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Tinzaparin fails to significantly reduce recurrent VTE compared with warfarin
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The use of daily tinzaparin for 6 months did not significantly reduce recurrent venous thromboembolism, major bleeding or death compared with warfarin in patients with active cancer and acute symptomatic venous thromboembolism, according to the results of a randomized trial.
However, use of tinzaparin (Innohep, LEO Pharma) did correspond with a lower rate of clinically relevant nonmajor bleeding.
Low–molecular-weight heparin is recommended over warfarin for the treatment of acute symptomatic VTE in patients with active cancer. However, the recommendation is largely based on the results of a single trial.
Agnes Y.Y. Lee
Agnes Y.Y. Lee, MD, MSc, associate professor of medicine and medical director of the thrombosis program at University of British Columbia, and colleagues conducted a randomized, open-label international study to determine the safety and efficacy of tinzaparin vs. warfarin for the treatment of acute symptomatic VTE.
The researchers enrolled 900 adults with active cancer and objectively documented proximal deep vein thrombosis or pulmonary embolism between 2010 and 2013. All enrolled patients had a life expectancy of at least 6 months and no contraindications for anticoagulation.
The researchers randomly assigned 449 patients to once-daily tinzaparin (175 IU/kg) for 6 months. The other 451 patients received once-daily tinzaparin (175 IU/kg) for 5 to 10 days, followed by warfarin at a dose adjusted to maintain the international normalized ratio within therapeutic range for 6 months. The researchers followed patients for 180 days, and for 30 days following the last study medication dose.
Centrally adjudicated DVT, fatal or nonfatal PE and incidental VTE served as the primary efficacy endpoints. Major bleeding, clinically relevant nonmajor bleeding and mortality served as safety endpoints.
Treatment discontinuation before day 180 occurred in 140 patients assigned tinzaparin and 172 patients assigned warfarin. Progressive cancer served as the most frequently reported reason for discontinuation in both arms.
Six-month cumulative incidence of recurrent VTE was 7.2% (n = 31) in the tinzaparin group and 10.5% (n = 45) in the warfarin group (HR = 0.65; 95% CI, 0.41-1.03). The difference was not statistically significant.
Incidence of major bleeding (12 vs. 11; HR = 0.89; 95% CI, 0.4-1.99) and overall mortality (150 vs. 138; HR = 1.08; 95% CI, 0.85-1.36) occurred in similar rates in both treatment arms.
However, tinzaparin use produced a significant reduction in clinically relevant nonmajor bleeding incidence compared with warfarin (49 vs. 69; HR = 0.58; 95% CI, 0.4-0.84).
The researchers acknowledged limitations to their study, including a small sample size, potential bias associated with the open-label study design, and the large number of patients who withdrew consent or were lost to follow-up.
“Further studies are needed to assess whether the efficacy outcomes would be different in patients at higher risk [for] recurrent VTE,” Lee and colleagues wrote. – by Cameron Kelsall
Disclosure: Lee reports research funding and honoraria from Avivia, LEO Pharma, Pfizer and Sanofi. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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