Heparin Still Favored for Treating Venous Thromboembolism in Cancer Patients

By Will Boggs MD

August 19, 2015

NEW YORK (Reuters Health) - Low molecular weight heparin (LMWH) reduces recurrent venous thromboembolism (VTE) in patients with active cancer to an extent comparable with warfarin but with less clinically relevant bleeding, according to results from the Comparison of Acute Treatments in Cancer Hemostasis (CATCH) trial.

"The results should provide physicians more confidence to use or continue to use LMWH as first-line therapy for the treatment of VTE in patients with active cancer," Dr. Agnes Y.Y. Lee, from the University of British Columbia, Vancouver, Canada, told Reuters Health by email.

Current clinical guidelines recommend LMWH over vitamin K antagonist therapy for treating VTE in patients with cancer, but they rely on data from studies conducted more than a decade ago.

Dr. Lee and colleagues from 164 centers in Asia, Africa, Europe, and the Americas compared the efficacy and safety of the LMWH tinzaparin versus warfarin for treatment of acute, symptomatic VTE in 900 patients with active cancer.

Recurrent VTE occurred in 31 of 449 patients (7.2%) randomized to tinzaparin and in 45 of 451 patients (10.5%) randomized to warfarin (p=0.07), and symptomatic deep vein thrombosis (DVT) occurred in 12 tinzaparin and 24 warfarin patients, according to the August 18 JAMA report.

"Although the primary outcome did not reach statistical significance, I believe it was a power issue (because the incidence of warfarin was lower than expected) rather than a true lack of superior efficacy with tinzaparin over warfarin," Dr. Lee said.

The treatment groups did not differ in the rates of major bleeding, but clinically relevant nonmajor bleeding was 42% less likely among patients randomized to tinzaparin (p=0.004).

There were no significant differences between the groups in deaths or adverse events leading to study discontinuation.

Results were similar when the analysis was restricted to patients who adhered to the protocol.

"CATCH provides us with greater understanding of cancer-associated thrombosis (CAT), and reinforces that CAT is a diverse disease in terms of patient outcomes and treatment needs," Dr. Lee said. "The results, when combined with previous and ongoing studies, are likely to provide us with information that would help us identify those who require LMWH treatment, those who might do well on warfarin, and those who can be treated with a direct oral anticoagulant."

"More research in this area is desperately needed as the rising incidence of cancer and the longer life expectancy of patients living with cancer are going to drive up the incidence of CAT," Dr. Lee said.

Dr. Cihan Ay, from Medical University of Vienna, Austria, recently published the results of a meta-analysis of the efficacy and safety of anticoagulants for treating cancer patients with VTE. He told Reuters Health by email, "The CATCH trial reinforces the use of LMWH as the primary choice of treating VTE in patients with cancer over a period of six months to be effective and safe. Adding the CATCH results to an updated meta-analysis of trials comparing the different anticoagulant drugs for treating cancer-associated thrombosis underpins the recommendation of international practice guidelines favoring LMWH over oral anticoagulants."

"Novel anticoagulant drugs, the so-called direct oral anticoagulants (DOACs), have been approved for treatment of VTE in the general population as an alternative to standard treatment consisting of initial LMWH followed by vitamin K antagonists," Dr. Ay said. "It needs to be shown how DOACs perform in cancer patients with VTE in comparison to LMWH (or warfarin)."

Dr. Nick van Es, from Academic Medical Center, Amsterdam, the Netherlands, has also published research on anticoagulants in this setting. He told Reuters Health by email, "Although the CATCH trial failed to demonstrate the superiority of tinzaparin over vitamin K antagonist (VKA) in preventing recurrent VTE, the results are in line with previous trials. The combined results of all trials demonstrate that LMWH is associated with a lower risk of recurrent VTE than VKA, while the risk of major bleeding is comparable. Patients with active cancer and VTE should therefore receive treatment with LMWH."

"Several trials that are ongoing will compare LMWH with a DOAC for treatment of VTE in cancer patients (e.g., Hokusai VTE-cancer and Select-D)," Dr. van Es said.

Tinzaparin (Innohep, LEO Pharma) is available in 44 countries around the world (but not in the U.S.) for prevention and treatment of VTE.

LEO Pharma funded the study and had various relationships with five of the authors, including Dr. Lee.

SOURCE: http://bit.ly/1fnG4Ct

JAMA 2015.


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