Unfavourable effects of medically indicated oral anticoagulants on survival in idiopathic pulmonary fibrosis: methodological concerns

We read the correspondence of L. Kawano-Dourado and colleagues related to our article “Unfavourable effects of medically indicated oral anticoagulants on survival in idiopathic pulmonary fibrosis” with great interest [1]. There is compelling evidence of an association between disturbances in the coagulation system and idiopathic pulmonary fibrosis (IPF); however, results from the ACE-IPF (anticoagulant effectiveness in idiopathic pulmonary fibrosis) randomised controlled trial of the vitamin K antagonist warfarin demonstrated deleterious effects of anticoagulation in IPF [2]. Based on these data, the recent update of the international guideline on IPF gave a strong recommendation against the use of anticoagulants [3]. Yet, the potential risks of medically indicated anticoagulation on mortality and other clinical outcomes in IPF remain unexplored. This is an important clinical question as almost one in every five patients with IPF receives anticoagulants for different indications [4]. In this regard, our post hoc analysis, which describes that patients in the placebo groups treated with anticoagulants in the CAPACITY and ASCEND trials had a higher rate of all-cause and IPF-related mortality compared with non-users, adds further insights in to the potential hazard of anticoagulant use in IPF [1]. We agree with Kawano-Dourado and colleagues that these data should be interpreted in light of the inherent limitations of a post hoc analysis based on a small number of events. However, these data represent, to our knowledge, the largest cohort of IPF subjects in whom this question has been addressed. Furthermore, our data are in line with two retrospective studies in IPF populations that also report a significantly higher risk of mortality in association with the use of anticoagulants for medical indications [5, 6] and this important clinical problem has recently also been highlighted by others [7]. Comorbidities requiring anticoagulants may not explain unfavourable effects of these drugs on survival in IPF http://ow.ly/tmgm302VEXz