Switch From LMWH to Warfarin OK in Cancer-Related Thrombosis

Roxanne Nelson, BSN, RN

December 15, 2015

ORLANDO, Florida ― Switching to warfarin after 6 months of anticoagulant treatment with low-molecular-weight heparin (LMWH) appears to be safe in patients with cancer-associated thrombosis.

The switch did not lead to an increase in recurrent venous thromboembolism (VTE) or major bleeding or total bleeding, explained Chatree Chai-Adisaksopha, MD, McMaster University, Hamilton, Ontario, Canada, who presented the study findings here at the American Society of Hematology (ASH) 57th Annual Meeting.

"Warfarin is an acceptable alternative to low-molecular-weight heparin for patients with cancer-associated thrombosis," he said.

LMWH is considered to be the treatment of choice for anticoagulation therapy for cancer-associated thrombosis. It is recommended treatment be contined for at least 3 to 6 months after diagnosis. However, the data with respect to continuing LMWH treatment beyond 6 months are unclear, Dr Chai-Adisaksophia noted.

Because LMWH must be self-injected, warfarin, which can be taken orally, is often preferred.


The researchers compared the two options in a retrospective registry study. The cohort included 1502 patients who were enrolled in the RIETE Registry and who had already completed 6 months' treatment with an LMWH. About half of the patients continued receiving LMWH (n = 763); for the other half, therapy was changed to warfarin ( n = 739).

The primary outcome was time to objectively confirmed recurrence of deep vein thrombosis or pulmonary embolism.

The secondary outcome was major bleeding, defined as bleeding associated with a decrease in hemoglobin of 20 g/L or more requiring at least 2 units of red blood cell transfusion, bleeding into a critical organ, fatal bleeding, or nonmajor bleeding.

The authors observed that there were no significant differences in the two group with regard to recurrent VTE (hazard ratio [HR], 0.67; P = .06). The cumulative incidence of major bleeding was 2.6% in LMWH group, compared with 2.7% in warfarin group (HR, 1.05; P = .79).

The cumulative incidence of total bleeding was 6.7% in LMWH group and 7.0% in warfarin group (HR, 0.92: P = .70).

Adds More Evidence

"The face of cancer is changing, and for some patients, new treatments have turned cancer into chronic and indolent diseases," said Mary Cushman, MD, professor of medicine, Division of Hematology/Oncology, University of Vermont College of Medicine, in Burlington. "So patients are now living longer, and some for many years with cancer present, so anticoagulation in those patients is a long-term treatment. It has side effects, and for LMWH, is expensive in addition to the inconvenience of having to give it by daily injection.

"In our practice, every so often we will see someone with cancer long term, and they are on anticoagulants, and we don't know what to do," she told Medscape Medical News. "So this study is extremely helpful."

That said, it was a registry study, and although adjustment was made for factors that may have influenced recurrence risk, it was not randomized.

"But it did show that there was no difference when switching to warfarin, and that is reassuring," Dr Cushman said. "In our practice, we do try to switch patients if we can, in order to reduce the morbidity and expense. This study has very immediate applicability in clinical practice."

This study has very immediate applicability in clinical practice. Dr Mary Cushman

In cancer patients who develop thrombosis, up-front LMWH therapy is better than warfarin therapy for the first 6 months, Dr Cushman said. The risk for bleeding is similar but depends on how well the warfarin is managed, she pointed out.

In theory, adherence should be better with an oral medication, but Dr Cushman noted that in her experience, some patients do not mind the injections. "There are those who stay on it and really adhere to it," she said. "I haven't seen any research, but in my experience, when you tell a patient that they need an injection every day, they may view it as a more serious treatment — as compared to taking a pill. People are terrible at taking pills, so injections are a little special, so I've wondered about that, but as I said, I haven't seen research on that."

Dr Chai-Adisaksopha has disclosed no relevant relationships. Coauthor Manuel Monreal, MD, PhD, has relationships with Bayer, sanofi-aventis, Boehringer-Ingelheim, and Daiichi Sankyo.

American Society of Hematology (ASH) 57th Annual Meeting. Abstract 430. Presented December 7, 2015.


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