From Ancestry to Equity: Contemporary Insights into Racial Disparities in RAASI Associated Reductions in Heart Failure Hospitalizations

Abstract

Renin-angiotensin-aldosterone system inhibitors (RAASIs) are guideline recommended first line treatment for heart failure with reduced ejection fraction (HFrEF). Angiotensin converting enzyme inhibitors, angiotensin receptor blockers and angiotensin receptor blockers - neprilysin inhibitors (ACEIs, ARBs, and ARNIs) work by blocking RAAS and neprilysin pathways, improving vascular function and preventing heart damage. Over the past three decades, these therapies have significantly improved HFrEF outcomes, but a disparity in RAASI effectiveness for heart failure (HF) hospitalizations has been reported. Using data from cornerstone ACEI clinical trials, enalapril was documented as having almost no effect in Black HF patients with hospitalization rates similar in both treatment and placebo groups. In contrast, White HF patients experienced a significant 44% reduction in HF hospitalization risk. Mortality benefit of RAASI were similar among both Black and White HF patients, suggesting that the racial health disparity of RAASI benefit only subsists in the event of HF hospitalization. Limited evidence exists to explain these differences in outcomes for Black and White HFrEF patients treated with RAASI. This includes pharmacogenomics (PGx) and health disparities research, of HF patients taking RAASI. Therefore, disparities in the response and effectiveness of RAASI halt the progression of heart failure hospitalization benefit and survival improvements. This research innovatively incorporates PGx and health services research to address this significant racial disparity by leveraging data of a diverse, contemporary cohort of HFrEF patients (Henry Ford heart failure pharmacogenomic registry, HFPGR) that is inclusive of the patient’s continuous RAASI exposure through pharmacy claims data, event rates, social survey responses and ability to be linked to US census data. This specific research strongly aligns with recent calls and statements to integrate genetics and social determinants of health (SDoH) in HF research. Structured in three parts: the first two distinguish between self-identified race, genomic ancestry (Chapter 3) and SDoH (Chapter 4) to explain differences in HFrEF hospitalizations, while the third investigates SDoH associated with RAASI exposure in HFrEF patients (Chapter 5). The findings suggest that the racial disparity in RAASI hospitalization benefit among HFrEF patients has diminished. This improvement is likely due to advancements in background HF therapy, better insurance coverage among HFPGR patients, and robust RAASI exposure calculation using pharmacy claims data. While the results of this work help to demonstrate similar RAASI hospitalization benefit in both Black and White HFrEF patients, there is still work to be done. There are still limited explanations for higher HF prevalence and hospitalization rates in Black patients. Furthermore, the scope of HF therapies will continue to advance with new medicines and procedures over time. This is very promising for HF patients overall but, without driven effort and equitable intent to include groups of HF patients that are often underserved, those underserved groups may continue to experience health disparities. If the lack of knowledge surrounding health disparities in Black HF patients remains unknown and poor effectiveness in current therapies persists, then the improvements in the health of these specific HF patients will remain stagnant. This study underscores the need to prioritize equity in HF treatment and research, ensuring that advances benefit all HFrEF patients and contribute to reducing racial health disparities. Therefore, there is a need to continue to build upon previous research to help improve health outcomes of current and future HFrEF patients to ensure equitable treatment.