A meta-analysis of phase III randomized controlled trials with novel oral anticoagulants in atrial fibrillation: comparisons between direct thrombin inhibitors vs. factor Xa inhibitors and different dosing regimens.

Abstract

AIMS:

Previous studies evaluating the ability of novel oral anticoagulants (NOAC) to prevent thromboembolism in patients with non-valvular atrial fibrillation (AF) have identified differences between the efficacy and safety of the drugs tested. Whether these differences reflect differences in direct thrombin or Xa inhibition, different dosing regimens or specific aspects of each agent or trial has not yet been explored.

METHODS:

A search was performed on MEDLINE, EMBASE and COCHRANE, and ongoing studies were tracked on clinicaltrials.gov. Phase III randomized controlled trials of direct thrombin inhibitors (DTI) and factor Xa inhibitors (FXaI) vs. warfarin in patients with AF were eligible. Data were pooled using random-effects, according to the Mantel-Haenszel model. Sensitivity analyses were performed on DTI, FXaI, once-daily and twice-daily regimens.

RESULTS:

Seven studies were pooled, including a total of 80,290 patients. Both DTI and FXaI outperformed warfarin regarding stroke or systemic embolism, intracranial bleeding, total and cardiovascular mortality. No significant differences were found between DTI and FXaI or between once-daily and twice-daily regimens. Some drugs performed worse than warfarin regarding some secondary endpoints, including: edoxaban 30 mg bid on ischaemic stroke, dabigatran on acute myocardial infarction, dabigatran 150 mg bid and rivaroxaban 20mgod on gastrointestinal bleeding.

CONCLUSION:

Our pooled data do not support the hypothesis of a significant class-effect of DTI or FXaI, nor the benefit of once-daily vs. twice-daily dosing in the setting of AF, reinforcing that the choice of NOAC should be adapted to the specific patient and focused on the agent itself, rather than the pharmacological class or dosing regimen.

• Authors: Rui Providência, Erik Lerkevang Grove, Steen Husted, Sérgio Barra, Serge Boveda, João Morais
• Journal: Thrombosis research (Thromb Res) Vol. 134 Issue 6 Pg. 1253-64 (Dec 2014) ISSN: 1879-2472 [Electronic] United States
• PMID: 25457584 (Publication Type: Comparative Study, Journal Article, Meta-Analysis)

Chemical References

• Anticoagulants
• Antithrombins
• Factor Xa Inhibitors

Topics

• Administration, Oral
• Aged
• Anticoagulants (administration & dosage, adverse effects)
• Antithrombins (administration & dosage, adverse effects)
• Atrial Fibrillation (epidemiology)
• Causality
• Clinical Trials, Phase III as Topic
• Comorbidity
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Factor Xa Inhibitors (administration & dosage, adverse effects)
• Female
• Hemorrhage (chemically induced, epidemiology)
• Humans
• Male
• Randomized Controlled Trials as Topic
• Risk Factors
• Stroke (chemically induced)
• Thromboembolism (epidemiology, prevention & control)
• Treatment Outcome