High-Sensitivity Troponin I in Stable Patients with Atherosclerotic Disease in the TRA 2°P - TIMI 50 Trial

Alon Eisen; Marc P Bonaca; Petr Jarolim; Benjamin M Scirica; Harvey D White; Michal Tendera; Mikael Dellborg; Jose C Nicolau; Joao Morais; Keith A A Fox; Erin A Bohula; Sabina A Murphy; Eugene Braunwald; David A Morrow

doi:10.1373/clinchem.2016.264788

High-Sensitivity Troponin I in Stable Patients with Atherosclerotic Disease in the TRA 2°P - TIMI 50 Trial

Alon Eisen
, Marc P Bonaca
, Petr Jarolim
, Benjamin M Scirica
, Harvey D White
, Michal Tendera
, Mikael Dellborg
, Jose C Nicolau
, Joao Morais
, Keith A A Fox
, Erin A Bohula
, Sabina A Murphy
, Eugene Braunwald
, David A Morrow

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: Cardiac troponin I, measured with a high-sensitivity assay (hs-TnI), is well-established for risk prediction in acute coronary syndromes. However, its prognostic role in stable atherosclerotic disease, particularly for future myocardial infarction (MI), is less well defined.

METHODS: We measured hs-TnI (Abbott ARCHITECT) in 15833 patients with prior MI, ischemic stroke, or peripheral arterial disease from the placebo-controlled Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P)-Thrombolysis in Myocardial Infarction (TIMI) 50 trial of the platelet inhibitor vorapaxar, excluding patients with recent MI (<30 days). hs-TnI was categorized into 5 groups based on the detection limit (1.9 ng/L), 99th percentile reference limit (26 ng/L), and tertiles in between (1.9-26 ng/L), as well as sex-specific reference limits.

RESULTS: Higher hs-TnI concentration was associated with older age, male sex, and increased atherosclerosis burden. hs-TnI identified a graded 3-year risk of cardiovascular death, MI, or stroke from 5.0% to 18.6% (P < 0.001), driven by cardiovascular death and MI (P < 0.001). This risk was independent of established clinical risk indicators, B-type natriuretic peptide and C-reactive protein [adjusted hazard ratio 2.70 (95% CI, 1.96-3.71), P < 0.001 for hs-TnI >26 ng/L vs <1.9 ng/L]. In patients with prior MI, there was a pattern of greater absolute benefit with vorapaxar in patients with an increased hs-TnI (absolute risk difference 1.9% with hs-TnI >26 ng/L vs 0.3% with hs-TnI <1.9 ng/L; P interaction = 0.82).

CONCLUSIONS: In stable patients with established atherosclerosis, hs-TnI concentrations effectively stratified the risk of new or recurrent cardiovascular (CV) events, in particular CV death and MI. High-risk patients with prior MI identified by increased hs-TnI had a substantial absolute improvement in net clinical outcome with vorapaxar.

Original language	English
Pages (from-to)	307-315
Number of pages	9
Journal	Clinical Chemistry
Volume	63
Issue number	1
Early online date	30 Dec 2016
DOIs	https://doi.org/10.1373/clinchem.2016.264788
Publication status	E-pub ahead of print - 30 Dec 2016

Access to Document

10.1373/clinchem.2016.264788

Cite this

Eisen, A., Bonaca, M. P., Jarolim, P., Scirica, B. M., White, H. D., Tendera, M., Dellborg, M., Nicolau, J. C., Morais, J., Fox, K. A. A., Bohula, E. A., Murphy, S. A., Braunwald, E., & Morrow, D. A. (2016). High-Sensitivity Troponin I in Stable Patients with Atherosclerotic Disease in the TRA 2°P - TIMI 50 Trial. Clinical Chemistry, 63(1), 307-315. Advance online publication. https://doi.org/10.1373/clinchem.2016.264788

