Cardiovascular Outcomes with Exenatide in Type 2 Diabetes According to Ejection Fraction: The EXSCEL Trial

Oct 9, 2024European journal of heart failure

Heart health with exenatide in type 2 diabetes varies by heart pumping strength: The EXSCEL trial

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Abstract

In a study of 14,752 participants, the effect of exenatide on hospitalizations for heart failure varied significantly based on left ventricular ejection fraction (LVEF).

Participants with LVEF <40% had a hazard ratio of 1.52 for hospitalizations due to heart failure, indicating a potentially increased risk.
In contrast, those with LVEF ≥40% showed a hazard ratio of 0.74 for heart failure hospitalizations, suggesting a potentially decreased risk.
No significant interactions were found between treatment effects and LVEF for major adverse cardiovascular events, cardiovascular death, or all-cause mortality.
The risk of hospitalization for heart failure was also influenced by New York Heart Association (NYHA) class, particularly high in patients with NYHA class III/IV.
Obesity did not alter the effects of exenatide on hospitalizations for heart failure.

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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 (<40% or ≥40%). Outcomes were also evaluated according to New York Heart Association (NYHA) class and obesity. The main outcome was hospitalization for heart failure (HHF). A treatment-by-LVEF interaction was used. In EXSCEL (n = 14 752), 4749 participants had LVEF available at baseline; 455 (10%) with LVEF <40%, 4294 (90%) with LVEF ≥40%. LVEF modified the EQW effect on hHF: hazard ratio (HR) = 1.52 (95% confidence interval [CI] = 0.95-2.43) in participants with LVEF < 40% and HR = 0.74 (95% CI = 0.55-1.01) in those with LVEF ≥ 40% (p-interaction = 0.012). No significant treatment-by-LVEF interactions (p-interaction >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.

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Cardiovascular Outcomes with Exenatide in Type 2 Diabetes According to Ejection Fraction: The EXSCEL Trial

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