Serial Measurement of High Sensitivity Troponin I and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus in the EXAMINE Trial
Background—We sought to describe the relationship between changes in high-sensitivity cardiac troponin I (hsTnI) and cardiovascular (CV) outcomes.
Methods—The Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) was a phase IIIb clinical outcomes trial designed to evaluate the CV safety of alogliptin, a non-selective dipeptidyl peptidase 4 (DPP-4) inhibitor. Patients with type 2 diabetes mellitus (T2DM), glycated hemoglobin between 6.5%-11% (or 7%-11% if they were on insulin), and a recent acute coronary syndrome (between 15-90 days prior to 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 ACS in order to mitigate the potential for persistent hsTnI elevation following ACS (n=3808). The primary endpoint of the trial was CV death, MI, or stroke. CV death or heart failure (HF) was a pre-specified, adjudicated secondary endpoint.
Results—At baseline, hsTnI was detectable (≥1.9 ng/L) in 93% of patients and above the 99th% URL in 16%. There was a strong relationship between increasing hsTnI, both at baseline and 6 months, and the incidence of CV 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 CV events. Stable patients with hsTnI ≥99th% URL at 6 months were at increased risk of CV death, MI, or stroke when compared to patients with hsTnI <99th% URL irrespective of whether hsTnI was newly elevated (28.1% vs. 8.8%; HRadj 2.65, 95%CI 1.64-4.28, p<0.001) or persistently so (22.5% vs. 8.8%; HRadj 1.90, 95%CI 1.33-2.70, p<0.001). Alogliptin neither increased nor decreased the risk of CV events compared to placebo in patients with high baseline hsTnI (22.3% vs. 23.0%; HR 0.87, 95% CI 0.60-1.25 p=0.44).
Conclusions—Serial assessment of hsTnI revealed a substantial proportion of patients with T2DM 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 based on risk.
Clinical Trial Registration—https://clinicaltrials.gov Identifier: NCT00968708
- Received July 22, 2016.
- Revision received February 3, 2017.
- Accepted February 17, 2017.