Balancing individual benefits and risks of warfarin in patients with atrial fibrillation

Background: Anticoagulation with warfarin reduces the risk of ischaemic stroke in patients with atrial fibrillation (AF) but may increase the risk of bleeding. A positive benefit-risk balance in the overall AF population has been well established, but hardly studied on an individual level. Objectives: To estimate benefits and risks of warfarin treatment for the individual and identify characteristics determining the benefit-risk balance. Methods: The study cohort consisted of patients with AF exposed to warfarin in the Clinical Practice Research Datalink (CPRD). Outcomes of interest were ischaemic stroke, transient ischaemic attack, haemorrhagic stroke and major bleed. The probability of an outcome dur-ing exposure was estimated with a Cox proportional hazard model. Attributable risks for each outcome were estimated using the individual probabilities and relative rates of warfarin effects (based on meta-analyses of trials). Each outcome was weighted by 1-year mortality. The individual net benefit was calculated as the weighted sum of benefits minus adverse effects and then characterized as being less favourable (net benefit <0.5), neutral (net benefit 0.5-1.5) or favourable (net benefit > 1.5). Logistic regression was used to identify characteristics that explained a less favourable net benefit. Results: The study population included 33,772 patients with AF exposed to warfarin. The mean net benefit was 1.17 (SD 16.0) ischaemic stroke cases or equivalent prevented. Characteristics that were associated with a less favourable benefit-risk balance were age > 85 years (OR 2.82, 95% CI 2.37-3.36), presence of congestive heart failure (OR 2.67, 2.27-3.14), cancer (OR 2.51, 2.19-2.88), minor bleed (OR 2.68, 2.25- 3.18) and renal insufficiency (OR 3.30, 2.37-4.60). Hypertension (OR 0.41, 0.36-0.46) and vascular disease (OR 0.16, 0.13-0.19) were associated with a favourable benefit-risk balance. Conclusions: We confirmed that the net benefit of warfarin for the overall AF population is positive. However, there is a large variation of benefit-risk balance across this population for individual patients.