Studies have suggested a procoagulant state may be involved in promoting fibrosis via cell-surface receptor–mediated pathways providing biological plausibility for a mechanistic link between thrombosis and lung fibrosis. It is less clear what role systemic anticoagulants may have in preventing this effect in patients with idiopathic pulmonary fibrosis ( IPF ).
The 2011guideline included one study, an open randomized trial that compared oral Warfarin plus Prednisolone against Prednisolone alone in 56 patients with IPF. Treatment with Warfarin led to a reduction in the secondary outcome of idiopathic pulmonary fibrosis acute exacerbation-associated mortality.
This trial was associated with significant methodological concerns, specifically the lack of a clear description of how randomization or concealment of allocation was undertaken, the lack of a description of how patient drop-out was managed, and a failure to exclude pulmonary embolus as a potential cause for clinical deterioration.
For these reasons, in addition to the absence of a placebo control, it was considered to have a high risk of bias and was excluded from pooled analysis in this treatment update.
One randomized controlled trial ( RCT ) published since the 2011 guideline randomized 145 patients with idiopathic pulmonary fibrosis to oral Warfarin ( target international normalized ratio, INR, 2.0–3.0 ) versus placebo control. This study was stopped early after a mean follow-up of 28 weeks because of a lack of benefit from warfarin and a signal for potential harm with treatment.
Despite a relatively low number of events, a significant increase in mortality was seen with Warfarin at interim analysis ( relative risk [ RR ], 4.73; 95% confidence interval [CI], 1.42–15.77; low confidence ), although this was not associated with bleeding complications. No significant difference was seen between groups in terms of FVC change ( low confidence ) or percentage of patients with a greater than 10% decrease in FVC during the study period ( low confidence ). There was also a trend toward more serious adverse events in patients receiving Warfarin ( RR, 1.77; 95% CI, 0.94–3.33; low confidence ).
The guideline recommend that clinicians not use Warfarin anticoagulation in patients with idiopathic pulmonary fibrosis who do not have a known alternative indication for its use ( strong recommendation against, low confidence in estimates of effect ).
This recommendation places a high value on potential adverse outcomes such as death. The Committee members felt that the increased risk for mortality required a strong recommendation against using oral Warfarin as a treatment for idiopathic pulmonary fibrosis in patients with IPF.
However, this recommendation applies only to oral Warfarin with a target international normalized ratio of 2.0–3.0 and does not include the use of other anticoagulants for other indications.
Patients who have an alternate and/or known indication for anticoagulation, such as venous thromboembolic disease or atrial fibrillation, should follow treatment guidelines for these conditions independent of their underlying idiopathic pulmonary fibrosis. Given that there were no net benefits of oral Warfarin cost was considered irrelevant. ( Xagena )
Source: American Thoracic Society, 2015