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Renin-Angiotensin-Aldosterone System Inhibitor Use and Mortality in Pulmonary Hypertension

Insights From the Veterans Affairs Clinical Assessment Reporting and Tracking Database
Published:October 04, 2020DOI:https://doi.org/10.1016/j.chest.2020.09.258

      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.

      Key Words

      Abbreviations:

      AA (aldosterone antagonist), ACEI (angiotensin converting enzyme inhibitor), ARB (angiotensin receptor blocker), BNP (B-type natriuretic peptide), CART (Clinical Assessment Reporting and Tracking), HR (hazard ratio), PAH (pulmonary arterial hypertension), PAWP (pulmonary artery wedge pressure), PH (pulmonary hypertension), PVR (pulmonary vascular resistance), RAAS (renin-angiotensin-aldosterone system), RHC (right heart catheterization), RV (right ventricle), VA (Department of Veterans Affairs)
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