Abstract
Among patients with heart failure (HF) and reduced ejection fraction (HFrEF), those with atrial fibrillation (AF) may respond differently to certain treatments than patients without AF. We investigated the efficacy and safety of dapagliflozin in patients with HFrEF with and without AF in the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure trial (DAPA-HF). We also examined the effect of dapagliflozin on new-onset AF. The primary outcome was the composite of an episode of worsening HF (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular death. Of the 4744 patients randomized, 1910 (40.3%) had 'any AF' (history of AF or AF on enrolment electrocardiogram). Compared with placebo, dapagliflozin reduced the risk of worsening HF or cardiovascular death to a similar extent in patients with and without any AF [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.62-0.92 and 0.74, 95% CI 0.62-0.88, respectively; p for interaction=0.88]. Consistent benefits were observed for the components of the primary outcome, all-cause mortality, and improvement of Kansas City Cardiomyopathy Questionnaire total symptom score. Among patients without AF at baseline, dapagliflozin did not significantly reduce the risk of new-onset AF compared with placebo (HR 0.86, 95% CI 0.60-1.22). However, patients with new-onset AF had a 5 to 6-fold higher risk of adverse outcomes when compared to those without incident AF. Dapagliflozin, compared with placebo, reduced the risk of worsening HF events, cardiovascular death, and all-cause death, and improved symptoms, in patients with and without AF. Dapagliflozin did not reduce the risk of new-onset AF.
Highlights
Dapagliflozin reduced the risk of worsening heart failure (HF) or cardiovascular death to a similar extent in patients with and without any Atrial fibrillation (AF) [hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.62–0.92 and 0.74, 95% CI 0.62–0.88, respectively; p for interaction = 0.88]
Dapagliflozin reduced the risk of worsening heart failure events and death, and improved symptoms, irrespective of atrial fibrillation (AF) status
Dapagliflozin did not reduce the risk of new-onset AF. (A) Effects of dapagliflozin compared with placebo on clinical outcomes according AF status at baseline. (B) Cumulative incidence of new-onset AF in DAPA-HF according to randomized treatment assignment in patients without AF at baseline
Summary
Atrial fibrillation (AF) and heart failure (HF) with reduced ejection fraction (HFrEF) often coexist, and each increases the likelihood and complicates the course and treatment of the other.[1,2] Patients with HFrEF and AF are generally older, have a greater symptom burden, lower quality of life, and more comorbidity than those without AF.[3,4,5,6] Patients with AF are at higher risk of adverse outcomes, including HF hospitalization and death, AF may be a marker of more advanced HF, rather than an independent prognostic risk factor.[1,3,4,5,6,7,8,9,10,11,12] Patients with paroxysmal AF may be at higher risk than those with persistent or permanent AF.[3]Sodium–glucose co-transporter 2 (SGLT2) inhibitors, originally developed as glucose-lowering agents for type 2 diabetes, are a valuable new treatment for HFrEF, including in patients without diabetes.[13,14] Their effects in HFrEF patients with AF is of interest, from two perspectives. Some treatments cannot be used in AF (e.g. ivabradine) and the effectiveness of others may be modified by the presence of AF (e.g. beta-blockers, cardiac resynchronization therapy and, most recently, omecamtiv mecarbil).[15,16,17,18] Second, new-onset AF is associated with a high risk of adverse outcomes, including HF hospitalization, stroke, and all-cause death in patients with HFrEF,[3,4,5,11,19,20] and some guideline-recommended therapies for HFrEF reduce the incidence of new-onset AF.[6,15,21,22,23]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
