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Effects of dapagliflozin in DAPA-HF according to background heart failure therapy.

Journal article
Authors Kieran F Docherty
Pardeep S Jhund
Silvio E Inzucchi
Lars Köber
Mikhail N Kosiborod
Felipe A Martinez
Piotr Ponikowski
David L DeMets
Marc S Sabatine
Olof Bengtsson
Mikaela Sjöstrand
Anna Maria Langkilde
Akshay S Desai
Mirta Diez
Jonathan G Howlett
Tzvetana Katova
Charlotta Ljungman
Eileen O´Meara
Mark C Petrie
Morten Schou
Subodh Verma
Pham Nguyen Vinh
Scott D Solomon
John J V McMurray
Published in European heart journal
ISSN 1522-9645
Publication year 2020
Published at Institute of Medicine, Department of Molecular and Clinical Medicine
Language en
Subject categories Cardiovascular medicine


In the DAPA-HF trial, the SGLT2 inhibitor dapagliflozin reduced the risk of worsening heart failure (HF) and death in patients with HF and reduced ejection fraction. We examined whether this benefit was consistent in relation to background HF therapy.In this post hoc analysis, we examined the effect of study treatment in the following yes/no subgroups: diuretic, digoxin, mineralocorticoid receptor antagonist (MRA), sacubitril/valsartan, ivabradine, implanted cardioverter-defibrillating (ICD) device, and cardiac resynchronization therapy. We also examined the effect of study drug according to angiotensin-converting enzyme inhibitor/angiotensin receptor blocker dose, beta-blocker (BB) dose, and MRA (≥50% and <50% of target dose). We analysed the primary composite endpoint of cardiovascular death or a worsening HF event. Most randomized patients (n = 4744) were treated with a diuretic (84%), renin-angiotensin system (RAS) blocker (94%), and BB (96%); 52% of those taking a BB and 38% taking a RAS blocker were treated with ≥50% of the recommended dose. Overall, the dapagliflozin vs. placebo hazard ratio (HR) was 0.74 [95% confidence interval (CI) 0.65-0.85] for the primary composite endpoint (P < 0.0001). The effect of dapagliflozin was consistent across all subgroups examined: the HR ranged from 0.57 to 0.86 for primary endpoint, with no significant randomized treatment-by-subgroup interaction. For example, the HR in patients taking a RAS blocker, BB, and MRA at baseline was 0.72 (95% CI 0.61-0.86) compared with 0.77 (95% CI 0.63-0.94) in those not on all three of these treatments (P-interaction 0.64).The benefit of dapagliflozin was consistent regardless of background therapy for HF.

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