C103-22 Association of Angiotensin-Converting Enzyme Inhibitor (ACEI) and Angiotensin Receptor Blocker (ARB) Use With Mortality and Health Care Utilization in Idiopathic Pulmonary Fibrosis: A Large-Scale, Propensity-Matched Cohort Study

Abstract Rationale The Renin-Angiotensin-Aldosterone System (RAAS) is known to influence inflammation, cell proliferation, and fibrosis within lung tissue. Angiotensin II promotes fibrotic pathways, often via transforming growth factor-beta (TGF-β), while other RAAS components are protective. Preclinical models show that modulating the RAAS with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) may alter the progression of lung fibrosis. Hence, RAAS inhibition could represent a viable therapeutic strategy for idiopathic pulmonary fibrosis (IPF); however, this lacks validation from human studies. Methods We conducted a retrospective, propensity score-matched cohort study using the TriNetX database, a global research network providing de-identified electronic medical records from over 100 participating institutions. Adults with a diagnosis of IPF between January 1, 2015, and January 1, 2024, were included. Exposure to ACEI/ARB was defined as prescription within 3 months before or up to 1 year after IPF diagnosis; non-users had no ACEI/ARB exposure during this period. Outcomes included emergency department (ED) visits, inpatient and intensive care unit (ICU) admissions, influenza and pneumonia, acute respiratory distress syndrome (ARDS), mechanical ventilation and all-cause mortality, reported over a median follow-up of 365 days from enrollment. Patients were matched for age, sex, race/ethnicity, smoking status, and underlying comorbidities. Cox proportional hazards models were used to assess the association between the use of ACEIs and ARBs and IPF outcomes with hazard ratios (HRs) and 95% confidence intervals (CIs). Results A total of 12,625 IPF patients receiving ACEIs or ARBs were compared to 28,420 non-users. After matching, 10,852 pairs of patients were analyzed. ACEI or ARB use was associated with significantly lower all-cause mortality than non-users (HR 0.870, 95% CI 0.818 - 0.926, p 0.001) Table 1. However, patients in the ACEI/ARB cohort had significantly higher risks of ED visits (HR 1.120, 95% CI 1.054 - 1.19, p 0.001), inpatient admissions (HR 1.272, 95% CI 1.211 - 1.337 p 0.001), ICU admissions (HR 1.091, 95% CI 1.008 - 1.182, p = 0.030), and mechanical ventilation (HR 1.199, 95% CI 1.005 - 1.429, p = 0.043) compared with matched nonusers. Risks of influenza and pneumonia, as well as ARDS, did not significantly differ. Conclusions The use of ACEI/ARB was associated with a significant reduction in all-cause mortality in patients with IPF, supporting their therapeutic potential. However, this survival benefit is coupled with an increase in ED visits and inpatient and ICU admissions. Future research is needed to clarify the risks and benefits of RAAS inhibition in patients with IPF. This abstract is funded by: None