Dabigatran in nonvalvular atrial fibrillation: From clinical trials to real-life experience

Atrial fibrillation is the most common arrhythmia in over-midlife patients. In addition to systolic heart failure, cerebral thromboembolism represents the most dramatic complication of this rhythm disorder, contributing to morbidity and mortality. Traditionally, anticoagulation has been considered the main strategy in preventing stroke and systemic embolism in atrial fibrillation patients and vitamin K-dependent antagonists have been widely used in clinical practice. Recently, the development of direct oral anticoagulants has certainly improved the management of this disease, providing, for the first time, the opportunity to go beyond vitamin K-dependent antagonists limits. In the RE-LY trial, dabigatran 150mg twice daily was superior to warfarin in the prevention of stroke or systemic embolism and dabigatran 110mg twice daily was noninferior. Both doses greatly reduced hemorrhagic stroke, and dabigatran 110mg twice daily significantly reduced major bleeding compared with warfarin. Based on these results, dabigatran, a direct thrombin inhibitor, was the first direct oral anticoagulant to receive the regulatory approval for nonvalvular atrial fibrillation patients. To date, a specific reversal agent has just been approved as an antidote for this molecule. This review provides a summary of randomized trials, postmarket registries and specific clinical-settings summary on dabigatran in nonvalvular atrial fibrillation

Clinical course of patients with symptomatic isolated superficial vein thrombosis: the ICARO follow-up study

Essentials Late sequelae of isolated superficial vein thrombosis (iSVT) have rarely been investigated. We studied 411 consecutive outpatients with acute iSVT with a median follow-up of three years. Male sex and cancer are risk factors for future deep vein thrombosis or pulmonary embolism. Patients without cancer appear to be at a negligible risk for death. Summary: Background Studies of long-term thromboembolic complications and death following acute isolated superficial vein thrombosis (iSVT) of the lower extremities are scarce. Objectives To investigate the course of iSVT in the setting of an observational multicenter study. Methods We collected longitudinal data of 411 consecutive outpatients with acute, symptomatic, objectively diagnosed iSVT who were previously included in the cross-sectional ICARO study. Four patients followed for < 30 days and 79 with concomitant deep vein thrombosis (DVT) or pulmonary embolism (PE) were excluded from the present analysis. The primary outcome was symptomatic DVT or PE. The safety outcomes were major bleeding and all-cause death. Results The median follow-up time was 1026 days (interquartile range 610\ue2\u80\u931796). Symptomatic DVT/PE occurred in 52 (12.9%) patients, giving annualized rates of 1.3% (95% confidence interval [CI] 0.3\ue2\u80\u933.9%) on anticoagulant treatment and 4.4% (95% CI 3.2\ue2\u80\u935.8%) off anticoagulant treatment. Male sex (adjusted hazard ratio [HR] 2.03 [95% CI 1.16\ue2\u80\u933.54]) and active solid cancer (adjusted HR 3.14 [95% CI 1.11\ue2\u80\u938.93]) were associated with future DVT/PE, whereas prior DVT/PE failed to show significance, most likely because of bias resulting from prolonged anticoagulant treatment. Three major bleeding events occurred on treatment, giving an annualized rate of 1.4% (95 CI 0.3\ue2\u80\u934.0%). Death was recorded in 16 patients (annualized rate: 1.1% [95% CI 0.6\ue2\u80\u931.7%]), and was attributable to cancer (n = 8), PE (n = 1), cardiovascular events (n = 3), or other causes (n = 4). Conclusions The long-term risk of DVT/PE after anticoagulant discontinuation for acute iSVT is clinically relevant, especially in males and in the presence of active cancer. The risk of death appears to be negligible in patients without cancer