Tinzaparin vs. Warfarin for Cancer-Associated Acute VTE
What is the efficacy and safety of tinzaparin versus warfarin for the treatment of acute, symptomatic venous thromboembolism (VTE) in patients with active cancer?
In CATCH, a randomized, open-label study with blinded central adjudication of outcomes, 164 centers enrolled patients on four continents. Between August 2010 and November 2013, adult patients with active cancer (receiving anticancer therapy or diagnosis within 6 months) and an objectively documented proximal deep venous thrombosis (DVT) or pulmonary embolism (PE) and a life expectancy >6 months were randomized to either tinzaparin or warfarin for 6 months. Follow-up was at least 180 days. Primary efficacy outcome was a composite of recurrent DVT, fatal or nonfatal PE, and incidental VTE. Safety outcomes included major bleeding, clinically relevant nonmajor bleeding, and overall mortality.
Nine hundred patients were randomized with recurrent VTE in 31/449 (7.2% 6-month cumulative incidence) tinzaparin-treated patients and 45/451 (10.5%) warfarin-treated patients (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.41-1.03). There was no difference in major bleeding (12 patients in tinzaparin group vs. 11 patients in warfarin group, HR, 0.89; 95% CI, 0.40-1.99) or overall mortality (150 patients in tinzaparin group vs. 138 patients in warfarin group, HR, 1.08; 95% CI, 0.85-1.36). There was a significant reduction in clinically relevant nonmajor bleeding with tinzaparin (49/449 for tinzaparin vs. 69/451 for warfarin, HR, 0.58; 95% CI, 0.40-0.84).
The authors concluded that the use of full-dose tinzaparin as compared to warfarin did not significantly reduce recurrent VTE, mortality, or major bleeding among acute VTE patients with active cancer. The authors did note a lower rate of clinically relevant nonmajor bleeding in the tinzaparin group as compared to warfarin-treated patients.
In North America, use of low molecular weight heparin (LMWH) is common for patients with an acute VTE and active cancer, based on the CLOT trial (N Engl J Med 2003;349:146-53) and a few, smaller studies. This current trial provides a larger, global, contemporary assessment of VTE recurrence risk among cancer patients, but with lower than expected rates of recurrent VTE. Perhaps related to the heterogeneity in cancer-associated VTE recurrence risk, the study demonstrated no significant benefit in the use of LMWH (tinzaparin) as compared to warfarin for preventing VTE recurrence. However, there did appear to be a trend toward lower recurrent VTE rates in the tinzaparin group, with a p value of 0.07 and a 95% CI that barely crossed 1 (0.41-1.03). Also, with only 17% of patients enrolled from North American and Western European centers and tinzaparin’s lack of availability in the United States, there is a question of generalizability to these patient populations. Nonetheless, while most practitioners will likely continue to use LMWH for cancer-associated acute VTE, this trial provides evidence that warfarin therapy is still effective and a reasonable alternative for preventing cancer-associated VTE recurrence.
Keywords: Anticoagulants, Hemorrhage, Heparin, Low-Molecular-Weight, Neoplasms, Primary Prevention, Pulmonary Embolism, Venous Thromboembolism, Venous Thrombosis, Warfarin
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