Unfavourable effects of medically indicated oral anticoagulants on survival in idiopathic pulmonary fibrosis.
Procoagulant and antifibrinolytic activity has been associated with idiopathic pulmonary fibrosis (IPF); however, investigation of anticoagulant therapy in IPF has suggested deleterious effects. This post hoc analysis evaluated the effect of medically indicated anticoagulation on mortality and other clinical outcomes in IPF.Patients randomised to placebo (n=624) from three controlled trials in IPF were analysed by oral anticoagulant use. End-points included all-cause and IPF-related mortality, disease progression, hospitalisation, and adverse events, over 1 year.At baseline, 32 (5.1%) patients randomised to placebo were prescribed anticoagulants for non-IPF indications, 29 (90.6%) of whom received warfarin. Unadjusted analyses demonstrated significantly higher all-cause and IPF-related mortality at 1 year in baseline anticoagulant users versus nonusers (15.6% versus 6.3%, p=0.039 and 15.6% versus 3.9%, p=0.002, respectively). In multivariate analyses, baseline use of anticoagulants was an independent predictor of IPF-related mortality (hazard ratio 4.7, p=0.034), but not other end-points. Rates of bleeding and cardiac events did not differ significantly between groups. In an exploratory analysis, anticoagulant use at any time during the study was an independent predictor of all end-points.This post hoc analysis suggests that anticoagulants used for non-IPF indications may have unfavourable effects in IPF patients. Future studies are needed to explore this relationship further.
Center for Interstitial and Rare Lung Diseases, Pneumology and Respiratory Critical Care Medicine, Thoraxklinik, University of Heidelberg, and Translational Lung Research Center Heidelberg (TLRCH), Heidelberg, Germany; Member of the German Center for Lung Research (DZL), Germany kreuter@uni-heidelberg.de.
Michael
M
Kreuter
Dept of Pulmonary Medicine, Erasmus Medical Center, University Hospital Rotterdam, Rotterdam, The Netherlands.
Marlies S
MS
Wijsenbeek
Dept of Respiratory Medicine, Thomayer Hospital, Prague, Czech Republic.
Martina
M
Vasakova
Medical University Clinic, Canton Hospital Baselland and University of Basel, Liestal, Switzerland.
Paolo
P
Spagnolo
Firestone Institute for Respiratory Health, Dept of Medicine, Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
Martin
M
Kolb
Interstitial and Rare Lung Disease Unit, Ruhrlandklinik, University Hospital, University of Duisburg-Essen, Essen, Germany.
Ulrich
U
Costabel
Policy Analysis Inc. (PAI), Brookline, MA, USA.
Derek
D
Weycker
F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Klaus-Uwe
KU
Kirchgaessler
National Institute for Health Research Biomedical Research Unit, Royal Brompton Hospital and Fibrosis Research Group, National Heart and Lung Institute, Imperial College, London, UK.
Toby M
TM
Maher
D000284:Administration, Oral; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D001777:Blood Coagulation; D018450:Disease Progression; D005260:Female; D006470:Hemorrhage; D006760:Hospitalization; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009026:Mortality; D016016:Proportional Hazards Models; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014859:Warfarin / Q000009:adverse effects* / Q000627:therapeutic use
D000925:Anticoagulants; D014859:Warfarin