Randomized Comparison of the Outcome of Single Versus Multiple Arterial Grafts trial (ROMA):Women—a trial dedicated to women to improve coronary bypass outcomes

Central MessageROMA:Women is the first cardiac surgery trial dedicated to women and will inform sex-specific CABG guidelines regarding the use of multiple arterial grafts in women.See Commentary on page XXX. ROMA:Women is the first cardiac surgery trial dedicated to women and will inform sex-specific CABG guidelines regarding the use of multiple arterial grafts in women. See Commentary on page XXX. In the United States every year approximately 240,000 patients undergo coronary artery bypass grafting (CABG), and of them approximately 25% are women.1Bowdish M.E. D'Agostino R.S. Thourani V.H. Schwann T.A. Krohn C. Desai N. et al.STS Adult Cardiac Surgery Database: 2021 update on outcomes, quality, and research.Ann Thorac Surg. 2021; 111: 1770-1780Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar,2Kim K.M. Arghami A. Habib R. Daneshmand M.A. Parsons N. Elhalabi Z. et al.The society of thoracic surgeons adult cardiac surgery Database: 2022 update on outcomes and research.Ann Thorac Surg. 2023; 115: 566-574Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar Data suggest that the use of more than 1 arterial graft for CABG (multiple arterial grafting [MAG]) may be associated with improved outcomes compared with the use of only one arterial graft (single arterial grafting [SAG]), but the evidence is mixed, and there are reasons to believe that the MAG treatment effect may differ by sex. Herein, we summarize the current evidence on MAG and highlight the need for a trial testing the MAG hypothesis in women. At least 9 meta-analyses have pooled data from observational studies comparing the use of the right internal thoracic artery (RITA) or the radial artery (RA) versus the saphenous vein (SV) for CABG.3Urso S. Nogales E. González J.M. Sadaba R. Tena M.Á. Bellot R. et al.Bilateral internal thoracic artery versus single internal thoracic artery: a meta-analysis of propensity score-matched observational studies.Interact Cardiovasc Thorac Surg. 2019; 29: 163-172Crossref Scopus (17) Google Scholar, 4Yi G. Shine B. Rehman S.M. Altman D.G. Taggart D.P. Effect of bilateral internal mammary artery grafts on long-term survival: a meta-analysis approach.Circulation. 2014; 130: 539-545Crossref PubMed Scopus (237) Google Scholar, 5Buttar S.N. Yan T.D. Taggart D.P. Tian D.H. Long-term and short-term outcomes of using bilateral internal mammary artery grafting versus left internal mammary artery grafting: a meta-analysis.Heart. 2017; 103: 1419-1426Crossref PubMed Scopus (130) Google Scholar, 6Kajimoto K. Yamamoto T. Amano A. Coronary artery bypass revascularization using bilateral internal thoracic arteries in diabetic patients: a Systematic review and meta-analysis.Ann Thorac Surg. 2015; 99: 1097-1104Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar, 7Taggart D.P. D'Amico R. Altman D.G. Effect of arterial revascularisation on survival: a systematic review of studies comparing bilateral and single internal mammary.Lancet. 2001; 358: 870-875Abstract Full Text Full Text PDF PubMed Scopus (631) Google Scholar, 8Takagi H. Goto S.N. Watanabe T. Mizuno Y. Kawai N. Umemoto T. A meta-analysis of adjusted hazard ratios from 20 observational studies of bilateral versus single internal thoracic artery coronary artery bypass grafting.J Thorac Cardiovasc Surg. 2014; 148: 1282-1290Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar, 9Deo S.V. Altarabsheh S.E. Shah I.K. Cho Y.H. McGraw M. Sarayyepoglu B. et al.Are two really always better than one? Results, concerns and controversies in the use of bilateral internal thoracic arteries for coronary artery bypass grafting in the elderly: a systematic review and meta-analysis.In J Surg. 2015; 16: 163-170Google Scholar, 10Zhou P. Zhu P. Nie Z. Zheng S. Is the era of bilateral internal thoracic artery grafting coming for diabetic patients? An