Dapagliflozin Provides Consistent Benefit Across Spectrum of Body Weight in HFpEF

New data from an analysis of the landmark DELIVER trial is providing clinicians with insight into the effects of dapagliflozin (Farxiga) on heart failure outcomes and KCCQ scores among people with heart failure with preserved ejection fraction (HFpEF) across the spectrum of body weight.

A prespecified analysis of the phase 3 trial, which was presented at ESC Congress 2022, investigators detail the effects of dapagliflozin across 5 different body weight categories, with results indicating dapagliflozin reduced the risk of the trial’s primary composite out to a similar extent across World Health Organizations BMI categories.

“Obesity is common in patients with HFpEF and is associated with higher rates of heart failure hospitalization and worse health status. Treatment with dapagliflozin improves cardiovascular outcomes across the spectrum of BMI, leads to greater symptom improvement in patients with obesity, compared with those without, and has the additional benefit of causing modest weight loss,” wrote investigators in their conclusion.

As the obesity epidemic continues to grow in the US and abroad, knowledge related to the effects of guideline-directed medical therapies for various disease states serves to have a substantial impact on patient care. With this in mind, the current study was designed as a prespecified analysis of the phase 3 DELIVER trial, which randomized more than 6200 patients with heart failure with mildly reduced ejection fraction (HFmrEF) or HFpEF to dapagliflozin or placebo therapy with a primary endpoint defined as a composite of worsening heart failure and cardiovascular death.

In the original trial, a primary outcome event was identified among 16.4% (n=512) of the dapagliflozin group and among 19.5% (n=610) of the placebo group (HR, 0.82 [95% CI, 0.73 to 0.92]; P <.001) during a median of 2.3 (IQR, 1.7 to 2.8) years of follow-up. Further analysis indicated use of dapagliflozin was associated with a reduction in rate of hospitalization for heart failure or urgent visit for heart failure (HR, 0.79 [95% CI, 0.69 to 0.91]) and cardiovascular death (HR, 0.88 [95% CI, 0.74 to 1.05]) compared with placebo.

Of the 6263 who underwent randomization in the DELIVER trial, 6257 had a recorded BMI measurement at baseline. Among these, 21.5% were considered normal weight, 33.1% were considered overweight, 25.2% had Class I obesity, 12.8% had Class II obesity, and 6.6% had Class III obesity, according to WHO criteria. Compared to their counterparts with normal BMI, those with obesity were younger, more often female, more likely to be White. Investigators also noted patients with obesity also had higher systolic and diastolic blood pressure, a higher HbA1c, and were more likely to have a diagnosis of type 2 diabetes than patients with a normal weight.

Upon analysis, results indicated use of dapagliflozin was associated with similar reduction in risk of the trial’s primary outcome across BMI categories, with HRs of 0.89 (95% CI, 0.69 to 1.15) for normal weight, 0.87 (95% CI, 0.70 to 1.08) for overweight, 0.74 (95% CI, 0.58 to 0.93) for Class I obesity, 0.78 (95% CI, 0.57 to 1.08) for Class II obesity, and 0.72 (95% CI, 0.47 to 1.08) for Class III obesity (P for interaction=.82). Further analysis suggested the effects of dapagliflozin on out outcomes, including cardiovascular death, worsening heart failure, total heart failure events, and all-cause mortality, were consistent across BMI categories (P for all >.4).

Among the 6257 included in this prespecified analysis, 5792 had KCCQ-TSS scores recorded at baseline and 4485 had a recorded measurement at 8 months. When assessing change in KCCQ-TSS scores, results indicated the degree of improvement associated with Dapagliflozin use was greater in those with higher BMIs, with a placebo-corrected change of 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, among those with normal weight, overweight, Class I obesity, Class II obesity, and Class III obesity, respectively (P for interaction=.03). In analyses assessing change in body weight, results indicated t , with a placebo-corrected weight loss of –0.88 (−1.28, –0.47) kg among those considered normal weight, –0.65 (−1.04, –0.26) kg among those considered overweight, –1.42 (−1.89, –0.94) kg among those with Class I obesity, –1.17 (−1.94, –0.40) kg among those with Class II obesity, and –2.5 (−4.4, –0.64) kg among those with Class III obesity (P for interaction=.002).

“The key finding of this study was that dapagliflozin was equally efficacious in reducing the primary composite outcome of worsening HF or cardiovascular death across the spectrum of BMI in DELIVER, including among participants who were obese. Treatment with dapagliflozin also led to an improvement in symptoms measured with the KCCQ-TSS and which was greater in patients with a higher BMI,” investigators added.

This study, "Dapagliflozin for heart failure according to body mass index: the DELIVER trial,” was published in the European Heart Journal.