title: Relationship between time to invasive assessment and clinical outcomes of patients undergoing an early invasive strategy after fibrinolysis for ST-segment elevation myocardial infarction: a patient-level analysis of the randomized early routine invasive clinical trials.
abstract: OBJECTIVE
  This study investigated the relationship between time to invasive assessment and outcomes among ST-segment elevation myocardial infarction patients randomized to early angiography after fibrinolysis.
  
  
  BACKGROUND
  The optimal timing of coronary angiography after fibrinolysis and the association with clinical outcomes is uncertain.
  
  
  METHODS
  Patient-level data from 6 randomized trials, with a median time to angiography <12 h after fibrinolysis, were pooled. The primary endpoint was 30-day death or reinfarction. The key secondary endpoint was in-hospital major bleeding. The relationship between fibrinolysis to angiography time and symptom onset to angiography time with outcomes was studied using 2- and 4-h intervals, respectively, and in multivariable models.
  
  
  RESULTS
  Among 1,238 patients, the median fibrinolysis to angiography time was 165 min, and the median symptom onset to angiography time was 5.33 h. The primary and key secondary endpoints occurred in 5.7% and 4.7%, respectively. These main endpoints did not vary significantly with increasing fibrinolysis to angiography time. Early angiography (<2 h) after fibrinolysis was not associated with increased bleeding. Recurrent ischemia increased with increasing fibrinolysis to angiography time (3.7% to 7.9%, p for trend = 0.02). Thirty-day and 1-year death/reinfarction and 30-day recurrent ischemia increased significantly with increasing symptom onset to angiography time. Neither fibrinolysis to angiography time nor symptom onset to angiography time was an independent predictor of the primary endpoint. Only symptom onset to angiography time was an independent predictor of 1-year death/reinfarction (hazard ratio: 1.07, 95% confidence interval: 1.02 to 1.12, p = 0.01).
  
  
  CONCLUSIONS
  Very early angiography (<2 h) after fibrinolysis was not associated with an increased risk of 30-day death/reinfarction or in-hospital major bleeding, and angiography within 4 h after fibrinolysis was associated with reduced 30-day recurrent ischemia. A shorter symptom onset to angiography time (<4 h) was associated with reduced 30-day and 1-year death/reinfarction and 30-day recurrent ischemia. In the current environment of regional networks of 24/7 primary percutaneous coronary intervention (PCI) centers, the clinical implication of these findings is that patients initially treated with fibrinolysis should also be promptly transferred to the nearest PCI center for immediate angiography and PCI. (Early Percutaneous Coronary Intervention [PCI] After Fibrinolysis Versus Standard Therapy in ST Segment Elevation Myocardial Infarction [STEMI] Patients; NCT01014182).
authors.affiliation: Schulich Heart Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. Electronic address: mina.madan@sunnybrook.ca.
authors.forename: Mina
authors.initials: M
authors.lastname: Madan
authors.affiliation: Department of Cardiology, Oslo University Hospital HF Ullevål, Oslo, Norway.
authors.forename: Sigrun
authors.initials: S
authors.lastname: Halvorsen
authors.affiliation: NIHR Cardiovascular BRU, Royal Brompton Hospital and NHLI Imperial College, London, United Kingdom.
authors.forename: Carlo
authors.initials: C
authors.lastname: Di Mario
authors.affiliation: Canadian Heart Research Centre, Toronto, Ontario, Canada.
authors.forename: Mary
authors.initials: M
authors.lastname: Tan
authors.affiliation: Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Westerhout
authors.affiliation: Southlake Regional Medical Centre, Newmarket, Ontario, Canada.
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Cantor
authors.affiliation: University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Michel R
authors.initials: MR
authors.lastname: Le May
authors.affiliation: Division of Cardiology, Federico II University, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Borgia
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Salerno, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Piscione
authors.affiliation: University Hospital, University of Saarland, Homburg/Saar, Germany.
authors.forename: Bruno
authors.initials: B
authors.lastname: Scheller
authors.affiliation: Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Armstrong
authors.affiliation: Hospital General Universitario Gregorio Marañón-Complutense University, Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Fernandez-Aviles
authors.affiliation: Hospital General Universitario Gregorio Marañón-Complutense University, Madrid, Spain.
authors.forename: Pedro L
authors.initials: PL
authors.lastname: Sanchez
authors.affiliation: Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: John J
authors.initials: JJ
authors.lastname: Graham
authors.affiliation: Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Yan
authors.affiliation: Canadian Heart Research Centre, Toronto, Ontario, Canada; Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Shaun G
authors.initials: SG
authors.lastname: Goodman
mesh_terms: D000368:Aged; D016009:Chi-Square Distribution; D017023:Coronary Angiography; D016208:Databases, Factual; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008390:Markov Chains; D008875:Middle Aged; D009010:Monte Carlo Method; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000401:mortality; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D015912:Thrombolytic Therapy / Q000009:adverse effects / Q000401:mortality; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents
keywords: fibrinolysis; myocardial infarction; percutaneous coronary intervention; timing of angiography