Jan F Scheitz1,2,3,4, Guillaume Pare5, Lesly A Pearce6, Hardi Mundl7, W Frank Peacock8, Anna Czlonkowska9, Mukul Sharma10, Christian H Nolte1,2,3,4, Ashkan Shoamanesh10, Scott D Berkowitz11, Thomas Krahn7,12, Matthias Endres1,2,3,4,13. 1. Center for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, Germany (J.F.S., C.H.N., M.E.). 2. Klinik und Hochschulambulanz für Neurologie, Charité-Universitätsmedizin Berlin, Germany (J.F.S., C.H.N., M.E.). 3. DZHK (German Centre for Cardiovascular Research), partner site Berlin, Germany (J.F.S., C.H.N., M.E.). 4. Berlin Institute of Health (BIH), Germany (J.F.S., C.H.N., M.E.). 5. Population Health Research Institute, McMaster University, Hamilton, ON, Canada (G.P.). 6. Biostatistics Consultant, Minot, ND (L.A.P.). 7. Bayer AG, Wuppertal, Germany (H.M., T.K.). 8. Baylor College of Medicine, Houston, TX (W.F.P.). 9. 2nd Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland (A.C.). 10. Department of Medicine (Neurology), Population Health Research Institute, McMaster University, Hamilton Health Sciences, Canada (M.S., A.S.). 11. Research & Development, Pharmaceuticals, Bayer U.S., LLC, Whippany (S.D.B.). 12. Department of Pharmacology and Personalised Medicine, Maastricht University, the Netherlands (T.K.). 13. DZNE (German Center for Neurodegenerative Disease), partner site Berlin, Germany (M.E.).
Abstract
BACKGROUND AND PURPOSE: Optimal secondary prevention for patients with embolic stroke of undetermined source (ESUS) remains unknown. We aimed to assess whether high-sensitivity cardiac troponin T (hs-cTnT) levels are associated with major vascular events and whether hs-cTnT may identify patients who benefit from anticoagulation following ESUS. METHODS: Data were obtained from the biomarker substudy of the NAVIGATE ESUS trial, a randomized controlled trial testing the efficacy of rivaroxaban versus aspirin for secondary stroke prevention in ESUS. Patients were dichotomized at the hs-cTnT upper reference limit (14 ng/L, Gen V, Roche Diagnostics). Cox proportional hazard models were computed to explore the association between hs-cTnT, the combined cardiovascular end point (recurrent stroke, myocardial infarction, systemic embolism, cardiovascular death), and recurrent ischemic stroke. RESULTS: Among 1337 patients enrolled at 111 participating centers in 18 countries (mean age 67±9 years, 61% male), hs-cTnT was detectable in 95% and at/above the upper reference limit in 21%. During a median follow-up of 11 months, the combined cardiovascular end point occurred in 68 patients (5.0%/y, rivaroxaban 28 events, aspirin 40 events; hazard ratio, 0.67 [95% CI, 0.41-1.1]), and recurrent ischemic stroke occurred in 50 patients (4.0%/y, rivaroxaban 16 events, aspirin 34 events, hazard ratio 0.45 [95% CI, 0.25-0.81]). Annualized combined cardiovascular end point rates were 8.2% (9.5% rivaroxaban, 7.0% aspirin) for those above hs-cTnT upper reference limit and 4.8% (3.1% rivaroxaban, 6.6% aspirin) below with a significant treatment modification (P=0.04). Annualized ischemic stroke rates were 4.7% above hs-cTnT upper reference limit and 3.9% below, with no suggestion of an interaction between hs-cTnT and treatment (P=0.3). CONCLUSIONS: In patients with ESUS, hs-cTnT was associated with increased cardiovascular event rates. While fewer recurrent strokes occurred in patients receiving rivaroxaban, outcomes were not stratified by hs-cTn results. Our findings support using hs-cTnT for cardiovascular risk stratification but not for decision-making regarding anticoagulation therapy in patients with ESUS. REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02313909.
BACKGROUND AND PURPOSE: Optimal secondary prevention for patients with embolic stroke of undetermined source (ESUS) remains unknown. We aimed to assess whether high-sensitivity cardiac troponin T (hs-cTnT) levels are associated with major vascular events and whether hs-cTnT may identify patients who benefit from anticoagulation following ESUS. METHODS: Data were obtained from the biomarker substudy of the NAVIGATE ESUS trial, a randomized controlled trial testing the efficacy of rivaroxaban versus aspirin for secondary stroke prevention in ESUS. Patients were dichotomized at the hs-cTnT upper reference limit (14 ng/L, Gen V, Roche Diagnostics). Cox proportional hazard models were computed to explore the association between hs-cTnT, the combined cardiovascular end point (recurrent stroke, myocardial infarction, systemic embolism, cardiovascular death), and recurrent ischemic stroke. RESULTS: Among 1337 patients enrolled at 111 participating centers in 18 countries (mean age 67±9 years, 61% male), hs-cTnT was detectable in 95% and at/above the upper reference limit in 21%. During a median follow-up of 11 months, the combined cardiovascular end point occurred in 68 patients (5.0%/y, rivaroxaban 28 events, aspirin 40 events; hazard ratio, 0.67 [95% CI, 0.41-1.1]), and recurrent ischemic stroke occurred in 50 patients (4.0%/y, rivaroxaban 16 events, aspirin 34 events, hazard ratio 0.45 [95% CI, 0.25-0.81]). Annualized combined cardiovascular end point rates were 8.2% (9.5% rivaroxaban, 7.0% aspirin) for those above hs-cTnT upper reference limit and 4.8% (3.1% rivaroxaban, 6.6% aspirin) below with a significant treatment modification (P=0.04). Annualized ischemic stroke rates were 4.7% above hs-cTnT upper reference limit and 3.9% below, with no suggestion of an interaction between hs-cTnT and treatment (P=0.3). CONCLUSIONS: In patients with ESUS, hs-cTnT was associated with increased cardiovascular event rates. While fewer recurrent strokes occurred in patients receiving rivaroxaban, outcomes were not stratified by hs-cTn results. Our findings support using hs-cTnT for cardiovascular risk stratification but not for decision-making regarding anticoagulation therapy in patients with ESUS. REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02313909.
Entities:
Keywords:
biomarker; proportional hazards models; rivaroxaban; stroke; troponin T