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Effect of Apixaban on All-Cause Death in Patients with Atrial Fibrillation: a Meta-Analysis Based on Imputed Placebo Effect
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2017 (English)In: Cardiovascular Drugs and Therapy, ISSN 0920-3206, E-ISSN 1573-7241, Vol. 31, no 3, p. 295-301Article in journal (Refereed) Published
Abstract [en]

PURPOSE: Vitamin K antagonists (VKAs) are the standard of care for stroke prevention in patients with atrial fibrillation (AF); therefore, there is not equipoise when comparing newer oral anticoagulants with placebo in this setting.

METHODS: To explore the effect of apixaban on mortality in patients with AF, we performed a meta-analysis of apixaban versus placebo using a putative placebo analysis based on randomized controlled clinical trials that compared warfarin, aspirin, and no antithrombotic control. We used data from two prospective randomized controlled trials for our comparison of apixaban versus warfarin (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) and apixaban versus aspirin (Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment). Using meta-analysis approaches, we indirectly compared apixaban with an imputed placebo with respect to the risk of death in patients with AF. We used results from meta-analyses of randomized trials as our reference for the comparison between warfarin and placebo/no treatment, and aspirin and placebo/no treatment.

RESULTS: In these meta-analyses, a lower rate of death was seen both with warfarin (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.57-0.97) and aspirin (OR 0.86, 95% CI 0.69-1.07) versus placebo/no treatment. Using data from ARISTOTLE and AVERROES, apixaban reduced the risk of death by 34% (95% CI 12-50%; p = 0.004) and 33% (95% CI 6-52%; p = 0.02), respectively, when compared with an imputed placebo. The pooled reduction in all-cause death with apixaban compared with an imputed placebo was 34% (95% CI 18-47%; p = 0.0002).

CONCLUSIONS: In patients with AF, indirect comparisons suggest that apixaban reduces all-cause death by approximately one third compared with an imputed placebo.

Place, publisher, year, edition, pages
2017. Vol. 31, no 3, p. 295-301
Keywords [en]
Apixaban, Aspirin, Atrial fibrillation, Mortality, Placebo, Warfarin
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:uu:diva-342534DOI: 10.1007/s10557-017-6728-zISI: 000407366100007PubMedID: 28516318OAI: oai:DiVA.org:uu-342534DiVA, id: diva2:1184591
Available from: 2018-02-21 Created: 2018-02-21 Last updated: 2018-03-22Bibliographically approved

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Wallentin, Lars

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