Effect of dapagliflozin in patients with heart failure with mildly reduced or preserved ejection fraction treated with beta-blockers: the DELIVER trial

Abstract Background While beta-blockers are not recommended for the treatment of HFpEF according to the latest ESC and AHA/ACC/HFSA guidelines, these therapies remain commonly used for comorbidity management. There has been concern that beta-blockers might adversely influence clinical outcomes by limiting chronotropic response in HFpEF. Purpose To examine the contemporary use and implications of beta-blocker use in patients with HFmrEF or HFpEF. Methods In the DELIVER trial, a total of 6,263 patients with symptomatic HF with LVEF >40% were randomized to dapagliflozin or placebo across 20 countries. Efficacy and safety outcomes were examined according to beta-blocker use at randomization. The primary outcome was cardiovascular death or worsening HF. Results Overall, beta-blockers were used in 5,177 patients (83%), with wide variation ranging from Mexico (60%) to Poland (93%). Nearly all patients taking beta-blockers had at least 1 potential indication (n = 5,106 [99%]), such as hypertension (n = 4,623 [89%]), atrial fibrillation/flutter (n= 2,969 [57%]), coronary artery disease (n= 2,744 [53%]), or previous LVEF< = 40% that has since improved (n = 991 [19%]). Beta-blocker use was not associated with a higher risk of the primary outcome in covariate-adjusted models (HR 0.68 [95% CI 0.59-0.80]; Left Panel). Dapagliflozin consistently reduced the risk of the primary outcome in patients taking beta-blockers (HR 0.82 [95% CI 0.72- 0.94]) and those not taking beta-blockers (HR 0.79 [95% CI 0.61-1.03]; P for interaction = 0.85), with similar findings for key secondary endpoints (Right Panel). Adverse events were balanced between patients randomized to dapagliflozin and placebo, regardless of background beta-blocker use. Conclusions In patients with HFmrEF or HFpEF enrolled in DELIVER, 4 out of 5 participants were treated with a beta-blocker, with virtually all these patients having at least 1 potential indication for use. Beta-blocker use was not associated with a higher risk of worsening HF or cardiovascular death. Dapagliflozin consistently and safely reduced clinical events, irrespective of background beta-blocker use.