Serial measurement of high-sensitivity troponin i and cardiovascular outcomes in patients with type 2 diabetes mellitus in the examine trial (examination of cardiovascular outcomes with alogliptin versus standard of care)

Matthew A. Cavender, William B. White, Petr Jarolim, George L. Bakris, William Cushman, Stuart Kupfer, Qi Gao, Cyrus R. Mehta, Faiez Zannad, Christopher P. Cannon, David A. Morrow

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: We aimed to describe the relationship between changes in highsensitivity cardiac troponin I (hsTnI) and cardiovascular outcomes. METHODS: The EXAMINE trial (Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care) was a phase IIIb clinical outcomes trial designed to evaluate the cardiovascular safety of alogliptin, a nonselective dipeptidyl peptidase 4 inhibitor. Patients with type 2 diabetes mellitus, glycohemoglobin between 6.5% and 11% (or between 7% and 11% if they were on insulin), and a recent acute coronary syndrome (between 15 and 90 days before randomization) were eligible for the trial. hsTnI was measured using the Abbott ARCHITECT assay at baseline and 6 months in patients randomized in the EXAMINE trial. This analysis was restricted to patients randomized =30 days after qualifying acute coronary syndrome to mitigate the potential for persistent hsTnI elevation after acute coronary syndrome (n=3808). The primary end point of the trial was cardiovascular death, myocardial infarction, or stroke. Cardiovascular death or heart failure was a prespecified, adjudicated secondary end point. RESULTS: At baseline, hsTnI was detectable (=1.9 ng/L) in 93% of patients and?99th percentile upper reference limit in 16%. There was a strong relationship between increasing hsTnI, both at baseline and 6 months, and the incidence of cardiovascular events through 24 months (P<0.001 for each). Patients with undetectable hsTnI at baseline and 6 months were at the lowest risk of future cardiovascular events. Stable patients with hsTnI =99th percentile upper reference limit at 6 months were at increased risk of cardiovascular death, myocardial infarction, or stroke compared with patients with hsTnI 99 percentile upper reference limit irrespective of whether hsTnI was newly elevated (28.1% versus 8.8%; adjusted hazard ratio, 2.65; 95% confidence interval, 1.64-4.28; P<0.001) or persistently so (22.5% versus 8.8%; adjusted hazard ratio, 1.90; 95% confidence interval, 1.33-2.70; P<0.001). Alogliptin neither increased nor decreased the risk of cardiovascular events compared with placebo in patients with high baseline hsTnI (22.3% versus 23.0%; hazard ratio, 0.87; 95% confidence interval, 0.60-1.25; P=0.44). CONCLUSIONS: Serial assessment of hsTnI revealed a substantial proportion of patients with type 2 diabetes mellitus without clinically recognized events had dynamic or persistently elevated values and were at high risk of recurrent events. hsTnI may have a role in personalizing preventive strategies in patients with diabetes mellitus based on risk.

Original languageEnglish (US)
Pages (from-to)1911-1921
Number of pages11
JournalCirculation
Volume135
Issue number20
DOIs
StatePublished - May 16 2017

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Troponin
Troponin I
Standard of Care
Type 2 Diabetes Mellitus
Acute Coronary Syndrome
Confidence Intervals
alogliptin
Stroke
Myocardial Infarction
Dipeptidyl-Peptidase IV Inhibitors
Random Allocation
Diabetes Mellitus
Heart Failure
Placebos
Clinical Trials

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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Serial measurement of high-sensitivity troponin i and cardiovascular outcomes in patients with type 2 diabetes mellitus in the examine trial (examination of cardiovascular outcomes with alogliptin versus standard of care). / Cavender, Matthew A.; White, William B.; Jarolim, Petr; Bakris, George L.; Cushman, William; Kupfer, Stuart; Gao, Qi; Mehta, Cyrus R.; Zannad, Faiez; Cannon, Christopher P.; Morrow, David A.

In: Circulation, Vol. 135, No. 20, 16.05.2017, p. 1911-1921.

