title: Timing of invasive strategy in NSTE-ACS patients and effect on clinical outcomes: A systematic review and meta-analysis of randomized controlled trials.
abstract: BACKGROUND
  Previous randomized controlled trials (RCTs) have produced conflicting results on the effects of early versus delayed invasive strategy in NSTE-ACS patients.
  
  
  OBJECTIVE
  To perform up to date meta-analysis on the pooled data sample comparing early versus delayed invasive strategy, and to explore potential causes for the observed high statistical heterogeneity.
  
  
  METHODS
  MEDLINE via Pubmed, Central, Google Scholar, Clinical Trials Registry, Current controlled study and ClinicalTrials.gov registry and relevant conference proceedings were searched. RCTs were included that directly compared early versus delayed invasive strategy and reported rates of death, new myocardial infarction (MI) and/or recurrent ischemia.
  
  
  RESULTS
  10 RCTs with 6089 patients were included. Time to coronary angiography varied from 0.5 to 24 h in the early and from 20.5 to 86 h in the delayed group. Meta-analysis showed no significant difference in mortality (OR = 0.83, 95%CI 0.64-1.08, P = 0.16), and similar new MI rates (OR = 1.02, 95%CI 0.63-1.64, P = 0.94). The rate of recurrent ischemia was reduced in patients undergoing early coronary angiography (OR = 0.56, 95%CI 0.40-0.79, P = 0.001). Subgroup analysis indicated that the rate of new MI tended to depend on the study-specific endpoint definition (p for difference between subgroups 0.11), while a meta-regression revealed association of new MI rates with the within-study delay to coronary angiography (p = 0.05).
  
  
  CONCLUSIONS
  Early invasive strategy appears to reduce the occurrence of recurrent ischemia, but confers no mortality benefit. The true effect on the occurrence of new MI is obscured by the high between-study heterogeneity that stems mainly from non-uniform timing of early intervention and new MI definitions across the trials.
authors.affiliation: Department of Cardiology, Clinical Center of Serbia, Belgrade, Serbia.
authors.forename: Dejan
authors.initials: D
authors.lastname: Milasinovic
authors.affiliation: Department of Cardiology, Clinical Center of Serbia, Belgrade, Serbia; Emergency Department, Department of Cardiology, Clinical Center of Serbia, Belgrade, Serbia.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Milosevic
authors.affiliation: Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Institute for Medical Statistics and Informatics, Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Marinkovic
authors.affiliation: Department of Cardiology, Clinical Center of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Vladan
authors.initials: V
authors.lastname: Vukcevic
authors.affiliation: Department of Cardiology, Clinical Center of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Arsen
authors.initials: A
authors.lastname: Ristic
authors.affiliation: Department of Cardiology, Clinical Center of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Emergency Department, Department of Cardiology, Clinical Center of Serbia, Belgrade, Serbia.
authors.forename: Milika
authors.initials: M
authors.lastname: Asanin
authors.affiliation: Department of Cardiology, Clinical Center of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia. Electronic address: gorastan@sbb.rs.
authors.forename: Goran
authors.initials: G
authors.lastname: Stankovic
mesh_terms: D054058:Acute Coronary Syndrome / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D000368:Aged; D016009:Chi-Square Distribution; D017023:Coronary Angiography; D001026:Coronary Artery Bypass / Q000009:adverse effects / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D016017:Odds Ratio; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects / Q000401:mortality; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D012307:Risk Factors; D013997:Time Factors; D061665:Time-to-Treatment; D016896:Treatment Outcome
keywords: Early invasive strategy; Meta-analysis; NSTE-ACS; Randomized controlled trial