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

Eur Heart J. 2009 Mar;30(6):645-54. doi: 10.1093/eurheartj/ehn438. Epub 2008 Sep 29.

Abstract

Aims: 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.

Methods and 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.

Conclusion: 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.

Publication types

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

MeSH terms

  • Acute Coronary Syndrome / mortality
  • Acute Coronary Syndrome / therapy*
  • Adrenergic beta-Antagonists / therapeutic use
  • Aged
  • Aspirin / therapeutic use
  • Biomarkers / blood
  • Coronary Angiography
  • Female
  • Hospitalization / statistics & numerical data
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / mortality
  • Myocardial Infarction / therapy*
  • Myocardial Revascularization / methods*
  • Myocardial Revascularization / mortality
  • Myocardial Revascularization / statistics & numerical data
  • Patient Selection
  • Platelet Aggregation Inhibitors / therapeutic use
  • Selection Bias
  • Survival Analysis
  • Treatment Outcome
  • Troponin T / blood

Substances

  • Adrenergic beta-Antagonists
  • Biomarkers
  • Platelet Aggregation Inhibitors
  • Troponin T
  • Aspirin