ACE Inhibitors Linked to Reduced Mortality in Idiopathic Pulmonary Fibrosis

Why It Matters

If confirmed, repurposing inexpensive, well‑tolerated ACE inhibitors could improve survival in a disease with limited therapeutic options and high mortality.

Key Takeaways

• ACE inhibitors linked to 18% lower IPF mortality
• Study analyzed 3,579 UK IPF patients
• No mortality benefit seen in COPD control group
• Findings suggest disease‑specific antifibrotic effect
• Randomized trials required to confirm causality

Pulse Analysis

Idiopathic pulmonary fibrosis remains one of the deadliest interstitial lung diseases, with median survival of three to five years despite the availability of antifibrotic agents such as nintedanib and pirfenidone. The therapeutic landscape is constrained by modest effects on long‑term mortality, prompting clinicians and researchers to look for existing drugs that could modify disease progression. ACE inhibitors, long‑standing treatments for hypertension and heart failure, have emerged as candidates because the renin‑angiotensin system is implicated in fibrotic signaling pathways. Such repurposing strategies also reduce development timelines compared with novel drug discovery.

In a recent analysis published in Chest, researchers leveraged the UK Clinical Practice Research Datalink to follow 3,579 patients diagnosed with IPF between 2002 and 2019. After propensity matching with an equal COPD cohort and adjusting for age, sex, smoking, comorbidities and socioeconomic status, ACE‑inhibitor use was associated with a hazard ratio of 0.82, translating into an 18 % relative reduction in all‑cause mortality. Importantly, the same association was absent in the COPD control group, reinforcing the hypothesis that the survival benefit is disease‑specific rather than a generic cardiovascular effect. Sensitivity analyses upheld the association, suggesting robustness against residual confounding.

If subsequent randomized trials confirm causality, ACE inhibitors could become a low‑cost, widely accessible adjunct to existing antifibrotics, potentially extending survival without adding significant adverse effects. Their established safety profile would simplify regulatory pathways and allow rapid integration into clinical practice, especially for patients already receiving cardiovascular therapy. Moreover, the findings revive interest in targeting the renin‑angiotensin axis for fibrotic lung disease, opening avenues for novel combination regimens and biomarker‑driven patient selection. Health‑economic models would likely show favorable cost‑effectiveness given the drugs' generic status.

ACE inhibitors linked to reduced mortality in idiopathic pulmonary fibrosis

By Keith Loria · February 11, 2026

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 represents 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 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 (COPD) to determine whether any observed survival effect was specific to IPF rather than attributable to a general cardiovascular benefit.

• The mean age of participants was 74 years, and approximately 36 % were female.

• Among patients with IPF, 37 % 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 non‑users.

Notably, no similar survival association was observed in the matched COPD 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 non‑user groups, 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,” the authors wrote, adding 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.

The absence of a similar survival signal in the COPD 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 remains short of definitive proof.