Littleton Shana D R, Lanfear David E, Dorsch Michael P, Liu Bin, Luzum Jasmine A
University of Michigan College of Pharmacy, Ann Arbor, Michigan.
Henry Ford Health System, Detroit, Michigan.
J Card Fail. 2025 May;31(5):800-809. doi: 10.1016/j.cardfail.2024.09.012. Epub 2024 Oct 22.
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.
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.
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).
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.
肾素-血管紧张素-醛固酮系统抑制剂（RAASi）是射血分数降低的心力衰竭（HFrEF）患者的主要治疗药物，部分原因是为了预防住院。然而，RAASi是否能降低黑人患者的住院风险尚不完全清楚，因为之前临床试验中黑人患者的入组率较低，且之前的一项荟萃分析显示存在显著的种族差异：RAASi可降低白人患者的住院率，但对黑人患者无效。以往的研究依赖于自我认定的种族而非基因组血统。因此，本研究旨在探讨自我认定的种族和基因组血统在RAASi相关的HFrEF住院率降低的种族差异中的作用。
主要结局是首次心力衰竭住院时间。对亨利·福特心力衰竭药物基因组注册研究（HFPGR）和GUIDE-IT多中心随机对照试验的数据进行分析，采用Cox比例风险模型，对临床风险因素、作为竞争风险的死亡以及随时间变化的RAASi暴露进行未调整/调整分析。对约鲁巴非洲血统的比例进行量化。在HFPGR和GUIDE-IT中均对自我认定的种族进行分析。仅在HFPGR中进行基因组血统分析，因为GUIDE-IT中没有该信息。采用固定效应荟萃分析合并HFPGR和GUIDE-IT中种族的结果。
HFPGR共有1010例HFrEF患者（黑人=509例，白人=501例），其中852例进行了血统量化（约鲁巴非洲血统>80%=381例，约鲁巴非洲血统<5%=471例）。GUIDE-IT有810例HFrEF患者（黑人=322例，白人=488例）。RAASi暴露与心力衰竭住院之间的关联在种族上无显著差异（种族*RAASi暴露交互作用的荟萃分析P值=0.49；黑人患者RAASi暴露的风险比[HR，95%置信区间]=0.89[0.64-1.23]，P=0.47；白人患者=1.20[0.83-1.75]，P=0.34）。按血统分析时结果相似（血统*RAASi暴露交互作用的P值=0.57；约鲁巴非洲血统>80%=0.93[0.51-1.69]，P=0.80；约鲁巴非洲血统<5%=1.29[0.57-2.92]，P=0.54）。
与之前的荟萃分析不同，对2个HFrEF患者数据集的这项更新分析表明，RAASi相关的心力衰竭住院率降低不存在种族差异。随着时间的推移，这种种族差异的变化可能归因于背景心力衰竭治疗的改善、医疗保健使用方面的种族差异以及更先进统计方法的应用。
