Tim Lahm1, Edward Hess2, Anna E Barón3, Thomas M Maddox4, Mary E Plomondon2, Gaurav Choudhary5, Bradley A Maron6, Roham T Zamanian7, Peter J Leary8. 1. Richard L. Roudebush Veterans Affairs Medical Center, Indianapolis, IN; Indiana University School of Medicine, Indianapolis, IN. Electronic address: tlahm@iu.edu. 2. Veterans Affairs Eastern Colorado Health Care System, Denver, CO. 3. Veterans Affairs Eastern Colorado Health Care System, Denver, CO; Colorado School of Public Health, Denver, CO. 4. Washington University School of Medicine Division of Cardiology and Healthcare Innovation Lab, St. Louis, MO. 5. Providence Veterans Affairs Medical Center, Providence, RI; Alpert Medical School of Brown University, Providence, RI. 6. Veterans Affairs Boston Healthcare System, Boston, MA; Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA. 7. Stanford University Division of Pulmonary, Allergy, and Critical Care Medicine and Vera Moulton Wall Center for Pulmonary Vascular Disease, Stanford, CA. 8. University of Washington, Seattle, WA.
Abstract
BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) contributes to pulmonary hypertension (PH) pathogenesis. Although animal data suggest that RAAS inhibition attenuates PH, it is unknown if RAAS inhibition is beneficial in PH patients. RESEARCH QUESTION: Is RAAS inhibitor use associated with lower mortality in a large cohort of patients with hemodynamically confirmed PH? STUDY DESIGN AND METHODS: We used the Department of Veterans Affairs Clinical Assessment Reporting and Tracking Database to study retrospectively relationships between RAAS inhibitors (angiotensin converting enzyme inhibitors [ACEIs], angiotensin receptor blockers [ARBs], and aldosterone antagonists [AAs]) and mortality in 24,221 patients with hemodynamically confirmed PH. We evaluated relationships in the full and in propensity-matched cohorts. Analyses were adjusted for demographics, socioeconomic status, comorbidities, disease severity, and comedication use in staged models. RESULTS: ACEI and ARB use was associated with improved survival in unadjusted Kaplan-Meier survival analyses in the full cohort and the propensity-matched cohort. This relationship was insensitive to adjustment, independent of pulmonary artery wedge pressure, and also was observed in a cohort restricted to individuals with precapillary PH. AA use was associated with worse survival in unadjusted Kaplan-Meier survival analyses in the full cohort; however, AA use was associated less robustly with mortality in the propensity-matched cohort and was not associated with worse survival after adjustment for disease severity, indicating that AAs in real-world practice are used preferentially in sicker patients and that the unadjusted association with increased mortality may be an artifice of confounding by indication of severity. INTERPRETATION: ACEI and ARB use is associated with lower mortality in veterans with PH. AA use is a marker of disease severity in PH. ACEIs and ARBs may represent a novel treatment strategy for diverse PH phenotypes.
BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) contributes to pulmonary hypertension (PH) pathogenesis. Although animal data suggest that RAAS inhibition attenuates PH, it is unknown if RAAS inhibition is beneficial in PH patients. RESEARCH QUESTION: Is RAAS inhibitor use associated with lower mortality in a large cohort of patients with hemodynamically confirmed PH? STUDY DESIGN AND METHODS: We used the Department of Veterans Affairs Clinical Assessment Reporting and Tracking Database to study retrospectively relationships between RAAS inhibitors (angiotensin converting enzyme inhibitors [ACEIs], angiotensin receptor blockers [ARBs], and aldosterone antagonists [AAs]) and mortality in 24,221 patients with hemodynamically confirmed PH. We evaluated relationships in the full and in propensity-matched cohorts. Analyses were adjusted for demographics, socioeconomic status, comorbidities, disease severity, and comedication use in staged models. RESULTS: ACEI and ARB use was associated with improved survival in unadjusted Kaplan-Meier survival analyses in the full cohort and the propensity-matched cohort. This relationship was insensitive to adjustment, independent of pulmonary artery wedge pressure, and also was observed in a cohort restricted to individuals with precapillary PH. AA use was associated with worse survival in unadjusted Kaplan-Meier survival analyses in the full cohort; however, AA use was associated less robustly with mortality in the propensity-matched cohort and was not associated with worse survival after adjustment for disease severity, indicating that AAs in real-world practice are used preferentially in sicker patients and that the unadjusted association with increased mortality may be an artifice of confounding by indication of severity. INTERPRETATION: ACEI and ARB use is associated with lower mortality in veterans with PH. AA use is a marker of disease severity in PH. ACEIs and ARBs may represent a novel treatment strategy for diverse PH phenotypes.
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