Effects of Dapagliflozin in HFpEF Not Influenced by Glycemic Status

In patients with heart failure with preserved ejection fraction, glycemic status does not affect the effects of dapagliflozin therapy.

The clinical benefits of dapagliflozin therapy for patients with heart failure (HF) with preserved ejection fraction appear to be consistent across a continuous glycemic range, according to results of an international, multicenter, double-blind, randomized, placebo-controlled trial published in The Lancet Diabetes & Endocrinology.

The DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure; ClinicalTrials.gov Identifier: NCT03619213) trial was conducted at 350 centers in 20 countries between 2018 and 2021. Patients (N=6259) with HF and left ventricular ejection fraction (LVEF) greater than 40% were stratified by type 2 diabetes (T2D) status and randomly assigned in a 1:1 ratio to receive 10 mg dapagliflozin or placebo once daily. The composite primary outcome was the time from randomization to worsening HF or cardiovascular (CV) death.

The patients were normoglycemic (n=1175), had prediabetes (n=1934), or T2D (n=3150). The 3 cohorts had a mean age of 71.3, 73.0, and 71.0 years; 56.2%, 53.6%, and 57.7% were men; 67.5%, 70.5%, and 72.3% were White; 77.5%, 77.1%, and 73.3% had New York Heath Association class II; LVEF was 54.3%, 54.3%, and 54.0%; and hemoglobin A1c was 5.4%, 6.0%, and 7.4%, respectively.

During a median follow-up of 2.3 years, the primary composite outcome occurred at an incidence rate (IR) of 6.9 per 100 person-years among the normoglycemic cohort, 7.6 per 100 person-years among the prediabetes cohort, and 10.1 per 100 person-years among the T2D cohort. Compared with normoglycemia, prediabetes was not associated with risk for the primary outcome (hazard ratio [HR], 1.09; 95% CI, 0.90-1.31) but T2D was (HR, 1.46; 95% CI, 1.24-1.73; P <.0001).

In patients with heart failure with mildly reduced or preserved ejection [fraction], dapagliflozin imparts substantial cardiovascular benefits across a broad range of glycaemia.

Stratified by study arm, among the normoglycemic group the composite outcome IRs were 7.8 and 6.0 per 100 person-years and among patients with dysglycemia were 8.2 and 7.1 per 100 person-years for patients randomly assigned to receive placebo and dapagliflozin, respectively. Among both the normoglycemia and dysglycemia cohorts, dapagliflozin decreased the risk for the composite outcome by 1.8 and 1.1 per 100 person-years, respectively.

In a post-hoc analysis of T2D subgroups, similar dapagliflozin treatment effects were observed among subgroups, with the exception of a significant interaction for sulfonylurea use (Pinteraction =.0026).

The rates of serious adverse events were 41.2% for the normoglycemia, 41.7% for the prediabetes, and 47.5% for the T2D cohorts. There was no evidence that treatment assignment affected the serious adverse event rate.

This analysis may have been limited by not performing more rigorous glycemic evaluations to better classify the degree of dysglycemia.

”In patients with heart failure with mildly reduced or preserved ejection [fraction], dapagliflozin imparts substantial cardiovascular benefits across a broad range of glycaemia,” the study authors wrote.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

This article originally appeared on The Cardiology Advisor

References:

Inzucchi SE, Claggett BI, Vaduganathan M, et al. Efficacy and safety of dapagliflozin in patients with heart failure with mildly reduced or preserved ejection fraction by baseline glycaemic status (DELIVER): a subgroup analysis from an international, multicentre, double-blind, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. Published online November 10, 2022. doi:10.1016/S2213-8587(22)00308-4