Physicians' Academy for Cardiovascular Education

SGLT2i efficacious and safe regardless of baseline ARNI treatment in HFrEF

Effect of Dapagliflozin in Patients With HFrEF Treated With Sacubitril/Valsartan: The DAPA-HF Trial

Literature - Solomon SD, Jhund PS, Claggett BL et al., - J Am Coll Cardiol Heart Fail. 2020. doi: 10.1016/j.jchf.2020.04.008.

Introduction and methods

Sacubitril/valsartan treatment reduced CV death or HF hospitalization in HFrEF patients compared with enalapril in the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial [1]. In the Dapagliflozin And Prevention of Adverse outcomes in Heart Failure (DAPA-HF) trial, dapagliflozin (10 mg) reduced the composite of CV death or worsening HF in HFrEF patients with or without diabetes [2, 3]. Here, dapagliflozin had a beneficial effect in a subset of patients receiving sacubitril/valsartan at baseline. However, the safety of combined therapy with dapagliflozin and sacubitril/valsartan was unknown.

This study evaluated in detail the efficacy and safety of dapagliflozin in HFrEF patients (n=4744) who were on sacubitril/valsartan (n=508) and in patients who were not on this treatment (n=4236) at baseline in the DAPA-HF trial. Primary outcome was a composite of worsening HF, defined as either an unplanned HF hospitalization or an urgent HF visit that required intravenous diuretic therapy, or CV death. Secondary outcomes included a composite of CV death or HF hospitalization, the total number of hospitalizations for HF and CV death, change in the Kansas City Cardiomyopathy Questionnaire Clinical Total Symptom Score (KCCQ-TSS), worsening renal function, and death from any cause. The prespecified safety analyses included occurrence of AEs. AEs included serious AEs, AEs associated with discontinuation of study treatment, and AEs of interest (i.e., volume depletion, renal events, major hypoglycemia, bone fractures, diabetic ketoacidosis, amputations, Fournier’s gangrene, and laboratory findings of note).

Main results


Benefit and safety of dapagliflozin compared to placebo was similar between those taking sacubitril/valsartan and those not taking sacubitril/valsartan at baseline in HFrEF patients in the DAPA-HF trial. According to the authors, the findings suggest that use of both agents together could further lower morbidity and mortality in patients with HFrEF.


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Find this article online at J Am Coll Cardiol Heart Fail

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