Evaluation of the acute coronary syndrome safety profile of dabigatran etexilate in patients undergoing major orthopedic surgery: findings from four Phase 3 trials
Autor: | Martin Feuring, Joseph A. Caprini, Andreas Clemens, Bengt I. Eriksson, Stefan Hantel, John J. Smith, Janet Schnee, Gregory W. Barsness |
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Rok vydání: | 2012 |
Předmět: |
Adult
Male Acute coronary syndrome Internationality Drug-Related Side Effects and Adverse Reactions Pyridines MedDRA Risk Assessment law.invention Dabigatran Postoperative Complications Randomized controlled trial law Risk Factors medicine Humans Acute Coronary Syndrome Adverse effect Aged business.industry Incidence Anticoagulants Thrombosis Hematology Middle Aged medicine.disease Survival Analysis Discontinuation Clinical trial Survival Rate Orthopedics Treatment Outcome Direct thrombin inhibitor Anesthesia Benzimidazoles business medicine.drug |
Zdroj: | Thrombosis research. 130(3) |
ISSN: | 1879-2472 |
Popis: | Introduction Several anticoagulants have been associated with a ‘rebound effect’ that potentially increases the risk of thrombosis and cardiovascular events following discontinuation. Four Phase 3 trials of dabigatran etexilate in major orthopedic surgery incorporated measures to assess the risk of acute coronary syndrome (ACS) events during and after treatment. Materials and methods Patients in RE-MOBILIZE®, RE-MODEL™, RE-NOVATE®, and RENOVATE® II were randomized to dabigatran etexilate (150 mg or 220 mg once daily) or enoxaparin for 6–35 days, and followed for up to 90 days. ACS data were tabulated from investigator-reported serious adverse events using ACS-specific Medical Dictionary for Regulatory Authorities (MedDRA) lower-level terms. To ensure that all ACS events were identified in the initial three studies, RE-MOBILIZE®, RE-MODEL™, and RE-NOVATE®, a broader list of MedDRA terms was prespecified that would trigger treatment-blinded adjudication. Results When pooling the four trials, patients receiving dabigatran etexilate 220 mg had the fewest treatment-emergent, investigator-reported ACS events (6 [0.16%] vs 14 [0.51%] for dabigatran 150 mg and 13 [0.35%] for enoxaparin). Corresponding post-treatment rates were 2 (0.06%), 1 (0.04%), and 4 (0.11%). Similarly, treatment-emergent centrally adjudicated definite or likely ACS events in the first three trials were fewer in patients on dabigatran 220 mg (16 [0.60%]) than dabigatran 150 mg (26 [0.95%]) and enoxaparin (20 [0.74%]). The corresponding numbers post treatment were 2, 2, and 7. None of these between-group differences were statistically significant. Conclusion No increased ACS signal was detected with dabigatran etexilate compared with enoxaparin during or after treatment. |
Databáze: | OpenAIRE |
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