IN idiopathic pulmonary fibrosis, ACE inhibitor use was associated with lower all-cause mortality in propensity matched EHR cohorts.
ACE Inhibitor Use and IPF Mortality
Angiotensin-converting enzyme (ACE) inhibitors are widely prescribed antihypertensives with established cardioprotective effects. Prior mechanistic and clinical work has raised the possibility that ACE inhibitor therapy could also influence fibrotic pathways, potentially slowing disease progression in idiopathic pulmonary fibrosis (IPF). In a new real-world analysis, ACE inhibitor use was independently associated with improved survival among patients with IPF.
Researchers evaluated whether ACE inhibitor use was linked to reduced all-cause mortality in IPF and whether any association was also present in chronic obstructive pulmonary disease (COPD), which served as a comparator cohort.
How the Study Was Designed
This retrospective study used linked electronic health records and outcomes data, including primary care records, hospital admission data, and death registration data. Patients with IPF were stratified by ACE inhibitor use, defined as at least three prescriptions within the five years before diagnosis. The investigators then used propensity score matching to align groups on age, sex, and smoking history, aiming to reduce baseline differences between users and non-users.
Multivariable Cox regression models adjusted for potential confounders including age, sex, BMI, smoking status, indices of multiple deprivation, diabetes mellitus, chronic kidney disease, and common cardiovascular comorbidities. In the IPF cohort, competing risk analyses were also applied to account for cause-specific mortality.
Survival Signal Seen in IPF, Not COPD
The analysis included 3,579 patients with IPF and matched COPD control participants (mean age 74 years; 36% female). ACE inhibitor use was more common in IPF than in COPD. In IPF, ACE inhibitor use was associated with lower all-cause mortality (hazard ratio 0.82; 95% CI 0.75–0.91; P≤.001). In COPD, no comparable association was observed (hazard ratio 1.09; 95% CI 0.96–1.23; P=.180).
While these findings support drug repurposing interest in IPF, the observational design cannot confirm causality. The authors noted that prospective trials are warranted to test whether ACE inhibitor therapy can directly improve outcomes in IPF.
Reference: Ozaltin B et al. Mortality Outcomes and Angiotensin-Converting Enzyme Inhibitor Use in Patients With Idiopathic Pulmonary Fibrosis. Chest. 2026;169(1):139-147.
