Use of Aspirin to Reduce Risk of Initial Vascular Events in Patients at Moderate Risk of Cardiovascular Disease (ARRIVE): A Randomised, Double-blind, Placebo-controlled Trial
Trial Reference
Gaziano JM, Brotons C, Coppolecchia R, et al. Use of Aspirin to Reduce Risk of Initial Vascular Events in Patients at Moderate Risk of Cardiovascular Disease (ARRIVE): A Randomised, Double-blind, Placebo-controlled Trial. Lancet 2018; August 26:https://doi.org/10.1016/S0140-6736(18)31924-X
Expert Comment
Pablo Avanzas, Consultant in Interventional Cardiology, Hospital Universitario Central de Asturias
Background
The use of aspirin in the primary prevention of cardiovascular events remains controversial. The authors aimed to assess the efficacy and safety of aspirin versus placebo in patients with a moderate estimated risk of a first cardiovascular event.
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. The authors excluded patients at high risk of gastrointestinal bleeding or other bleeding, or diabetes. Patients were randomly assigned (1:1) 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. 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).
Conclusion
Numerous studies have investigated the benefits and risks of aspirin in the acute management of cardiovascular events and in longer-term secondary prevention among people with cardiovascular disease. Fewer large-scale trials were done in the primary prevention of cardiovascular disease before the design of the ARRIVE trial. There remains a gap in the understanding of benefits and risks of aspirin use in patients at moderate risk of cardiovascular disease.
Findings of the ARRIVE trial add to our understanding of the use of aspirin in primary prevention in several ways. First, the study was designed to assess the benefit of 100 mg per day of enteric-coated aspirin versus placebo in the reduction of incident myocardial infarction, stroke, and related cardiovascular conditions in people considered to be at moderate risk, with the exclusion of patients with diabetes. An additional objective of ARRIVE was to assess the safety and tolerability of aspirin in these patients in the setting of decreasing population-wide cardiovascular risk. Finally, ARRIVE assessed the role of aspirin with a background of modern preventive and therapeutic strategies.
The main message of this investigation is that once-daily aspirin failed to reduce the rate of primary cardiovascular events in patients with no known cardiovascular disease and moderate cardiovascular risk. Nonetheless, the findings with respect to aspirin’s effects are consistent with those observed in the previously published low-risk primary prevention studies.