Dabigatran and Postmarketing Reports of Bleeding

From the Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD.
New England Journal of Medicine (Impact Factor: 55.87). 03/2013; 368(14). DOI: 10.1056/NEJMp1302834
Source: PubMed


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 . . .

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    • "This controversy lead to a FDA initiative through Mini-Sentinel, a pilot post-marketing surveillance system. A preliminary report [FDA, 2012] and a publication showed that bleeding risk with dabigatran was actually lower than with warfarin both for intracranial and gastrointestinal hemorrhage, attributing the large number of reported bleeding events as a 'a salient example of stimulated reporting' [Southworth et al. 2013]. Controversy persisted [Institute for Safe Medication Practices, 2013] and so did postmarketing surveillance with Mini-Sentinel. "
    Therapeutic Advances in Neurological Disorders 08/2015; DOI:10.1177/1756285615601360 · 3.14 Impact Factor
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    • "A subgroup analysis in secondary stroke prevention with 3,623 patients showed a nonsignificant trend in favor of dabigatran etexilate having greater efficacy, with a significantly lower rate of CH [10]. Dabigatran etexilate has also been shown in postmarketing surveillance studies to be both safe [11] and cost-effective [12]. Clinical guidelines recommend the use of dabigatran etexilate over VKA in "
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    ABSTRACT: Introduction: Our aim was to analyze our clinical experience with dabigatran etexilate in secondary stroke prevention. Methods: We retrospectively included patients starting dabigatran etexilate for secondary stroke prevention from March 2010 to December 2012. Efficacy and safety variables were registered. Results: 106 patients were included, median follow-up of 12 months (range 1-31). Fifty-six females (52.8%), mean age 76.4 (range 50-95, SD 9.8), median CHADS2 4 (range 2-6), CHA2DS2-VASc 5 (range 2-9), and HAS-BLED 2 (range 1-5). Indication for dabigatran etexilate was ischemic stroke in 101 patients and acute cerebral hemorrhage (CH) due to warfarin in 5 (4.7%). Dabigatran etexilate 110 mg bid was prescribed in 71 cases (67%) and 150 mg bid was prescribed in the remaining. Seventeen patients (16%) suffered 20 complications during follow-up. Ischemic complications (10) were 6 transient ischemic attacks (TIA), 3 ischemic strokes, and 1 acute coronary syndrome. Hemorrhagic complications (10) were CH (1), gastrointestinal bleeding (6), mild hematuria (2), and mild metrorrhagia (1), leading to dabigatran etexilate discontinuation in 3 patients. Patients with previous CH remained uneventful. Three patients died (pneumonia, congestive heart failure, and acute cholecystitis) and 9 were lost during follow-up. Conclusions: Dabigatran etexilate was safe and effective in secondary stroke prevention in clinical practice, including a small number of patients with previous history of CH.
    BioMed Research International 07/2014; 2014:567026. DOI:10.1155/2014/567026 · 3.17 Impact Factor
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    • "Few data exist regarding the safety of NOACs in clinical practice, and the available information reflects the limitations of post-authorization studies, such as reporting bias. Recent evidence provides contradiction to earlier safety reports that suggested that the major bleeding rates in patients receiving NOACs in clinical practice did not exceed the rates reported in the pivotal trials [21] [33]. "
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    ABSTRACT: Dabigatran etexilate (DE), rivaroxaban, and apixaban are nonvitamin K antagonist oral anticoagulants (NOACs) that have been compared in clinical trials with existing anticoagulants (warfarin and enoxaparin) in several indications for the prevention and treatment of thrombotic events. All NOACs presented bleeding events despite a careful selection and control of patients. Compared with warfarin, NOACs had a decreased risk of intracranial hemorrhage, and apixaban and DE (110 mg BID) had a decreased risk of major bleeding from any site. Rivaroxaban and DE showed an increased risk of major gastrointestinal bleeding compared with warfarin. Developing strategies to minimize the risk of bleeding is essential, as major bleedings are reported in clinical practice and specific antidotes are currently not available. In this paper, the following preventive approaches are reviewed: improvement of appropriate prescription, identification of modifiable bleeding risk factors, tailoring NOAC’s dose, dealing with a missed dose as well as adhesion to switching, bridging and anesthetic procedures.
    BioMed Research International 06/2014; 2014(Article ID 616405). DOI:10.1155/2014/616405 · 3.17 Impact Factor
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