Pfizer Atrial Fibrillation Research
Title: Apixaban versus Warfarin in Patients with Atrial Fibrillation
Objective: In this randomized, double-blind trial, we compared apixaban (at a dose of 5mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause.
Year: 2011
Source: New England Journal of Medicine
Link: http://www.nejm.org/doi/full/10.1056/NEJMoa1107039
Clinical Area: Cardiology
| Sample Size Section in Paper/Protocol: |
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''The primary non inferiority hypothesis required that apixaban preserve at least 50% of the relative reduction in the risk of stroke or systemic embolism associated with warfarin (62%) in six previous, major randomized, controlled trials.10 This hypothesis provided a lower 95% confidence interval of 1.88 for the relative risk with placebo as compared with warfarin, and one half of this value was 1.44 (or 1.38 on a log scale).
We estimated that with the occurrence of the primary outcome in 448 patients, the study would have 90% power to ensure that the upper boundary of the 99% confidence interval for the relative risk would be less than 1.44 and that the upper boundary of the 95% confidence interval for the relative risk would be less than 1.38, on the assumption that apixaban and warfarin had identical effects. On the basis of the overall event rate during the trial, we planned to recruit 18,000 patients in order to reach this number of events with approximately 2 years of follow-up.”
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From Protocol: Incidence rate = 1.2 events per hundred person-years
Average Follow-up = 2.1 years | Expected Dropout = 1%
Note: Only the 99% confidence interval with 1.44 relative risk analysis replicated since protocol states this was analysis with higher sample size.
Summary of Necessary Parameter Estimates for Sample Size Calculation:
| Parameter |
Value |
| Significance Level (1-Sided) |
0.005 |
| Non-Inferiority Margin |
1.44 |
| Power |
90% |
| Incidence Rate per Year |
0.012 |
| Average Follow-Up (Years) |
2.1% |
| Expected Dropout |
1% |
