DOACs Should Be Standard of Care in Cancer-Associated Thrombosis

Direct oral anticoagulants (DOACs) — the standard of care for treating venous thrombosis in noncancer patients — should also be the go-to for treating cancer-associated thrombosis (CAT), except in patients with a high risk of bleeding, a new analysis suggests.

“Our meta-analysis finds that cancer patients who experience acute venous thrombosis events (VTEs) and [who] were treated with direct oral anticoagulants experienced a 41% decrease in the rate of thrombosis recurrence compared with dalteparin, without significantly increasing major bleeding,” Irbaz Riaz, MBBS, a hematologist and oncologist at the Mayo Clinic in Rochester, Minnesota, said in a statement.

“Taken together, these data suggest that DOAC therapy may improve efficacy compared with dalteparin without sacrificing safety in many cases,” Riaz and colleagues write.

The study, published online January 18 in the Mayo Clinic Proceedings, is a “living” interactive systematic review, which allows researchers to update their findings as new evidence emerges. The review has been ongoing since September 2018 and currently includes four randomized controlled trials with almost 2900 patients.

In the study, the authors compared various outcomes — VTE recurrence, major bleeding, and clinically relevant nonmajor bleeding — in patients taking one of three DOACs or dalteparin (Fragmin), a low-molecular-weight heparin.

The DOACs included edoxaban (Savaysa) at 60 mg once a day, rivaroxaban (Xarelto) at 15 mg twice daily for 3 weeks followed by 20 mg once a day, and apixaban (Eliquis) 10 mg twice a day for 7 days followed by 5 mg twice a day. Dalteparin was given at a dose of 200 IU/kg daily for 1 month followed by 150 IU/kg daily thereafter.

Two of the trials included patients with active cancer plus those with a history of cancer, and the other two only included patients with active cancer. Almost 40% of patients had deep vein thrombosis (DVT) as their qualifying VTE event and over 60% had locally advanced or metastatic disease.

The authors found that, overall, DOACs significantly decreased recurrent VTE events (odds ratio [OR], 0.59) compared with dalteparin, without significantly increasing major bleeding (OR, 1.34; 95% CI, 0.83 – 2.18).

More specifically, 82 (5.6%) VTE recurrent events occurred in the DOAC group and 132 (9.1%) in the dalteparin group. As for major bleeding, 69 (4.8%) events occurred in the DOACs arm and 52 (3.6%) in the dalteparin arm, but the difference was not statistically significant.

The risk of clinically relevant nonmajor bleeding events, however, was significantly higher for those receiving DOACs vs dalteparin (OR, 1.69; 95% CI, 1.13-2.42).

Looking at individual DOACs, the authors reported rivaroxaban and apixaban both significantly reduced patients’ risk of VTE recurrence compared with dalteparin — rivaroxaban by 59% and apixaban by 42% — though not compared to each other.

Edoxaban significantly increased the risk of major bleeding compared with dalteparin (OR, 1.73), and rivaroxaban significantly increased the risk of clinically relevant nonmajor bleeding (OR, 4.09).

This subgroup analysis indicates that apixaban may have an edge over the other two DOACs, the authors note. Compared with dalteparin, apixaban was the only DOAC that did not increase the risk of major bleeding and clinically relevant nonmajor bleeding (OR, 0.66; 95% CI, 0.46 – 0.95).

Overall, the results suggest that the DOACs did not increase the risk of gastrointestinal bleeding but did increase the risk of genitourinary bleeding compared with dalteparin. In contrast, intracranial bleeds, fatal bleeding, and mortality were similar between all treatment groups.

Given the evidence, the authors conclude that “DOACs should be considered a standard of care for the treatment of CAT, with caution in patients with high risk of bleeding.”

Funding for the study was provided by the National Cancer Care Network and Pfizer EMBRACE. Riaz has disclosed no relevant financial relationships.

Mayo Clinic Proceedings. Published online January 18, 2022. Abstract

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