Goals
Obesity is common and is associated with unique phenotypic characteristics in heart failure with preserved ejection fraction (HFpEF). Therefore, it is important to understand the efficacy and safety of new therapies in patients with HFpEF and obesity. The effects of dapagliflozin were examined according to body mass index (BMI) among patients in the Evaluating Dapagliflozin to Improve the Lives of Patients with Heart Failure with Reserved Ejection Fraction trial.
Methods and results
Body mass index was analyzed by World Health Organization (WHO) categories and as a continuous variable. The body mass index ranged between 15.2 and 50 kg/m 2 with a mean value of 29.8 (standard deviation ± 6.1) kg/m 2. The proportions, by WHO category, were: normal weight 1343 (21.5%); overweight 2073 (33.1%); Obesity class I 1574 (25.2%); Class II obesity 798 (12.8%); and Class III obesity 415 (6.6%).
Compared with placebo, dapagliflozin reduced the risk of the primary outcome to a similar extent in these categories: hazard ratio (95% confidence interval): 0.89 (0.69–1.15), 0. 87 (0.70–1.08), 0.74 (0.58–0.93), 0.78 (0.57–1.08) and 0.72 (0.47–1.08), respectively (P-interaction = 0.82).
The placebo-corrected change in Kansas City Cardiomyopathy Questionnaire total symptom score with dapagliflozin at 8 months was: 0.9 (−1.1, 2.8), 2.5 (0.8, 4, 1), 1.9 (−0.1, 3.8), 2.7 (−0.5, 5.8), and 8.6 (4.0, 13.2) points, respectively ( P - interaction = 0.03). Placebo-corrected weight change at 12 months was: -0.88 (-1.28, -0.47), -0.65 (-1.04, -0.26), -1.42 ( -1.89, -0.94), -1.17 (-1.94, -0.40)) and –2.50 (-4.4, –0.64) kg (P-interaction = 0.002 ).
Summary of the background and key findings of this study. BMI, body mass index; CV, cardiovascular; DELIVER, evaluation of dapagliflozin to improve the lives of patients with heart failure due to reserved ejection fraction; HFmrEF, heart failure with mildly reduced ejection fraction; HFpEF, heart failure with preserved ejection fraction; KCCQ-TSS, Kansas City Cardiomyopathy Questionnaire Total Symptom Score.
Conclusions Obesity is common in patients with HFpEF and is associated with higher rates of hospitalization for heart failure and worse health status. Treatment with dapagliflozin improves cardiovascular outcomes across the BMI spectrum, leads to greater symptom improvement in patients with obesity compared to those without obesity, and has the additional benefit of causing modest weight loss. |
