In a subgroup analysis of the pooled results of the EINSTEIN-DVT and EINSTEIN-PE trials reported in The Lancet Haematology, Prins et al found that the recurrence rate for venous thromboembolism in cancer patients receiving anticoagulant therapy with oral rivaroxaban (Xarelto) was similar to that in those receiving subcutaneous enoxaparin followed by vitamin K antagonist. Rivaroxaban was associated with less major bleeding but not less clinically relevant bleeding.
In the two trials, 8,281 patients with deep-vein thrombosis or pulmonary embolism were randomly assigned to receive rivaroxaban at 15 mg twice daily for 21 days followed by 20 mg once daily or standard therapy consisting of subcutaneous enoxaparin at 1.0 mg/kg twice daily and warfarin or acenocoumarol (target INR of 2.0 to 3.0). The trials included 655 patients with active cancer (at entry or diagnosed during treatment); of these, 354 received rivaroxaban, and 301 received enoxaparin/vitamin K antagonist.
Recurrence and Bleeding
Among patients with active cancer, recurrent venous thromboembolism was observed in 5% of rivaroxaban patients and 7% of enoxaparin/vitamin K antagonist patients (hazard ratio [HR] = 0.67, 95% confidence interval [CI] = 0.35–1.30). Major bleeding occurred in 2% vs 5% (HR = 0.42, 95% CI = 0.18–0.99), and clinically relevant bleeding occurred in 14% vs 16% (HR = 0.80, 95% CI = 0.54–1.20).
Rates Higher in Patients With Active Cancer
Among patients in the trial without active cancer but with a history of cancer, rates of recurrent venous thromboembolism were 2% among 233 patients in the rivaroxaban group vs 2% among 236 in the standard therapy group (HR = 0.98, 95% CI = 0.28–3.43), similar to the rates of 2% in 3,563 without cancer in the rivaroxaban group vs 2% of 3,594 without cancer in the standard therapy group (HR = 0.93, 95% CI = 0.66–1.30). Frequency of recurrence was higher both among patients with active cancer at baseline (2% of 258 vs 4% of 204, HR = 0.62, 95% CI = 0.21–1.79) and among those diagnosed with cancer during the studies (10% of 96 vs 12% of 97, HR = 0.80, 95% CI = 0.34–1.88).
Similarly, rates of major bleeding in patients with history of cancer (< 1% vs 2%, HR = 0.23, 95% CI = 0.03–2.06) were similar to those in patients without cancer (1% vs 1%, HR = 0.58, 95% CI = 0.37–0.91), and higher in those with active cancer at baseline (2% vs 4%, HR = 0.47, 95% CI = 0.15–1.45) and those diagnosed with cancer during the studies (3% vs 7%, HR = 0.33, 95% CI = 0.08–1.31).
The investigators concluded: “In patients with active cancer and venous thromboembolism, rivaroxaban had similar efficacy to prevent recurrence of venous thromboembolism and reduced the number major bleeding events compared with treatment with enoxaparin and a vitamin K antagonist, although there was no difference between groups for clinically relevant bleeding. Based on these results, a head-to-head comparison of rivaroxaban with long-term low-molecular weight heparin in patients with cancer is warranted.”
Martin Prins, MD, of Maastricht University Medical Center, is the corresponding author for The Lancet Haematology article.
The study was funded by Bayer HealthCare Pharmaceuticals and Janssen Research & Development. For full disclosures of the study authors, visit www.thelancet.com.
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