Pooling individual off-pump and on-pump coronary artery bypass patient records from three contemporary multicenter, randomized, controlled trials: an individual participant data meta-analysis protocol
Abstract
Background: For over three decades, the comparative effectiveness of off-pump versus on-pump coronary artery bypass grafting (CABG) has been debated. Although randomized controlled trials (RCTs) generally report modest long-term advantages for on-pump CABG, potential off-pump benefits remain uncertain particularly among high-risk patients. To address this knowledge gap, this CABG individual participant data meta-analysis (CABG-IPD-MA) will analyze de-identified patient records from the only three multicenter RCTs reporting 5-year follow-up (ROOBY, GOPCABE, and CORONARY) and test five protocol-driven hypotheses.
Methods: Across short-term, intermediate, and longer-term periods, this PRISMA-IPD-compliant study will use a one-stage IPD meta-analysis framework to compare off-pump versus on-pump CABG for two co-primary endpoints [i.e., all-cause mortality and a composite metric comprised all-cause death, nonfatal acute myocardial infarction, and repeat revascularization (i.e., repeat CABG or percutaneous coronary intervention)] at 1 and 5 years; at 30 days/in-hospital, perioperative stroke will also be included in the composite. Secondary endpoints include individual sub-components of the composite endpoint and resource-utilization; resource-utilization analyses will be exploratory-only. Eligible studies included all post-2001 multicenter RCTs reporting off-pump versus on-pump post-CABG 5-year outcomes. Re-verified June 2025, the original 2019 PRISMA-IPD-guided systematic review identified only three eligible RCTs; prior publications reported these RCTs as having low Cochrane risk-of-bias. All three RCTs’ participants ( n = 9494) will be included. This CABG-IPD-MA study’s hierarchical hypotheses will evaluate: (1) overall unadjusted treatment effects; (2) overall risk-adjusted treatment effects; (3) prespecified high-risk subgroups’ risk-adjusted treatment effects; (4) the impact of complete revascularization; and (5) the concordance between this CABG-IPD-MA study’s findings with an aggregate-data meta-analysis findings. All primary CABG-IPD-MA analyses will utilize an intention-to-treat framework. Prespecified sensitivity analyses will evaluate findings under alternative treatment-conversion and high-risk restrictions.
Discussion: By pooling and harmonizing individual patient-level records from the only three contemporary multicenter RCTs reporting long-term follow-up, this study was designed to provide precise, clinically relevant assessments of off-pump versus on-pump benefits. These CABG-IPD-MA analyses will evaluate short-, intermediate-, and long-term outcomes exploring whether specific patient subgroups may derive any differential treatment benefits. Findings are expected to generate high-quality, clinically actionable evidence to support future patient-centered decision-making, clinical guideline refinements, and health policy decision-making.
