The ELIXA Trial: Lixisenatide Safe for Cardiovascular Disease

The glucose-lowering medication lixisenatide was found to neither increase nor decrease cardiovascular (CV) events compared with placebo in patients afflicted with type 2 diabetes and acute coronary syndrome.

Results from the Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial, presented at the ESC Congress 2015, “demonstrate the cardiovascular safety of lixisenatide,” remarked Eldrin F. Lewis, MD, MPH, member of the ELIXA trial’s executive committee, physician in the Cardiovascular Medicine Division, Brigham and Women’s Hospital, and associate professor at Harvard Medical School, Boston, USA.

Researchers assessed the safety of lixisenatide using a primary outcome of composite CV death, heart attacks, stroke, and hospitalization for unstable angina. For the study, 6,068 patients with type 2 diabetes and history of myocardial infarction (83%) or hospitalization for unstable angina (17%) were randomized to either receive daily injections of lixisenatide or placebo for a minimum of 10 months.

The primary outcome occurred in 13.4% of the lixisenatide group compared with 13.2% of the placebo group.

This ELIXA trial served as the catalyst for the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA) to establish guidelines for clinical trials to thoroughly ensure CV safety within glucose-lowering therapies.

Though the study was unable to establish the superiority of lixisenatide over placebo for CV safety, “the neutral effects on cardiovascular events are all within the limits of the EMA’s and FDA’s guidelines,” said Lewis. “In addition, lixisenatide provided a modest benefit in terms of weight gain.”

Lixisenatide was also found safe in patients with histories of heart failure. In patients with chronic heart failure history prior to randomization, 10% had hospitalization for heart failure during follow up compared with 2.4% patients without chronic heart failure history.

Lewis also said that patients who were hospitalized for heart failure actually had a risk of all-cause death that was 9-fold greater than the individuals who were not hospitalized for heart failure. “This excess mortality suggests that these are important events to capture among patients with diabetes.”