Why does primary angioplasty not work in registries? Quantifying the susceptibility of real-world comparative effectiveness data to allocation bias

Circ Cardiovasc Qual Outcomes. 2012 Nov;5(6):759-66. doi: 10.1161/CIRCOUTCOMES.112.966853. Epub 2012 Nov 13.


Background: Meta-analysis of registries (comparative effectiveness research) shows that primary angioplasty and fibrinolysis have equivalent real-world survival. Yet, randomized, controlled trials consistently find primary angioplasty superior. Can unequal allocation of higher-risk patients in registries have masked primary angioplasty benefit?

Methods and results: First, we constructed a model to demonstrate the potential effect of allocation bias. We then analyzed published registries (55022 patients) for allocation of higher-risk patients (Killip class ≥1) to determine whether the choice of reperfusion therapy was affected by the risk level of the patient. Meta-regression was used to examine the relationship between differences in allocation of high-risk patient to primary angioplasty or fibrinolysis and mortality. Initial modeling suggested that registry outcomes are sensitive to allocation bias of high-risk patients. Across the registries, the therapy receiving excess high-risk patients had worse mortality. Unequal distribution of high-risk status accounted for most of the between-registry variance (adjusted R(2)(meta)=83.1%). Accounting for differential allocation of higher-risk patients, primary angioplasty gave 22% lower mortality (odds ratio, 0.78; 95% confidence interval, 0.64-0.97; P=0.029). We derive a formula, called the number needed to abolish, highlighting situations in which comparative effectiveness studies are particularly vulnerable to this bias.

Conclusions: In ST-segment elevation myocardial infarction, clinicians' preference for management of a few high-risk patients can shift mortality substantially. Comparative effectiveness research in any disease is vulnerable to this, especially diseases with an immediately identifiable high-risk subgroup that clinicians prefer to allocate to 1 therapy. For this reason, preliminary indications from registry-based comparative effectiveness research should be definitively tested by randomized, controlled trials.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angioplasty, Balloon, Coronary* / adverse effects
  • Angioplasty, Balloon, Coronary* / mortality
  • Comparative Effectiveness Research* / statistics & numerical data
  • Evidence-Based Medicine
  • Humans
  • Models, Statistical
  • Multivariate Analysis
  • Myocardial Infarction / mortality
  • Myocardial Infarction / therapy*
  • Odds Ratio
  • Patient Selection*
  • Practice Patterns, Physicians'* / statistics & numerical data
  • Research Design* / statistics & numerical data
  • Risk Assessment
  • Risk Factors
  • Sample Size
  • Selection Bias
  • Thrombolytic Therapy* / adverse effects
  • Thrombolytic Therapy* / mortality
  • Treatment Outcome