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Thromb Haemost 2005; 94(03): 522-527
DOI: 10.1160/TH05-02-0096
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Prognostic factors for recurrence of venous thromboembolism (VTE) or bleeding during long-term secondary prevention of VTE with ximelagatran

Henry Eriksson
1   Department of Medicine, Sahlgrenska University Hospital/Östra, Gothenburg, Sweden
,
Torbjörn Lundström
2   AstraZeneca R&D Mölndal, Mölndal, Sweden
,
Karin Wåhlander
2   AstraZeneca R&D Mölndal, Mölndal, Sweden
,
Solveig Billing Clason
2   AstraZeneca R&D Mölndal, Mölndal, Sweden
,
Sam Schulman
3   Hamilton Health Sciences-General Hospital, Hamilton, Ontario, Canada
,
for the THRIVE III Investigators › Author Affiliations Financial support: This study was sponsored by AstraZeneca Research and Development, Mölndal, Sweden
Further Information

Publication History

Received: 07 February 2005

Accepted after major revision: 10 May 2005

Publication Date:
07 December 2017 (online)

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Summary

The oral direct thrombin inhibitor ximelagatran (24 mg twice daily) has been shown to significantly reduce the incidence of recurrent venous thromboembolism (VTE) vs. placebo over 18 months, with no significant influence on bleeding (THRIVE III). The influence of potential prognostic factors on the risk of recurrent VTE or major and/or minor bleeding and their impact on ximelagatran treatment was evaluated in theTHRIVE III study population. The effect of sex, age, body weight, renal function, malignancy, type of initialVTE event, and history of previousVTE events was investigated in the intention-to-treat population using Cox proportionate hazard modelling. Ximelagatran was administered to 612 patients and placebo to 611 patients. Within the placebo group, risk of recurrent VTE was higher among men than women (hazard ratio [HR]: 2.50,95% confidence interval [CI] 1.49, 4.17), and in patients with one or more than one previous VTE event (HR: 1.73, 95% CI 1.00, 2.99). There was a higher risk of bleeding among women than men in both the ximelagatran (HR: 1.49, 95% CI 1.06, 2.09) and placebo (HR: 1.48, 95% CI 1.01, 2.15) groups, and in placebo-treated patients with an initial pulmonary embolism (HR: 1.53, 95% CI 1.06, 2.23) compared to those with initial deep vein thrombosis. There were no significant interactions between treatment effect and any of the potential prognostic factors. In conclusion, the superior efficacy of ximelagatran vs. placebo was maintained in all subgroups. Long-term use of oral ximelagatran, without coagulation monitoring or dose adjustment, should be feasible and well tolerated in a wide cross-section of patients for the secondary prevention of VTE.

Keywords

Oral direct thrombin inhibitor - risk factors - THRIVE III - venous thromboembolism - ximelagatran
 

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