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Aims: People with diabetes are at high risk for cardiovascular events including heart failure (HF). We examined the effect of the glucagon‐like peptide 1 agonist dulaglutide on incident HF events and other cardiovascular outcomes in those with or without prior HF in the randomized placebo‐controlled Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial. 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 HF event was defined as an adjudication‐confirmed hospitalization or urgent evaluation for HF. 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 HF event (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.77–1.12; p = 0.456). In the 853 (8.6%) participants with HF at baseline, there was no change in either MACE or HF events with dulaglutide as compared to participants without HF (p = 0.44 and 0.19 for interaction, respectively). Combined cardiovascular death and HF 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 HF 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. [ABSTRACT FROM AUTHOR]

Dulaglutide and cardiovascular and heart failure outcomes in patients with and without heart failure: a post-hoc analysis from the REWIND randomized trial. We thank Dr's Ferriera and Neves for their response to our recent post-hoc analysis of the REWIND trial and their interest in further analysis of the subgroup of patients that had a history of heart failure (HF), but did not have HF at the baseline visit.[1] HF is a heterogeneous diagnosis with variable prognosis depending on a number of variables such as cardiac function, medical and device therapy, concomitant diseases and functional status.[[2]] The authors correctly point out that there was a relatively low proportion of patients that were diagnosed as having HF at baseline (8.6%) compared to other glucagon-like peptide 1 receptor agonist studies.[[4], [6]] Possible explanations for this difference may lie in the lower risk population from REWIND as compared to the other studies and the fact that HF was not a criterion for entry into the study.[8] Further, as described as a limitation in the manuscript, HF at baseline was determined by the site primary investigators who were not required to provide supporting data such as ejection fraction, brain natriuretic peptide, or history of HF hospitalizations. Reply to the letter regarding the article 'Dulaglutide and cardiovascular and heart failure outcomes in patients with and without heart failure: a post-hoc analysis from the REWIND randomized trial'. [Extracted from the article]