@article{8c5a821422654e718233dc458fa82553,

title = "High-Sensitivity Troponin I in Stable Patients with Atherosclerotic Disease in the TRA 2°P - TIMI 50 Trial",

abstract = "BACKGROUND: Cardiac troponin I, measured with a high-sensitivity assay (hs-TnI), is well-established for risk prediction in acute coronary syndromes. However, its prognostic role in stable atherosclerotic disease, particularly for future myocardial infarction (MI), is less well defined.METHODS: We measured hs-TnI (Abbott ARCHITECT) in 15833 patients with prior MI, ischemic stroke, or peripheral arterial disease from the placebo-controlled Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P)-Thrombolysis in Myocardial Infarction (TIMI) 50 trial of the platelet inhibitor vorapaxar, excluding patients with recent MI (<30 days). hs-TnI was categorized into 5 groups based on the detection limit (1.9 ng/L), 99th percentile reference limit (26 ng/L), and tertiles in between (1.9-26 ng/L), as well as sex-specific reference limits.RESULTS: Higher hs-TnI concentration was associated with older age, male sex, and increased atherosclerosis burden. hs-TnI identified a graded 3-year risk of cardiovascular death, MI, or stroke from 5.0\% to 18.6\% (P < 0.001), driven by cardiovascular death and MI (P < 0.001). This risk was independent of established clinical risk indicators, B-type natriuretic peptide and C-reactive protein [adjusted hazard ratio 2.70 (95\% CI, 1.96-3.71), P < 0.001 for hs-TnI >26 ng/L vs <1.9 ng/L]. In patients with prior MI, there was a pattern of greater absolute benefit with vorapaxar in patients with an increased hs-TnI (absolute risk difference 1.9\% with hs-TnI >26 ng/L vs 0.3\% with hs-TnI <1.9 ng/L; P interaction = 0.82).CONCLUSIONS: In stable patients with established atherosclerosis, hs-TnI concentrations effectively stratified the risk of new or recurrent cardiovascular (CV) events, in particular CV death and MI. High-risk patients with prior MI identified by increased hs-TnI had a substantial absolute improvement in net clinical outcome with vorapaxar.",

author = "Alon Eisen and Bonaca, \{Marc P\} and Petr Jarolim and Scirica, \{Benjamin M\} and White, \{Harvey D\} and Michal Tendera and Mikael Dellborg and Nicolau, \{Jose C\} and Joao Morais and Fox, \{Keith A A\} and Bohula, \{Erin A\} and Murphy, \{Sabina A\} and Eugene Braunwald and Morrow, \{David A\}",

note = "{\textcopyright} 2016 American Association for Clinical Chemistry.",

year = "2016",

month = dec,

day = "30",

doi = "10.1373/clinchem.2016.264788",

language = "English",

volume = "63",

pages = "307--315",

journal = "Clinical Chemistry",

issn = "0009-9147",

publisher = "Oxford University Press",

number = "1",

}

Eisen, A, Bonaca, MP, Jarolim, P, Scirica, BM, White, HD, Tendera, M, Dellborg, M, Nicolau, JC, Morais, J, Fox, KAA, Bohula, EA, Murphy, SA, Braunwald, E & Morrow, DA 2016, 'High-Sensitivity Troponin I in Stable Patients with Atherosclerotic Disease in the TRA 2°P - TIMI 50 Trial', Clinical Chemistry, vol. 63, no. 1, pp. 307-315. https://doi.org/10.1373/clinchem.2016.264788

TY - JOUR

T1 - High-Sensitivity Troponin I in Stable Patients with Atherosclerotic Disease in the TRA 2°P - TIMI 50 Trial

