XARELTO®: Safety profile in the treatment and reduction in the risk of recurrent deep vein thrombosis (DVT) and pulmonary embolism (PE)
REDUCTION IN THE RISK OF RECURRENT DVT/PE AND A PROVEN SAFETY PROFILE1
SIMILAR RATES OF MAJOR AND CLINICALLY RELEVANT NONMAJOR BLEEDING DURING INITIAL TREATMENT1
LESS MAJOR BLEEDING* DURING INITIAL TREATMENT1
†Not adjusted for multiplicity.
<1% MAJOR BLEEDING IN PATIENTS WITH DVT/PE TREATED FOR REDUCTION IN THE RISK OF RECURRENCE‡2
‡After completion of at least 6 months of initial treatment.
CONSISTENT§ CLINICAL AND REAL-WORLD SAFETY OUTCOMES—TIME AND TIME AGAIN1,3
§Results are not intended for direct comparison with clinical trials because the real-world studies were observational trials. Differences in study designs, patient populations, definitions of safety or efficacy outcomes, as well as data collection methods, make it difficult to make comparisons either with clinical trials or with each other.
≤1% MAJOR BLEEDING IN CLINICAL AND REAL-WORLD OUTCOMES1,3
ǁResults presented here reflect a single real-world study. Other real-world studies may show different results.
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® 20 mg and 10 mg with aspirin (100 mg) in patients with VTE who completed 6 to 12 months of treatment and were in equipoise regarding the need for continued 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 or more; a transfusion of 2 or more 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.
*Bleeding event occurred after the first dose and up to 2 days after the last dose of study drug. Although a patient may have had ≥2 events, the patient is counted only once in a category.
¶Propensity score matched population.
HCP = healthcare professional; HR = hazard ratio; INR = international normalized ratio; NOAC = non-vitamin K antagonist oral anticoagulant; VKA = vitamin K antagonist; VTE = venous thromboembolism.