High-sensitivity troponin T and risk stratification in patients with atrial fibrillation during treatment with apixaban or warfarin.
OBJECTIVE
The aim of this study was to evaluate the prognostic value of high-sensitivity troponin T (hs-TnT) in addition to clinical risk factors and the CHA2DS2VASc (congestive heart failure, hypertension, 75 years of age and older, diabetes mellitus, previous stroke or transient ischemic attack, vascular disease, 65 to 74 years of age, female) risk score in patients with atrial fibrillation (AF).


BACKGROUND
The level of troponin is a powerful predictor of cardiovascular events and mortality.


METHODS
A total of 14,897 patients with AF were randomized to treatment with apixaban or warfarin in the ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) trial. The associations between baseline hs-TnT levels and outcomes were evaluated using adjusted Cox regression models.


RESULTS
Levels of hs-TnT were measurable in 93.5% of patients; 75% had levels >7.5 ng/l, 50% had levels >11.0 ng/l, and 25% had levels >16.7 ng/l. During a median 1.9-year period, the annual rates of stroke or systemic embolism ranged from 0.87% in the lowest hs-TnT quartile to 2.13% in the highest hs-TnT quartile (adjusted hazard ratio [HR]: 1.94; 95% confidence interval [CI]: 1.35 to 2.78; p = 0.0010). The annual rates in the corresponding groups ranged from 0.46% to 4.24% (adjusted HR: 4.31; 95% CI: 2.91 to 6.37; p < 0.0001) for cardiac death and from 1.26% to 4.21% (adjusted HR: 1.91; 95% CI: 1.43 to 2.56; p = 0.0001) for major bleeding. Adding hs-TnT levels to the CHA2DS2VASc score improved the C statistic from 0.620 to 0.635 for stroke or systemic embolism (p = 0.0226), from 0.592 to 0.711 for cardiac death (p < 0.0001), and from 0.591 to 0.629 for major bleeding (p < 0.0001). Apixaban reduced rates of stroke, mortality, and bleeding regardless of the hs-TnT level.


CONCLUSIONS
Levels of hs-TnT are often elevated in patients with AF. The hs-TnT level is independently associated with an increased risk of stroke, cardiac death, and major bleeding and improves risk stratification beyond the CHA2DS2VASc risk score. The benefits of apixaban as compared with warfarin are consistent regardless of the hs-TnT level. (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation [ARISTOTLE]; NCT00412984).
Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden; Section of Cardiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden. Electronic address: ziad.hijazi@ucr.uu.se.
Ziad
Z
Hijazi
Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden; Section of Cardiology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Lars
L
Wallentin
Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden; Section of Clinical Chemistry, Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Agneta
A
Siegbahn
Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
Ulrika
U
Andersson
Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
John H
JH
Alexander
Department of Cardiology, Oslo University Hospital Ulleval and Faculty of Medicine, Institute for Clinical Medicine, University of Oslo, Oslo, Norway.
Dan
D
Atar
Mayo Clinic College of Medicine, Rochester, Minnesota.
Bernard J
BJ
Gersh
Bristol-Myers Squibb, Princeton, New Jersey.
Michael
M
Hanna
Division of Emergency Care, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
Veli Pekka
VP
Harjola
University of Adelaide, Adelaide, South Australia, Australia.
John D
JD
Horowitz
Medical Department, Hospital Unit West, Herning/Holstbro, Denmark.
Steen
S
Husted
Boston University Medical Center, Boston, Massachusetts.
Elaine M
EM
Hylek
Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
Renato D
RD
Lopes
BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, United Kingdom.
John J V
JJ
McMurray
Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina.
Christopher B
CB
Granger
D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D015415:Biomarkers / Q000097:blood; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011720:Pyrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D011728:Pyridones / Q000008:administration & dosage / Q000627:therapeutic use*; D018570:Risk Assessment / Q000379:methods*; D020521:Stroke / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D015996:Survival Rate / Q000639:trends; D020107:Troponin T / Q000097:blood*; D014481:United States / Q000453:epidemiology; D014859:Warfarin / Q000008:administration & dosage / Q000627:therapeutic use*
D000925:Anticoagulants; D015415:Biomarkers; D011720:Pyrazoles; D011728:Pyridones; D020107:Troponin T; C522181:apixaban; D014859:Warfarin
AF; CI; HR; IDI; NRI; atrial fibrillation; cardiac troponin; confidence interval; hazard ratio; high-sensitivity troponin T; hs-TnT; integrated discrimination improvement measure; net reclassification improvement; risk stratification; stroke risk