Dabigatran and Postmarketing Reports of Bleeding
ABSTRACT In the months following the approval of the oral anticoagulant dabigatran (Pradaxa, Boehringer Ingelheim) in October 2010, the Food and Drug Administration (FDA) received through the FDA Adverse Event Reporting System (FAERS) many reports of serious and fatal bleeding events associated with use of the drug. Because dabigatran is an anticoagulant, reports of bleeding were anticipated, but the rate of reported incidents was unusually high and was greater than the concurrent rate of reported bleeding incidents with warfarin, which had been the anticoagulant of choice for nearly 60 years before dabigatran was approved. In contrast, the controlled trial that supported . . .
SourceAvailable from: Don C RockeyNature Reviews Gastroenterology & Hepatology 01/2015; DOI:10.1038/nrgastro.2015.7 · 10.81 Impact Factor
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ABSTRACT: Direct oral anticoagulants have recently emerged as an attractive choice for patients requiring anticoagulation treatment. They have a rapid onset of action and can be administered at fixed doses without the need for routine anticoagulation monitoring. They may present fewer interactions than warfarin but further experience is needed to assess the clinical significance of the interactions with cytochrome CYP3A and P-gp inhibitors/inducers. A higher rate of bleeding has been observed in association with antiplatelet agents or non-steroidal anti-inflammatory drugs. Their safety profile has not been sufficiently studied in the elderly, and in patients with liver disease or severe renal impairment. Dose adjustment is necessary in patients with moderate renal impairment and a higher bleeding rate has been observed in this subgroup, although not higher than with warfarin. The clinical settings that require monitoring of coagulation assays have not yet been specified. Reversal of their anticoagulant effect may be problematic in case of severe bleeding. Therefore, despite the obvious advantages of the direct oral anticoagulants, experience is still lacking for many patient subgroups in which they should be withheld awaiting more data.
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ABSTRACT: Increasing age and renal impairment are risk factors for venous thrombosis but also for anticoagulant-induced bleeding. In large-scale phase III trials, non-VKA oral anticoagulants (NOACs) were at least as effective and safe for the treatment of acute venous thromboembolism as warfarin. Here, we review the efficacy and safety of dabigatran, rivaroxaban, apixaban and edoxaban in the subgroups of elderly patients (≥75 years) and patients with impaired renal function (creatinine clearance ≤50 ml/min). In all phase III trials, the efficacy of NOACs in the prevention of recurrent VTE was conserved both in the elderly subgroup and in the subgroup with impaired renal function. In a meta-analysis of the pooled results, NOACs reduced VTE recurrence compared with warfarin in elderly patients. In elderly patients and patients with impaired renal function, the safety of NOACs was in line with the results of the overall study. NOACs may offer an effective, safer and more convenient alternative for VKAs also in the elderly. However, the efficacy/safety profile of NOACs in the aged population needs to be confirmed in real-life.