updated meta-analysis.J Thorac Cardiovasc Surg. 2019; 158: 1559-1570Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar, 11Gaudino M. Rahouma M. Abouarab A. Leonard J. Kamel M. Di Franco A. et al.Radial artery versus saphenous vein as the second conduit for coronary artery bypass surgery: a meta-analysis.J Thorac Cardiovasc Surg. 2019; 157: 1819-1825.e10Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar All have reported longer postoperative survival in the MAG group, with hazard ratios (HRs) for mortality ranging from 0.65 to 0.81. In the most recent meta-analysis of 32 propensity-score matched studies and 31,688 patients, RITA use was associated with a significant reduction in long-term mortality (HR, 0.78; 95% confidence interval [CI], 0.71-0.86).3Urso S. Nogales E. González J.M. Sadaba R. Tena M.Á. Bellot R. et al.Bilateral internal thoracic artery versus single internal thoracic artery: a meta-analysis of propensity score-matched observational studies.Interact Cardiovasc Thorac Surg. 2019; 29: 163-172Crossref Scopus (17) Google Scholar Similarly, in a meta-analysis of 14 studies and 20,931 patients at 6.6 years of follow-up, mortality was 24.5% in patients who received the RA versus 34.2% in patients who received the SV (incidence rate ratio [IRR], 0.74, 95% CI, 0.63-0.87).11Gaudino M. Rahouma M. Abouarab A. Leonard J. Kamel M. Di Franco A. et al.Radial artery versus saphenous vein as the second conduit for coronary artery bypass surgery: a meta-analysis.J Thorac Cardiovasc Surg. 2019; 157: 1819-1825.e10Abstract Full Text Full Text PDF PubMed Scopus (42) Google Scholar However, comparative observational studies are open to treatment allocation bias, and it has been suggested that unmeasured confounders, and not true treatment effect, may be the reason for the reported differences.12Gaudino M. Di Franco A. Rahouma M. Tam D.Y. Iannaccone M. Deb S. et al.Unmeasured confounders in observational studies comparing bilateral versus single internal thoracic artery for coronary artery bypass grafting: a meta-analysis.J Am Heart Assoc. 2018; 7: e008010Crossref PubMed Scopus (107) Google Scholar The randomized evidence in support of the MAG hypothesis is limited. In the Arterial Revascularization Trial (ART), the only adequately powered randomized trial comparing MAG with SAG, no difference in survival or event-free survival at 10 years was found between the 2 groups.13Taggart D.P. Benedetto U. Gerry S. Altman D.G. Gray A.M. Lees B. et al.Bilateral versus single internal-thoracic-artery grafts at 10 years.N Engl J Med. 2019; 380: 437-446Crossref PubMed Scopus (307) Google Scholar In ART, however, the crossover rate was high (single internal thoracic artery to bilateral internal thoracic artery: 38/1554 = 2.4%, bilateral internal thoracic artery to single internal thoracic artery: 215/1548 = 13.9%) and the RA was used in almost 22% of the patients in the single internal thoracic artery group; in a post-hoc analysis comparing SAG with MAG, a significant benefit in both outcomes was found in the MAG group. In the Radial Artery Database International ALliance (RADIAL), a pooled analysis of individual data from 6 randomized trials comparing the use of the RA versus the SV for CABG, there was a significant reduction in the incidence of the composite outcome of death, myocardial infarction, or repeat revascularization at 5 years of follow-up in favor of the RA (HR, 0.67; 95% CI, 0.49-0.90),14Gaudino M. Benedetto U. Fremes S. Biondi-Zoccai G. Sedrakyan A. Puskas J.D. et al.Radial-artery or saphenous-vein grafts in coronary-artery bypass surgery.N Engl J Med. 2018; 378: 2069-2077Crossref PubMed Scopus (373) Google Scholar and when follow-up was extended to 10 years, patients who received the RA also had a lower incidence of the composite of death and myocardial infarction (HR, 0.77; 95% CI, 0.63-0.94) and lower mortality (HR, 0.73; 95% CI, 0.57-0.93).15Gaudino M. Benedetto U. Fremes S. Ballman K. Biondi-Zoccai G. Sedrakyan A. et