Chest. 2020 Oct 5:S0012-3692(20)34851-0. doi: 10.1016/j.chest.2020.09.258. Online ahead of print.
BACKGROUND: 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.
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 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.
RESULTS: 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.
INTERPRETATION: 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.