Spontaneous MI After Non-ST-Segment Elevation Acute Coronary Syndrome Managed Without Revascularization: The TRILOGY ACS Trial

J Am Coll Cardiol. 2016 Mar 22;67(11):1289-97. doi: 10.1016/j.jacc.2016.01.034.


Background: Patients with acute coronary syndrome (ACS), especially those receiving medical management without revascularization, are at high risk for spontaneous myocardial infarction (MI), but its frequency and predictors are unknown.

Objectives: This study sought to characterize spontaneous MI events in a randomized population during 30 months of follow-up and develop a prediction model for spontaneous MI to assign risk of spontaneous MI events in ACS populations.

Methods: We analyzed data from the randomized TRILOGY ACS (TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medically manage Acute Coronary Syndromes) trial of aspirin plus prasugrel or clopidogrel following ACS. The trial included 9,326 patients with non-ST-segment elevation myocardial infarction (NSTEMI)/unstable angina (UA) who were managed medically without planned revascularization. Our study population included 9,294 patients. A multivariable Cox proportional hazards model was developed to determine predictors of time to first spontaneous MI event through 30 months. After model validation, we developed a calculator for model implementation.

Results: Among 9,294 patients, 695 spontaneous MI events occurred over a median of 17 months, representing 94% of adjudicated MI events (n = 737). The Kaplan-Meier event rate of spontaneous MI through 30 months was 10.7%. The strongest predictors of spontaneous MI were older age, NSTEMI versus UA as index event, diabetes mellitus, no pre-randomization angiography, and higher baseline creatinine values. The model exhibited good predictive capabilities (c-index = 0.732) and had good calibration, especially for patients with low-to-moderate risk of spontaneous MI.

Conclusions: Spontaneous MI following a medically managed UA/NSTEMI event is common. Baseline characteristics can be used to predict subsequent risk of spontaneous MI in this population. These findings provide insight into the long-term natural history of medically managed UA/NSTEMI patients and could be used to optimize risk stratification and treatment of these patients. (A Comparison of Prasugrel and Clopidogrel in Acute Coronary Syndrome Subjects [TRILOGY ACS]; NCT00699998).

Keywords: acute coronary syndrome; risk prediction; spontaneous myocardial infarction.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / complications
  • Acute Coronary Syndrome / drug therapy*
  • Aged
  • Aspirin / administration & dosage*
  • Clopidogrel
  • Coronary Angiography
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Electrocardiography*
  • Female
  • Follow-Up Studies
  • Global Health
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Myocardial Infarction / diagnosis
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / etiology*
  • Myocardial Revascularization
  • Platelet Aggregation Inhibitors / administration & dosage
  • Prasugrel Hydrochloride / administration & dosage*
  • Proportional Hazards Models
  • Risk Assessment / methods*
  • Survival Rate
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Time Factors
  • Treatment Outcome


  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Prasugrel Hydrochloride
  • Ticlopidine
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT00699998