al.Association of radial artery graft vs saphenous vein graft with long-term cardiovascular outcomes among patients undergoing coronary artery bypass grafting: a systematic review and meta-analysis.JAMA. 2020; 324: 179Crossref PubMed Scopus (84) Google Scholar In the Radial Artery Patency and Clinical Outcomes (RAPCO) trial at 15 years, in a cohort of patients older than 70 years of age, those who received a RA, had a lower incidence of the composite outcome of all-cause death, myocardial infarction, and repeat revascularization compared with those that received a SV (HR, 0.71; 95% CI, 0.52-0.98).16Hamilton G.W. Raman J. Moten S. Matalanis G. Rosalion A. Dimagli A. et al.Radial artery vs. internal thoracic artery or saphenous vein grafts: 15-year results of the RAPCO trials.Eur Heart J. 2023; : ehad108Google Scholar Current guidelines generally support the use of MAG in patients with long life expectancy with Level of Evidence B.17Lawton J.S. Tamis-Holland J.E. Bangalore S. Bates E.R. Beckie T.M. Bischoff J.M. et al.2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines.Circulation. 2022; 145: e4-e17PubMed Google Scholar,18Neumann F.J. Sousa-Uva M. Ahlsson A. Alfonso F. Banning A.P. Benedetto U. et al.2018 ESC/EACTS Guidelines on myocardial revascularization.Eur Heart J. 2019; 40: 87-165Crossref PubMed Scopus (4093) Google Scholar However, the uptake in the cardiac surgical community has been limited, with less than 15% of patients with CABG receiving MAG in the United States, and 20% to 30% receiving MAG in Europe, even when patients meet guideline criteria for MAG.19Gaudino M. Rahouma M. Habib R.H. Hameed I. Robinson N.B. Farrington W.J. et al.Surgeons' coronary bypass practice patterns in the United States.J Am Coll Cardiol. 2020; 76: 1714-1715Crossref PubMed Scopus (9) Google Scholar, 20Jabagi H. Tran D.T. Hessian R. Glineur D. Rubens F.D. Impact of gender on arterial revascularization strategies for coronary artery bypass grafting.Ann Thorac Surg. 2018; 105: 62-68Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar, 21Gaudino M. Chikwe J. Falk V. Lawton J.S. Puskas J.D. Taggart D.P. Transatlantic Editorial: the use of multiple arterial grafts for coronary revascularization in Europe and North America.Ann Thorac Surg. 2020; 109: 1631-1636Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar Several reports have indicated that the key reason for the underuse of MAG by cardiac surgeons is the limited available randomized data in support of its clinical benefits.22Mastrobuoni S. Gawad N. Price J. Chan V. Ruel M. Mesana T.G. et al.Use of bilateral internal thoracic artery during coronary artery bypass graft surgery in Canada: the bilateral internal thoracic artery survey.J Thorac Cardiovasc Surg. 2012; 144: 874-879Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar,23Jayakumar S. Gasparini M. Treasure T. Burdett C. Jozsa F. et al.Cardiothoracic Trainees Research CollaborativeHow do surgeons decide? Conduit choice in coronary artery bypass graft surgery in the UK.Interact Cardiovasc Thorac Surg. 2019; 29: 179-186Crossref PubMed Scopus (19) Google Scholar The Randomized comparison of the Outcome of single versus Multiple Arterial grafts trial (ROMA; NCT03217006) was designed to provide a definitive answer to the MAG question. ROMA has completed enrollment (4370 patients in >80 international centers) in April 2023, and the primary outcome results will available in 4 or 5 years (the trial analysis is event-driven).24Gaudino M. Alexander J.H. Bakaeen F.G. Ballman K. Barili F. Calafiore A.M. et al.Randomized comparison of the clinical outcome of single versus multiple arterial grafts: the ROMA trial—rationale and study protocol†.Eur J Cardiothorac Surg. 2017; 52: 1031-1040Crossref PubMed Google Scholar As there is evidence that surgeons' experience with MAG may significantly affect its outcomes,12Gaudino M. Di Franco A. Rahouma M. Tam D.Y. Iannaccone M. Deb S. et al.Unmeasured confounders in observational studies comparing bilateral versus single internal thoracic artery for coronary artery bypass grafting: a meta-analysis.J Am Heart Assoc. 