Race in Heart Failure: A Pooled Participant-Level Analysis of the Global PARADIGM-HF and PARAGON-HF Trials

Henri Lu; Brian L Claggett; Milton Packer; Maria A Pabon; Marc A Pfeffer; Eldrin F Lewis; Carolyn S P Lam; Jean Rouleau; Michael R Zile; Martin Lefkowitz; Akshay S Desai; Pardeep S Jhund; John J V McMurray; Scott D Solomon; Muthiah Vaduganathan

doi:10.1016/j.jchf.2024.08.008

Race in Heart Failure: A Pooled Participant-Level Analysis of the Global PARADIGM-HF and PARAGON-HF Trials

JACC Heart Fail. 2024 Aug 31:S2213-1779(24)00609-7. doi: 10.1016/j.jchf.2024.08.008. Online ahead of print.

Authors

Affiliations

¹ Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Division of Cardiology, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
² Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
³ Baylor University Medical Center, Baylor Heart and Vascular Institute, Dallas, Texas, USA.
⁴ Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford University, Palo Alto, California, USA.
⁵ National Heart Centre Singapore and Duke-National University of Singapore, Singapore.
⁶ Institut de Cardiologie de Montréal, Université de Montréal, Montréal, Quebec, Canada.
⁷ Medical University of South Carolina, Charleston, South Carolina, USA.
⁸ Novartis, East Hanover, New Jersey, USA.
⁹ British Heart Foundation Glasgow Cardiovascular Research Centre, Glasgow, United Kingdom of Great Britain and Northern Ireland.
¹⁰ Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: mvaduganathan@bwh.harvard.edu.

PMID: 39387766
DOI: 10.1016/j.jchf.2024.08.008

Abstract

Background: Mechanisms of disease pathobiology, prognosis, and potentially treatment responses might vary by race in patients with heart failure (HF).

Objectives: The authors aimed to examine the safety and efficacy of sacubitril/valsartan among patients with HF by self-reported race.

Methods: PARADIGM-HF (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and PARAGON-HF (Prospective Comparison of ARNI with ARB Global Outcomes in HF With Preserved Ejection Fraction) were global, randomized clinical trials testing sacubitril/valsartan against a renin-angiotensin system inhibitor ([RASi], enalapril or valsartan, respectively) in patients with HF and left ventricular ejection fraction ≤40% (PARADIGM-HF) or left ventricular ejection fraction ≥45% (PARAGON-HF). Patients with self-reported race were categorized as White, Asian, or Black. We assessed the composite of first HF hospitalization or cardiovascular death, its components, and angioedema across races.

Results: Among 12,097 participants, 9,451 (78.1%) were White, 2,116 (17.5%) were Asian, and 530 (4.4%) were Black. Over a median follow-up of 2.5 years, Black (adjusted HR: 1.68; 95% CI: 1.42-1.98) and Asian patients (adjusted HR: 1.32; 95% CI: 1.18-1.47) experienced higher risks of the primary outcome compared with White patients. Treatment effects of sacubitril/valsartan vs RASi on the primary endpoint were consistent among White (HR: 0.84; 95% CI: 0.77-0.91), Asian (HR: 0.92; 95% CI: 0.78-1.10), and Black patients (HR: 0.79; 95% CI: 0.58-1.07; P_interaction = 0.58). Rates of severe angioedema were higher with sacubitril/valsartan vs RASi (White: 0.2% vs 0.1%; Black: 1.5% vs 0.0%; Asian: 0.1% vs 0.1%).

Conclusions: In a pooled experience of 2 global trials, Black and Asian patients exhibited a higher risk of cardiovascular events than White patients. The benefits of sacubitril/valsartan were consistent across races. Risks of severe angioedema were low but numerically higher with sacubitril/valsartan. (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure [PARADIGM-HF]; NCT01035255; Prospective Comparison of ARNI with ARB Global Outcomes in HF With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).

Keywords: heart failure; race; sacubitril/valsartan.

Associated data

ClinicalTrials.gov/NCT01920711