Amino Terminal Pro–B-Type Natriuretic Peptide, Secondary Stroke Prevention, and Choice of Antithrombotic Therapy

Abstract

Because of its association with atrial fibrillation and heart failure, we hypothesized that amino terminal pro-B-type natriuretic peptide (NT-proBNP) would identify a subgroup of patients from the Warfarin-Aspirin Recurrent Stroke Study, diagnosed with inferred noncardioembolic ischemic strokes, where anticoagulation would be more effective than antiplatelet agents in reducing risk of subsequent events. NT-proBNP was measured in stored serum collected at baseline from participants enrolled in Warfarin-Aspirin Recurrent Stroke Study, a previously reported randomized trial. Relative effectiveness of warfarin and aspirin in preventing recurrent ischemic stroke or death over 2 years was compared based on NT-proBNP concentrations. About 95% of 1028 patients with assays had NT-proBNP below 750 pg/mL, and among them, no evidence for treatment effect modification was evident. For 49 patients with NT-proBNP >750 pg/mL, the 2-year rate of events per 100 person-years was 45.9 for the aspirin group and 16.6 for the warfarin group, whereas for 979 patients with NT-proBNP ≤750 pg/mL, rates were similar for both treatments. For those with NT-proBNP >750 pg/mL, the hazard ratio was 0.30 (95% confidence interval: 0.12-0.84; P=0.021) significantly favoring warfarin over aspirin. A formal test for interaction of NT-proBNP with treatment was significant (P=0.01). For secondary stroke prevention, elevated NT-proBNP concentrations may identify a subgroup of ischemic stroke patients without known atrial fibrillation, about 5% based on the current study, who may benefit more from anticoagulants than antiplatelet agents. Clinical Trial Registration- This trial was not registered because enrollment began before 2005.