AU - Eisen, Alon

AU - Bonaca, Marc P

AU - Jarolim, Petr

AU - Scirica, Benjamin M

AU - White, Harvey D

AU - Tendera, Michal

AU - Dellborg, Mikael

AU - Nicolau, Jose C

AU - Morais, Joao

AU - Fox, Keith A A

AU - Bohula, Erin A

AU - Murphy, Sabina A

AU - Braunwald, Eugene

AU - Morrow, David A

PY - 2016/12/30

Y1 - 2016/12/30

N2 - BACKGROUND: Cardiac troponin I, measured with a high-sensitivity assay (hs-TnI), is well-established for risk prediction in acute coronary syndromes. However, its prognostic role in stable atherosclerotic disease, particularly for future myocardial infarction (MI), is less well defined.METHODS: We measured hs-TnI (Abbott ARCHITECT) in 15833 patients with prior MI, ischemic stroke, or peripheral arterial disease from the placebo-controlled Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P)-Thrombolysis in Myocardial Infarction (TIMI) 50 trial of the platelet inhibitor vorapaxar, excluding patients with recent MI (<30 days). hs-TnI was categorized into 5 groups based on the detection limit (1.9 ng/L), 99th percentile reference limit (26 ng/L), and tertiles in between (1.9-26 ng/L), as well as sex-specific reference limits.RESULTS: Higher hs-TnI concentration was associated with older age, male sex, and increased atherosclerosis burden. hs-TnI identified a graded 3-year risk of cardiovascular death, MI, or stroke from 5.0% to 18.6% (P < 0.001), driven by cardiovascular death and MI (P < 0.001). This risk was independent of established clinical risk indicators, B-type natriuretic peptide and C-reactive protein [adjusted hazard ratio 2.70 (95% CI, 1.96-3.71), P < 0.001 for hs-TnI >26 ng/L vs <1.9 ng/L]. In patients with prior MI, there was a pattern of greater absolute benefit with vorapaxar in patients with an increased hs-TnI (absolute risk difference 1.9% with hs-TnI >26 ng/L vs 0.3% with hs-TnI <1.9 ng/L; P interaction = 0.82).CONCLUSIONS: In stable patients with established atherosclerosis, hs-TnI concentrations effectively stratified the risk of new or recurrent cardiovascular (CV) events, in particular CV death and MI. High-risk patients with prior MI identified by increased hs-TnI had a substantial absolute improvement in net clinical outcome with vorapaxar.

AB - BACKGROUND: Cardiac troponin I, measured with a high-sensitivity assay (hs-TnI), is well-established for risk prediction in acute coronary syndromes. However, its prognostic role in stable atherosclerotic disease, particularly for future myocardial infarction (MI), is less well defined.METHODS: We measured hs-TnI (Abbott ARCHITECT) in 15833 patients with prior MI, ischemic stroke, or peripheral arterial disease from the placebo-controlled Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2°P)-Thrombolysis in Myocardial Infarction (TIMI) 50 trial of the platelet inhibitor vorapaxar, excluding patients with recent MI (<30 days). hs-TnI was categorized into 5 groups based on the detection limit (1.9 ng/L), 99th percentile reference limit (26 ng/L), and tertiles in between (1.9-26 ng/L), as well as sex-specific reference limits.RESULTS: Higher hs-TnI concentration was associated with older age, male sex, and increased atherosclerosis burden. hs-TnI identified a graded 3-year risk of cardiovascular death, MI, or stroke from 5.0% to 18.6% (P < 0.001), driven by cardiovascular death and MI (P < 0.001). This risk was independent of established clinical risk indicators, B-type natriuretic peptide and C-reactive protein [adjusted hazard ratio 2.70 (95% CI, 1.96-3.71), P < 0.001 for hs-TnI >26 ng/L vs <1.9 ng/L]. In patients with prior MI, there was a pattern of greater absolute benefit with vorapaxar in patients with an increased hs-TnI (absolute risk difference 1.9% with hs-TnI >26 ng/L vs 0.3% with hs-TnI <1.9 ng/L; P interaction = 0.82).CONCLUSIONS: In stable patients with established atherosclerosis, hs-TnI concentrations effectively stratified the risk of new or recurrent cardiovascular (CV) events, in particular CV death and MI. High-risk patients with prior MI identified by increased hs-TnI had a substantial absolute improvement in net clinical outcome with vorapaxar.

U2 - 10.1373/clinchem.2016.264788

DO - 10.1373/clinchem.2016.264788

M3 - Article

C2 - 28062625

SN - 0009-9147

VL - 63

SP - 307

EP - 315

JO - Clinical Chemistry

JF - Clinical Chemistry

IS - 1

ER -

High-Sensitivity Troponin I in Stable Patients with Atherosclerotic Disease in the TRA 2°P - TIMI 50 Trial

Abstract

Access to Document

Fingerprint

Cite this