Abstract
The benefits of aspirin therapy for the secondary prevention of cardiovascular disease clearly outweigh the risks of bleeding, and low-dose aspirin is uniformly recommended in this setting. However, no clear consensus exists about whether, and if so in whom, aspirin therapy is appropriate for the primary prevention of cardiovascular disease. Three trials of low-dose aspirin versus placebo in three populations at increased risk of myocardial infarction or ischaemic stroke in the absence of established cardiovascular disease were reported in 2018. The ASPREE trial in elderly people was terminated early for futility because aspirin had no effect on disability-free survival but significantly increased the risk of major haemorrhage and, unexpectedly, all-cause mortality. In the ASCEND trial in patients with diabetes mellitus and no evidence of vascular disease, aspirin significantly reduced serious vascular events but increased major bleeding. In the ARRIVE trial in people with multiple risk factors for cardiovascular disease, aspirin had no effect on major cardiovascular events but increased gastrointestinal bleeding. The aim of this Review is to place these new results in the context of previous evidence on aspirin for the primary prevention of cardiovascular disease and to appraise whether the new evidence is likely to enable the more targeted use of aspirin in particular individuals for whom the net benefit is both clinically worthwhile and statistically definite.
Key points
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The benefits of aspirin therapy for the secondary prevention of cardiovascular disease (CVD) clearly outweigh the risks of bleeding, but whether to recommend low-dose aspirin for primary prevention of CVD is controversial.
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Use of risk scores for vascular events and major extracranial bleeds to classify individual participant data from a meta-analysis shows that individuals at the highest risk of vascular events are also at the highest risk of bleeding.
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In 2018, results from three trials of low-dose aspirin in three populations at increased risk of myocardial infarction or ischaemic stroke in the absence of established CVD added to the evidence base.
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Overall, other than for myocardial infarction, the effects of aspirin on the other major efficacy and safety outcomes seem similar in all the primary prevention trials, including the three (ASPREE, ASCEND and ARRIVE) completed in 2018.
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The main challenge when assessing the net benefit of aspirin is that benefits and risks are strongly correlated; therefore, identifying large numbers of people at high risk of vascular ischaemia but low risk of bleeding is difficult.
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New approaches are required to overcome this challenge, perhaps combining coronary imaging to identify apparently healthy people at substantially increased risk of vascular events with gastroprotectant therapy to reduce the risk of bleeding.
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C.P. reports consulting and lecture fees from Acticor Biotech, Amgen, Bayer, GlaxoSmithKline and Zambon and institutional research grants from Bayer, Cancer Research UK (Catalyst Award — Aspirin for Cancer Prevention Collaboration), the European Commission and the Italian Drug Agency (AIFA); he serves as chairperson of the Scientific Advisory Board of the International Aspirin Foundation. C.B. reports grants from Boehringer Ingelheim, the British Heart Foundation, the Medical Research Council and the UK National Institute for Health Research.
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Patrono, C., Baigent, C. Role of aspirin in primary prevention of cardiovascular disease. Nat Rev Cardiol 16, 675–686 (2019). https://doi.org/10.1038/s41569-019-0225-y
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