Relationship Between Peak Troponin Values and Long-Term Ischemic Events Among Medically Managed Patients With Acute Coronary Syndromes

Abstract

Background: The relationship between troponin level and outcomes among patients with non-ST-segment elevation ACS is established, but the relationship of troponin level with long-term outcomes among medically managed non-ST-segment elevation ACS patients receiving contemporary antiplatelet therapy is inadequately defined.

Methods and results: In 6763 medically managed non-ST-segment elevation ACS patients randomized in TRILOGY ACS (Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes) (prasugrel versus clopidogrel), we examined relationships between categories of peak troponin/upper limit of normal (ULN) ratio within 48 hours of the index ACS event (≈4.5 days before randomization) and 30-month outcomes (cardiovascular death, myocardial infarction, or stroke; cardiovascular death or myocardial infarction; and all-cause death). Patients with peak troponin levels <1×ULN were younger, were more often women, and had lower GRACE risk scores than those in other troponin groups. Those with ratios ≥5×ULN were more frequently smokers but less often had prior myocardial infarction or percutaneous coronary intervention. Diabetes mellitus prevalence, body mass index, serum creatinine, and hemoglobin were similar across groups. For all end points, statistically significant differences in 30-month event rates were observed between peak troponin categories. The relationship was linear for 30-month mortality (<1×ULN, n=1849 [6.2%]; 1 to <3×ULN, n=1203 [9.6%]; 3 to <5×ULN, n=581 [10.8%]; and ≥5×ULN, n=3405 [12.8%]) but plateaued for composite end points beyond peak troponin values ≥3×ULN. There was no statistically significant heterogeneity in treatment effect by peak troponin ratio for any end point.

Conclusions: Among medically managed non-ST-segment elevation ACS patients selected for medical management, there was a graded relationship between increasing peak troponin and long-term ischemic events but no heterogeneity of treatment effect for prasugrel versus clopidogrel according to peak troponin.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00699998.

Keywords: acute coronary syndromes; myocardial infarction; risk stratification; troponin.

© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Figures

Figure 1

Cumulative Kaplan–Meier estimates of 30‐month ischemic outcomes by 48‐hour peak troponin elevation. For visualization of the numerical results presented in Table 2, Kaplan–Meier failure curves are presented for each efficacy end point. See Table 2 for relevant log‐rank P values. MI indicates myocardial infarction; ULN, upper limit of normal.

Figure 2

Forty‐eight‐hour peak troponin ratio and 30‐day platelet reactivity unit (PRU). For patients enrolled in the Platelet Function Substudy, a box plot is used to assess the unadjusted association of peak troponin elevation with 30‐day PRU, as well as the interaction with study treatment (P<0.001). ULN indicates upper limit of normal.