Research output: Contribution to journalArticle

Cavender, Matthew A. ; White, William B. ; Jarolim, Petr ; Bakris, George L. ; Cushman, William ; Kupfer, Stuart ; Gao, Qi ; Mehta, Cyrus R. ; Zannad, Faiez ; Cannon, Christopher P. ; Morrow, David A. / Serial measurement of high-sensitivity troponin i and cardiovascular outcomes in patients with type 2 diabetes mellitus in the examine trial (examination of cardiovascular outcomes with alogliptin versus standard of care). In: Circulation. 2017 ; Vol. 135, No. 20. pp. 1911-1921.
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abstract = "BACKGROUND: We aimed to describe the relationship between changes in highsensitivity cardiac troponin I (hsTnI) and cardiovascular outcomes. METHODS: The EXAMINE trial (Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care) was a phase IIIb clinical outcomes trial designed to evaluate the cardiovascular safety of alogliptin, a nonselective dipeptidyl peptidase 4 inhibitor. Patients with type 2 diabetes mellitus, glycohemoglobin between 6.5{\%} and 11{\%} (or between 7{\%} and 11{\%} if they were on insulin), and a recent acute coronary syndrome (between 15 and 90 days before randomization) were eligible for the trial. hsTnI was measured using the Abbott ARCHITECT assay at baseline and 6 months in patients randomized in the EXAMINE trial. This analysis was restricted to patients randomized =30 days after qualifying acute coronary syndrome to mitigate the potential for persistent hsTnI elevation after acute coronary syndrome (n=3808). The primary end point of the trial was cardiovascular death, myocardial infarction, or stroke. Cardiovascular death or heart failure was a prespecified, adjudicated secondary end point. RESULTS: At baseline, hsTnI was detectable (=1.9 ng/L) in 93{\%} of patients and?99th percentile upper reference limit in 16{\%}. There was a strong relationship between increasing hsTnI, both at baseline and 6 months, and the incidence of cardiovascular events through 24 months (P<0.001 for each). Patients with undetectable hsTnI at baseline and 6 months were at the lowest risk of future cardiovascular events. Stable patients with hsTnI =99th percentile upper reference limit at 6 months were at increased risk of cardiovascular death, myocardial infarction, or stroke compared with patients with hsTnI 99 percentile upper reference limit irrespective of whether hsTnI was newly elevated (28.1{\%} versus 8.8{\%}; adjusted hazard ratio, 2.65; 95{\%} confidence interval, 1.64-4.28; P<0.001) or persistently so (22.5{\%} versus 8.8{\%}; adjusted hazard ratio, 1.90; 95{\%} confidence interval, 1.33-2.70; P<0.001). Alogliptin neither increased nor decreased the risk of cardiovascular events compared with placebo in patients with high baseline hsTnI (22.3{\%} versus 23.0{\%}; hazard ratio, 0.87; 95{\%} confidence interval, 0.60-1.25; P=0.44). CONCLUSIONS: Serial assessment of hsTnI revealed a substantial proportion of patients with type 2 diabetes mellitus without clinically recognized events had dynamic or persistently elevated values and were at high risk of recurrent events. hsTnI may have a role in personalizing preventive strategies in patients with diabetes mellitus based on risk.",
author = "Cavender, {Matthew A.} and White, {William B.} and Petr Jarolim and Bakris, {George L.} and William Cushman and Stuart Kupfer and Qi Gao and Mehta, {Cyrus R.} and Faiez Zannad and Cannon, {Christopher P.} and Morrow, {David A.}",
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TY - JOUR

T1 - Serial measurement of high-sensitivity troponin i and cardiovascular outcomes in patients with type 2 diabetes mellitus in the examine trial (examination of cardiovascular outcomes with alogliptin versus standard of care)

AU - Cavender, Matthew A.

AU - White, William B.

AU - Jarolim, Petr

AU - Bakris, George L.

AU - Cushman, William

AU - Kupfer, Stuart

AU - Gao, Qi

AU - Mehta, Cyrus R.

AU - Zannad, Faiez

AU - Cannon, Christopher P.

AU - Morrow, David A.

