title: Diverging associations of an intended early invasive strategy compared with actual revascularization, and outcome in patients with non-ST-segment elevation acute coronary syndrome: the problem of treatment selection bias.
abstract: OBJECTIVE
  In several observational studies, revascularization is associated with substantial reduction in mortality in patients with non-ST-segment elevation acute coronary syndrome (nSTE-ACS). This has strengthened the belief that routine early angiography would lead to a reduction in mortality. We investigated the association between actual in-hospital revascularization and long-term outcome in patients with nSTE-ACS included in the ICTUS trial.
  
  
  RESULTS
  The study population of the present analysis consists of ICTUS participants who were discharged alive after initial hospitalization. The ICTUS trial was a randomized, controlled trial in which 1200 patients were randomized to an early invasive or selective invasive strategy. The endpoints were death from hospital discharge until 4 year follow-up and death or spontaneous myocardial infarction (MI) until 3 years. Among 1189 patients discharged alive, 691 (58%) underwent revascularization during initial hospitalization. In multivariable Cox regression analyses, in-hospital revascularization was independently associated with a reduction in 4 year mortality and 3 year event rate of death or spontaneous MI: hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.37-0.96] and 0.46 (95% CI 0.31-0.68). However, when intention-to-treat analysis was performed, no differences in cumulative event rates were observed between the early invasive and selective invasive strategies: HR 1.10 (95% CI 0.70-1.74) for death and 1.27 (95% CI 0.88-1.85) for death or spontaneous MI.
  
  
  CONCLUSIONS
  The ICTUS trial did not show that an early invasive strategy resulted in a better outcome than a selective invasive strategy in patients with nSTE-ACS. However, similar to retrospective analyses from observational studies, actual revascularization was associated with lower mortality and fewer MI. Whether an early invasive strategy leads to a better outcome than a selective invasive strategy cannot be inferred from the observation that revascularized patients have a better prognosis in non-randomized studies.
authors.affiliation: Department of Cardiology, B2-137, Academic Medical Center, Meibergdreef 9, PO Box 22660, 1100 DD Amsterdam, The Netherlands.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hirsch
authors.forename: Fons
authors.initials: F
authors.lastname: Windhausen
authors.forename: Jan G P
authors.initials: JG
authors.lastname: Tijssen
authors.forename: Anthonius J M
authors.initials: AJ
authors.lastname: Oude Ophuis
authors.forename: Willem J
authors.initials: WJ
authors.lastname: van der Giessen
authors.forename: P Marc
authors.initials: PM
authors.lastname: van der Zee
authors.forename: Jan Hein
authors.initials: JH
authors.lastname: Cornel
authors.forename: Freek W A
authors.initials: FW
authors.lastname: Verheugt
authors.forename: Robbert J
authors.initials: RJ
authors.lastname: de Winter
mesh_terms: D054058:Acute Coronary Syndrome / Q000401:mortality / Q000628:therapy*; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D017023:Coronary Angiography; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality / Q000628:therapy*; D009204:Myocardial Revascularization / Q000379:methods* / Q000401:mortality / Q000706:statistics & numerical data; D018579:Patient Selection; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D015983:Selection Bias; D016019:Survival Analysis; D016896:Treatment Outcome; D020107:Troponin T / Q000097:blood
chemical_list: D000319:Adrenergic beta-Antagonists; D015415:Biomarkers; D010975:Platelet Aggregation Inhibitors; D020107:Troponin T; D001241:Aspirin