Tinzaparin is more effective than warfarin in preventing clot recurrence in cancer patients

Data from the international CATCH study (Comparison of Acute Treatment in Cancer Haemostasis) confirm that the low-molecular-weight-heparin (LMWH) tinzaparin is more effective than warfarin, in preventing the recurrence of venous blood clots in cancer patients. While tinzaparin did not meet statistical significance in reducing recurrent venous thromboembolism (VTE), it did show statistically significant activity in reducing the incidence of deep vein thrombosis (DVT) in veins above the knee. There was no difference in the mortality or incidence of major bleeding events between both study arms, but significantly fewer patients experienced clinically relevant, non-major bleeding with tinzaparin as compared to warfarin.

VTE presents a significant challenge for cancer patients and their physicians. VTE includes DVT, a blood clot that forms in a major vein of the leg or in the arms, pelvis, or other large veins in the body, as well as pulmonary embolism (PE), a potentially deadly condition that occurs when the clot breaks off and travels to the lungs. The current clinical practice guidelines recommend the use of LMWHs rather than warfarin to reduce this risk. However, these recommendations were based largely on a single trial. Given the lack of confirmatory trials or trials including different medications, warfarin remains a commonly used anticoagulant treatment in cancer patients. In order to confirm previous findings that LMWHs are superior to warfarin in preventing recurrent VTE among cancer patients, a total of 900 cancer patients with DVT or PE were enrolled in a randomized, phase III trial (CATCH) comparing the efficacy and safety of the LMWH tinzaparin with warfarin.

The 900 patients in the CATCH study were randomized (stratified by geographic region, tumor characteristics and history of VTE) to receive either tinzaparin 175 IU/kg once daily for 6 months (N= 449) or initial tinzaparin 175 IU/kg once daily for 5–10 days overlapped and followed by dose-adjusted warfarin (target INR 2.0–3.0) (N= 451) for 6 months. The primary efficacy outcome was time to recurrent VTE verified by objective, standard imaging and blinded central adjudication; this was a composite primary endpoint that included symptomatic DVT and/or PE, incidental proximal DVT and/or PE and fatal PE. The primary safety endpoint was incidence of major bleeding.

The mean age of participants in the study was 59 years and 59% was female. A total of 77% of patients had a baseline ECOG performance status of 0-1 and 23% had a performance status of 2. The most common primary tumor sites were gynaecologic (23%), colorectal (13%), lung (12%), breast (9%) and 10% had hematologic malignancies. At the time of randomization, 55% of the patients had metastatic disease and 44% had received prior cancer treatment (chemotherapy, surgery and/or radiation). During the treatment period, 31 patients (6.9%) treated with tinzaparin experienced recurrent VTE compared with 45 (10%) patients treated with warfarin (HR[95% CI]: 0.65 [0.41-1.03]; p=0.07). Symptomatic, non-fatal DVT occurred in 12 patients (2.7%) in the tinzaparin arm and in 24 (5.3%) patients in the warfarin arm (HR[95%CI]: 0.48 [0.24–0.96]; p=0.04). Symptomatic, non-fatal PE occurred in 3 patients in the tinzaparin arm and in 2 patients in the warfarin arm. Fatal PE on the other hand occurred in 17 (3.8%) patients in each arm (HR [95%CI]: 0.96 [0.49-1.88]; p = 0.90). There was no difference in the incidence of major bleeding events (2.9% in the tinzaparin arm and 2.7% in the warfarin arm), but significantly fewer patients experienced clinically relevant non-major bleeding with tinzaparin as compared to warfarin (11% vs. 16% respectively; p= 0.03).

In patients with active cancer and acute venous thromboembolism, tinzaparin reduced the risk of recurrent VTE from 10% to 6.9%, significantly lowered the risk of symptomatic DVT by 52% (p=0.04) and did not increase major bleeding despite full dose. Moreover, tinzaparin significantly reduced the incidence of clinically relevant, non major bleeding (p=0.03). As the largest randomized, controlled trial on the treatment of thrombosis among cancer patients, this study reinforces the clinical guidelines supporting the use of LMWHs instead of warfarin to prevent recurrent blood clots in cancer patients.

Reference

Lee A, Kamphuisen P, Meyer G, et al. A Randomized Trial of Long-Term Tinzaparin, a Low Molecular Weight Heparin (LMWH), Versus Warfarin for Treatment of Acute Venous Thromboembolism (VTE) in Cancer Patients - the CATCH Study. Presented at ASH 2014; Abstract #LBA-2.