PY - 2017/5/16

Y1 - 2017/5/16

N2 - BACKGROUND: We aimed to describe the relationship between changes in highsensitivity cardiac troponin I (hsTnI) and cardiovascular outcomes. METHODS: The EXAMINE trial (Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care) was a phase IIIb clinical outcomes trial designed to evaluate the cardiovascular safety of alogliptin, a nonselective dipeptidyl peptidase 4 inhibitor. Patients with type 2 diabetes mellitus, glycohemoglobin between 6.5% and 11% (or between 7% and 11% if they were on insulin), and a recent acute coronary syndrome (between 15 and 90 days before randomization) were eligible for the trial. hsTnI was measured using the Abbott ARCHITECT assay at baseline and 6 months in patients randomized in the EXAMINE trial. This analysis was restricted to patients randomized =30 days after qualifying acute coronary syndrome to mitigate the potential for persistent hsTnI elevation after acute coronary syndrome (n=3808). The primary end point of the trial was cardiovascular death, myocardial infarction, or stroke. Cardiovascular death or heart failure was a prespecified, adjudicated secondary end point. RESULTS: At baseline, hsTnI was detectable (=1.9 ng/L) in 93% of patients and?99th percentile upper reference limit in 16%. There was a strong relationship between increasing hsTnI, both at baseline and 6 months, and the incidence of cardiovascular events through 24 months (P<0.001 for each). Patients with undetectable hsTnI at baseline and 6 months were at the lowest risk of future cardiovascular events. Stable patients with hsTnI =99th percentile upper reference limit at 6 months were at increased risk of cardiovascular death, myocardial infarction, or stroke compared with patients with hsTnI 99 percentile upper reference limit irrespective of whether hsTnI was newly elevated (28.1% versus 8.8%; adjusted hazard ratio, 2.65; 95% confidence interval, 1.64-4.28; P<0.001) or persistently so (22.5% versus 8.8%; adjusted hazard ratio, 1.90; 95% confidence interval, 1.33-2.70; P<0.001). Alogliptin neither increased nor decreased the risk of cardiovascular events compared with placebo in patients with high baseline hsTnI (22.3% versus 23.0%; hazard ratio, 0.87; 95% confidence interval, 0.60-1.25; P=0.44). CONCLUSIONS: Serial assessment of hsTnI revealed a substantial proportion of patients with type 2 diabetes mellitus without clinically recognized events had dynamic or persistently elevated values and were at high risk of recurrent events. hsTnI may have a role in personalizing preventive strategies in patients with diabetes mellitus based on risk.

AB - BACKGROUND: We aimed to describe the relationship between changes in highsensitivity cardiac troponin I (hsTnI) and cardiovascular outcomes. METHODS: The EXAMINE trial (Examination of Cardiovascular Outcomes With Alogliptin Versus Standard of Care) was a phase IIIb clinical outcomes trial designed to evaluate the cardiovascular safety of alogliptin, a nonselective dipeptidyl peptidase 4 inhibitor. Patients with type 2 diabetes mellitus, glycohemoglobin between 6.5% and 11% (or between 7% and 11% if they were on insulin), and a recent acute coronary syndrome (between 15 and 90 days before randomization) were eligible for the trial. hsTnI was measured using the Abbott ARCHITECT assay at baseline and 6 months in patients randomized in the EXAMINE trial. This analysis was restricted to patients randomized =30 days after qualifying acute coronary syndrome to mitigate the potential for persistent hsTnI elevation after acute coronary syndrome (n=3808). The primary end point of the trial was cardiovascular death, myocardial infarction, or stroke. Cardiovascular death or heart failure was a prespecified, adjudicated secondary end point. RESULTS: At baseline, hsTnI was detectable (=1.9 ng/L) in 93% of patients and?99th percentile upper reference limit in 16%. There was a strong relationship between increasing hsTnI, both at baseline and 6 months, and the incidence of cardiovascular events through 24 months (P<0.001 for each). Patients with undetectable hsTnI at baseline and 6 months were at the lowest risk of future cardiovascular events. Stable patients with hsTnI =99th percentile upper reference limit at 6 months were at increased risk of cardiovascular death, myocardial infarction, or stroke compared with patients with hsTnI 99 percentile upper reference limit irrespective of whether hsTnI was newly elevated (28.1% versus 8.8%; adjusted hazard ratio, 2.65; 95% confidence interval, 1.64-4.28; P<0.001) or persistently so (22.5% versus 8.8%; adjusted hazard ratio, 1.90; 95% confidence interval, 1.33-2.70; P<0.001). Alogliptin neither increased nor decreased the risk of cardiovascular events compared with placebo in patients with high baseline hsTnI (22.3% versus 23.0%; hazard ratio, 0.87; 95% confidence interval, 0.60-1.25; P=0.44). CONCLUSIONS: Serial assessment of hsTnI revealed a substantial proportion of patients with type 2 diabetes mellitus without clinically recognized events had dynamic or persistently elevated values and were at high risk of recurrent events. hsTnI may have a role in personalizing preventive strategies in patients with diabetes mellitus based on risk.

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DO - 10.1161/CIRCULATIONAHA.116.024632

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JO - Circulation

JF - Circulation

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