One ineligible participant was mistakenly considered eligible and was consented and randomized.
EVH indicates endoscopic vein harvesting; OVH, open vein harvesting.
Trial Protocol and Statistical Analysis Plan
eAppendix. Supplementary Methods
Data Sharing Statement
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Zenati MA, Bhatt DL, Stock EM, et al. Intermediate-Term Outcomes of Endoscopic or Open Vein Harvesting for Coronary Artery Bypass Grafting: The REGROUP Randomized Clinical Trial. JAMA Netw Open. 2021;4(3):e211439. doi:10.1001/jamanetworkopen.2021.1439
Endoscopic vein harvesting (EVH) for coronary artery bypass grafting (CABG) was introduced in the 1990s to reduce the rates of leg wound complications.1 Technical mastery of EVH requires a significant learning curve.2 In 2009, a study in 3000 patients raised the concern that, compared with conventional harvesting, EVH was associated with a 50% increase in mortality.3 With the aim of assessing the safety of EVH, we report the intermediate-term results of the Randomized Endo-Vein Graft Prospective (REGROUP) trial.4,5
The randomized clinical trial was approved by the institutional review board at each participating center. Patients gave written informed consent before participation. This study is reported following the Consolidated Standards of Reporting Trials (CONSORT) reporting guideline. The trial protocol and statistical analysis plan are available in Supplement 1. This study is registered on ClinicalTrials.gov (Identifier: NCT01850082).
In the Randomized Endo-Vein Graft Perspective (REGROUP) trial, participants undergoing CABG at 16 Department of Veterans Affairs (VA) medical centers from March 2014 through April 2017 were randomized to either EVH or open vein harvest (OVH) in a 1:1 ratio. The primary outcome of the REGROUP trial was defined as the first occurrence of a major adverse cardiac event (MACE) composite comprised of all-cause mortality, nonfatal myocardial infarction (MI), or repeat revascularization, over the active follow-up phase; we previously reported no difference in MACE between the 2 groups, with a median follow-up of 2.7 years.5 The prespecified secondary outcome was the first occurrence of MACE over the combined active and passive follow-up phases (eAppendix in Supplement 2). Only expert EVH harvesters (ie, individuals who had performed >100 EVHs with <5% conversions to OVH) were allowed to perform the procedures. Inclusion criteria for patients were age 18 years or older, elective or urgent CABG, and plan to undergo at least 1 CABG using a saphenous-vein graft. Assessments occurred at baseline, intraoperatively, postoperatively, at discharge or 30 days after surgery if still hospitalized, at 6 weeks, and every 3 months thereafter until the end of the active follow-up phase; intermediate-term MACE outcomes were collected passively for an additional 2 years by merging VA and non-VA records as well as Medicare parts A and B records. Sample size calculations estimated a need for a total of 1150 patients. Kaplan-Meier nonparametric survival estimates depicted the unadjusted impact of vein harvesting technique on MACE. Multivariable survival analyses were performed. P values were 2-sided, and statistical significance was set at P = .05. Analyses were conducted using SAS statistical software version 9.4 (SAS Institute). Data were analyzed in August 2020.
A total of 1150 participants (mean [SD] age, 66.4 [6.9] years; 1143 [99.5%] men) were randomized, including 574 patients (49.9%) randomized to OVH and 576 patients (50.1%) randomized to EVH, and followed-up for MACE (Figure 1). Groups were balanced regarding age, sex, smoking status, race/ethnicity, body mass index, and comorbid conditions.5 The median (interquartile range) intermediate-term follow-up was 4.70 (3.84-5.45) years. During the entire follow-up, the primary outcome of MACE occurred in 126 patients (21.9%) in the EVH group, compared with 135 patients (23.5%) in the OVH group (hazard ratio [HR], 0.92; 95% CI, 0.72-1.18; P = .52) (Figure 2). Death from any cause occurred in 69 patients (12.0%) in the EVH group and 76 patients (13.2%) in the OVH group (HR, 0.90; 95% CI, 0.65-1.25; P = .52); nonfatal MI occurred in 37 patients (6.4%) in the EVH group and 42 patients (7.3%) in the OVH group (HR, 0.87; 95% CI, 0.56-1.36; P = .54); and repeat revascularization occurred in 45 patients (7.8%) in the EVH group and 56 patients (9.8%) in the OVH group (HR, 0.79; 95% CI, 0.54-1.17; P = .25). An adjusted multivariable Cox regression model found no significant difference in MACE risk.
