TY - JOUR
T1 - Renin-Angiotensin-Aldosterone System Inhibitor Use and Mortality in Pulmonary Hypertension
T2 - Insights From the Veterans Affairs Clinical Assessment Reporting and Tracking Database
AU - Lahm, Tim
AU - Hess, Edward
AU - Barón, Anna E.
AU - Maddox, Thomas M.
AU - Plomondon, Mary E.
AU - Choudhary, Gaurav
AU - Maron, Bradley A.
AU - Zamanian, Roham T.
AU - Leary, Peter J.
N1 - Funding Information:
FUNDING/SUPPORT: T. L. is supported by the Department of Veterans Affairs [Merit Review Award 1I01BX002042] and the National Institutes of Health [Grants 1R56HL134736-01A1 and 1R01HL144727-01A1 ]. T. M. M. is supported by the National Institutes of Health National Center for Advancing Translational Sciences [Grant 1U24TR002306-01 ]. G. C. is supported by the Department of Veterans Affairs [Merit Review Award I01CX001892] and the National Institutes of Health [Grants R01HL128661 and R01HL148727 ]. B. A. M. is supported by the National Institutes of Health [Grants HL139613-01, HL1535-02, and HL145420], the Cardiovascular Medical Research Education Foundation, the McKenzie Family Charitable Trust, and the Boston Biomedical Innovations Center. P. J. L. is supported by the National Institutes of Health [Grants R33HL142539 and R01HL152724].
Funding Information:
Financial/nonfinancial disclosures: The authors have reported to CHEST the following: T. L. has received consultancy fees from Bayer and research reagents from Eli Lilly & Company and is the site primary investigator for a clinical trial funded by Complexa, Inc. T. M. M. has received consultancy fees from Creative Educational Concepts, Inc., and Atheneum Partners; is advising Myia Labs, for which his employer is receiving equity compensation in the company, but is receiving no individual compensation from the company; and is a compensated director for a New Mexico-based foundation, the J. F. Maddox Foundation. G. C. has received an investigator-initiated grant from Novartis. B. A. M. has served as a consultant for Actelion; and is coinventor of patents or patent applications that are related to pulmonary hypertension (U.S. Patent #9,605,047; PCT/US2015/ 029672; Provisional ID: #62475955; Provisional ID: #24624; Provisional ID: #24622). R. T. Z. has received consultancy fees from Morphogen-IX, Vivus, and Actelion; his institution has received research grants from Action, United Therapeutics, and Tenax. P. J. L. has received consultancy fees from Bayer and has been the site principle investigator for trials and registries funded by United Therapeutics, Actelion, and Bayer. None declared (E. H., A. E. B., M. E. P.).
Publisher Copyright:
© 2020
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
KW - aldosterone
KW - angiotensin converting enzyme
KW - epidemiology
KW - pharmacology
KW - pulmonary hypertension
UR - http://www.scopus.com/inward/record.url?scp=85102284332&partnerID=8YFLogxK
U2 - 10.1016/j.chest.2020.09.258
DO - 10.1016/j.chest.2020.09.258
M3 - Article
C2 - 33031831
AN - SCOPUS:85102284332
VL - 159
SP - 1586
EP - 1597
JO - Chest
JF - Chest
SN - 0012-3692
IS - 4
ER -