title: Major bleeding with vitamin K antagonist anticoagulants in pulmonary hypertension.
abstract: Vitamin K antagonists are advised in pulmonary arterial hypertension patients despite a lack of safety data. We reviewed major bleeding in three classes of pulmonary hypertension patients, all receiving vitamin K antagonists. Bleeding event rates were 5.4 per 100 patient-years for patients with idiopathic pulmonary arterial hypertension, 19 per 100 patient-years for connective tissue disease related pulmonary arterial hypertension patients and 2.4 per 100 patient-years for chronic thromboembolic pulmonary hypertension patients. Life tables analysis showed that event-free survival was worse in patients with connective tissue disease related pulmonary hypertension than in patients with idiopathic pulmonary arterial hypertension (Wilcoxon=12.8; p<0.001), and patients with chronic thromboembolic pulmonary hypertension (Wilcoxon=23.2; p<0.001). Patients with idiopathic pulmonary arterial hypertension suffered more events than patients with chronic thromboembolic pulmonary hypertension (Wilcoxon=7.2; p<0.01). Major bleeding was independent of age, sex, target international normalised ratio (INR) range, documented INR, vitamin K antagonist type, or right atrial pressure, but was associated with use of prostacyclin analogues. Major bleeding risk during vitamin K antagonist therapy differs among groups of patients with pulmonary hypertension. Further research regarding optimal anticoagulant therapy is needed, as well as risk-benefit analyses for pulmonary hypertension patients with a higher bleeding propensity.
authors.affiliation: Dept of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Ivo R
authors.initials: IR
authors.lastname: Henkens
authors.forename: Thomas
authors.initials: T
authors.lastname: Hazenoot
authors.forename: Anco
authors.initials: A
authors.lastname: Boonstra
authors.forename: Menno V
authors.initials: MV
authors.lastname: Huisman
authors.forename: Anton
authors.initials: A
authors.lastname: Vonk-Noordegraaf
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects*; D018572:Disease-Free Survival; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000188:drug therapy*; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D012189:Retrospective Studies; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D005343:Fibrinolytic Agents; D014812:Vitamin K