Direct Oral Anticoagulants: New Standard of Care for VTE in Patients with Cancer?

April 2018 Vol 9, No 4

Direct oral anticoagulants (DOACs) may replace low molecular weight heparin (LMWH) as standard of care for management of venous thromboembolism (VTE) in cancer patients, judging by the results of 2 randomized trials presented at ASH 2017. The caveat is that DOACs are associated with more bleeding, especially in patients with gastrointestinal (GI) cancer, who should continue to receive LMWH.

These trials were the first to compare the newer DOAC agents versus LMWH in cancer patients, who are known to be at increased risk of VTE. Until now, oncologists have had no good data on which to recommend a DOAC over LMWH.

Edoxaban versus Dalteparin

In the Hokusai-VTE trial, edoxaban (DOAC) was noninferior to dalteparin (LMWH). At 12 months, first recurrent VTE or major bleeding occurred in 12.8% of patients treated with edoxaban versus 13.5% receiving dalteparin. Over the first 6 months, recurrent VTE or major bleeding was observed in 10.5% of patients in the edoxaban arm versus 10.7% for dalteparin, but major bleeding was more frequent with edoxaban.

“Evidence-based guidelines recommend LMWH for the prevention and treatment of VTE in cancer patients. These drugs are given subcutaneously for 6 months or longer, and burdensome injections limit their adoption,” said Gary E. Raskob, PhD, Dean and Regents Professor, College of Public Health, University of Oklahoma, Oklahoma City.

“Hokusai-VTE, the largest trial of DOAC versus LMWH in patients with cancer, showed that treatment with oral edoxaban was noninferior to subcutaneous injections of dalteparin, an LMWH. The lower rate of recurrent VTE observed with edoxaban is offset by a similar increase in risk of major bleeding,” Dr Raskob said. “There were more upper gastrointestinal bleeds, mainly in patients with gastrointestinal cancer, suggesting that use of DOAC should be limited in these patients.”

Hokusai-VTE was conducted at 114 sites in Australia, New Zealand, North America, and Europe and included 1046 patients with various types of cancer and acute or symptomatic VTE. Patients were randomized to receive LMWH for 5 days followed by edoxaban 60 mg/day versus dalteparin and treated for at least 6 months and a maximum of 12 months.

Although major bleeding was more frequent with edoxaban (6.3% vs 3.2%), no episode of fatal bleeds occurred in either group. Major bleeding events were reported in 17 patients treated with edoxaban, most of whom had gastric cancer and GI bleeds, versus 3 in the dalteparin group.

Major bleeding was less severe, however, in the edoxaban arm, Dr Raskob said.

At 1 year, event-free survival (with no recurrent VTE or bleeding) was about 55% in both arms.

Rivaroxaban versus Dalteparin

The select-d trial randomized 406 cancer patients with associated incidental or symptomatic VTE to receive 6 months of treatment with dalteparin or rivaroxaban.

Annie Young, PhD, Professor of Nursing, University of Warwick, Coventry, England, who presented the results, said that patients with GI cancer were excluded because they are at higher risk for bleeds compared with other types of cancer.

The 6-month rate of recurrent VTE was 4% for rivaroxaban versus 11% for dalteparin.

Six-month overall survival rate was 75% for rivaroxaban and 70% for dalteparin.

Major bleeds were reported in 5% of the rivaroxaban and 3% of the dalteparin group. The rate of clinically relevant nonmajor bleeding was 12% with rivaroxaban versus 3% with dalteparin. One fatal bleeding event occurred on each arm. Most major bleeding events were GI, and there were no bleeds in the central nervous system.

“Clinicians are already adopting DOACs into practice for these patients. Now they have data from this study to indicate that DOACs are potentially safe in patients with cancer. We conclude that in terms of therapeutic decision-making, a careful discussion between the patient and physician should focus on risk of recurrence and the risk of bleeding,” Dr Young stated.

“I think these studies will usher in a new standard of care for VTE, a common situation that oncologists face,” said ASH Secretary Robert Brodsky, MD, Director, Division of Hematology, Johns Hopkins Medicine, Baltimore, MD, who moderated a press conference at ASH.

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Last modified: November 5, 2020

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