2018; 7: e008010Crossref PubMed Scopus (107) Google Scholar,25Schwann T.A. Habib R.H. Wallace A. Shahian D.M. O'Brien S. Jacobs J.P. et al.Operative outcomes of multiple-arterial versus single-arterial coronary bypass grafting.Ann Thorac Surg. 2018; 105: 1109-1119Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar surgeons participating in ROMA were selected based on a minimum number of MAG cases (n = 250) or expert vetting by the trial's principle investigators. In ROMA, only 16% of the enrolled patients (approximately 690) are women. CABG outcomes have consistently been reported to be worse in women compared with men. In a meta-analysis of 84 studies and 903,346 patients, women undergoing CABG were at greater risk for operative (odds ratio [OR], 1.77; 95% CI, 1.64-1.92) and late mortality (IRR, 1.16; 95% CI, 1.06-1.26) compared with men.26Bryce Robinson N. Naik A. Rahouma M. Morsi M. Wright D. Hameed I. et al.Sex differences in outcomes following coronary artery bypass grafting: a meta-analysis.Interact Cardiovasc Thorac Surg. 2021; 33: 841-847Crossref Scopus (11) Google Scholar Similar results were reported in a patient-level meta-analysis of the largest CABG trials.27Gaudino M. Di Franco A. Alexander J.H. Bakaeen F. Egorova N. Kurlansky P. et al.Sex differences in outcomes after coronary artery bypass grafting: a pooled analysis of individual patient data.Eur Heart J. 2021; 43: 18-28Crossref PubMed Scopus (36) Google Scholar In a study including more than 1.2 million patients and based on the United States Adult Cardiac Surgery Database of the Society of Thoracic Surgeons, the sex-related gap in early CABG outcomes did not improve from 2011 to 2020.28Gaudino M. Chadow D. Rahouma M. Soletti G.J. Sandner S. Perezgrovas-Olaria R. et al.Operative outcomes of women undergoing coronary artery bypass surgery in the US, 2011 to 2020.JAMA Surg. 2023; 58: 494-502Crossref Scopus (4) Google Scholar Reasons for differences in outcomes are likely multifactorial. Current diagnostic and treatment algorithms for coronary artery disease are based on data from a predominantly male population and are biased toward the presentation of myocardial ischemia in men, leading to substantial delay in diagnosis and referral for treatment in women.29Alam M. Bandeali S.J. Kayani W.T. Ahmad W. Shahzad S.A. Jneid H. et al.Comparison by meta-analysis of mortality after isolated coronary artery bypass grafting in women versus men.Am J Cardiol. 2013; 112: 309-317Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar On average, women present with coronary artery disease at older ages than men. Due to delays in referral for CABG, they also present with more cardiovascular risk factors, including diabetes, hypertension, peripheral vascular disease, and dyslipidemia, which put them at greater risk of postoperative complications, including sternal wound infections.30Abramov D. Tamariz M.G. Sever J.Y. Christakis G.T. Bhatnagar G. Heenan A.L. et al.The influence of gender on the outcome of coronary artery bypass surgery.Ann Thorac Surg. 2000; 70: 800-805Abstract Full Text Full Text PDF PubMed Scopus (201) Google Scholar, 31Ahmed W.A. Tully P.J. Knight J.L. Baker R.A. Female sex as an independent predictor of morbidity and survival after isolated coronary artery bypass grafting.Ann Thorac Surg. 2011; 92: 59-67Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar, 32Koch C.G. Khandwala F. Nussmeier N. Blackstone E.H. Gender and outcomes after coronary artery bypass grafting: a propensity-matched comparison.J Thorac Cardiovasc Surg. 2003; 126: 2032-2043Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar Women are also more likely to present for surgery with heart failure or under emergency situations such as cardiogenic shock or acute myocardial infarction.30Abramov D. Tamariz M.G. Sever J.Y. Christakis G.T. Bhatnagar G. Heenan A.L. et al.The