Overestimation of anticoagulant benefit in patients with atrial fibrillation and low life expectancy: evidence from 12 randomized trials.

IMPORTANCE: Patients with atrial fibrillation have a high rate of all-cause mortality that is only partially attributable to vascular outcomes. While the competing risk of death affects expected anticoagulant benefit, guidelines do not account for the competing risk of death.

OBJECTIVE: Compare anticoagulant benefit for patients with atrial fibrillation estimated with the CHA DS -VASc model vs. a Competing Risk Model that accounts for the competing risk of death and does not assume a consistent growth in treatment benefit over time.

DESIGN: Secondary analysis of randomized controlled trials (RCTs).

SETTING: 12 RCTs randomizing patients with atrial fibrillation to oral anticoagulants or either placebo or antiplatelets.

PARTICIPANTS: 7933 adults with non-valvular atrial fibrillation.

EXPOSURE: Predicted anticoagulant absolute risk reduction (ARR) by guideline-endorsed model (CHA DS -VASc) vs. a Competing Risk Model that uses the same inputs as CHA DS -VASc but accounts for the competing risk of death and allows for non-linear growth in benefit over time.

MAIN OUTCOME MEASURES: Ischemic stroke or systemic embolism.

RESULTS: 7933 participants had a median life expectancy of 8 years (IQR 6, 12), determined by comorbidity-adjusted life tables. 43% were randomized to oral anticoagulation (median age 73 years, 36% women). The guideline-endorsed CHA DS -VASc model estimated a larger ARR than the Competing Risk Model (median ARR at 3 years, 6.9% vs. 5.2%). ARR differences varied by life expectancies: for those with life expectancies in the highest decile, 3-year ARR difference (CHA DS -VASc model â€" Competing Risk Model 3-year risk) was -1.2% (42% relative underestimation); for those with life expectancies in the lowest decile, 3-year ARR difference was 5.9% (91% relative overestimation).

CONCLUSION AND RELEVANCE: Anticoagulants are exceptionally effective at reduced stroke risk. However, anticoagulant benefits were misestimated with CHA DS -VASc, which does not account for the competing risk of death nor decelerating treatment benefit over time. Overestimation was most pronounced in patients with the lowest life expectancy and when benefit was estimated over a multi-year horizon.