ACE Inhibitors Linked to Reduced Mortality in Patients with Idiopathic Pulmonary Fibrosis

Angiotensin-converting enzyme (ACE) inhibitors were found to be independently associated with reducing all-cause mortality in patients with idiopathic pulmonary fibrosis (IPF), according to a recent study published in the Chest Journal.¹

ACE inhibitors piqued the interest of researchers looking to repurpose the drug originally used to manage a wide variety of diseases like arterial hypertension and congestive heart failure. These diseases also happen to be common in patients with IPF, in addition to diabetes mellitus and other cardiovascular comorbidities. IPF typically presents in patients above the age of 50 years and predominantly affects male individuals. The median survival time after diagnosis is 3 to 5 years. However, this study’s findings suggest that using ACE inhibitors may improve survival rates and, in turn, increase survival time for patients with IPF.

Researchers used patient-level electronic health records from the Clinical Practice Research Data (CPRD) GP Online Database. Patients included in the final analysis were diagnosed with IPF between January 1, 2002, and January 19, 2019, and were between the ages of 40 and 85 years.

All-cause mortality in patients with IPF was compared with that of patients with chronic obstructive pulmonary disease (COPD), both of whom were treated with ACE inhibitors. Previous studies have identified overlapping comorbidities and shared genetic loci between the 2 diseases.² Therefore, increasing the need to investigate the safety and efficacy of therapies to assess the difference in outcomes may present different outcomes in either disease.^1,2

There was a total of 3579 patients with IPF in the cohort, and they were matched 1:1 with 3579 patients with COPD for comparison. In the IPF cohort, 1328 patients used ACE inhibitors, and 1061 patients were in the COPD cohort. The mean age across both cohorts was 74 years, and 36% of patients were female.¹

In the IPF cohort, there were 1117 (86%) deaths in the ACE inhibitor user group when compared with 1900 (84%) deaths in the nonuser group. In the Cox regression analysis, ACE inhibitors were significantly associated with survival (HR, 0.99; 95% CI, 0.92-1.06; P = .72). However, in the multivariable Cox regression analysis, ACE inhibitors were found to be independently associated with reduced mortality (HR, 0.82; 95% CI, 0.75-0.91; P < .00).

The cause of mortality in patients using ACE inhibitors was either respiratory-related (45%) or cardiovascular-related (18%). When compared with the ACE inhibitor nonusers, 48% were respiratory related and 11% were cardiovascular related. However, in the analysis accounting for all competing causes of death, ACE inhibitors were not significantly associated with a reduction in respiratory-related mortality.

When compared with the COPD cohort, there were 717 (20%) deaths in the ACE inhibitor users group and 1692 (47%) in the nonusers group. Overall, ACE inhibitors had no significant effect on mortality (HR, 1.09; 95% CI, 0.96-1.23; P = .180).

The study’s retrospective observational design limits causal inference, and residual confounding may persist despite propensity score matching. IPF diagnoses were based on electronic health record codes, which could introduce miscoding, though survival rates suggest minimal impact.

“These findings highlight the value of investigating well-established medications for new therapeutic roles in progressive diseases such as IPF, in which current treatment options are limited,” the study authors concluded. “We encourage the design and execution of prospective trials to validate these findings and explore ACE inhibitors as a therapeutic option in IPF.”

References

1. Ozaltin B, Chapman R, Follet T, et al. Mortality outcomes and angiotensin converting enzyme inhibitor use in patients with idiopathic pulmonary fibrosis. Chest. 2026;169(1):139-147. doi:10.1016/j.chest.2025.07.4077

2. Kalra S, Julienne H, Tern C, Aschard H, Cho MH. Genetic Overlap of idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). Am J Respir Crit Care Med. 2025;211:A2508. doi:10.1164/ajrccm.2025.211.Abstracts.A2508