Treatment of Cancer-Associated Venous Thromboembolism in the Age of Direct Oral Anticoagulants

C. Ay; J. Beyer-Westendorf; I. Pabinger


Ann Oncol. 2019;30(6):897-907. 

In This Article

Real-world Data and Observational Studies

Despite guideline recommendations to use LMWH in patients with cancer-associated VTE, emerging real-world data show that DOACs have been widely used in patients with active cancer even before evidence from randomized trials or guideline recommendations supported this practice. Results from real-world studies offer important insights from clinical practice, but they provide lower-level evidence relative to randomized controlled trials and must therefore be interpreted cautiously due to potential patient and treatment selection biases. Although patients with active cancer were more likely to be treated with parenteral anticoagulant relative to patients without cancer in the GARFIELD-VTE registry, 22.8% of patients with cancer received DOACs.[35] A large retrospective study of patients with cancer who developed VTE and received anticoagulants identified 707 patients treated with rivaroxaban versus 1061 treated with warfarin and 660 treated with LMWH.[36] After adjusting for baseline characteristics between treatment cohorts, overall VTE recurrence was significantly lower by 28% in patients treated with rivaroxaban versus LMWH and by 26% in patients receiving rivaroxaban relative to warfarin, and major bleeding rates were similar in patients taking rivaroxaban relative to LMWH or warfarin.[36] A single-center retrospective cohort study found no significant difference in recurrent VTE or bleeding between 190 DOAC-treated patients versus 290 LMWH-treated patients,[37] and comparison of 98 prospective registry patients taking rivaroxaban for cancer-associated VTE versus 168 contemporary patients treated with enoxaparin found no difference in VTE recurrence or bleeding rates.[38] Smaller retrospective studies found DOACs generally at least as safe and effective as LMWH in patients with cancer.[39–44] Meta-analysis of observational studies is difficult due to population and end point heterogeneity, but a recent systematic review of DOACs for treatment of cancer-associated thrombosis reported lower rates of recurrent VTE in patients treated with DOACs versus LMWH in all but one observational study and higher rates of major bleeding only in two studies restricted to patients with gastrointestinal or gynecological cancers.[45]