Equal Treatment, Unequal Outcomes? Debunking the Racial Disparity in Renin Angiotensin Aldosterone System Inhibitor-Associated Reduction in Heart Failure Hospitalizations.

Background: Renin angiotensin aldosterone system inhibitors (RAASi) are a mainstay treatment in patients with heart failure with reduced ejection fraction (HFrEF) in part to prevent hospitalizations. However, whether RAASi reduce the risk of hospitalization in Black patients is not entirely clear because enrollment of Black patients in previous clinical trials was low and a previous meta-analysis showed a significant racial disparity: reduction in hospitalizations with an RAASi in White patients but not Black patients. Previous studies relied on the use of self-identified race instead of genomic ancestry. Therefore, this study aimed to investigate the role of self-identified race and genomic ancestry in the racial disparity in RAASi-associated reductions in HFrEF hospitalizations.

Methods: The primary outcome was time to first heart failure hospitalization. Data from the Henry Ford Heart Failure Pharmacogenomic Registry (HFPGR) and the GUIDE-IT multi-center randomized control trial were analyzed with Cox proportional hazards models un/adjusted for clinical risk factors, death as a competing risk, and time-varying RAASi exposure. The proportion of Yoruba African ancestry was quantified. Analyses of self-identified race were performed in both the HFPGR and GUIDE-IT. Analysis of genomic ancestry was only performed in the HFPGR since this information was not available in GUIDE-IT. A fixed effect meta-analysis combined results of both the HFPGR and GUIDE-IT for race.

Results: The HFPGR had 1010 total HFrEF patients (Black = 509 and White = 501) with 852 having ancestry quantification (>80% Yoruba African Ancestry = 381 and <5% Yoruba African Ancestry = 471). GUIDE-IT had 810 HFrEF patients (Black = 322 and White = 488). There was no significant difference in the association of RAASi exposure with heart failure hospitalization by race (meta-analysis P value for race*RAASi exposure interaction = .49; Black patients hazard ratio [HR, 95% confidence interval] for RAASi exposure = 0.89 [0.64-1.23)], P = .47; White patients = 1.20 [0.83-1.75], P = .34). Results were similar when analyzed by ancestry (P value for ancestry*RAASi exposure interaction = 0.57; >80% Yoruba African Ancestry = 0.93 [0.51-1.69], P = .80; <5% Yoruba African Ancestry = 1.29 [0.57-2.92], P = .54).

Conclusions: In contrast to a previous meta-analysis, this more contemporary analysis of 2 HFrEF patient datasets demonstrates the absence of a racial disparity in RAASi-associated reductions in heart failure hospitalizations. The difference in this racial disparity over time may be due to improvements in background heart failure therapies, racial differences in health care usage, and the use of more advanced statistical approaches.