title: Spontaneous MI After Non-ST-Segment Elevation Acute Coronary Syndrome Managed Without Revascularization: The TRILOGY ACS Trial.
abstract: 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.
  
  
  OBJECTIVE
  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).
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina; Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina. Electronic address: renato.lopes@duke.edu.
authors.forename: Renato D
authors.initials: RD
authors.lastname: Lopes
authors.affiliation: Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Leonardi
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Neely
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Neely
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina; Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina.
authors.forename: E Magnus
authors.initials: EM
authors.lastname: Ohman
authors.affiliation: Ospedale Maggiore di Parma, Parma, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Ardissino
authors.affiliation: Kerckhoff Heart and Thorax Centre, Bad Nauheim, Germany.
authors.forename: Christian W
authors.initials: CW
authors.lastname: Hamm
authors.affiliation: Division of Cardiology, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada; Canadian VIGOUR Centre, Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Shaun G
authors.initials: SG
authors.lastname: Goodman
authors.affiliation: Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts.
authors.forename: Deepak L
authors.initials: DL
authors.lastname: Bhatt
authors.affiliation: Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand.
authors.forename: Harvey D
authors.initials: HD
authors.lastname: White
authors.affiliation: Centre for Chronic Disease Control and Public Health Foundation of India, New Delhi, India.
authors.forename: Dorairaj
authors.initials: D
authors.lastname: Prabhakaran
authors.affiliation: Cordoba National University, Cordoba, Argentina.
authors.forename: Felipe
authors.initials: F
authors.lastname: Martinez
authors.affiliation: Heart Institute-InCor, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Jose C
authors.initials: JC
authors.lastname: Nicolau
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Winters
authors.affiliation: Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland, United Kingdom.
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
authors.affiliation: Canadian VIGOUR Centre, Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina; Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Roe
mesh_terms: D054058:Acute Coronary Syndrome / Q000150:complications / Q000188:drug therapy*; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage*; D000077144:Clopidogrel; D017023:Coronary Angiography; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D014943:Global Health; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D009204:Myocardial Revascularization; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D000068799:Prasugrel Hydrochloride / Q000008:administration & dosage*; D016016:Proportional Hazards Models; D018570:Risk Assessment / Q000379:methods*; D015996:Survival Rate; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine; D001241:Aspirin
keywords: acute coronary syndrome; risk prediction; spontaneous myocardial infarction