*Results are not intended for direct comparison with clinical trials because the real-world studies were observational trials with no comparator arm. Differences in study designs, patient populations, definitions of safety or efficacy outcomes, as well as data collection methods, make it difficult to make direct comparisons either with clinical trials or with each other.
RECORD1 trial design: Randomized, double-blind, clinical trial comparing the efficacy and safety of XARELTO® with enoxaparin for DVT prophylaxis in patients undergoing hip replacement surgery. Patients were randomized to receive either oral rivaroxaban 10 mg once daily for 31 to 39 days (with placebo injection), beginning 6 to 8 hours after wound closure, or subcutaneous enoxaparin 40 mg once daily for 31 to 39 days (with placebo tablet), beginning 12 hours before surgery and resuming 6 to 8 hours after wound closure.
Primary outcomes: The primary efficacy outcome was composite of any DVT, nonfatal PE, or death from any cause at 36 days (range, 30 to 42). Major VTE was a composite of proximal DVT, nonfatal PE, and VTE-related death. The principal safety outcome was major bleeding, beginning after the first dose of study drug and for up to 2 days after the last dose. Major bleeding was defined as bleeding that was fatal, bleeding into a critical organ (ie, retroperitoneal, intracranial, intraocular, or intraspinal), bleeding that required reoperation, or clinically overt extrasurgical site bleeding associated with a fall in hemoglobin ≥2 g/dL or requiring the transfusion of ≥2 units of blood or packed cells.
RECORD2 trial design: Randomized, double-blind, clinical trial of extended-duration XARELTO® with short-term enoxaparin for DVT prophylaxis in 2509 patients undergoing hip replacement surgery. Patients were randomized to receive either oral rivaroxaban 10 mg once daily for 31 to 39 days (with placebo injection for 10 to 14 days), beginning 6 to 8 hours after wound closure, or subcutaneous enoxaparin 40 mg once daily for 10 to 14 days (with placebo tablet for 31 to 39 days), beginning 12 hours before surgery and resuming 6 to 8 hours after wound closure.
Primary outcomes: Primary efficacy outcome was composite of DVT (symptomatic or asymptomatic detected by mandatory bilateral venography), nonfatal PE, and all-cause mortality up to day 30 to 42. Analyses were done in the modified intention-to-treat population, which consisted of all patients who had received at least one dose of study medication, had undergone planned surgery, and had adequate assessment of thromboembolism. Major VTE was a composite of proximal DVT, nonfatal PE, and VTE-related death. The principal safety outcome was major bleeding, beginning after the first dose of study drug and for up to 2 days after the last dose. Major bleeding was defined as bleeding that was fatal, bleeding into a critical organ (ie, retroperitoneal, intracranial, intraocular, or intraspinal), bleeding that required reoperation, or clinically overt extrasurgical site bleeding associated with a fall in hemoglobin ≥2 g/dL or requiring the transfusion of ≥2 units of blood or packed cells.
RECORD3 trial design: Randomized, double-blind clinical trial compared the efficacy and safety of XARELTO® with enoxaparin for DVT prophylaxis in 2531 patients undergoing knee replacement surgery. Patients were randomized to receive either: oral rivaroxaban 10 mg once daily for 10 to 14 days (with placebo injection), beginning 6 to 8 hours after wound closure, or subcutaneous enoxaparin 40 mg once daily for 10 to 14 days (with placebo tablet), beginning 12 hours before surgery and resuming 6 to 8 hours after wound closure.
Primary outcomes: The primary efficacy outcome was composite of any DVT, nonfatal PE, and all-cause mortality up to day 17 after surgery. Patients had mandatory bilateral venography between days 11 and 154. Major VTE was a composite of proximal DVT, nonfatal PE, and VTE-related death. Principal safety outcome was major bleeding, beginning after the first dose of study drug and for up to 2 days after the last dose. Major bleeding was defined as bleeding that was fatal, bleeding into a critical organ (ie, retroperitoneal, intracranial, intraocular, or intraspinal), bleeding that required reoperation, or clinically overt extrasurgical site bleeding associated with a fall in hemoglobin ≥2 g/dL or requiring the transfusion of ≥2 units of blood or packed cells.
XAMOS study design: Noninterventional, open-label, multicenter study of patients undergoing hip (or hip fracture surgery) or knee replacement surgery between February 2009 and June 2011.
XAMOS primary outcomes were symptomatic thromboembolic events, bleeding events, uncommon adverse events, and all-cause mortality. The primary safety outcome was major bleeding defined in the RECORD studies.
Limitations: This is an open-label study. The propensity score design does not address reporting bias.
◇For VTE prophylaxis in acutely ill medical patients at risk for thromboembolic complications who are not at high risk of bleeding.
DOAC = direct oral anticoagulant; PE = pulmonary embolism; VTE = venous thromboembolism (ie, DVT or PE).
