A meta-analysis from 11 trials found that aspirin reduced the risk of non-fatal myocardial infarction by 22% and death by 6%, at the cost of a 59% increase in gastrointestinal bleeding and a 33% increase in haemorrhagic stroke. The authors conclude that in patients at low cardiovascular disease risk, the relative benefit of aspirin translates into marginal absolute benefit, making its use largely unjustifiable.
The benefit of aspirin for patients with established cardiovascular disease outweighs the risk of bleeding, but the role of aspirin for individuals with no overt cardiovascular disease is more controversial.
In a meta-analysis of 118,445 individuals from 11 trials of aspirin for primary cardiovascular disease prevention, aspirin reduced the relative risk of non-fatal myocardial infarction by 22% and death by 6%, at the cost of a 59% increase in gastrointestinal bleeding and a 33% increase in haemorrhagic stroke.
This compromise in bleeding complications has called into question the level of baseline cardiovascular disease risk for which use of aspirin in primary prevention is clinically acceptable. Indeed, in patients at low cardiovascular disease risk, the relative benefit of aspirin translates into marginal absolute benefit, making its use largely unjustifiable.
To better define the net benefit of aspirin for primary prevention, four more trials were designed to include individuals at higher cardiovascular disease risk: two of patients with diabetes (ASCEND and ACCEPT-D), one of patients of advanced age (ASPREE), and one of patients at moderate cardiovascular disease risk (ARRIVE; appendix).
Davide Capadanno at the division of cardiology, AOU “Policlinico Vittorio Emanuele”, PO Rodolico, writes in The Lancet that J Michael Gaziano and colleagues now report the results of of the trials.
In the study in The Lancet, researchers led by Professor J Michael Gaziano, at the Brigham and Women's Hospital, say that the use of aspirin in the primary prevention of cardiovascular events remains controversial. They aim to assess the efficacy and safety of aspirin versus placebo in patients with a moderate estimated risk of a first cardiovascular event.
Summary
Methods: ARRIVE is a randomised, double-blind, placebo-controlled, multicentre study done in seven countries. Eligible patients were aged 55 years (men) or 60 years (women) and older and had an average cardiovascular risk, deemed to be moderate on the basis of the number of specific risk factors. We excluded patients at high risk of gastrointestinal bleeding or other bleeding, or diabetes. Patients were randomly assigned (1:1) with a computer-generated randomisation code to receive enteric-coated aspirin tablets (100 mg) or placebo tablets, once daily. Patients, investigators, and others involved in treatment or data analysis were masked to treatment allocation. The primary efficacy endpoint was a composite outcome of time to first occurrence of cardiovascular death, myocardial infarction, unstable angina, stroke, or transient ischaemic attack. Safety endpoints were haemorrhagic events and incidence of other adverse events, and were analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00501059.
Findings: Between July 5, 2007, and Nov 15, 2016, 12 546 patients were enrolled and randomly assigned to receive aspirin (n=6270) or placebo (n=6276) at 501 study sites. Median follow-up was 60 months. In the intention-to-treat analysis, the primary endpoint occurred in 269 (4·29%) patients in the aspirin group versus 281 (4·48%) patients in the placebo group (hazard ratio [HR] 0·96; 95% CI 0·81–1·13; p=0·6038). Gastrointestinal bleeding events (mostly mild) occurred in 61 (0·97%) patients in the aspirin group versus 29 (0·46%) in the placebo group (HR 2·11; 95% CI 1·36–3·28; p=0·0007). The overall incidence rate of serious adverse events was similar in both treatment groups (n=1266 [20·19%] in the aspirin group vs n=1311 [20·89%] in the placebo group. The overall incidence of adverse events was similar in both treatment groups (n=5142 [82·01%] vs n=5129 [81·72%] in the placebo group). The overall incidence of treatment-related adverse events was low (n=1050 [16·75%] vs n=850 [13·54%] in the placebo group; p<0·0001). There were 321 documented deaths in the intention-to-treat population (n=160 [2·55%] vs n=161 [2·57%] of 6276 patients in the placebo group).
Interpretation: The event rate was much lower than expected, which is probably reflective of contemporary risk management strategies, making the study more representative of a low-risk population. The role of aspirin in primary prevention among patients at moderate risk could therefore not be addressed. Nonetheless, the findings with respect to aspirin's effects are consistent with those observed in the previously published low-risk primary prevention studies.
Authors
J Michael Gaziano, Carlos Brotons, Rosa Coppolecchia, Claudio Cricelli, Harald Darius, Philip B Gorelick, George Howard, Thomas A Pearson, Peter M Rothwell, Luis Miguel Ruilope, Michal Tendera, Gianni Tognoni,
Deepak L Bhatt at the Brigham and Women's Hospital and Harvard Medical School writes in a commentary in The Lancet that dual antiplatelet therapy for at least a year is the standard of care after an acute coronary syndrome. Attempts to shorten the duration of therapy have resulted in an increase in myocardial infarction. Therefore, strategies to de-escalate the duration or intensity of dual antiplatelet therapy are of interest.
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