XARELTO®: Safety profile in deep vein thrombosis (DVT) prophylaxis after hip or knee replacement surgery

PROVEN SAFETY PROFILE AFTER HIP OR KNEE REPLACEMENT SURGERY

COMPARABLE MAJOR BLEED RATES VERSUS ENOXAPARIN AFTER HIP REPLACEMENT SURGERY1-3

RATES OF BLEEDING IN RECORD1

  • Following XARELTO® treatment, the majority of major bleeding complications (≥60%) occurred in the first week after surgery

RATES OF BLEEDING IN RECORD2

COMPARABLE MAJOR BLEED RATES VERSUS ENOXAPARIN AFTER KNEE REPLACEMENT SURGERY4

RATES OF BLEEDING IN RECORD3

  • Following XARELTO® treatment, the majority of major bleeding complications (≥60%) occurred in the first week after surgery

CONSISTENT* CLINICAL AND REAL-WORLD SAFETY OUTCOMES—TIME AND TIME AGAIN1-5

*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.

RATES OF MAJOR BLEEDING IN CLINICAL TRIALS AND REAL-WORLD EVIDENCE

RECORD11

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.

RECORD22

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.

RECORD34

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.

XAMOS5

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.

*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.

A treatment-emergent bleeding event was defined as one occurring any time following the first dose of double-blind study medication (which may have been prior to administration of active drug) until 2 days after the last dose of double-blind study medication.

Hemorrhagic wound complications were defined as a composite of excessive wound hematoma and reported surgical site bleeding.

PE = pulmonary embolism; VTE = venous thromboembolism.