Physicians' Academy for Cardiovascular Education

SGLT2i in HFrEF is beneficial across all BMI categories

Efficacy of dapagliflozin in heart failure with reduced ejection fraction according to body mass index

Literature - Adamson C, Jhund PS, Docherty KF et al., - Eur J Heart Fail. 2021 Jul 16. doi: 10.1002/ejhf.2308.

Introduction and methods

Multiple studies have shown that an obesity-paradox exists in HFrEF. Patients with overweigt or obesity had better survival rates than non-obese patients [1-6]. In addition, it was shown that weight loss was associated with worse survival [7-11]. This analysis of the DAPA-HF trial investigated whether the risk of outcomes varied by baseline BMI. Moreover, the effects of dapagliflozin on outcomes stratified by baseline BMI and the effects of dapagliflozin on weight were studied.

DAPA-HF included adult patients with HFrEF (NYHA classes II to IV, LVEF ≤40%, elevated NT-proBNP, and standard HF drug and device therapy). Patients were randomized in a 1:1 ratio to receive either dapagliflozin (10 mg once daily) or matching placebo. A total of 4742 patients were included in the current analysis. Patients were stratified according to BMI: underweight (<18.5 kg/m²), normal weight (18.5-24.9 kg/m²), overweight (25.0-29.9 kg/m²), obesity class I (30.0-34.9 kg/m²), obesity class II (35.0-39.9 kg/m²), and obesity class III (≥40 kg/m²). Due to a low number of patients in the classes underweight, obesity class II and III, some classes were combined: underweight/normal weight (n=1348, 28.4%), overweight (n=1722, 36.3%), obesity class I (n=411, 9.3%), obesity class II or III (n=659, 13.9%). The primary composite outcome was first event of CV death or worsening HF event (HF hospitalization or urgent HF visit requiring IV therapy). Adverse events of interest were discontinuation of study drug due to adverse event, volume depletion, renal adverse event, bone fracture, amputation, and major hypoglycemia. Change in body weight from baseline was investigated as an exploratory endpoint. Median follow-up was 18.2 months.

Main results


This analysis of the DAPA-HF trial confirmed that a obesity-paradox exists in HFrEF. A U-shaped relationship between rates of CV death or worsening HF events and BMI was found with lowest rates in patients with a BMI of ~30 kg/m². Dapagliflozin was beneficial to a similar extend in all BMI categories.


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Find this article online at Eur J Heart Fail.

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