Comparative Effectiveness of CABG and PCI

Mark A Hlatky, MD Stanford University

April 26, 2013

Background

CABG and PCI are alternatives for coronary revascularization >1 million done each year

PCI most used for single-vessel disease CABG most used for extensive triple-

vessel disease Either feasible for “mid-severity” CAD Effects on mortality uncertain

Comparative Effectiveness

CABG vs. PCI in various studies RCTs Observational studies

Focus on overall comparison Heterogeneity of treatment effect

suggested Diabetes in BARI trial

Clinical Subgroup Issues

Concerns about “fishing” for big differences, post-hoc tests

Proper methods Treatment by covariate interaction tests Large samples needed to detect

heterogeneity Broad conclusions simpler to apply In practice In policy

Pooling RCT Data

Many more patients and events available by pooling multiple RCTs

Collaboration of 10 RCTs of CABG vs PCI in multivessel disease

Pooled individual patient data Time-to-event outcomes Treatment-by-covariate tests 7812 patients, 1203 deaths

Lancet 2009;373:1190-1197

Outcomes in Subgroups

HTE in 10 RCTs

Diabetes a strong modifier HR 0.70 vs. 0.98 5 year survival difference 8.7% vs. 0.5%

Age also modifed comparative effectiveness

Variations in other subgroups, but interaction tests not significant PAD, HF

Lancet 2009;373:1190-1197

RCT Limitations

Patient selection limits generalization Fewer comorbidities Under-represented groups

Selected providers Sample sizes just large enough to detect

main effects Heterogeneity more likely to be present in

less artificial populations

Medicare CABG-PCI Study

Observational data of “real world” patients and providers

Large numbers available, routine data collection

We used 20% Medicare sample 1992 to 2008 to identify Patients ≥66 years old Fee-for-service coverage Multivessel PCI or Multivessel, isolated CABG

Methods

Propensity score matching Forced match on year, diabetes, age ± 1

year Treatment * covariate interactions pre-

specified Relative differences (hazard ratios) Absolute differences (5 year survivals,

life-years added) Individual predictions for the 105,156

patients Ann Intern Med 2013

Main Findings

CABG had lower mortality overall HR 0.92 [CI 0.90-0.95, p<0.001] 5 year survival 74.1% vs. 71.9%

Significant treatment effect modification by: Diabetes – HR 0.88 vs. 0.95 Heart failure – HR 0.84 vs. 0.96 PAD – HR 0.85 vs. 0.95 Tobacco use – HR 0.82 vs. 0.94

Treatment effectiveness varied substantially 41% of patients had better survival with PCI

Ann Intern Med 2013

Life-Years Added by CABG Over Five Years

Life Years Added in Subgroups

Discussion

HTE for CABG and PCI found in pooled RCTs and observational analysis

Broad agreement on key modifiers Residual selection bias could affect

results in observational analysis Methods for HTE needed