Renin-Angiotensin-Aldosterone System Inhibitor Use and Mortality in Pulmonary Hypertension: Insights from the Veterans Affairs CART Database.
The renin-angiotensin-aldosterone system (RAAS) contributes to pulmonary hypertension (PH) pathogenesis. While animal data suggest RAAS inhibition attenuates PH, it is unknown if RAAS inhibition is beneficial in PH patients.Is RAAS inhibitor use associated with lower mortality in a large cohort of patients with hemodynamically confirmed PH?We used the Department of Veterans Affairs Clinical Assessment Reporting and Tracking Database to retrospectively study 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 co-medication use in staged models.ACEI/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 observed in a cohort restricted to individuals with pre-capillary PH. AA use was associated with worse survival in unadjusted Kaplan-Meier survival analyses in the full cohort; however, AA use was less robustly associated with mortality in the propensity-matched cohort and not associated with worse survival after adjustment for disease severity, indicating that that AAs in real-world practice are preferentially used in sicker patients and that the unadjusted association with increased mortality may be an artifice of confounding by indication of severity.ACEI/ARB use is associated with lower mortality in veterans with PH. AA use is a marker of disease severity in PH. ACEIs/ARBs may represent a novel treatment strategy for diverse PH phenotypes.