High-sensitivity troponin I for risk assessment in patients with atrial fibrillation: insights from the Apixaban for Reduction in Stroke and other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.
BACKGROUND
High-sensitivity troponin-I (hs-TnI) measurement improves risk assessment for cardiovascular events in many clinical settings, but the added value in atrial fibrillation patients has not been described.


RESULTS
At randomization, hs-TnI was analyzed in 14 821 atrial fibrillation patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial comparing apixaban with warfarin. The associations between hs-TnI concentrations and clinical outcomes were evaluated by using adjusted Cox analysis. The hs-TnI assay detected troponin (≥1.3 ng/L) in 98.5% patients, 50% had levels >5.4, 25% had levels >10.1, and 9.2% had levels ≥23 ng/L (the 99th percentile in healthy individuals). During a median of 1.9 years follow-up, annual rates of stroke or systemic embolism ranged from 0.76% in the lowest hs-TnI quartile to 2.26% in the highest quartile (>10.1 ng/L). In multivariable analysis, hs-TnI was significantly associated with stroke or systemic embolism, adjusted hazard ratio 1.98 (1.42-2.78), P=0.0007. hs-TnI was also significantly associated with cardiac death; annual rates ranged from 0.40% to 4.24%, hazard ratio 4.52 (3.05-6.70), P<0.0001, in the corresponding groups, and for major bleeding hazard ratio 1.44 (1.11-1.86), P=0.0250. Adding hs-TnI levels to the CHA2DS2VASc score improved c-statistics from 0.629 to 0.653 for stroke or systemic embolism, and from 0.591 to 0.731 for cardiac death. There were no significant interactions with study treatment.


CONCLUSIONS
Troponin-I is detected in 98.5% and elevated in 9.2% of atrial fibrillation patients. The hs-TnI level is independently associated with a raised risk of stroke, cardiac death, and major bleeding and improves risk stratification beyond the CHA2DS2VASc score. The benefits of apixaban in comparison with warfarin are consistent regardless of hs-TnI levels.


BACKGROUND
http://www.clinicaltrials.gov. Unique identifier: NCT00412984.
Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden (Z.H., A.S., U.A., L.W.); Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden (Z.H., U.A., L.W.); Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden (A.S.); Duke University, Medical Center, Durham, NC (C.B.G., J.H.A., R.D.L.); Department of Cardiology, Oslo University Hospital and Faculty of Medicine, Institute for Clinical Medicine, University of Oslo, Oslo, Norway (D.A.); Mayo Clinic College of Medicine, Rochester, MN (B.J.G.); Bristol-Myers Squibb, Princeton, NJ (P.M.); Division of Emergency Care, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland (V.-P.H.); University of Adelaide, Adelaide, Australia (J.H.); Medical Department, Hospital Unit West, Herning/Holstbro, Denmark (S.H.); Boston University Medical Center, Boston, MA (E.M.H.); and BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, United Kingdom (J.J.V.M.).
Ziad
Z
Hijazi
Agneta
A
Siegbahn
Ulrika
U
Andersson
Christopher B
CB
Granger
John H
JH
Alexander
Dan
D
Atar
Bernard J
BJ
Gersh
Puneet
P
Mohan
Veli-Pekka
VP
Harjola
John
J
Horowitz
Steen
S
Husted
Elaine M
EM
Hylek
Renato D
RD
Lopes
John J V
JJ
McMurray
Lars
L
Wallentin
D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D003643:Death; D004311:Double-Blind Method; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects; D006470:Hemorrhage / Q000139:chemically induced / Q000401:mortality; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000008:administration & dosage* / Q000009:adverse effects; D011728:Pyridones / Q000008:administration & dosage* / Q000009:adverse effects; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D012680:Sensitivity and Specificity; D020521:Stroke / Q000401:mortality / Q000517:prevention & control*; D013923:Thromboembolism / Q000401:mortality / Q000517:prevention & control; D016896:Treatment Outcome; D019210:Troponin I / Q000097:blood*; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D011720:Pyrazoles; D011728:Pyridones; D019210:Troponin I; C522181:apixaban; D014859:Warfarin
atrial fibrillation; biological markers; cardiovascular diseases; risk assessment; troponin