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Published on: February 28, 2012
Estimating Vitamin K Antagonist Anticoagulation Benefit in People With Atrial Fibrillation Accounting for Competing
Sachin J Shah1, Carl van Walraven2, Sun Young Jeon3
1Division of General Internal Medicine, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA (S.J.S., D.E.S.).
Insights
Competing risks of death significantly alter anticoagulant benefit estimates in atrial fibrillation patients. The standard CHA2DS2-VASc model overestimates benefits, particularly for those with shorter life expectancies.
Area of Science:
- Cardiology
- Clinical Trials
- Pharmacology
Background:
- Atrial fibrillation (AF) patients face high mortality, partly from non-vascular causes.
- The competing risk of death can diminish the perceived benefit of anticoagulation.
- Assessing anticoagulant efficacy requires accounting for competing risks.
Purpose of the Study:
- To evaluate if competing risks materially impact the estimated anticoagulant benefit in AF patients.
- To compare the guideline-endorsed CHA2DS2-VASc model with a competing risk model for estimating VKA benefit.
Main Methods:
- Secondary analysis of 12 randomized controlled trials involving AF patients treated with VKAs versus placebo or antiplatelets.
- Estimated absolute risk reduction (ARR) of VKAs for stroke/systemic embolism using CHA2DS2-VASc and a competing risk model.
- Compared benefit estimates based on varying life expectancies.
Main Results:
- The CHA2DS2-VASc model overestimated VKA's ARR compared to the competing risk model (median 3-year ARR: 6.9% vs. 5.2%).
- Benefit overestimation by CHA2DS2-VASc was more pronounced in patients with lower life expectancies.
- For lowest decile life expectancy, the 3-year ARR difference was 4.7%; for highest decile, it was -1.3%.
Conclusions:
- Vitamin K antagonist (VKA) anticoagulants are highly effective in reducing stroke risk in AF.
- The CHA2DS2-VASc model overestimates VKA benefits by not accounting for competing risks and nonlinear benefit.
- Benefit overestimation is greatest with shorter life expectancies and longer estimation horizons.
Background:
Patients with atrial fibrillation have a high mortality rate that is only partially attributable to vascular outcomes. The competing risk of death may affect the expected anticoagulant benefit. We determined if competing risks materially affect the guideline-endorsed estimate of anticoagulant benefit.
Methods:
We conducted a secondary analysis of 12 randomized controlled trials that randomized patients with atrial fibrillation to vitamin K antagonists (VKAs) or either placebo or antiplatelets. For each participant, we estimated the absolute risk reduction (ARR) of VKAs to prevent stroke or systemic embolism using 2 methods-first using a guideline-endorsed model (CHA2DS2-VASc) and then again using a competing risk model that uses the same inputs as CHA2DS2-VASc but accounts for the competing risk of death and allows for nonlinear growth in benefit. We compared the absolute and relative differences in estimated benefit and whether the differences varied by life expectancy.
Results:
A total of 7933 participants (median age, 73 years, 36% women) had a median life expectancy of 8 years (interquartile range, 6-12), determined by comorbidity-adjusted life tables and 43% were randomized to VKAs. The CHA2DS2-VASc model estimated a larger ARR than the competing risk model (median ARR at 3 years, 6.9% [interquartile range, 4.7%-10.0%] versus 5.2% [interquartile range, 3.5%-7.4%]; P<0.001). ARR differences varied by life expectancies: for those with life expectancies in the highest decile, 3-year ARR difference (CHA2DS2-VASc model - competing risk model 3-year risk) was -1.3% (95% CI, -1.3% to -1.2%); for those with life expectancies in the lowest decile, 3-year ARR difference was 4.7% (95% CI, 4.5%-5.0%).
Conclusions:
VKA anticoagulants were exceptionally effective at reducing stroke risk. However, VKA benefits were misestimated with CHA2DS2-VASc, which does not account for the competing risk of death nor decelerating treatment benefit over time. Overestimation was most pronounced when life expectancy was low and when the benefit was estimated over a multiyear horizon.
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