influence of gender on the outcome of coronary artery bypass surgery.Ann Thorac Surg. 2000; 70: 800-805Abstract Full Text Full Text PDF PubMed Scopus (201) Google Scholar, 31Ahmed W.A. Tully P.J. Knight J.L. Baker R.A. Female sex as an independent predictor of morbidity and survival after isolated coronary artery bypass grafting.Ann Thorac Surg. 2011; 92: 59-67Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar, 32Koch C.G. Khandwala F. Nussmeier N. Blackstone E.H. Gender and outcomes after coronary artery bypass grafting: a propensity-matched comparison.J Thorac Cardiovasc Surg. 2003; 126: 2032-2043Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar, 33Vogel B. Acevedo M. Appelman Y. Bairey Merz C.N. Chieffo A. Figtree G.A. et al.The Lancet Women and Cardiovascular Disease Commission: reducing the global burden by 2030.Lancet. 2021; 397: 2385-2438Abstract Full Text Full Text PDF PubMed Scopus (303) Google Scholar Physiologically, women also have smaller coronary arteries than men, independent of body size, which increases the technical complexity of CABG.34Sheifer S.E. Canos M.R. Weinfurt K.P. Arora U.K. Mendelsohn F.O. Gersh B.J. et al.Sex differences in coronary artery size assessed by intravascular ultrasound.Am Heart J. 2000; 139: 649-652Crossref PubMed Google Scholar,35O'Connor G.T. Morton J.R. Diehl M.J. Olmstead E.M. Coffin L.H. Levy D.G. et al.Differences between men and women in hospital mortality associated with coronary artery bypass graft surgery. The Northern New England Cardiovascular Disease Study Group.Circulation. 1993; 88: 2104-2110Crossref PubMed Scopus (279) Google Scholar In addition, the pathophysiology of myocardial ischemia in women is more often related to coronary hyperreactivity, microvascular dysfunction, and distal microembolization, which may be only partially relieved by CABG.36von Mering G.O. Arant C.B. Wessel T.R. McGorray S.P. Bairey Merz C.N. Sharaf B.L. et al.Abnormal coronary vasomotion as a prognostic indicator of cardiovascular events in women: results from the National Heart, Lung, and Blood Institute–sponsored Women's Ischemia Syndrome Evaluation (WISE).Circulation. 2004; 109: 722-725Crossref PubMed Scopus (336) Google Scholar, 37Burke A.P. Virmani R. Galis Z. Haudenschild C.C. Muller J.E. Task force #2—what is the pathologic basis for new atherosclerosis imaging techniques?.J Am Coll Cardiol. 2003; 41: 1874-1886Crossref PubMed Google Scholar, 38Reynolds H.R. Srichai M.B. Iqbal S.N. Slater J.N. Mancini G.B.J. Feit F. et al.Mechanisms of myocardial infarction in women without angiographically obstructive coronary artery disease.Circulation. 2011; 124: 1414-1425Crossref PubMed Scopus (322) Google Scholar Women report also lower quality of life (QOL) after CABG compared with men.39Gijsberts C.M. Agostoni P. Hoefer I.E. Asselbergs F.W. Pasterkamp G. Nathoe H. et al.Gender differences in health-related quality of life in patients undergoing coronary angiography.Open Heart. 2015; 2: e000231Crossref PubMed Scopus (35) Google Scholar,40Martin L.M. Holmes S.D. Henry L.L. Schlauch K.A. Stone L.E. Roots A. et al.Health-related quality of life after coronary artery bypass grafting surgery and the role of gender.Cardiovasc Revasc Med. 2012; 13: 321-327Crossref PubMed Scopus (16) Google Scholar Differences in reported QOL between sexes could be due to the difference in symptoms that women experience (including more frequent dyspnea),41Kendel F. Dunkel A. Müller-Tasch T. Steinberg K. Lehmkuhl E. Hetzer R. et al.Gender differences in health-related quality of life after coronary bypass surgery: results from a 1-year follow-up in propensity-matched men and women.Psychosom Med. 2011; 73: 280-285Crossref PubMed Scopus (25) Google Scholar differences in the mechanism of angina (microvascular vs epicardial disease), and differences in coronary disease and comorbidities at the time of referral for CABG.40Martin L.M. Holmes S.D. Henry L.L. Schlauch K.A. Stone L.E. Roots A. et al.Health-related quality of life after coronary artery bypass grafting surgery and the role of gender.Cardiovasc Revasc Med. 2012; 13: 321-327Crossref PubMed Scopus (16) Google Scholar In a meta-analysis of QOL after CABG including 14 randomized trials and 13,595 participants from 15 countries,42Creber R.M. Dimagli A. Spadaccio C. Myers A. Moscarelli M. Demetres M. et al.Effect of coronary artery bypass grafting on quality of life: a meta-analysis of randomized trials.Eur Heart J Qual Care Clin Outcomes. 