Physicians' Academy for Cardiovascular Education

No overall benefit of use of aspirin in primary prevention setting in diabetes patients and individuals with moderate CV risk

ESC 2018 - Munich

News - Aug. 26, 2018

A randomized trial of aspirin versus placebo for primary cardiovascular prevention in 15,480 people with diabetes (ASCEND)

Presented at the ESC congress 2018 by: Prof Jane Armitage (Oxford, UK)

Aspirin to Reduce Risk of Initial Vascular Events): A Study to Assess the Efficacy and Safety of Aspirin in Patients at Moderate Risk of Cardiovascular Disease (ARRIVE)

Presented at the ESC congress 2018 by: Prof J Michael Gaziano (Boston, MA, USA)

Background

The benefit of aspirin has been well established in secondary prevention in patients with CVD and most guidelines support the use of low-dose aspirin in this setting. However, efficacy and safety of aspirin in the primary prevention of CV events remains controversial. More specifically, diabetes patients are at increased risk of heart attacks and strokes, but it is unclear whether aspirin treatment can prevent a first CV event.

The ASCEND trial enrolled 15,480 diabetes patients with no history of CVD, who were randomized to either 100 mg aspirin or placebo (and to omega-3 fatty acid supplementation, discussed in another article). The primary outcome was serious vascular events (SVE), a composite of non-fatal myocardial infarction (MI), non-fatal stroke, TIA or CV death, and the safety outcome was major bleeding. Follow-up was >99% complete for morbidity and mortality.

The ARRIVE trial, a randomized, double-blind, placebo-controlled, primary-care based multicenter trial, examined the efficacy and safety of 100 mg aspirin vs placebo in 12,546 subjects with a moderate estimated risk of first acute CV event (20-30% 10-year CVD risk, 10-20% CHD risk) without known diabetes or CVD. The primary endpoint was time to first occurrence of a composite of CV death, Ml, unstable angina (UA), stroke and transient ischemic attack (TIA) and safety endpoints included bleeding events and incidence of adverse events.

Main results

ASCEND

ARRIVE

Conclusion

There was no netto CV benefit for use of aspirin in a primary prevention setting of diabetes patients or individuals with moderate CV risk. Although use of aspirin reduced SVE in diabetes patients, the CV benefit was counterbalanced by the increased risk of bleeding.

During the discussions of both presentations in the press conference, it was mentioned that the individuals in these trials were well controlled for risk factors and Professor J. Michael Gaziano, principal investigator of the ARRIVE trial, of the Brigham and Women's Hospital, Boston, US, said: “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.” Dr. Armitage also noted that the risk of patients in the ASCEND trial can get quite low with treatment with other medications; aspirin did not add to this.

The effect of cancer that had been seen in smaller, observational studies, was not confirmed in ASCEND. Patients enrolled in ASCEND will be followed at 5 and 10 years beyond the end of the study, to evaluate whether an increased risk of gastrointestinal cancer may appear at a later stage. In the currently studied period, no such effect was seen.

Part of the discussion was dedicated to the differences seen between the intention-to-treat and per protocol analyses in the ARRIVE trial. Discontinuation of the study drug was seen over time (compliance rate in the per protocol analysis was 60%), and selective drop-in occurred as well. Gaziano said that in those who were not specifically selected for aspirin use (by their physician because they developed TIA, or risk), the results were more similar to what has been seen before.

In light of these neutral trial outcomes, it was concluded that overall the use of aspirin remains a decision that should involve a discussion between physicians and patients to weigh benefits and risks.

Results of the ARRIVE are published in The Lancet.

Results of the ASCEND are published in NEJM.

-Our reporting is based on the information provided at the ESC congress-

The ARRIVE study was published simultaneously in the The Lancet The ASCEND study was published simultaneously in the NEJM