XARELTO^®: Safety profile in initial treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE)

EINSTEIN DVT/PE^1,2

Trial design: Randomized, phase 3, multicenter, open-label, parallel group, active-controlled, event-driven noninferiority studies (EINSTEIN DVT and EINSTEIN PE) with patients receiving XARELTO^®  at an initial dose of 15 mg twice daily with food for the first 3 weeks, followed by XARELTO^® 20 mg once daily with food or enoxaparin 1 mg/kg twice daily for at least 5 days with VKA, then VKA only after target INR (2.0-3.0) was reached. Patients were included with a DVT if they had acute, symptomatic, objectively confirmed proximal DVT, without symptomatic PE and were included with a PE if they had acute, symptomatic PE with objective confirmation, with or without symptomatic DVT. Patients were treated for 3, 6, or 12 months at HCP discretion.

Primary outcomes: The primary efficacy outcome was symptomatic recurrent fatal or nonfatal PE or DVT and the principal safety outcome was clinically relevant bleeding, defined as a composite of major and nonmajor clinically relevant bleeding. Bleeding was defined as major if it was clinically overt and associated with a decrease in hemoglobin level of ≥2 g/dL; if bleeding led to the transfusion of ≥2 units of red cells; or if bleeding was intracranial or retroperitoneal, occurred in another critical site, or contributed to death. Clinically relevant nonmajor bleeding was defined as overt bleeding that did not meet the criteria for major bleeding but was associated with medical intervention, unscheduled contact with the physician, interruption or discontinuation of the study drug, or discomfort or impairment of activities of daily life.

HoT-PE³

Trial design: A prospective, multicenter, single-arm, investigator-initiated, and academically sponsored management trial to investigate the efficacy and safety of early transition from hospital to ambulatory treatment in low-risk acute PE (identified through a modified Hestia criteria) in patients taking XARELTO^® (15 mg twice daily for the first 3 weeks, followed by 20 mg once daily for at least 3 months). At the discretion of the treating physician for patients with CrCl >50 mL/min, a reduced maintenance dose (15 mg once daily) was prescribed if the individual risk for bleeding was deemed to outweigh the risk for recurrent VTE. A total of 4 patients received the reduced dose.

Primary outcomes: The primary outcome was symptomatic recurrent VTE or PE-related death within 3 months of enrollment. Safety outcomes were major bleeding (defined by ISTH criteria), clinically relevant nonmajor bleeding, and serious adverse events.