title: Risk of recurrent venous thromboembolism or bleeding in relation to thrombophilic risk factors in patients receiving ximelagatran or placebo for long-term secondary prevention of venous thromboembolism.
abstract: The impact of prothrombotic abnormalities on the risk of recurrent venous thromboembolism (VTE) and bleeding in patients receiving long-term anticoagulation remains unclear. This analysis evaluated the influence of potential prothrombotic risk factors (antithrombin, protein C, protein S, factor V Leiden mutation, prothrombin gene G20210A mutation, cardiolipin antibodies, number of risk factors) on the risk of recurrent VTE or bleeding during treatment with oral ximelagatran (24 mg twice daily) or placebo for 18 months [THRombin Inhibitor in Venous thromboEmbolism (THRIVE) III trial]. Of the 1223 patients in the intention-to-treat population, prothrombotic state was analysed in 559 patients receiving ximelagatran and 540 patients receiving placebo. It is possible that patients at a high risk of recurrent VTE were poorly represented in this analysis because of selection bias. Prothrombotic risk factors were reported in 41% of patients (8% had > or = 2 factors). No significant interactions were found between ximelagatran treatment and potential prothrombotic risk factors for the risk of recurrent VTE or bleeding by Cox proportionate hazard modelling. There was no clear evidence for a higher risk of recurrent VTE or bleeding across subgroups according to the potential prothrombotic factors analysed in this study.
authors.affiliation: AstraZeneca Research and Development Mölndal, Mölndal, Sweden. karin.wahlander@astrazeneca.com
authors.forename: Karin
authors.initials: K
authors.lastname: Wåhlander
authors.forename: Henry
authors.initials: H
authors.lastname: Eriksson
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Lundström
authors.forename: Solveig
authors.initials: S
authors.lastname: Billing Clason
authors.forename: Ulrika
authors.initials: U
authors.lastname: Wall
authors.forename: Per
authors.initials: P
authors.lastname: Nyström
authors.forename: Peter
authors.initials: P
authors.lastname: Wessman
authors.forename: Sam
authors.initials: S
authors.lastname: Schulman
mesh_terms: D017153:Antibodies, Anticardiolipin / Q000097:blood; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D000991:Antithrombins / Q000032:analysis; D001384:Azetidines / Q000009:adverse effects* / Q000627:therapeutic use; D001596:Benzylamines / Q000009:adverse effects* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001780:Blood Coagulation Tests; D005006:Ethnicity; D005060:Europe; D005165:Factor V / Q000032:analysis; D006470:Hemorrhage / Q000097:blood / Q000139:chemically induced*; D006801:Humans; D016016:Proportional Hazards Models; D017293:Protein S / Q000032:analysis; D012008:Recurrence; D012306:Risk; D013923:Thromboembolism / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy; D019851:Thrombophilia / Q000208:ethnology / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D017153:Antibodies, Anticardiolipin; D000925:Anticoagulants; D000991:Antithrombins; D001384:Azetidines; D001596:Benzylamines; D015415:Biomarkers; D017293:Protein S; C095381:factor V Leiden; C426686:ximelagatran; D005165:Factor V