A novel analysis of DAPA-HF investigated the efficacy of dapagliflozin on ventricular arrhythmia (VA), resuscitated cardiac arrest (RCA), and sudden death. The results showed a significantly reduced likelihood for the composite outcome by 21% [1].

The DAPA-HF (NCT03036124) trial evaluated dapagliflozin’s efficacy to prevent adverse outcomes of heart failure (HF) in patients with HF and reduced ejection fraction (HFrEF). The main results showed a 26% risk reduction of the composite primary endpoint of cardiovascular (CV) death or worsening of HF. DAPA-HF included 4,744 patients with a left ventricular ejection fraction (LVEF) ≤40% and an NT-proBNP ≥600pg/mL who were in NYHA class 2–4. The mean age was 67 years, mean LVEF 31%, 45% suffered from diabetes, and 41% from chronic kidney disease. The primary outcome of this new analysis consisted of a composite of VA, RCA, or sudden death. Furthermore, sensitivity analyses were performed, and predictors of the primary outcome were identified.

Dr James Curtain (University of Glasgow, Scotland) presented the results and stated that “315 patients or 6.6% of the total study cohort experienced a primary outcome event of which the majority, 64%, were adjudicated sudden death. VA accounted for 33% of the primary outcome events and there were 8 RCAs.”

Comparing the cohort of patients without a primary outcome event to those who were subject to VA, RCA, or sudden death, the latter were significantly more often men, had a history of prior VA, a lower LVEF, and had a lower eGFR. Also, primary outcome events were more likely to occur in those on a loop diuretic or having a defibrillating device. Among the significant independent predictors of VA, RCA, or sudden death were male sex, higher NTproBNP, history of VA or myocardial infarction. The risk of a primary outcome event was reduced by higher values of LVEF, systolic blood pressure, or serum sodium.

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“Dapagliflozin compared with placebo reduced the incidence of the primary outcome VA, RCA, or sudden death by 21% with an HR of 0.79 and P-value of 0.037,” said Dr Curtain. He further elaborated that the results of the competing risk analysis including all-cause death were effectively the same with an incidence reduction by 20%. In his summary, Dr Curtain also pointed out that the effect of dapagliflozin was generally consistent across key subgroups and within several sensitivity analyses examining composites excluding non-sustained ventricular tachycardia or including only more serious VA.

 Curtain J. DAPA-HF. Session: Late-breaking science in Heart Failure. ESC Congress 2021-The Digital Experience, 27-30 August.

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