Citation: Michael Kreuter,David J. Lederer,Maria Molina-Molina,Imre Noth,Claudia Valenzuela,Lutz Frankenstein,Derek Weycker,Mark Atwood,Klaus-Uwe Kirchgaessler,Vincent Cottin, (2019). Association of Angiotensin Modulators With the Course of Idiopathic Pulmonary Fibrosis. CHEST, Volume 156, Issue 4, October 2019, Pages 706-714. https://www.sciencedirect.com/science/article/pii/S0012369219308827

Background

Angiotensin peptides have been implicated in idiopathic pulmonary fibrosis (IPF) pathogenesis. Angiotensin modulators are used to treat arterial hypertension, a frequent comorbidity of IPF. This post hoc analysis evaluated associations of antihypertensive treatments with disease-related outcomes in IPF.

Methods

All patients randomized to placebo (n = 624) in the CAPACITY and ASCEND studies were categorized by antihypertensive treatment at baseline. Outcomes of disease progression (first occurrence of ≥ 10% absolute decline in % predicted FVC, ≥ 50-m decline in 6-min walk distance, or death) and all-cause mortality were assessed over 52 weeks.

Results

At baseline, 111 and 121 patients were receiving an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin II receptor blocker (ARB), respectively; 392 were receiving neither. In multivariable analyses adjusted for differences in baseline characteristics compared with the non-ACEi/ARB group, ACEi treatment (hazard ratio [HR], 0.6 [95% CI, 0.4-0.9]; P = .026), but not ARB (HR, 0.9 [95% CI, 0.6-1.2]; P = .413), was associated with slower disease progression. Furthermore, the increase in all-cause mortality associated with cardiovascular disease was not observed in the ACEi group (HR, 1.1 [95% CI, 0.5-2.9]; P = .782), which presented a similar percentage of IPF-related mortality as the non-ACEi/ARB group (3.6% vs 3.6%). In contrast, patients in the ARB group had greater risk of all-cause mortality (HR, 2.5 [95% CI, 1.2-5.2]). These observations were validated in a pooled analysis that included patients from the INSPIRE trial.

Conclusions

Prospective clinical trials are needed to evaluate whether angiotensin modulators may be beneficial to clinical outcomes in IPF.

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