XARELTO®: Clinical trials and real-world evidence in the treatment and reduction in the risk of recurrent deep vein thrombosis (DVT) and pulmonary embolism (PE)
HOW MUCH PUBLISHED DATA SUPPORTS YOUR FIRST-CHOICE NOAC?
EINSTEIN DVT/PE 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 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 clinically relevant nonmajor 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.
EINSTEIN CHOICE trial design: A randomized, phase 3, double-blind, active-comparator, event-driven, superiority study comparing the efficacy and safety of once-daily XARELTO® at doses of 20 mg or 10 mg to aspirin (100 mg) in patients with VTE who had completed 6 to 12 months of treatment and were in equipoise regarding the need for extended anticoagulation. Study drugs were administered up to 12 months.
Because the benefit-risk assessment favored once-daily XARELTO® at the 10-mg dose versus aspirin (100 mg) compared to XARELTO® 20 mg once daily versus aspirin, the XARELTO® 10-mg dose is approved to reduce the risk of recurrent DVT/PE.
Primary outcomes: The primary efficacy outcome was symptomatic recurrent fatal or nonfatal VTE, and the principal safety outcome was major bleeding.
XALIA study design: A multinational, noninterventional, observational study evaluating the safety and efficacy of XARELTO® compared with standard anticoagulation therapy in patients with DVT across centers in Europe, Israel, and Canada from June 2012 to March 2014. Results shown are for propensity score-adjusted population.
Primary outcomes: Incidences of treatment-emergent adverse events of major bleeding, symptomatic recurrent VTE, and all-cause mortality. Major bleeding was defined as: overt bleeding associated with a fall in hemoglobin of ≥20 g/L; a transfusion of ≥2 units of packed red blood cells or whole blood; critical site bleeding (intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, and retroperitoneal); or fatal bleeding.
Limitations: There were more higher-risk patients at baseline assigned to standard anticoagulation therapy compared to patients assigned to XARELTO®. To address selection bias between the treatment arms, the protocol included a prespecified propensity score analysis. The propensity score design may balance baseline covariates between the treatment groups, but the impact of unmeasured characteristics and confounders (such as a possible reporting bias) cannot be assessed.
*Patients included in the propensity score adjusted analysis.
HCP = healthcare professional; INR = international normalized ratio; NOAC = non-vitamin K antagonist oral anticoagulant; SOC = standard of care; VKA = vitamin K antagonist; VTE = venous thromboembolism.