This randomized clinical trial found that there was no significant difference in MACE occurrence among patients who underwent EVH compared with those who underwent OVH for CABG over a median follow-up of 4.7 years. The saphenous vein is the most common supplementary conduit for CABG, but concerns have been raised about long-term ischemic events when EVH is used. This uncertainty has translated into variable adoption rates of EVH in North America (>80% of patients) compared with Europe (<50% of patients).6
The intermediate-term results of REGROUP are reassuring and demonstrate no significant difference in cardiovascular events between endoscopic or open approaches; leg-wound complications were reduced with EVH.5 Limitations of this study include lack of imaging evaluation of graft patency and use of only expert harvesters. These results provide strong reassurance that EVH is safe up to 4.7 years after the procedure; a 10-year follow-up is planned.
Accepted for Publication: January 21, 2021.
Published: March 15, 2021. doi:10.1001/jamanetworkopen.2021.1439
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Zenati MA et al. JAMA Network Open.
Corresponding Author: Marco A. Zenati, MD, Division of Cardiac Surgery, Department of Surgery, Veterans Affairs Boston Healthcare System, Brigham and Women’s Hospital, Harvard Medical School, 1400 VFW Pkwy, Boston, MA 02132 (email@example.com).
Author Contributions: Dr Zenati had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Zenati, Bhatt, Stock, Bakaeen, Biswas.
Acquisition, analysis, or interpretation of data: Zenati, Bhatt, Stock, Hattler, Wagner, Biswas.
Drafting of the manuscript: Zenati, Stock, Bakaeen.
Critical revision of the manuscript for important intellectual content: Zenati, Bhatt, Stock, Hattler, Wagner, Biswas.
Statistical analysis: Zenati, Stock, Wagner, Biswas.
Obtained funding: Zenati.
Administrative, technical, or material support: Zenati, Hattler, Wagner, Biswas.
Supervision: Zenati, Bhatt, Bakaeen, Biswas.
Conflict of Interest Disclosures: Dr Bhatt reported receiving grants from Abbot, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cardax, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lexicon, Lilly, the Medicines Company, Medtronic, MyoKardia, Pfizer, PhaseBio, PLx Pharma, Regeneron, Roche, and Sanofi Aventis; personal fees from the American College of Cardiology, Bayer, Belvoir Publications, Biotronik, Boehringer Ingelheim, Boston Scientific, Canadian Medical and Surgical Knowledge Translation Research Group, CellProthera, Cleveland Clinic, Contego Medical, CSI St Jude Medical, CSL Behring, Duke Clinical Research Institute, Elsevier, Ferring Pharmaceuticals, HMP Global, Harvard Clinical Research Institute (now Baim Institute for Clinical Research), K2P, Level Ex, Mayo Clinic, Medtelligence/ReachMD, MJH Life Sciences, Mount Sinai School of Medicine, MyoKardia, Population Health Research Institute, Slack Publications, Society of Cardiovascular Patient Care, Svelte, TobeSoft, and WebMD; serving on advisory boards for Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Level Ex, Medscape Cardiology, PhaseBio, PLx Pharma, and Regado Biosciences; serving on a board of directors for the Boston VA Research Institute, Society of Cardiovascular Patient Care, and TobeSoft; serving as chair of the American Heart Association Quality Oversight Committee, NCDR-ACTION Registry Steering Committee, and VA Clinical Assessment Rerporting and Tracking Program Research and Publications Committee; serving on data monitoring committees for Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute), PORTICO trial (funded by St Jude Medical, now Abbott), Cleveland Clinic (including for a trial funded by Edwards), Contego Medical, Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for a trial funded by Daiichi Sankyo), and Population Health Research Institute; serving as a trustee for the American College of Cardiology; serving as deputy editor of Clinical Cardiology; conducting research without compensation for FlowCo, Merck, Novo Nordisk, and Takeda outside the submitted work. Dr Wagner reported receiving grants from the US Department of Veterans Affairs outside the submitted work. No other disclosures were reported.
Funding/Support: This work was supported by award No. CSP#588 from the Office for Research and Development, Cooperative Studies Program of the US Department of Veterans Affairs.
Role of the Funder/Sponsor: The Veterans Health Administration and Office of Research and Development had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript and decision to submit the manuscript for publication other than trial sponsoring and oversight as detailed in the study protocol and statistical analysis plan.
Disclaimer: The views and opinions expressed herein are those of the authors and do not necessarily represent that of the US Department of Veterans Affairs or the US government.
Data Sharing Statement: See Supplement 3.
Additional Contributions: We thank the veterans who participated in this trial, the investigators and research coordinators at the participating centers, the members of the executive committee, the data and safety monitoring committee, the clinical events adjudicators, and the Office of Research and Development.
Additional Information: REGROUP ClinicalTrials.gov number: NCT01850082.