Efficacy of Dapagliflozin in Black Versus White Patients With Heart Failure and Reduced Ejection Fraction.

Kieran F Docherty, Modele O Ogunniyi, Inder S Anand, Akshay S Desai, Mirta Diez, Jonathan G Howlett, Jose C Nicolau, Eileen O'Meara, Subodh Verma, Silvio E Inzucchi, Lars Køber, Mikhail N Kosiborod, Daniel Lindholm, Felipe A Martinez, Olof Bengtsson, Piotr Ponikowski, Marc S Sabatine, Mikaela Sjöstrand, Scott D Solomon, Anna Maria Langkilde, Pardeep S Jhund, John J V McMurray

Journal: JACC. Heart failure 2022;10(1):52-64

PMID: 34969498

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Abstract

OBJECTIVES

This study sought to investigate the efficacy and safety of dapagliflozin in Black and White patients with heart failure (HF) with reduced ejection fraction (HFrEF) enrolled in DAPA-HF (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure).

BACKGROUND

Black patients may respond differently to certain treatments for HFrEF than White patients.

METHODS

Patients with New York Heart Association functional class II to IV with an ejection fraction of ≤40% and elevated N-terminal pro-B-type natriuretic peptide were eligible for DAPA-HF. Because >99% of Black patients were randomized in the Americas, this post hoc analysis considered Black and White patients enrolled only in North and South America. The primary outcome was the composite of a worsening HF event (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular death.

RESULTS

Of the 4,744 patients randomized in DAPA-HF, 1,494 (31.5%) were enrolled in the Americas. Of these, 1,181 (79.0%) were White, and 225 (15.1%) were Black. Black patients had a higher rate of worsening HF events, but not mortality, compared with White patients. Compared with placebo, dapagliflozin reduced the risk of the primary endpoint similarly in Black patients (HR: 0.62; 95% CI: 0.37-1.03) and White patients (HR: 0.68; 95% CI: 0.52-0.90; P-interaction = 0.70). Consistent benefits were observed for other prespecified outcomes, including the composite of total (first and repeat) HF hospitalizations and cardiovascular death (P-interaction = 0.43) and Kansas City Cardiomyopathy Questionnaire total symptom score. Study drug discontinuation and serious adverse events were not more frequent in the dapagliflozin group than in the placebo group in either Black or White patients.

CONCLUSIONS

Dapagliflozin reduced the risk of worsening HF and cardiovascular death, and it improved symptoms, similarly in Black and White patients without an increase in adverse events. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124).

Address: British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom.; Division of Cardiology, Emory University School of Medicine, Atlanta, Georgia, USA.; Department of Medicine, University of Minnesota Medical School and VA Medical Center, Minneapolis, Minnesota, USA.; Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.; Division of Cardiology, Institute Cardiovascular de Buenos Aires, Buenos Aires, Argentina.; University of Calgary, Cardiac Sciences and Medicine, Calgary, Alberta, Canada.; Instituto do Coracao, Hospital das Clínicas Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.; Deparment of Cardiology, Institute of Cardiology Montreal, Montreal, Montreal, Canada.; Division of Cardiac Surgery, St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.; Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut, USA.; Department of Cardiology, Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark.; Saint Luke's Mid America Heart Institute, University of Missouri-Kansas City, Kansas City, Missouri, USA.; AstraZeneca, Gothenburg, Sweden.; National University of Cordoba, Cordoba, Argentina.; Wroclaw Medical University, Wroclaw, Poland.; TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.; British Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom. Electronic address: [email protected].

DOI: 10.1016/j.jchf.2021.08.006