High-Sensitivity Cardiac Troponin T for Risk Stratification in Patients With Embolic Stroke of Undetermined Source
Jan F Scheitz1,2,3,4, Guillaume Pare5, Lesly A Pearce6
1Center for Stroke Research Berlin, Charité-Universitätsmedizin Berlin, Germany (J.F.S., C.H.N., M.E.).
Insights
High-sensitivity cardiac troponin T (hs-cTnT) levels predict major vascular events in patients with embolic stroke of undetermined source (ESUS). However, hs-cTnT did not guide anticoagulation therapy decisions in this study.
Area of Science:
- Cardiology
- Neurology
- Biomarker Research
Background:
- Optimal secondary prevention strategies for embolic stroke of undetermined source (ESUS) are not well-defined.
- High-sensitivity cardiac troponin T (hs-cTnT) is a potential biomarker for cardiovascular risk stratification.
Purpose of the Study:
- To evaluate the association between hs-cTnT levels and major vascular events in ESUS patients.
- To determine if hs-cTnT can identify ESUS patients who may benefit from anticoagulation therapy.
Main Methods:
- Analysis of the biomarker substudy from the NAVIGATE ESUS trial, a randomized controlled trial comparing rivaroxaban and aspirin.
- Patients were stratified based on hs-cTnT levels relative to the upper reference limit (14 ng/L).
- Cox proportional hazard models were used to assess the association between hs-cTnT and cardiovascular outcomes, including recurrent ischemic stroke.
Main Results:
- hs-cTnT was detectable in 95% of 1337 ESUS patients; 21% had levels at/above the upper reference limit.
- Elevated hs-cTnT levels were associated with higher rates of combined cardiovascular events (8.2% vs 4.8% per year).
- A significant treatment modification was observed for combined cardiovascular events based on hs-cTnT levels (P=0.04), but not for recurrent ischemic stroke (P=0.3).
Conclusions:
- hs-cTnT levels are associated with increased cardiovascular event rates in ESUS patients, supporting their use in risk stratification.
- The study did not find evidence that hs-cTnT results should guide anticoagulation therapy decisions in ESUS.
- While rivaroxaban showed a trend towards fewer recurrent strokes, outcomes were not clearly stratified by hs-cTnT levels.
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.
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