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Highlights from

European Society of Cardiology

Congress 2018

Munich 25-29 August 2018

ARRIVE: No reduction in rate of first CV events with aspirin in moderate-risk patients

Take-home messages
  • No overall reduction was observed in the primary composite endpoint of CV events
  • In the per protocol analysis, aspirin reduced the risk of a first myocardial infarction by 47%
  • No difference in fatal bleeding rates was observed between aspirin and placebo
“While no overall reduction was observed in the primary composite endpoint of CV events, results from ARRIVE are generally consistent with many other studies that tended to demonstrate aspirin’s ability to lower the risk of first non-fatal myocardial infarction without affecting risk of total stroke.”

Professor Michael Gaziano
Brigham and Women's Hospital, Boston, US

Late-breaking data from the randomised controlled ARRIVE (Aspirin to Reduce Risk of Initial Vascular Events; NCT00501059) trial have shown that low-dose aspirin does not reduce the rate to first cardiovascular (CV) events in people at moderate CV risk.

Presenting the findings of the primary care-based trial at ESC Congress 2018 was principal investigator, Professor Michael Gaziano from the Brigham and Women's Hospital, Boston, US. Results were also published simultaneously in The Lancet.

Results from the intent-to-treat analysis showed that aspirin treatment, compared to placebo, did not significantly reduce the rate of CV events in the study population (hazard ratio (HR): 0.96; 95% CI, 0.81-1.13; p=0.60).

“While no overall reduction was observed in the primary composite endpoint of CV events, results from ARRIVE are generally consistent with many other studies that tended to demonstrate aspirin’s ability to lower the risk of first non-fatal myocardial infarction without affecting risk of total stroke,” said the preventive cardiologist, adding that it emerged that they had a lower risk population than intended.

Aspirin is established for its preventative value against secondary CV events but its role in preventing initial CV events remains controversial, with conflicting recommendations for and against its use, despite 30 years of trials.

Seeking some clarification, in ARRIVE, the investigators aimed to assess the efficacy and safety of aspirin versus placebo in patients with a moderate estimated risk of a first CV event.

The randomised, double-blind, placebo-controlled, multicentre study enrolled patients aged 55 (men) or 60 (women) years or older with moderate CV risk, which was defined as a 20-30% risk of a CV event in 10 years. Risk factors included smoking, elevated lipids and high blood pressure. Those at risk of gastrointestinal bleed and who had diabetes were excluded.

Participants were randomly assigned 1:1 to 100 mg aspirin daily or placebo and followed for a median of 60 months. A composite outcome of time to first occurrence of CV death, myocardial infarction, unstable angina, stroke or transient ischaemic attack comprised the primary endpoint. Safety endpoints included haemorrhagic events and incidence of other adverse events.

A total of 12,546 (around 30% women) patients were randomised to aspirin (n=6,270) or placebo (n=6,276). “While estimated 10-year CV risk was over 17%, the observed CV event rates were considerably less than anticipated,” remarked Professor Gaziano. This corresponded to a lower risk population with a 10-year event rate below 9%. The finding suggests that this was in fact a low-risk population, he added. “This may have been because some participants were taking medications to lower blood pressure and lipids, which protected them from disease.”

In the intent-to-treat analysis, the primary endpoint occurred in 269 (4·29%) individuals in the aspirin arm versus 281 (4·48%) in the placebo group.

In the per protocol analysis, aspirin reduced the risk of a first myocardial infarction (fatal and non-fatal) by 47% (HR: 0·53; 95% CI, 0·36-0·79; p=0·0014). The risk of a first non-fatal myocardial infarction was reduced by 45% (HR: 0·55; 95% CI, 0·36-0·84; p=0·0056).

With respect to safety findings, the overall incidence of treatment-related adverse events was low at 16·75% in the aspirin group versus 13·54% in the placebo group; (p<0·0001). Gastrointestinal bleedings were mostly mild and 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; intent-to-treat population). There was no difference in fatal bleeding rates. Also, no effects were seen on short-term cancer rates but the length of follow-up was insufficient to assess longer-term outcomes.

In conclusion, Professor Gaziano pointed out that the decision about use of aspirin in moderate-risk patients, “should involve a thoughtful discussion between clinician and patient given the need to weigh the CV and cancer benefits against the bleeding risks, patient preferences, cost and other factors. We need to add more data on older individuals and in women, and more data are coming from other completed trials,” he added.

Based on Gaziano JM, Brotons C, 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. Presented on Sunday, 26 August 2018.

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The content and interpretation of these conference highlights are the views and comments of the speakers/authors.

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