Analysis of the bypass angioplasty revascularization investigation trial using a multistate model of clinical outcomes.
Current cardiovascular randomized trials typically use composite outcomes. We hypothesized that the Bypass Angioplasty Revascularization Investigation (BARI) outcomes and conclusions would differ using a multistate model relative to the intervention for the composite outcome of death (D) and nonfatal Q-wave myocardial infarction (MI). We used a multistate model which uses transition paths to simultaneously assess multiple end points. Using the 10-year follow-up BARI data, we post hoc analyzed outcomes according to 3 transition paths: (1) from intervention to MI; (2) from intervention to death; and (3) from MI to death. Of 1,829 patients randomized to the intervention of percutaneous transluminal coronary angioplasty or coronary artery bypass grafting (CABG), 700 (38%) experienced the composite event D/MI which included 230 (13%) nonfatal MI and 470 (26%) death without antecedent nonfatal MI, whereas 79 of 230 (34%) experienced death after nonfatal MI. Outcomes of the 3 individual transition paths were analyzed by a multistate model. In contrast to standard survival analyses, after adjustment for baseline clinical covariates, outcomes after percutaneous transluminal coronary angioplasty or CABG were not significantly different for intervention to MI (p = 0.33) or intervention to death (p = 0.23), but MI to death favored CABG (p = 0.02). Deconstruction of the BARI data using a multistate model identifies a significant difference in individual transition-stage outcomes and therefore trial conclusions in contrast to the standard methods of survival analysis. These observations suggest multistate models should be considered in the design and analysis of randomized cardiovascular trials which use composite outcomes.
Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Xiao
X
Zhang
Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Quanlin
Q
Li
Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Andre
A
Rogatko
Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
Mourad
M
Tighiouart
Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
Regina M
RM
Hardison
Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
Maria Mori
MM
Brooks
Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
Sheryl F
SF
Kelsey
Cedars-Sinai Medical Center, Los Angeles, California.
Sanjay
S
Kaul
Barbra Streisand Women's Heart Center, Cedars-Sinai Heart Institute, Los Angeles, California. Electronic address: merz@cshs.org.
C Noel
CN
Bairey Merz
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000379:methods*; D002170:Canada / Q000453:epidemiology; D002423:Cause of Death / Q000639:trends; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000601:surgery*; D004562:Electrocardiography; D005260:Female; D005544:Forecasting; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000209:etiology; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects / Q000379:methods*; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000209:etiology; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D014481:United States / Q000453:epidemiology