Twice- or once-daily dosing of novel oral anticoagulants for stroke prevention: a fixed-effects meta-analysis with predefined heterogeneity quality criteria.

Abstract

BACKGROUND:

A number of novel oral anticoagulants (direct thrombin inhibitors or factor Xa inhibitors) are in clinical use for various indications. The dosing regimens differ between twice-daily and once-daily dosing for the prevention of stroke in patients with atrial fibrillation. With the availability of the results from four phase 3 studies (>70,000 patients), we explored whether twice-daily or once-daily dosing provides better risk-benefit balance among novel oral anticoagulants.

METHODS:

We conducted a strict, stepwise, fixed-effects meta-analysis with predefined heterogeneity quality criteria to generate the most appropriate common estimates for twice-daily (BID) or once-daily (QD) dosing regimens. An indirect comparison of these dosing regimens with fixed-effects meta-analysis common estimates (where available), or individual compound results, was done respectively.

RESULTS:

Comparing indirectly BID vs QD dosing regimens resulted in hazard ratios (HR [95% confidence interval]) for stroke and systemic embolism of 0.75 (0.58-0.96) for dabigatran 150 mg BID, and 0.91 (0.73-1.13) for apixaban BID vs the QD dosing regimen. For ischemic stroke, the HR of BID vs QD was 0.85 (0.69-1.05). For intracranial hemorrhage, BID vs rivaroxaban QD was 0.57 (0.37-0.88) and, vs edoxaban QD, 0.81 (0.54-1.22). Due to heterogeneity, common estimates for major bleeding QD or BID were not justified, therefore indirect comparison of regimens were not possible. All non-vitamin K antagonist oral anticoagulants reduced all-cause mortality vs warfarin with a HR of 0.90 (0.86-0.96) without differences between regimen.

CONCLUSIONS:

Based on the available phase 3 study evidence, the twice-daily dosing regimen of non-vitamin K antagonist oral anticoagulants appears to offer a more balanced risk-benefit profile with respect to stroke prevention and intracranial hemorrhage.

• Authors: Andreas Clemens, Herbert Noack, Martina Brueckmann, Gregory Y H Lip
• Journal: PloS one (PLoS One) Vol. 9 Issue 6 Pg. e99276 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24911432 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)

Chemical References

• Anticoagulants

Topics

• Administration, Oral
• Anticoagulants (administration & dosage, pharmacokinetics)
• Drug Administration Schedule
• Humans
• Premedication
• Stroke (etiology, mortality, prevention & control)
• Treatment Outcome