Does once-weekly exenatide affect the risk of hospitalization for heart failure in patients with type 2 diabetes according to baseline LVEF?
Once-weekly exenatide may have divergent effects on heart failure hospitalization depending on baseline LVEF, potentially increasing risk in patients with LVEF <40% while decreasing it in those with LVEF ≥40%.
AIMS: Glucagon-like peptide-1 receptor agonists reduce major adverse cardiovascular events (MACE) and cardiovascular mortality in people with type 2 diabetes (T2D). However, previous studies suggest the effects on heart failure outcomes vary according to left ventricular ejection fraction (LVEF). We aimed to evaluate the effects of exenatide on cardiovascular events according to LVEF in people with T2D. METHODS AND RESULTS: Post-hoc analysis of the Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial evaluating the effects of once-weekly exenatide (EQW) versus placebo on cardiovascular outcomes according to baseline LVEF (0.10) were observed for MACE, cardiovascular death or all-cause mortality. The risk of HHF was also modified by baseline NYHA class (HR 0.91, 95% CI 0.65-1.27 for NYHA class I/II; HR 1.84, 95% CI 0.95-3.59 for NYHA class III/IV; p-interaction = 0.062), mostly driven by the LVEF <40% subgroup. Obesity did not modify the effects of EQW on HHF. CONCLUSIONS: The EQW effect on HHF was influenced by LVEF, with a potentially decreased risk in participants with LVEF ≥40% and increased risk in those with LVEF <40%. The risk of HHF was particularly high in participants with LVEF <40% and NYHA class III/IV. LVEF did not modify the effect of EQW on atherosclerotic outcomes.
Neves et al. (Wed,) studied this question.