Exenatide reduced all-cause death by 21% (HR 0.79) in patients without heart failure, but had no significant effect on mortality in those with heart failure (HR 1.05).
Does once-weekly exenatide reduce all-cause death and heart failure hospitalizations in patients with type 2 diabetes mellitus with and without baseline heart failure?
Once-weekly exenatide reduced first plus recurrent heart failure hospitalizations in patients with type 2 diabetes, but its mortality benefits were attenuated in those with baseline heart failure.
Background: Once-weekly exenatide (EQW) had a neutral effect on hospitalization for heart failure (HHF) in the EXSCEL study (Exenatide Study of Cardiovascular Event Lowering), with no differential treatment effect on major adverse cardiac events by baseline heart failure (HF) status. EQW’s effects on secondary end points based on HHF status have not been reported. The objective was to explore the effects of EQW on secondary end points in patients with and without baseline HF and test the effects of EQW on recurrent HHF events. Methods: The prespecified analysis of the randomized controlled EXSCEL trial, which enrolled patients with type 2 diabetes mellitus with and without additional cardiovascular disease, analyzed EQW effects on all-cause death, each major adverse cardiac event component, first HHF, and repeat HHF, by baseline HF status (regardless of ejection fraction). A subgroup analysis of the population stratified by preserved or reduced baseline ejection fraction was performed. Results: Of 14 752 EXSCEL participants, 2389 (16.2%) had HF at baseline. Compared with those without HF at baseline, patients with preexisting HF were older, and more likely to be male and white, with a higher burden of other cardiovascular diseases. Overall, those assigned to EQW had a lower incidence of all-cause death (hazard ratio HR, 0.86 95% CI, 0.77–0.97) and the composite outcome of all-cause death or HHF (HR, 0.89 95% CI, 0.80–0.99). When stratified by presence or absence of baseline HF, there was no observed reduction in all-cause death with EQW with baseline HF (HR, 1.05 95% CI, 0.85–1.29), while the risk of mortality was reduced with EQW in the no-HF group (HR, 0.79 95% CI, 0.68–0.92) with an interaction P value of 0.031. The reduction in all-cause death or HHF seen with EQW in patients without baseline HF (HR, 0.81 95% CI, 0.71–0.93) was not seen in patients with baseline HF (HR, 1.07 95% CI, 0.89–1.29; interaction P =0.015). First, plus recurrent, HHF was reduced in the exenatide group versus placebo (HR, 0.82 95% CI, 0.68–0.99; P =0.038). Conclusions: In EXSCEL, the use of EQW in patients with or without HF was well tolerated, but benefits of EQW on reduction in all-cause death and first hospitalization for HF were attenuated in patients with baseline HF. Clinical Trial Registration: https://www.clinicaltrials.gov . Unique identifier: NCT01144338.
Fudim et al. (2019) studied this question. Exenatide reduced all-cause death by 21% (HR 0.79) in patients without heart failure, but had no significant effect on mortality in those with heart failure (HR 1.05).