2022; 8: 259-268Crossref PubMed Scopus (9) Google Scholar there was a significant increase in QOL scores from before surgery to 1-year postoperatively in both sexes, but women had significantly lower QOL improvement than men. However, 78% of the study participants were men and these limited data are inadequate to address the issue of sex differences in QOL relative to more durable revascularization (MAG vs SAG). Women are significantly less likely to receive MAG than men. A study on 19,557 patients reported that RITA is underused in women (OR for RITA use in men vs women 1.68, 95% CI, 1.16-2.39) and that the annual increase in RITA use among women was significantly lower than in men (0.73% per year vs 1.16% per year, respectively, P < .001).20Jabagi H. Tran D.T. Hessian R. Glineur D. Rubens F.D. Impact of gender on arterial revascularization strategies for coronary artery bypass grafting.Ann Thorac Surg. 2018; 105: 62-68Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar In another study including more than 1.2 million patients with CABG, women had significantly lower rates of RITA (2.9% vs 5.6%, P < .001) and RA use (3.2% vs 5.6%, P < .001), and lower odds than men of receiving MAG (adjusted OR, 0.78; 95% CI, 0.75-0.81, P < .001).43Jawitz O.K. Lawton J.S. Thibault D. O'Brien S. Higgins R.S.D. Schena S. et al.Sex differences in coronary artery bypass grafting techniques: a society of thoracic surgeons Database analysis.Ann Thorac Surg. 2022; 113: 1979-1988Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar Women have greater risk of sternal wound complications after CABG, and this risk is increased with the use of the RITA44Balachandran S. Lee A. Denehy L. Lin K.Y. Royse A. Royse C. et al.Risk factors for sternal complications after cardiac operations: a systematic review.Ann Thorac Surg. 2016; 102: 2109-2117Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar,45Gaudino M. Audisio K. Rahouma M. Robinson N.B. Soletti G.J. Cancelli G. et al.Association between sternal wound complications and 10-year mortality following coronary artery bypass grafting.J Thorac Cardiovasc Surg. 2021; Abstract Full Text PDF Scopus (7) Google Scholar; this may be one of the reasons for the lower RITA use in women. In a meta-analysis of 6 propensity-matched studies, women who received MAG had lower long-term mortality (IRR, 0.86; 95% CI, 0.76-0.96) compared with women who received SAG.46Robinson N.B. Lia H. Rahouma M. Audisio K. Soletti G. Demetres M. et al.Coronary artery bypass with single versus multiple arterial grafts in women: a meta-analysis.J Thorac Cardiovasc Surg. 2021; Google Scholar In another study of >63,000 patients based on the New York State Database, the benefit of MAG varied significantly between men and women, highlighting the need for MAG studies dedicated to women.47Gaudino M. Samadashvili Z. Hameed I. Chikwe J. Girardi L.N. Hannan E.L. Differences in long-term outcomes after coronary artery bypass grafting using single vs multiple arterial grafts and the association with sex.JAMA Cardiol. 