Dapagliflozin reduces risk for ventricular arrhythmia, cardiac arrest, sudden death
Compared with placebo, dapagliflozin reduced risk for ventricular arrhythmias, cardiac arrest and sudden death, according to new data from the DAPA-HF trial.
James P. Curtain, MBBS, clinical research fellow at BHF Cardiovascular Centre at the University of Glasgow, U.K., and colleagues conduced a post hoc analysis of DAPA-HF by reviewing serious adverse event reports for ventricular arrhythmias, cardiac arrest and adjudicated cases of sudden cardiac death. The results were presented at the virtual European Society of Cardiology Congress and published in the European Heart Journal.
The analysis included 4,744 patients with HF with reduced ejection fraction with or without diabetes (mean age, 67 years; 76% men). As Healio previously reported, in the main results of DAPA-HF, dapagliflozin (Farxiga, AstraZeneca) 10 mg once daily reduced risk for CV death or worsening HF events by 26% compared with placebo at a median follow-up of 18.2 months.
In this population, “the two main modes of cardiovascular death are sudden death and death due to worsening heart failure,” Curtain said during a presentation. “Many deaths are due to ventricular arrhythmias. In this analysis, we examined the effect of dapagliflozin on the risk of ventricular arrhythmias, resuscitated cardiac arrest and sudden death.”
Independent predictors of the composite outcome of interest, first occurrence of any serious ventricular arrhythmia, resuscitated cardiac arrest or sudden death included log-transformed N-terminal pro-B-type natriuretic peptide level, history of ventricular arrhythmia, left ventricular ejection fraction, systolic BP, history of MI, male sex, BMI, serum sodium concentration, nonwhite race, treatment with dapagliflozin and use of cardiac resynchronization therapy, according to the researchers.
The composite outcome of interest occurred in 5.9% of the dapagliflozin group compared with 7.4% of the placebo group (HR = 0.79; 95% CI, 0.63-0.99; P = .037), Curtain said during the presentation.
“The result was effectively the same” in a competing risks analysis including all-cause death (HR = 0.8; 95% CI, 0.64-0.99; P = .043), he said.
Analyses of individual components were “consistent with the results of the primary outcome,” he said.
In subgroup analyses, results were consistent with the main analysis findings except for NT-proBNP, in which the treatment effect of dapagliflozin was greater in those with a level at or below the median compared with those with a level above it (P for interaction = .032), Curtain said. However, when NT-proBNP was modeled continuously, no interaction between NT-proBNP and the effect of randomized treatment on the primary outcome was found.
In addition, he said, “the effect of dapagliflozin was consistent in several sensitivity analyses examining composites excluding nonsustained [ventricular tachycardia] or including only more serious ventricular arrhythmias.”
Reference:
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Curtain J, et al. Late-Breaking Science in Heart Failure. Presented at: European Society of Cardiology Congress; Aug. 27-30, 2021 (virtual meeting).