Effect of Warfarin Treatment on Survival of Patients with Pulmonary Arterial Hypertension (PAH) in the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL)
Background—Long-term anticoagulation is recommended in idiopathic PAH (IPAH). In contrast, limited data support anticoagulation in PAH associated with systemic sclerosis (SSc-PAH). We assessed the effect of warfarin anticoagulation on survival in IPAH and SSc-PAH patients enrolled in REVEAL, a longitudinal registry of Group I PAH.
Methods and Results—Patients who initiated warfarin on study (n = 187) were matched 1:1 with patients never on warfarin, by enrollment site, etiology, and diagnosis status. Descriptive analyses were conducted to compare warfarin users and nonusers by etiology. Survival analyses with and without risk adjustment were performed from time of warfarin initiation or a corresponding quarterly update in matched pairs to avoid immortal time bias. Time-varying covariate models were used as sensitivity analyses. Mean warfarin treatment was 1 year; mean international normalized ratios were 1.9 (IPAH) and 2.0 (SSc-PAH). Two-thirds of patients initiating warfarin discontinued treatment prior to last study assessment. There was no survival difference with warfarin in IPAH patients (adjusted HR, 1.37; P = 0.21) or in SSc-PAH patients (adjusted HR, 1.60; P = 0.15) compared with matched controls. However, SSc-PAH patients receiving warfarin within the previous year (HR, 1.57; P = 0.031) or any time postbaseline (HR, 1.49; P = 0.046) had increased mortality compared with warfarin-naïve patients.
Conclusions—No significant survival advantage was observed in IPAH patients who started warfarin. In SSc-PAH patients, long-term warfarin was associated with poorer survival than in patients not receiving warfarin, even after adjusting for confounders.
- Received August 6, 2015.
- Accepted September 25, 2015.
Circulation is published on behalf of the American Heart Association, Inc., by Wolters Kluwer. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.