2021; 6: 401-409Crossref Scopus (27) Google Scholar It is important to note that in all the published randomized trials, the MAG treatment effect was different by sex and larger in women. In the ART trial, the HR for the MAG treatment effect was 1.00, 95% CI 0.84 to 1.18 for men versus 0.78, 0.53 to 1.13 for women, but women represented only 14% of the enrolled population and the interaction P was not significant (.23). In all RADIAL analyses, sex was a significant treatment effect modifier (interaction P = .01 and .004 at 5 and 10 years, respectively), suggesting that women derived greater benefit than men from the use of MAG.14Gaudino M. Benedetto U. Fremes S. Biondi-Zoccai G. Sedrakyan A. Puskas J.D. et al.Radial-artery or saphenous-vein grafts in coronary-artery bypass surgery.N Engl J Med. 2018; 378: 2069-2077Crossref PubMed Scopus (373) Google Scholar,15Gaudino M. Benedetto U. Fremes S. Ballman K. Biondi-Zoccai G. Sedrakyan A. et al.Association of radial artery graft vs saphenous vein graft with long-term cardiovascular outcomes among patients undergoing coronary artery bypass grafting: a systematic review and meta-analysis.JAMA. 2020; 324: 179Crossref PubMed Scopus (84) Google Scholar In the RAPCO trial, at subgroup analysis women derived a greater benefit from RA use than men (HR, 0.82; 95% CI, 0.58-1.18 for men vs 0.37, 95% CI, 0.17-0.79 for women, interaction P = .07), but only 43 of 225 (19.1%) of the patients included were women. Finally, in the only trial that did not find a beneficial effect for the RA compared with the saphenous vein, >99% of the enrolled patients (751/757) were men.48Goldman S. McCarren M. Sethi G.K. Holman W. Bakaeen F.G. Wagner T.H. et al.Long-term mortality follow-up of radial artery versus saphenous vein in coronary artery bypass grafting: a multicenter, randomized trial.Circulation. 2022; 146: 1323-1325Crossref Scopus (6) Google Scholar In summary, there is evidence that suggests that MAG may be beneficial in patients with CABG and that the MAG treatment effect is different by sex and larger in women, but all the CABG trials (including ROMA) have included only a minority of women and are largely underpowered to test the MAG hypothesis in women. It is possible that if the results of the primary analysis of ROMA are neutral in a prevalently male patient population, a signal for the benefit of MAG in women may be diluted and an important opportunity to improve CABG outcomes in women (a crucial need due to the current outcomes disparity) may be lost. This constitutes a strong rationale for an MAG trial dedicated to women. The ROMA:Women trial (NCT04124120, approved by the Weill Cornell Medicine, Institutional Review Board #1703018094, on April 4, 2023) will include all women enrolled in ROMA and will add 1310 women in order to test the MAG hypothesis in women with adequate statistical power. A dedicated analytic plan will assess and eventually address the presence of a cohort effect from the included ROMA patients. ROMA:Women will leverage the existing ROMA infrastructure increasing efficiency and minimizing enrollment time. The trial will use a nested trial design that has not been previously used in cardiac surgery trials (Figure 1). The trial represents a departure from typical cardiovascular and cardiac surgery trials by including a majority of women in its leadership (and also in the Steering Committee [21/27 = 77%]). We will also prioritize identification of women principal investigators and junior faculty at each site to improve the current disparity in female leadership in cardiovascular trials.49Soletti G.J. Perezgrovas-Olaria R. Dimagli A. Harik L. Rong L. Bairey Merz C.N. et al.Gender disparities in cardiac surgery trials: leadership, authorship, and patient enrollment.Ann Thorac Surg. 2023; https://doi.org/10.1016/j.athoracsur.2023.01.022Abstract Full Text Full Text PDF Scopus (2) Google Scholar The trial has been endorsed by the Expert Advisory Panel of the Global Cardiovascular Research Funders Forum Multinational Clinical Trials Initiative and will be funded by an international collaboration that also includes philanthropic and industry partners. The patient population consists of women referred for primary isolated CABG. Inclusion and exclusion criteria are identical to those of the ROMA trial (Table 1). The only exception is the 70 year age cut-off that was used in ROMA and will not be used in ROMA:Women. This decision is based on the fact that women are referred for CABG at an older age than men,29Alam M. Bandeali S.J. Kayani W.T. Ahmad W. Shahzad S.A. Jneid H. et al.Comparison by meta-analysis of mortality after isolated coronary artery bypass grafting in women versus men.Am J Cardiol. 