Michael Kreuter1, David J Lederer2, Maria Molina-Molina3, Imre Noth4, Claudia Valenzuela5, Lutz Frankenstein6, Derek Weycker7, Mark Atwood7, Klaus-Uwe Kirchgaessler8, Vincent Cottin9. 1. Center for Interstitial and Rare Lung Disease, Thoraxklinik, University of Heidelberg, Heidelberg, Germany. Electronic address: michael.kreuter@med.uni-heidelberg.de. 2. Columbia University Medical Center, New York, NY. 3. University Hospital of Bellvitge, Institut d'Investigació Biomédica de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain. 4. Division of Pulmonary and Critical Care, Department of Medicine, University of Virginia, Charlottesville, VA. 5. Pulmonology Department, Hospital Universitario de la Princesa, Madrid, Spain. 6. Department of Cardiology, Angiology, and Pulmonology, University of Heidelberg, Heidelberg, Germany. 7. Policy Analysis Inc. (PAI), Brookline, MA. 8. F. Hoffmann-La Roche Ltd., Basel, Switzerland. 9. Department of Respiratory Medicine, Reference Center for Rare Pulmonary Diseases, Louis Pradel Hospital, Claude Bernard University Lyon 1, UMR754, Lyon, France.
Abstract
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 anangiotensin-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. TRIAL REGISTRY: ClinicalTrials.gov; Nos.: NCT01366209, NCT00287716, NCT00287729, NCT00075998; URL: www.clinicaltrials.gov).
RCT Entities:
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. TRIAL REGISTRY: ClinicalTrials.gov; Nos.: NCT01366209, NCT00287716, NCT00287729, NCT00075998; URL: www.clinicaltrials.gov).
Authors: Whitney D Gannon; Michaela R Anderson; Anna J Podolanczuk; Steven M Kawut; Erin D Michos; Vincent Cottin; Michael Kreuter; Ganesh Raghu; R Graham Barr; David J Lederer Journal: Ann Am Thorac Soc Date: 2019-11
Authors: Michael Kreuter; David J Lederer; Vincent Cottin; Nicolas Kahn; Brett Ley; Carlo Vancheri; Derek Weycker; Mark Atwood; Klaus-Uwe Kirchgaessler; Christopher J Ryerson Journal: Eur Respir J Date: 2019-12-12 Impact factor: 16.671
Authors: S M Hasan Mahmud; Md Al-Mustanjid; Farzana Akter; Md Shazzadur Rahman; Kawsar Ahmed; Md Habibur Rahman; Wenyu Chen; Mohammad Ali Moni Journal: Brief Bioinform Date: 2021-09-02 Impact factor: 11.622