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 pulmonary arterial hypertension (IPAH). In contrast, limited data support anticoagulation in pulmonary arterial hypertension (PAH) associated with systemic sclerosis (SSc-PAH). We assessed the effect of warfarin anticoagulation on survival in IPAH and SSc-PAH patients enrolled in Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL), a longitudinal registry of group I PAH.


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 the 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 before the last study assessment. There was no survival difference with warfarin in IPAH patients (adjusted hazard ratio, 1.37; P=0.21) or in SSc-PAH patients (adjusted hazard ratio, 1.60; P=0.15) in comparison with matched controls. However, SSc-PAH patients receiving warfarin within the previous year (hazard ratio, 1.57; P=0.031) or any time postbaseline (hazard ratio, 1.49; P=0.046) had increased mortality in comparison 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.


BACKGROUND
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00370214.
From Tufts University School of Medicine, Boston, MA (I.R.P., K.E.R., N.S.H.); ICON Clinical Research, San Francisco, CA (D.P.M., G.P.S.); Actelion Pharmaceuticals US Inc., South San Francisco, CA (M.S., W.W.B.); and Boston University School of Medicine, Boston, MA (H.W.F.).
Ioana R
IR
Preston
From Tufts University School of Medicine, Boston, MA (I.R.P., K.E.R., N.S.H.); ICON Clinical Research, San Francisco, CA (D.P.M., G.P.S.); Actelion Pharmaceuticals US Inc., South San Francisco, CA (M.S., W.W.B.); and Boston University School of Medicine, Boston, MA (H.W.F.).
Kari E
KE
Roberts
From Tufts University School of Medicine, Boston, MA (I.R.P., K.E.R., N.S.H.); ICON Clinical Research, San Francisco, CA (D.P.M., G.P.S.); Actelion Pharmaceuticals US Inc., South San Francisco, CA (M.S., W.W.B.); and Boston University School of Medicine, Boston, MA (H.W.F.).
Dave P
DP
Miller
From Tufts University School of Medicine, Boston, MA (I.R.P., K.E.R., N.S.H.); ICON Clinical Research, San Francisco, CA (D.P.M., G.P.S.); Actelion Pharmaceuticals US Inc., South San Francisco, CA (M.S., W.W.B.); and Boston University School of Medicine, Boston, MA (H.W.F.).
Ginny P
GP
Sen
From Tufts University School of Medicine, Boston, MA (I.R.P., K.E.R., N.S.H.); ICON Clinical Research, San Francisco, CA (D.P.M., G.P.S.); Actelion Pharmaceuticals US Inc., South San Francisco, CA (M.S., W.W.B.); and Boston University School of Medicine, Boston, MA (H.W.F.).
Mona
M
Selej
From Tufts University School of Medicine, Boston, MA (I.R.P., K.E.R., N.S.H.); ICON Clinical Research, San Francisco, CA (D.P.M., G.P.S.); Actelion Pharmaceuticals US Inc., South San Francisco, CA (M.S., W.W.B.); and Boston University School of Medicine, Boston, MA (H.W.F.).
Wade W
WW
Benton
From Tufts University School of Medicine, Boston, MA (I.R.P., K.E.R., N.S.H.); ICON Clinical Research, San Francisco, CA (D.P.M., G.P.S.); Actelion Pharmaceuticals US Inc., South San Francisco, CA (M.S., W.W.B.); and Boston University School of Medicine, Boston, MA (H.W.F.).
Nicholas S
NS
Hill
From Tufts University School of Medicine, Boston, MA (I.R.P., K.E.R., N.S.H.); ICON Clinical Research, San Francisco, CA (D.P.M., G.P.S.); Actelion Pharmaceuticals US Inc., South San Francisco, CA (M.S., W.W.B.); and Boston University School of Medicine, Boston, MA (H.W.F.). hfarber@bu.edu.
Harrison W
HW
Farber
D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D019468:Disease Management; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D012042:Registries; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D016896:Treatment Outcome; D014859:Warfarin / Q000627:therapeutic use*
D000925:Anticoagulants; D014859:Warfarin
anticoagulants; hypertension; pulmonary; survival; therapy