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BibTeX
@article{greenberg2026pooling,
title = {{Pooling individual off-pump and on-pump coronary artery bypass patient records from three contemporary multicenter, randomized, controlled trials: an individual participant data meta-analysis protocol}},
author = {Samuel R. Greenberg and Mario Gaudino and Weiwei Tao and Daniel H. Wolbrom and Jie Yang and Frederick L. Grover and Kara A. Mollura and Lichun He and Wilko Reents and Andre Lamy and A. Laurie Shroyer and on behalf of the CABG-IPD-MA study team (see Supplementary Material 1) and Hossein Almassi and Ramin Ebrahimi and Brack Hattler and Jacquelyn Quin and Jessica Rove and Elaine Tseng and Faisal Bakaeen and Andreas Boening and Brendan Carr and P.J. Deveraux and Anno Diegeler and Stephen Fremes and Leonard Girardi and Salim Yusuf and Hyun Jy Chung and Joseph Collins and Annette Wiseman},
journal = {Trials},
year = {2026},
month = oct,
doi = {10.1186/s13063-026-10001-4},
url = {https://link.springer.com/10.1186/s13063-026-10001-4},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Pooling individual off-pump and on-pump coronary artery bypass patient records from three contemporary multicenter, randomized, controlled trials: an individual participant data meta-analysis protocol
AU - Samuel R. Greenberg
AU - Mario Gaudino
AU - Weiwei Tao
AU - Daniel H. Wolbrom
AU - Jie Yang
AU - Frederick L. Grover
AU - Kara A. Mollura
AU - Lichun He
AU - Wilko Reents
AU - Andre Lamy
AU - A. Laurie Shroyer
AU - on behalf of the CABG-IPD-MA study team (see Supplementary Material 1)
AU - Hossein Almassi
AU - Ramin Ebrahimi
AU - Brack Hattler
AU - Jacquelyn Quin
AU - Jessica Rove
AU - Elaine Tseng
AU - Faisal Bakaeen
AU - Andreas Boening
AU - Brendan Carr
AU - P.J. Deveraux
AU - Anno Diegeler
AU - Stephen Fremes
AU - Leonard Girardi
AU - Salim Yusuf
AU - Hyun Jy Chung
AU - Joseph Collins
AU - Annette Wiseman
PY - 2026
DA - 2026/10/05
JO - Trials
DO - 10.1186/s13063-026-10001-4
UR - https://link.springer.com/10.1186/s13063-026-10001-4
AB - Background: For over three decades, the comparative effectiveness of off-pump versus on-pump coronary artery bypass grafting (CABG) has been debated. Although randomized controlled trials (RCTs) generally report modest long-term advantages for on-pump CABG, potential off-pump benefits remain uncertain particularly among high-risk patients. To address this knowledge gap, this CABG individual participant data meta-analysis (CABG-IPD-MA) will analyze de-identified patient records from the only three multicenter RCTs reporting 5-year follow-up (ROOBY, GOPCABE, and CORONARY) and test five protocol-driven hypotheses. Methods: Across short-term, intermediate, and longer-term periods, this PRISMA-IPD-compliant study will use a one-stage IPD meta-analysis framework to compare off-pump versus on-pump CABG for two co-primary endpoints [i.e., all-cause mortality and a composite metric comprised all-cause death, nonfatal acute myocardial infarction, and repeat revascularization (i.e., repeat CABG or percutaneous coronary intervention)] at 1 and 5 years; at 30 days/in-hospital, perioperative stroke will also be included in the composite. Secondary endpoints include individual sub-components of the composite endpoint and resource-utilization; resource-utilization analyses will be exploratory-only. Eligible studies included all post-2001 multicenter RCTs reporting off-pump versus on-pump post-CABG 5-year outcomes. Re-verified June 2025, the original 2019 PRISMA-IPD-guided systematic review identified only three eligible RCTs; prior publications reported these RCTs as having low Cochrane risk-of-bias. All three RCTs’ participants ( n = 9494) will be included. This CABG-IPD-MA study’s hierarchical hypotheses will evaluate: (1) overall unadjusted treatment effects; (2) overall risk-adjusted treatment effects; (3) prespecified high-risk subgroups’ risk-adjusted treatment effects; (4) the impact of complete revascularization; and (5) the concordance between this CABG-IPD-MA study’s findings with an aggregate-data meta-analysis findings. All primary CABG-IPD-MA analyses will utilize an intention-to-treat framework. Prespecified sensitivity analyses will evaluate findings under alternative treatment-conversion and high-risk restrictions. Discussion: By pooling and harmonizing individual patient-level records from the only three contemporary multicenter RCTs reporting long-term follow-up, this study was designed to provide precise, clinically relevant assessments of off-pump versus on-pump benefits. These CABG-IPD-MA analyses will evaluate short-, intermediate-, and long-term outcomes exploring whether specific patient subgroups may derive any differential treatment benefits. Findings are expected to generate high-quality, clinically actionable evidence to support future patient-centered decision-making, clinical guideline refinements, and health policy decision-making.
SN - 1745-6215
ER -