ACE inhibitors linked to reduced mortality in idiopathic pulmonary fibrosis

Median survival following diagnosis of idiopathic pulmonary fibrosis (IPF) is typically three to five years, despite the availability of antifibrotic agents, such as Ofev (nintedanib) and Esbriet (pirfenidone), that slow disease progression but have limited impact on long-term mortality.

Given the high mortality burden and limited therapeutic arsenal, identifying existing medications with potential disease-modifying effects remains a priority in IPF research.

A new study suggests that angiotensin-converting enzyme (ACE) inhibitor therapy is independently associated with reduced all-cause mortality in patients with IPF. The findings, although far from the final word,raise the possibility that these commonly prescribed cardiovascular drugs could offer a survival benefit in a disease with limited treatment options.

Published in the January 2026 issue of Chest, the study represent one of the largest analyses to date examining mortality outcomes in patients with IPF who were treated with ACE inhibitors, a class of drugs that includes lisinopril, enalapril and benazepril.

Lead author Burcu Ozaltin, Ph.D., a former research fellow at the Centre for Medical Imaging Computing at the University College London, and her colleagues from collaborating institutions in Europe, utilized electronic health record data from the United Kingdom’s Clinical Practice Research Datalink, linked with hospital and national mortality data, to evaluate long-term outcomes in patients diagnosed with IPF.

Researchers identified 3,579 adults with IPF diagnosed between 2002 and 2019 and matched them with an equal number of patients with chronic obstructive pulmonary disease to determine whether any observed survival effect was specific to IPF rather than attributable to general cardiovascular benefit.

The mean age of participants was 74 years, and approximately 36% were female. Among patients with IPF, 37% of participants had received ACE inhibitors at least three times in the five years prior to diagnosis.

After adjusting for potential confounders, including age, sex, smoking status, body mass index, socioeconomic status, diabetes, chronic kidney disease and cardiovascular comorbidities, ACE inhibitor use was independently associated with a statistically significant reduction in all-cause mortality among patients with IPF. The hazard ratio was 0.82, indicating an 18% relative reduction in mortality risk compared with nonusers.

Notably, no similar survival association was observed in the matched chronic obstructive pulmonary disease cohort, suggesting the mortality benefit may be specific to IPF rather than reflecting a broader cardiovascular effect.

Although crude mortality rates were high in both user and nonuser groups, the study revealed that multivariable modeling demonstrated a robust survival signal favoring ACE inhibitor therapy after accounting for baseline differences. Sensitivity analyses further supported the association.

Ozaltin and her colleagues noted that while the observational design cannot establish causality, the findings are biologically plausible. IPF is characterized by progressive fibrosis and inflammation, and activation of the renin-angiotensin system has been implicated in fibrotic pathways. ACE inhibitors may exert antifibrotic or anti-inflammatory effects that extend beyond blood pressure control.

“ACE inhibitor therapy demonstrated a survival advantage in patients with IPF that was independent of co-existing comorbid conditions,” they wrote in the paper, noting that prospective clinical trials will be required to determine whether the relationship is causal.

Prior studies examining the impact of ACE inhibitors and related medications in IPF have produced mixed results, often limited by small sample sizes or inconsistent methodology. Ozaltin’s research, thanks to its large cohort and use of propensity matching and multivariable adjustment, provides more robust real-world evidence supporting a potential survival benefit.

However, the investigators cautioned that residual confounding cannot be ruled out. Patients receiving ACE inhibitors may differ in unmeasured ways from non-users, and the study was not designed to assess dose-response relationships or duration of therapy in detail

Still, the absence of a similar survival signal in the chronic obstructive pulmonary disease comparison group strengthens the argument that the association may reflect disease-specific mechanisms in IPF.

The authors concluded that randomized controlled trials are needed to confirm whether ACE inhibitors can be repurposed as a therapeutic strategy in IPF. If validated, the findings could have meaningful implications, given the drugs’ widespread availability, established safety profile and low cost.

For clinicians managing patients with IPF, the results add to the growing body of literature suggesting that ACE inhibitors may offer benefits beyond traditional cardiac indications, but the evidence is short of definitive proof.