies have shown that, as with antibiotics and thrombolytic therapy, a short course of treatment can have long-term benefits.2,5 Trials comparing short-term with long-term aspirin treatment are therefore required. The second major contributing factor was the meta-analysis by the Antiplatelet Trialists' Collaboration, which was state-of-the-art for its time but not robust by modern standards.6 This meta-analysis reanalyzed data from published trials and showed consistent bias in favor of aspirin (although later reports corrected the most extreme examples).7 The findings of the meta-analysis were driven largely by data from small positive trials, with a dearth of small negative trials.2,3,4 Most clinicians agree that meta-analysis is useful for confirming robust clinical trial results—which are lacking for long-term aspirin therapy—or calculating the size of trial required to provide a robust result; however, proof depending on meta-analysis alone is now generally considered weak.

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Authors and Affiliations

  1. University of Hull, Hull, UK

    John GF Cleland

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  1. John GF Cleland
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Correspondence to John GF Cleland.

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Competing interests

JGF Cleland was on the steering committee of the Warfarin/Aspirin Study in Heart Failure (WASH) and Warfarin and Antiplatelet Therapy in Chronic Heart Failure Trial (WATCH), which were partly funded by Dupont, Sanofi and Bristol-Myers Squibb.

Supplementary information

Supplementary Table 1

Key trials of long-term aspirin therapy for the prevention of cardiovascular events

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Cleland, J. Chronic aspirin therapy for the prevention of cardiovascular events: a waste of time, or worse?. Nat Rev Cardiol 3, 234–235 (2006). https://doi.org/10.1038/ncpcardio0540

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