Characterization of Patients with Embolic Strokes of Undetermined Source in the NAVIGATE ESUS Randomized Trial.

BACKGROUND: The New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs. ASA to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) trial is a randomized phase-III trial comparing rivaroxaban versus aspirin in patients with recent ESUS. AIMS: We aimed to describe the baseline characteristics of this large ESUS cohort to explore relationships among key subgroups. METHODS: We enrolled 7213 patients at 459 sites in 31 countries. Prespecified subgroups for primary safety and efficacy analyses included age, sex, race, global region, stroke or transient ischemic attack prior to qualifying event, time to randomization, hypertension, and diabetes mellitus. RESULTS: Mean age was 66.9 ± 9.8 years; 24% were under 60 years. Older patients had more hypertension, coronary disease, and cancer. Strokes in older subjects were more frequently cortical and accompanied by radiographic evidence of prior infarction. Women comprised 38% of participants and were older than men. Patients from East Asia were oldest whereas those from Latin America were youngest. Patients in the Americas more frequently were on aspirin prior to the qualifying stroke. Acute cortical infarction was more common in the United States, Canada, and Western Europe, whereas prior radiographic infarctions were most common in East Asia. Approximately forty-five percent of subjects were enrolled within 30 days of the qualifying stroke, with earliest enrollments in Asia and Eastern Europe. CONCLUSIONS: NAVIGATE-ESUS is the largest randomized trial comparing antithrombotic strategies for secondary stroke prevention in patients with ESUS. The study population encompasses a broad array of patients across multiple continents and these subgroups provide ample opportunities for future research.

Periprocedural bleeding and thromboembolic events with dabigatran compared with warfarin: results from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) randomized trial.

BACKGROUND: Dabigatran reduces ischemic stroke in comparison with warfarin; however, given the lack of antidote, there is concern that it might increase bleeding when surgery or invasive procedures are required. METHODS AND RESULTS: The current analysis was undertaken to compare the periprocedural bleeding risk of patients in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial treated with dabigatran and warfarin. Bleeding rates were evaluated from 7 days before until 30 days after invasive procedures, considering only the first procedure for each patient. A total of 4591 patients underwent at least 1 invasive procedure: 24.7% of patients received dabigatran 110 mg, 25.4% received dabigatran 150 mg, and 25.9% received warfarin, P=0.34. Procedures included: pacemaker/defibrillator insertion (10.3%), dental procedures (10.0%), diagnostic procedures (10.0%), cataract removal (9.3%), colonoscopy (8.6%), and joint replacement (6.2%). Among patients assigned to either dabigatran dose, the last dose of study drug was given 49 (35-85) hours before the procedure on comparison with 114 (87-144) hours in patients receiving warfarin, P<0.001. There was no significant difference in the rates of periprocedural major bleeding between patients receiving dabigatran 110 mg (3.8%) or dabigatran 150 mg (5.1%) or warfarin (4.6%); dabigatran 110 mg versus warfarin: relative risk, 0.83; 95% CI, 0.59 to 1.17; P=0.28; dabigatran 150 mg versus warfarin: relative risk, 1.09; 95% CI, 0.80 to 1.49; P=0.58. Among patients having urgent surgery, major bleeding occurred in 17.8% with dabigatran 110 mg, 17.7% with dabigatran 150 mg, and 21.6% with warfarin: dabigatran 110 mg; relative risk, 0.82; 95% CI, 0.48 to 1.41; P=0.47; dabigatran 150 mg: relative risk, 0.82; 95% CI, 0.50 to 1.35; P=0.44. CONCLUSIONS: Dabigatran and warfarin were associated with similar rates of periprocedural bleeding, including patients having urgent surgery. Dabigatran facilitated a shorter interruption of oral anticoagulation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.