Update in Hematology

Anticoagulation

Question: What dose of rivaroxaban, a direct factor Xa inhibitor, is safest and most effective for the prevention of venous thromboembolism (VTE) after total hip replacement?

Study Design: Randomized, double-blind, double-dummy trial.

Patients: Patients scheduled for elective total hip replacement surgery. Patients were excluded if they had had VTE, myocardial infarction, transient ischemic attack, or ischemic stroke during the past 6 months; were taking anticoagulants, platelet inhibitors, or other drugs influencing coagulation (except nonsteroidal anti-inflammatory drugs with a half-life <17 hours); had severe hypertension or severe liver or renal impairment; weighed less than 45 kg; or had abused alcohol or drugs.

Setting: 48 centers in 10 European countries and Israel.

Intervention: Once-daily oral rivaroxaban, 5 mg (n = 128), 10 mg (n = 142), 20 mg (n = 140), 30 mg (n = 143), or 40 mg (n = 142) given 6 to 8 hours after surgery, or once-daily subcutaneous enoxaparin, 40 mg given the evening before and at least 6 hours after surgery (n = 157). Study drug therapies were continued for 5 to 9 days.

Outcomes: Efficacy outcome was the composite of any deep venous thrombosis, objectively confirmed pulmonary embolism, and all-cause mortality. Safety outcome was the incidence of major bleeding events.

Sponsor: Bayer.

Results: The primary outcome occurred in fewer patients receiving rivaroxaban (ranging from 14.9% in the 5-mg dose group to 6.4% in the 40-mg dose group) than enoxaparin (25.2%), but investigators found no clear dose–response relationship (P = 0.09). Occurrence of major postoperative bleeding events was similar in the 5- and 10-mg dose groups and was greater with …