Dapagliflozin for HF and Similar Benefits in Black and White Patients Regardless of LVEF

Dapagliflozin had a similar effect in reducing the risk for worsening heart failure (HF) or cardiovascular death in Black and White patients with HF and a range of ejection fractions, according to a study in JACC: Heart Failure.

Researchers reported their findings on the effects of dapagliflozin in Black and White patients across the range of left ventricular ejection fraction (LVEF) in a pooled analysis of 2 clinical trials.

The DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) were randomized, double-blind, controlled trials of patients with symptomatic HF and increased natriuretic peptide levels that compared dapagliflozin 10 mg once daily with placebo. Participants with an LVEF of 40% or less were included in the DAPA-HF trial and DELIVER included patients with an LVEF of greater than 40%.

Both trials had the primary outcome of the composite of worsening HF (unplanned HF hospitalization or urgent visit for HF requiring an intravenous diuretic) or cardiovascular death.

Among the 11,007 patients in the trials, 3526 were randomized in North and South America. Of this group, 74.5% identified as White and 10.8% identified as Black or African American. The analysis included only the Black and White patients from the Americas. Compared with White patients, Black patients were much younger (64 vs 70 years), had a higher proportion of women (40.4% vs 34.3%), and were less likely to be current or former smokers.

Worsening HF or cardiovascular death occurred in 19.2% of White patients and 26.5% of Black patients. The event rate per 100 person-years was 11.6 (95% CI, 10.6-12.7) in White patients and 16.8 (95% CI, 13.8-20.4) in Black patients (adjusted hazard ratio [HR], 1.27; 95% CI, 1.01-1.59).

Black patients had a higher rate of worsening HF or cardiovascular death and worsening HF compared with White patients, which was not modified by LVEF (P_interaction ≥.92). The cardiovascular death rate was comparable in Black and White patients and was not modified by LVEF (P_interaction = .67).

Compared with placebo, dapagliflozin decreased the risk for worsening HF or cardiovascular death similarly in Black patients (HR, 0.69; 95% CI, 0.47-1.02) and White patients (HR, 0.73; 95% CI, 0.61-0.88), with no interaction occurring between race and treatment effect (P_interaction =.73).

Dapagliflozin’s number needed to treat to prevent 1 event during the median follow-up was 17 (95% CI, 12-33) for White patients and 12 (95% CI, 9-23) for Black patients.

Regarding safety outcomes, 4.6% of White patients who received dapagliflozin discontinued the drug owing to an adverse event vs 5.4% of Black patients.

Among several limitations, the analyses are not prespecified, and the prespecified inclusion and exclusion criteria in DAPA-HF and DELIVER precluded enrollment of very high-risk patients. In addition, the number and proportion of Black patients are small in both trials, and the association between race and clinical outcomes should be interpreted with caution owing to the observational design and absence of data on social determinants of health.

“…these data underscore the substantial and clinically important benefits, and favorable tolerability and safety profile, of dapagliflozin in patients with HF, across the spectrum of ejection fraction, irrespective of race,” wrote the investigators.

Disclosure: The DAPA-HF and DELIVER trials were funded by AstraZeneca. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.