It remains unclear whether daily aspirin lowers the risk of a cardiovascular event in individuals at  moderate risk of a first heart attack or stroke, according to late-breaking results from the ARRIVE study presented at the European Society of Cardiology (ESC) Congress 2018 and published in Lancet.

Although daily aspirin has been shown to provide benefit for preventing second events in patients with a previous heart attack or stroke, its use for preventing first events is less clear, and there are concerns about bleeding risks.

The ARRIVE study assessed the impact of daily aspirin on heart attacks, strokes, and bleeding in a population at moderate risk (defined as a 20–30% risk of a cardiovascular event in 10 years) of a first cardiovascular event. Men were at least 55 years old and had two to four cardiovascular risk factors, while women were at least 60 years old with three or more risk factors. Risk factors included smoking, elevated lipids, and high blood pressure.

A total of 12,546 participants were enrolled from primary care settings in the UK, Poland, Germany, Italy, Ireland, Spain, and the US. Participants were randomly allocated to receive a 100 mg enteric-coated aspirin tablet daily or placebo. The median follow-up was 60 months. The primary endpoint was time to first occurrence of a composite of cardiovascular death, myocardial infarction, unstable angina, stroke, and transient ischemic attack.

The average age of participants was 63.9 years and 29.7% were female. In the intention-to-treat analysis, which examines events according to the allocated treatment, the primary endpoint occurred in 269 (4.29%) individuals in the aspirin group versus 281 (4.48%) in the placebo group (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.81–1.13, p=0.60). In the per-protocol analysis, which assesses events only in a compliant subset of the study population, the primary endpoint occurred in 129 (3.40%) participants of the aspirin group versus 164 (4.19%) in the placebo group (HR 0.81, 95% CI 0.64–1.02, p=0.0756).

In the per-protocol analysis, aspirin reduced the risk of total and nonfatal myocardial infarction (HR 0.53, 95% CI 0.36–0.79, p=0.0014; HR 0.55, 95% CI 0.36–0.84, p=0.0056, respectively). The relative risk reduction of myocardial infarction in the aspirin group was 82.1%, and 54.3% in the 50–59 and 59–69 age groups, respectively.

All safety analyses were conducted according to intention-to-treat. Gastrointestinal bleedings, which were mostly mild, occurred in 61 (0.97%) individuals 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 of adverse events was similar between treatment groups. Drug-related adverse events were more frequent in the aspirin (16.75%) compared to placebo (13.54%) group (p<0.0001), the most common being indigestion, nosebleeds, gastro-oesophageal reflux disease, and upper abdominal pain.

“Aspirin did not reduce the occurrence of major cardiovascular events in this study. However, there were fewer events than expected, suggesting that this was, in fact, a low-risk population. This may have been because some participants were taking medications to lower blood pressure and lipids, which protected them from disease,” says Professor J. Michael Gaziano, principal investigator, of the Brigham and Women's Hospital in Boston.

 “The decision on whether to use aspirin for protection against cardiovascular disease should be made in consultation with a doctor, considering all the potential risks and benefits,” he adds.