Nonvitamin-K-antagonist oral anticoagulants in patients with atrial fibrillation and previous stroke or transient ischemic attack: a systematic review and meta-analysis of randomized controlled trials.

Abstract

BACKGROUND AND PURPOSE:

To assess whether the combined analysis of all phase III trials of nonvitamin-K-antagonist (non-VKA) oral anticoagulants in patients with atrial fibrillation and previous stroke or transient ischemic attack shows a significant difference in efficacy or safety compared with warfarin.

METHODS:

We searched PubMed until May 31, 2012, for randomized clinical trials using the following search items: atrial fibrillation, anticoagulation, warfarin, and previous stroke or transient ischemic attack. Studies had to be phase III trials in atrial fibrillation patients comparing warfarin with a non-VKA currently on the market or with the intention to be brought to the market in North America or Europe. Analysis was performed on intention-to-treat basis. A fixed-effects model was used as more appropriate than a random-effects model when combining a small number of studies.

RESULTS:

Among 47 potentially eligible articles, 3 were included in the meta-analysis. In 14 527 patients, non-VKAs were associated with a significant reduction of stroke/systemic embolism (odds ratios, 0.85 [95% CI, 074-0.99]; relative risk reduction, 14%; absolute risk reduction, 0.7%; number needed to treat, 134 over 1.8-2.0 years) compared with warfarin. Non-VKAs were also associated with a significant reduction of major bleeding compared with warfarin (odds ratios, 0.86 [95% CI, 075-0.99]; relative risk reduction, 13%; absolute risk reduction, 0.8%; number needed to treat, 125), mainly driven by the significant reduction of hemorrhagic stroke (odds ratios, 0.44 [95% CI, 032-0.62]; relative risk reduction, 57.9%; absolute risk reduction, 0.7%; number needed to treat, 139).

CONCLUSIONS:

In the context of the significant limitations of combining the results of disparate trials of different agents, non-VKAs seem to be associated with a significant reduction in rates of stroke or systemic embolism, hemorrhagic stroke, and major bleeding when compared with warfarin in patients with previous stroke or transient ischemic attack.

• Authors: George Ntaios, Vasileios Papavasileiou, Hans-Christoph Diener, Konstantinos Makaritsis, Patrik Michel
• Journal: Stroke (Stroke) Vol. 43 Issue 12 Pg. 3298-304 (Dec 2012) ISSN: 1524-4628 [Electronic] United States
• PMID: 23150654 (Publication Type: Comparative Study, Journal Article, Meta-Analysis, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review, Systematic Review)

Chemical References

• Anticoagulants
• Azetidines
• Benzylamines
• Vitamin K
• ximelagatran
• Warfarin

Topics

• Administration, Oral
• Anticoagulants (administration & dosage)
• Atrial Fibrillation (drug therapy)
• Azetidines (administration & dosage)
• Benzylamines (administration & dosage)
• Clinical Trials, Phase III as Topic
• Humans
• Ischemic Attack, Transient (drug therapy, prevention & control)
• Randomized Controlled Trials as Topic
• Stroke (drug therapy, prevention & control)
• Vitamin K (antagonists & inhibitors)
• Warfarin (administration & dosage)