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

• Published in: European journal of heart failure Vol. 23; no. 10; pp. 1662 - 1672
• Main Authors: Adamson, Carly, Jhund, Pardeep S., Docherty, Kieran F., Bělohlávek, Jan, Chiang, Chern‐En, Diez, Mirta, Drożdż, Jarosław, Dukát, Andrej, Howlett, Jonathan, Ljungman, Charlotta E.A., Petrie, Mark C., Schou, Morten, Inzucchi, Silvio E., Køber, Lars, Kosiborod, Mikhail N., Martinez, Felipe A., Ponikowski, Piotr, Sabatine, Marc S., Solomon, Scott D., Bengtsson, Olof, Langkilde, Anna Maria, Lindholm, Daniel, Sjöstrand, Mikaela, McMurray, John J.V.
• Format: Journal Article
• Language: English
• Published: Oxford, UK John Wiley & Sons, Ltd 01.10.2021
• Subjects: Adiposity; Benzhydryl Compounds; Body Mass Index; Cardiology and Cardiovascular Disease; Dapagliflozin; Focused Issue on Comorbidities; Glucosides - pharmacology; Heart Failure; Humans; Kardiologi och kardiovaskulära sjukdomar; Obesity; SGLT2 inhibitor; Stroke Volume; Heart failure; Body mass index; Obesity; Adiposity; Dapagliflozin; SGLT2 inhibitor
• ISSN: 1388-9842; 1879-0844; 1879-0844
• DOI: 10.1002/ejhf.2308

Aims In heart failure with reduced ejection fraction (HFrEF), there is an ‘obesity paradox’, where survival is better in patients with a higher body mass index (BMI) and weight loss is associated with worse outcomes. We examined the effect of a sodium–glucose co‐transporter 2 inhibitor according to baseline BMI in the Dapagliflozin And Prevention of Adverse‐outcomes in Heart Failure trial (DAPA‐HF). Methods and results Body mass index was examined using standard categories, i.e. 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). The primary outcome in DAPA‐HF was the composite of worsening heart failure or cardiovascular death. Overall, 1348 patients (28.4%) were under/normal‐weight, 1722 (36.3%) overweight, 1013 (21.4%) obesity class I and 659 (13.9%) obesity class II/III. The unadjusted hazard ratio (95% confidence interval) for the primary outcome with obesity class 1, the lowest risk group, as reference was: under/normal‐weight 1.41 (1.16–1.71), overweight 1.18 (0.97–1.42), obesity class II/III 1.37 (1.10–1.72). Patients with class I obesity were also at lowest risk of death. The effect of dapagliflozin on the primary outcome and other outcomes did not vary by baseline BMI, e.g. hazard ratio for primary outcome: under/normal‐weight 0.74 (0.58–0.94), overweight 0.81 (0.65–1.02), obesity class I 0.68 (0.50–0.92), obesity class II/III 0.71 (0.51–1.00) (P‐value for interaction = 0.79). The mean decrease in weight at 8 months with dapagliflozin was 0.9 (0.7–1.1) kg (P < 0.001). Conclusion We confirmed an ‘obesity survival paradox’ in HFrEF. We showed that dapagliflozin was beneficial across the wide range of BMI studied. Clinical Trial Registration: ClinicalTrials.gov NCT03036124. Key findings from the analyses of body mass index in the DAPA‐HF trial. BMI, body mass index; HFrEF, heart failure with reduced ejection fraction.