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Published on: February 28, 2012
Effect of Apixaban on All-Cause Death in Patients with Atrial Fibrillation: a Meta-Analysis Based on Imputed Placebo
Patrícia O Guimarães1, Renato D Lopes2, Daniel M Wojdyla1
1Duke Clinical Research Institute, Duke Health, Room 0311 Terrace Level, 2400 Pratt Street, Durham, NC, 27705, USA.
Insights
Apixaban significantly reduces all-cause mortality in atrial fibrillation (AF) patients compared to an imputed placebo. This finding supports its use in stroke prevention for AF.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Vitamin K antagonists (VKAs) are standard for stroke prevention in atrial fibrillation (AF).
- Direct placebo comparisons for newer anticoagulants are ethically challenging in AF.
- Indirect comparison methods are crucial for evaluating treatments in this context.
Purpose of the Study:
- To evaluate the effect of apixaban on all-cause mortality in patients with AF.
- To perform an indirect comparison of apixaban versus placebo using existing trial data.
Main Methods:
- Meta-analysis of apixaban versus warfarin (ARISTOTLE) and apixaban versus aspirin (AVERROES) trials.
- Utilized data from randomized controlled trials comparing warfarin and aspirin to placebo/no treatment.
- Employed meta-analysis to indirectly compare apixaban with an imputed placebo for mortality risk.
Main Results:
- Warfarin (OR 0.74) and aspirin (OR 0.86) showed reduced mortality versus placebo/no treatment.
- Apixaban demonstrated a 34% reduction in death versus imputed placebo in ARISTOTLE (CI 12-50%).
- Apixaban showed a 33% reduction in death versus imputed placebo in AVERROES (CI 6-52%).
- Pooled analysis indicated a 34% reduction in all-cause death with apixaban versus imputed placebo (CI 18-47%).
Conclusions:
- Indirect comparisons suggest apixaban significantly reduces all-cause mortality in AF patients.
- Apixaban offers approximately a one-third reduction in death compared to an imputed placebo.
- Findings support apixaban's role in managing AF patients to reduce mortality risk.
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.
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