Effects of dapagliflozin according to QRS duration across the spectrum of LVEF: An analysis of DAPA-HF and DELIVER

Abstract Aims To document the prevalence of QRS prolongation in patients with HFrEF and HFmrEF/HFpEF, the association between QRS duration and outcomes, and the effect of dapagliflozin according to QRS duration across the spectrum of LVEF. Methods A pooled analysis of the DAPA-HF and DELIVER trials, excluding patients with a paced rhythm and CRT was conducted. The information collected was used to categorize patients according to QRS duration based on the cutpoints used in the CRT trials, as follows: QRS <120 ms, QRS 120-149 ms, and QRS ≥ 150 ms. The data were analyzed according to these categories and using QRS duration as a continuous variable. Results Overall, 4004 patients had HFrEF, and 5820 had HFmrEF/HFpEF. QRS duration (ms) was <120 in 7039 patients (71.7%), 120–149 in 1725 (17.6%), and ≥150 in 1060 patients (10.8%). The median follow-up time was 23 months. The rate of the primary composite outcome of CV death or worsening HF was 9.2 (95%CI 8.7-9.7), 14.3 (13.0-15.7), and 15.9 (14.1-17.9) per100 patient-years in the <120, 120–149, and ≥150 ms groups, respectively. This gradient in event rates was observed both in HFrEF and HFmrEF/HFpEF. Dapagliflozin, compared with placebo, reduced the risk of the primary outcome, consistently, across the QRS duration subgroups: hazard ratio (95% CI) 0.75 (0.67-0.85), 0.79 (0.65-0.96) and 0.89 (0.70-1.13) in the <120, 120–149, and ≥150 ms groups, respectively (P for interaction 0.28). The effect of dapagliflozin on the primary outcome was consistent across the QRS duration regardless of HF phenotype i.e., HFrEF or HFmrEF/HFpEF. Conclusion Prolongation of QRS duration is associated with worse outcomes irrespective of HF phenotype. Dapagliflozin reduced the risk of the primary outcome, regardless of QRS duration, in DAPA-HF and DELIVER.KM curves according to QRS durationEffect of dapagliflozin on outcomes