High Sensitivity Troponin T and Risk Stratification in Patients With Atrial Fibrillation During Treatment With Apixaban or Warfarin

Study Questions:

In patients with atrial fibrillation and at least one CHADS2 risk factor for stroke or systemic embolism, what are the associations between high-sensitivity troponin T (hs-TnT) at baseline and clinical outcomes?

Methods:

This was a prespecified substudy of the ARISTOTLE trial (a double-blind, double-dummy, randomized clinical trial in which patients with at least one CHADS2 risk factor for stroke or systemic embolism were randomized to warfarin or apixaban). The substudy included 14,897 patients who provided blood samples at randomization and also had available results of hs-TnT. Adjusted Cox regression models were used to evaluate associations between baseline hs-TnT and outcomes.

Results:

99.4% of the patients had measurable hs-TnT. Higher hs-TnT levels were strongly and significantly associated with a higher rate of all outcomes in adjusted analyses. The annual rates of stroke or systemic embolism ranged from 0.87% in the lowest to 2.13% in the highest hs-TnT quartile (adjusted hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.35-2.78; p = 0.0010). Cardiac mortality increased gradually by higher hs-TnT levels reaching an adjusted HR of 4.31 (95% CI, 2.91-6.37; p < 0.0001) in the group with hs-TnT >16.7 ng/L (vs. the lowest quartile hs-TnT group). hs-TnT and CHA2DS2-VASc score provided statistically significant independent prognostic information; the addition of hs-TnT levels to the CHA2DS2-VASc score improved the C-statistic from 0.620 to 0.635 (p = 0.0226).

Conclusions:

The vast majority of patients with atrial fibrillation and at least one clinical risk factor for stroke have measurable levels of hs-TnT. The hs-TnT level is independently associated with an increased risk of stroke, cardiac death, and major bleeding.

Perspective:

This prespecified substudy of the ARISTOLE trial corroborates findings from a RE-LY biomarker substudy, establishing the independent prognostic value of troponin levels in patients with atrial fibrillation and at least one clinical risk factor for stroke. As the authors suggest, troponin levels may be particularly helpful in patients with low CHA2DS2-VASc scores who are still at elevated risk for stroke.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Anticoagulation Management and Atrial Fibrillation, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Stroke, Octamer Transcription Factor-1, Warfarin, Troponin T, Risk Factors, Pyrazoles, Prognosis, Biological Markers, Cardiology, Estrogens, Atrial Fibrillation, Embolism, Pyridones, Hemorrhage, Troponin


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