Large study finds net benefit for warfarin treatment
A retrospective cohort including all 182,678 Swedish Hospital Discharge Register patients with atrial fibrillation (260,000 patient-years) evaluated the net benefit of anticoagulation treatment decisions over an average of 1.5 years.3 The Swedish National Prescribed Drugs Registry, which includes all Swedish pharmacies, identified all patients who were prescribed warfarin during the study years of July 2005 through December 2008. The patients were divided into 2 groups, warfarin or no warfarin, and assigned risk scores using CHA2DS2-VASc and HAS-BLED.4,5
Researchers defined net benefit as the number of ischemic strokes avoided in patients taking warfarin, minus the number of excess intracranial bleeds. They assigned a weight of 1.5 to intracranial bleeds vs 1 for ischemic strokes to compensate for the generally more severe outcomes of intracranial bleeding.
Warfarin produced a net benefit at every CHA2DS2-VASc score greater than 0 (aggregate result of 3.9 fewer events per 100 patient-years; 95% CI, 3.8-4.1; NNT = 26). Kaplan-Meier composite plots of all-cause mortality, ischemic stroke, and intracranial bleeds showed a net benefit favoring warfarin use for all combinations of CHA2DS2-VASc greater than 0 (patients older than 65 years never have a CHA2DS2-VASc score of 0 because they’re assigned 1 point at ages 65 to 74 years and 2 points at 75 years and older) and HAS-BLED scores (all curves P < .00001).
Hazard ratios (HRs) of every combination of scores favored warfarin use (HRs ranged from 0.26-0.72; 95% CIs, less than 1 for all HRs; aggregate benefit at all risk scores: HR = 0.51; 95% CI, 0.50-0.52,). The risk of intracranial bleed, or any bleed, on warfarin at all risk strata was less than the corresponding risk of ischemic stroke (or thromboembolic event) without warfarin except among the lowest risk patients (CHA2DS2-VASc = 0). The difference between thromboses and hemorrhages increased as the CHA2DS2-VASc score increased. Of note, a smaller percentage of the highest risk patients were on warfarin.
EDITOR’S TAKEAWAY
We have solid evidence that, although the risks of systemic and intracranial bleeding from warfarin therapy in older patients with atrial fibrillation increase steadily with advancing age, so do the benefits in reduced ischemic stroke, myocardial infarction, thrombotic emboli, and overall cardiovascular death. Most important, the benefits continue to outweigh the risks by a factor of 2 to 4, even in the oldest age groups.