Dabigatran, bleeding, and the regulators

@article{Moore2014DabigatranBA,
  title={Dabigatran, bleeding, and the regulators},
  author={Thomas J. Moore and Michael R. Cohen and Donald R. Mattison},
  journal={BMJ : British Medical Journal},
  year={2014},
  volume={349}
}
Thomas J Moore and colleagues highlight the differences in how US and European regulators managed the safety problems of the new anticoagulant dabigatran and ask both to think again and mandate plasma monitoring of dabigatran 
View on BMJ
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78 Citations
Background Citations
13
Methods Citations
2

78 Citations

Citation Type

Citation Type

Dabigatran: how the drug company withheld important analyses
  • D. Cohen
  • Biology
    BMJ : British Medical Journal
  • 2014
TLDR
Recommendations for use of new generation oral anticoagulants may be flawed because regulators did not see evidence showing that monitoring drug plasma levels could improve safety, an investigation by The BMJ finds.
New oral anticoagulants: dosing and monitoring
TLDR
The two reports on the risk of gastrointestinal bleeding with new oral anticoagulants come as no surprise given the dosing regimens that have been adopted, but it is surprising that an individualised dosing strategy is not suggested.
A comprehensive appraisal of dabigatran etexilate clinical evidence and applications: a 10-year-long story.
TLDR
This review aims to summarize current evidence on dabigatran, starting from its pharmacological characteristics, and providing an updated overview of pivotal randomized controlled trials and real-world data on its efficacy and safety.
News and views The Dabigatran debate
TLDR
The debate to date about Dabigatran is reviewed, and whether or not support for the drug, alongside commissioning bodies, now need to retract, is asked.
The Dabigatran debate
TLDR
In light of the emerging concerns regarding the RE-LY trial and Dabigatran, highlighted by a recent BMJ investigation, it is asked whether or not support for the drug should be retracted.
Corrected and republished from: Regional anesthesia and antithrombotic agents: instructions for use.
This corrects the article DOI: 10.23736/S0375-9393.16.11414-2.
Bleeding and the new anticoagulants: strategies and concerns.
TLDR
Using their cell-based model of thrombin generation, the authors have compared the efficacy of recombinant factor VIIa and a fourfactor PCC in the presence of dabigatran and observed a good correlation with hemostasis in vivo in a mouse saphenous vein bleeding model.
Rivaroxaban presents a better pharmacokinetic profile than dabigatran in an obese non-diabetic stroke patient
Direct oral anticoagulants: to switch or not to switch?
TLDR
Both prescribing physicians and patients should consider the advantages and the disadvantages of DOACs compared with VKAs before deciding what is best for the individual patient.
Consideration of clinical variables for choosing new anticoagulant alternatives to warfarin for the management of non‐valvular atrial fibrillation
TLDR
Clinical parameters to consider when choosing an alternative to warfarin for a specific patient are detailed and summarized in a Comparison Table.
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References

SHOWING 1-10 OF 27 REFERENCES
Dabigatran and postmarketing reports of bleeding.
TLDR
The FDA used the Mini-Sentinel database to determine that the actual rates of bleeding events were not higher with dabigatran than with warfarin.
Dabigatran versus warfarin in patients with atrial fibrillation.
TLDR
Dabigatran appeared to be more efficacious in patients who weighed less and in patients with impaired renal function (in whom the drug ac­ cumulates), pointing to significant interpatient variability in response.
Efficacy and safety of dabigatran etexilate and warfarin in "real-world" patients with atrial fibrillation: a prospective nationwide cohort study.
Balancing the benefits and risks of 2 doses of dabigatran compared with warfarin in atrial fibrillation.
New oral anticoagulants: discussion on monitoring and adherence should start now!
TLDR
Optimization of dose adjustment based on therapeutic levels of the drug may be more appropriate than fixed dose therapy and the development and implementation in quantitative laboratory assays will enable further dose optimization.
Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients
TLDR
A definition of major bleeding that should be applicable to all agents that interfere with hemostasis is developed and is to seek approval from the regulatory authorities to enhance its incorporation into future clinical trial protocols.
Newly identified events in the RE-LY trial.
TLDR
After discussions with the Food and Drug Administration, the primary and secondary efficacy and safety data were checked for consistency, and the study database was reevaluated for possible underreporting of events.
The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy).
The promise of pharmacoepidemiology in helping clinicians assess drug risk.
TLDR
In considering their clinical role as alternatives to warfarin, these drugs illustrate the growing pains, vulnerabilities, and promise of 2 related, younger disciplines: pharmacoepidemiology and pharmacoeconomics.
Dabigatran versus warfarin in patients with mechanical heart valves.
TLDR
The use of dabigatran in patients with mechanical heart valves was associated with increased rates of thromboembolic and bleeding complications, as compared with warfarin, thus showing no benefit and an excess risk.
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