• Joseph Fares, Omar El Fadel, Joy Zhao, Michael Li, Jianxin Sun, Jesse Roman, Giorgos Loizidis, and Ross Summer.
• Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA; The Jane and Leonard Korman Respiratory Institute, Thomas Jefferson University, Philadelphia, PA.
• Chest. 2024 Sep 21.

BackgroundSarcoidosis is a multisystem inflammatory disease in which management and outcomes can vary widely. The renin-angiotensin-aldosterone system (RAAS) has been implicated in its pathogenesis, yet the impact of RAAS modulators on health outcomes in sarcoidosis remains poorly understood.Research QuestionHow do pharmacologic modulators of RAAS affect health outcomes in patients with a diagnosis of sarcoidosis?Study Design And MethodsWe conducted a large multicenter investigation using the TriNetX Research Network database. Patients included in this study were individuals with a diagnosis of sarcoidosis who were prescribed either an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB). All cohorts were matched for important covariates, and outcomes measured included mortality, cardiac and respiratory outcomes, and sepsis rates after sarcoidosis diagnosis.ResultsWe observed an increased mortality risk among patients with sarcoidosis prescribed ACEIs compared with patients prescribed ARB therapies. Furthermore, patients with sarcoidosis prescribed ACEIs showed worse cardiac and respiratory outcomes and increased sepsis rates compared with the ARB cohort.InterpretationOur findings suggest that ACEIs and ARBs have divergent effects on outcomes in patients with sarcoidosis. These findings highlight the potential pathogenic role of RAAS signaling in this disease and underscore the importance of carefully selecting RAAS modulators for individuals with sarcoidosis.Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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