2013; 112: 309-317Abstract Full Text Full Text PDF PubMed Scopus (81) Google Scholar so that the 70-year age cut-off (that makes sense in the predominantly male ROMA population) would greatly limit the generalizability of the results of ROMA:Women.Table 1Inclusion and exclusion criteria for ROMA:WomenInclusion and exclusion criteriaInclusion criteria1.Isolated CABG2.Primary (first-time) cardiac surgery procedure3.Significant disease of the left main coronary artery or of the left anterior descending and the circumflex coronary system with or without disease of the right coronary arteryExclusion criteria1.Planned single-graft CABG2.Emergency operation3.Left ventricular ejection fraction <35%4.Preoperative ST-elevation myocardial infarction within 48 h5.Any concomitant cardiac or noncardiac procedure6.Any previous cardiac operation7.Preoperative severe end-organ dysfunction, cancer or any comorbidity that reduces life expectancy to less than 5 y8.Inability to use either the saphenous vein or both the right internal thoracic artery and the radial artery as graftsCABG, Coronary artery bypass grafting. Open table in a new tab CABG, Coronary artery bypass grafting. The randomization procedure, interventions and treatment arms, outcome assessments, and follow-up protocol of ROMA:Women are identical to those of the parent ROMA trial. As in the ROMA trial, patients will be assigned to 1 of 2 groups: MAG or SAG (Figure 2). In all patients, the left internal thoracic artery will be anastomosed to the left anterior descending coronary artery. For patients randomized to the MAG group, the RITA or the RA (according to the surgeon's preference) will be used to graft the main target vessel of the circumflex coronary artery. As there is evidence that the efficacy of arterial grafts to the right coronary artery is reduced,50Glineur D. D'hoore W. de Kerchove L. Noirhomme P. Price J. Hanet C. et al.Angiographic predictors of 3-year patency of bypass grafts implanted on the right coronary artery system: a prospective randomized comparison of gastroepiploic artery, saphenous vein, and right internal thoracic artery grafts.J Thorac Cardiovasc Surg. 2011; 142: 980-988Abstract Full Text Full Text PDF PubMed Scopus (68) Google Scholar,51Schmidt S.E. Jones J.W. Thornby J.I. Miller C.C. Beall A.C. Improved survival with multiple left-sided bilateral internal thoracic artery grafts.Ann Thorac Surg. 1997; 64: 9-15Abstract Full Text Full Text PDF PubMed Scopus (157) Google Scholar the second arterial graft in the MAG group should be directed to the circumflex territory and not be used on the right coronary artery. For patients randomized to the SAG group, SV grafts will be used for all non-left anterior descending target vessels. Surgical revascularization will be performed with the current standard technique in use at the local centers. The findings of ROMA:Women will inform guidelines for the practice of CABG in women—a unique and biologically distinct patient population that has been underrepresented and poorly studied. At the moment, women receive significantly less MAG than men and have worse outcomes and QOL after CABG. Multiple studies have reported that a key reason for the underuse of MAG by cardiac surgeons is the limited randomized evidence in support of its clinical benefits. Should ROMA:Women support the MAG hypothesis, the results will lead to the endorsement of the use of MAG in women by guidelines and professional societies and to greater adoption of MAG in women undergoing CABG, improving clinical and patient-reported outcomes. As CABG is the most commonly performed adult cardiac surgery worldwide, the ROMA:Women findings will impact the health of hundreds of thousands of women globally.