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Dapagliflozin and Race in HF Across the EF Spectrum
Quick Takes
- The benefits of dapagliflozin for heart failure (HF) outcomes are consistent in Black and White patients across the range of ejection fractions, with a greater absolute benefit in Black patients due to their higher absolute risk.
- Black patients taking dapagliflozin for HF have a higher risk of worsening HF, but a similar risk of cardiovascular death and all-cause death compared to White patients.
Study Questions:
Do Black patients experience similar clinical outcomes as White patients taking dapagliflozin for heart failure (HF)?
Methods:
This study is a pooled analysis of two trials comparing dapagliflozin to placebo in patients with HF with reduced ejection fraction (EF) (DAPA-HF) and mid-range or preserved EF (DELIVER). Outcomes and response to treatment were compared between Black and White patients. Patients were assigned to a race subgroup based on self-identification. Patients were eligible if they were New York Heart Association (NYHA) functional class II-IV and had a left ventricular EF (LVEF) ≤40% (DAPA-HF) or >40% (DELIVER) and an elevated N-terminal pro–B-type natriuretic peptide. Notable exclusions included type 1 diabetes, symptomatic hypotension or systolic blood pressure <95 mm Hg, and an estimated glomerular filtration rate <30 mL/min/1.73 m2 (DAPA-HF) or <25 mL/min/1.73 m2 (DELIVER). Both trials enrolled patients both with and without type 2 diabetes and randomization was stratified by type 2 diabetes status. The primary endpoint from both DAPA-HF and DELIVER, a composite of worsening HF (unplanned hospitalization or urgent visit for HF requiring an intravenous diuretic) or cardiovascular (CV) death, was also used in this pooled analysis. In addition, the components of the primary endpoint, a composite of HF hospitalization (first and repeat) or CV death, death from any cause, and Kansas City Cardiomyopathy Questionnaire (KCCQ) scores were also compared between groups. Most Black patients were enrolled from the Americas so the comparator group was White patients enrolled from the same regions.
Results:
A total of 3,526 patients from the two trials were randomized from the Americas and were included in this analysis. Of these, 2,626 (74.5%) identified as White and 381 (10.8%) as Black. Significant differences existed between the two study groups. The Black patient population was younger (64 vs. 70 years), more often women (40.4% vs. 34.3%), and had higher systolic blood pressure and body mass index compared to White patients. Black patients more often had a history of hypertension, type 2 diabetes, and prior stroke, but less often had a history of atrial fibrillation. Black patients also had a longer duration of HF, worse NYHA functional class and KCCQ scores, lower LVEF, and were more likely to have had a prior HF hospitalization.
Black patients had a significantly higher risk of the composite of worsening HF or CV death (16.8 vs. 11.6 events per 100 person-years; adjusted hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.08-1.69) and worsening HF compared to White patients. Rates of HF hospitalization, CV death, and all-cause death were not statistically different between groups. Compared with placebo, dapagliflozin reduced the risk of the primary endpoint at similar rates in Black (HR, 0.69; 95% CI, 0.47-1.02) and White patients (HR, 0.73; 95% CI, 0.61-0.88) (p for interaction = 0.73). The mean increases in KCCQ scores were greater with dapagliflozin compared to placebo, regardless of race. The benefit of dapagliflozin was consistent across the range of LVEF in both Black and White patients.
Conclusions:
Black patients with HF had a higher risk of worsening HF, but a similar risk of CV or all-cause death compared to White patients. The beneficial effects of dapagliflozin were consistent in Black and White patients across the range of LVEF. Black patients had a greater absolute benefit due to their higher absolute risk.
Perspective:
Black populations have a higher incidence of HF compared to White populations and may also experience worse outcomes. Black patients are under-represented in clinical trials of HF therapies, and the low event rate among these relatively few participants make generalizing results for this high-risk population difficult. By pooling the results of these two clinical trials, there is a better understanding of the benefit of dapagliflozin across the spectrum of LVEF, regardless of race.
Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Heart Failure and Cardiac Biomarkers
Keywords: African Americans, Blood Pressure, Diabetes Mellitus, Type 2, Diuretics, Glomerular Filtration Rate, Heart Failure, Hypotension, Natriuretic Peptide, Brain, Risk, Secondary Prevention, Sodium-Glucose Transporter 2 Inhibitors, Stroke Volume
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