Mortality Outcomes and Angiotensin-Converting Enzyme Inhibitor Use in Patients With Idiopathic Pulmonary Fibrosis

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BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors are widely used antihypertensive agents with proven cardioprotective effects. Previous mechanistic and clinical studies have suggested that ACE inhibitor therapy may slow disease progression and reduce mortality in idiopathic pulmonary fibrosis (IPF). RESEARCH QUESTION: Does ACE inhibitor use associate with reduced all-cause mortality in a real-world population of patients with IPF, and if so, is the association also present in patients with COPD? STUDY DESIGN AND METHODS: A retrospective analysis was conducted by using electronic health records from the Clinical Practice Research Datalink GP Online Database (2019), linked with Hospital Episode Statistics Admitted Patient Care and Office for National Statistics death registration data. Patients with IPF and COPD were stratified based on ACE inhibitor use (defined as ≥ 3 prescriptions within the 5 years preceding diagnosis) and matched by age, sex, and smoking history using propensity score matching. Multivariable Cox regression analyses were performed, adjusting for age, sex, BMI, smoking status, indices of multiple deprivation, diabetes mellitus, chronic kidney disease, and common cardiovascular comorbidities. In the IPF cohort, competing risk analysis was used to account for cause-specific mortality. RESULTS: The study included 3,579 patients with IPF and matched COPD control participants (mean age, 74 years; 36% female). Among the IPF cohort, 1,328 (37%) were ACE inhibitor users, compared with 1,061 (30%) among patients with COPD. ACE inhibitor use was associated with improved survival, independent of coexisting comorbidities, in patients with IPF (hazard ratio, 0.82; 95% CI, 0.75-0.91; P ≤ .001), but a similar association was not found in patients with COPD (hazard ratio, 1.09; 95% CI, 0.96-1.23; P = .180). INTERPRETATION: In this study, ACE inhibitor therapy was independently associated with reduced all-cause mortality in IPF but not in COPD. Prospective trials are warranted to confirm these findings in IPF populations.

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