Evidence-based Appraisal of the DAPA-HF Trial

Abstract

Patient (HF) pg/mL AFib/flutter) standard HF (ICD, CRT, or both) and standard drug therapy (angiotensin converting enzyme inhibitor (ACEi), angiotensin II receptor blocker (ARB) or angiotensin receptor neprilysin inhibitor (ARNI), beta-blocker, unless contraindicated or not tolerated, with mineralocorticoid receptor antagonist (MRA) use encouraged). Those with recent treatment with or intolerance to an SGLT2 inhibitor, T1DM, hypotension symptoms or SBP < 95 mmHg, eGFR < 30 mL/min/1.73m 2 , or rapidly declining renal function were excluded. Citation: McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med 2019;381:1995-2008. The DAPA-HF trial evaluated the safety and efficacy of dapagliflozin in patients with HF with reduced ejection fraction regardless of the presence of diabetes. It was an international, multi-center, randomized, placebo-controlled study, with blinding of patients and all study personnel, a low percent of patients without final outcomes, and analyzed with the intention-to-treat principle. The primary outcome of the trial showed an absolute risk reduction of 4.9% and a relative risk reduction of 23.2%, with an NNT of 20, demonstrating that the composite outcome of worsening heart failure or death from cardiovascular causes was lower in the dapagliflozin group relative to placebo. Dapagliflozin was well tolerated with notable adverse reactions reported being volume depletion and renal adverse events in a similar number of events for both groups, and severe renal adverse events being lower with dapagliflozin. There are limitations when considering the generalizability of this study since the majority of the study population were classified as moderate heart failure. Additionally, the study demonstrated that there is a differential benefit between NYHA classes, with the primary benefit attributed to those classified as NYHA FC II. The ideal population for treatment with dapagliflozin are adults with HF with reduced ejection fraction and NYHA FC II-III symptoms, who are receiving standard HF device therapy (ICD, CRT or both) and standard drug therapy (ACEi/ARB/ARNI and beta-blocker unless contraindicated or resulting in unacceptable side effects), with MRA use being encouraged.