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).
Circulation
; 135(20): 1911-1921, 2017 May 16.
Article
em En
| MEDLINE
| ID: mdl-28246236
ABSTRACT
BACKGROUND:
We aimed to describe the relationship between changes in high-sensitivity 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. CLINICAL TRIAL REGISTRATION URL http//www.clinicaltrials.gov. Unique identifier NCT00968708.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piperidinas
/
Uracila
/
Troponina I
/
Diabetes Mellitus Tipo 2
/
Síndrome Coronariana Aguda
/
Padrão de Cuidado
Tipo de estudo:
Clinical_trials
/
Diagnostic_studies
/
Prognostic_studies
Limite:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Circulation
Ano de publicação:
2017
Tipo de documento:
Article