Abstract 53: Recurrent Stroke in the Warfarin versus Aspirin in Reduced Ejection Fraction (WARCEF) Trial

Background: WARCEF randomized 2305 patients in sinus rhythm with ejection fraction (EF) ≤35% to warfarin (INR 2.0-3.5) or aspirin 325 mg. Warfarin reduced the incident ischemic stroke (IIS) hazard rate by 48% over aspirin in a secondary analysis. The IIS rate in heart failure (HF) is too low to warrant routine anticoagulation but epidemiologic studies show that prior stroke increases the stroke risk in HF. We here explore IIS rates in WARCEF patients with and without baseline stroke to determine if a subgroup with an IIS rate high enough (3-5 per 100 patient-years [PY]) to give a clinically relevant warfarin effect can be identified. Methods: We compared the IIS rate between patients with baseline stroke and those without using the exact conditional score test for Poisson variables. We looked for risk factors for IIS , by comparing IIS rates between different levels of each potential risk factor. For EF we tried cut-off points of 10%, 15% and 20%. 15% was used as it was the highest EF that was associated with a significant increase in IIS rate. IIS and EF strata were balanced as to warfarin/aspirin assignment by the stratified randomized design. A multiple Poisson regression examined the simultaneous effects of all risk factors on IIS rate. Missing values were assigned the modal value. Results: Twenty of 248 (8.1%) patients with baseline stroke and 64 of 2048 (3.1%) without had IIS. IIS rates in patients with baseline stroke were significantly greater compared to patients without (rate ratio 2.67; 2.37 per 100PY and 0.89 per 100PY, respectively, p=0.0004). Fourteen of 219 (6.4%) patients with EF<15% and 70 of 2079 (3.4%) with EF ≥15% had IIS. IIS rates in patients with EF<15% and patients with EF ≥15% were 2.04 per 100PY and 0.95 per 100PY, respectively (p=0.012). IIS rate in patients with baseline stroke and EF<15% was 5.88 per 100PY. In the multiple Poisson regression analysis only stroke at baseline (p=0.0001) and EF<15% vs. ≥15% (p=.005) remained significant predictors of IIS. Conclusions: In a WARCEF exploratory analysis, prior stroke and EF<15% were risk factors for IIS. A clinically relevant stroke risk reduction might be obtainable with warfarin in HF patients with prior stroke and EF<15%.