Dulaglutide and Cardiovascular and Heart Failure Outcomes in Patients With and Without Heart Failure: A Post-hoc Analysis from the REWIND Randomized Trial
Abstract
AIMS: People with diabetes are at high risk for cardiovascular events including heart failure. We examined the effect of the glucagon-like peptide 1 agonist dulaglutide on incident heart failure events and other cardiovascular outcomes in those with or without prior heart failure the randomized placebo-controlled Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial (ClinicalTrials.gov number NCT01394952).
METHODS AND RESULTS: The REWIND major adverse cardiovascular event (MACE) outcome was the first occurrence of a composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes (including unknown causes). In this post-hoc analysis, a heart failure event was defined as an adjudication-confirmed hospitalization or urgent evaluation for heart failure.
Of the 9901 participants studied over a median follow-up of 5.4 years, 213/4949 (4.3%) randomly assigned to dulaglutide and 226/4952 (4.6%) participants assigned to placebo experienced a heart failure event (HR 0.93, 95% CI 0.77- 1.12; P=0.46). In the 853 (8.6%) participants with heart failure at baseline, there was no change in either MACE or heart failure events with dulaglutide as compared to participants without heart failure (p=0.44 and 0.19 for interaction, respectively).
Combined CV death and heart failure events were marginally reduced with dulaglutide compared to placebo (HR 0.88, 95% CI: 0.78-1.00; p=0.050) but unchanged in patients with and without heart failure at baseline (p=0.31). CONCLUSIONS: Dulaglutide was not associated with a reduction in HF events in patients with type 2 diabetes regardless of baseline HF status over 5.4 years of follow up.