Arterial versus venous conduits in coronary artery bypass grafting: a systematic review with meta-analysis

Arterial versus venous conduits in coronary artery bypass grafting: a systematic review with meta-analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review Arterial versus venous conduits in coronary artery bypass grafting: a systematic review with meta-analysis Shannon Thenagaran, S. Aleena Haider, Wael Tawfick This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8050782/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Coronary artery bypass grafting (CABG) remains a cornerstone of treatment for patients with multivessel coronary artery disease. While the use of the left internal mammary artery (LIMA) to the left anterior descending artery is the standard of care, the optimal choice of additional conduits—arterial versus venous—remains a subject of ongoing debate. Objectives: To compare mid- and long-term conduit patency, survival, and freedom from major adverse cardiac events (MACE) between arterial and venous conduits in CABG. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials from 2000 onwards comparing arterial and venous conduits for non-LAD targets in CABG. Primary outcomes were mid- and long-term survival, angiographic patency, and freedom from MACE. Studies were appraised for risk of bias using RoB-2 and evidence certainty was evaluated using GRADE. Results: Eleven RCTs including 2,848 participants were analyzed. Mid-term survival did not differ between arterial and venous conduits (log risk ratio 0.00; 95% CI -0.03 to 0.03). Long-term survival showed a modest benefit for arterial conduits (log risk ratio 0.23; 95% CI 0.09 to 0.37; P <0.001). Arterial conduits demonstrated higher mid-term patency (log risk ratio 0.06; 95% CI 0.02 to 0.11; P =0.01), and long-term patency data from a single study also favoured arterial grafts. Freedom from MACE was similar at mid-term (log risk ratio 0.00; 95% CI -0.04 to 0.05), while long-term data suggested a small, non-significant advantage for arterial grafts. Certainty of evidence ranged from moderate to low, primarily due to observer and performance bias and limited long-term data. Conclusions: Arterial conduits offer superior mid-term patency and show a trend toward improved long-term survival, supporting their selective use beyond the LIMA-LAD graft. However, given the modest clinical differences and low-certainty long-term data, venous conduits continue to play an essential role in CABG. Further large-scale, high-quality trials are needed to define the optimal conduit strategy in contemporary surgical practice. Cardiothoracic Surgery cardiothoracic surgery coronary artery bypass grafting arterial venous conduit graft CABG revascularisation Figures Figure 1 Figure 2 Figure 3 BACKGROUND Description of the condition Ischemic heart disease (IHD) refers to a range of clinical conditions caused by myocardial ischemia, which occurs when there is an imbalance between the myocardial blood supply and its demand. Since the primary pathophysiological issue in ischemic myocardium is insufficient blood flow, ischemia is linked not only to a lack of oxygen but also to a decrease in nutrient availability and an impaired removal of metabolic waste products (1). In the vast majority of patients with IHD, myocardial ischemia is caused by a decrease in coronary blood flow, typically resulting from atherosclerotic coronary artery disease (1). IHD manifestations are dependent on duration, severity, and the onset or acuity of the ischaemic episodes (1). These can broadly be classified into acute coronary syndromes (ACS) and chronic coronary syndrome/disease. ACS results from a sudden critical reduction in coronary blood flow causing a spectrum of clinical conditions with varying degrees of severity ranging from unstable angina to ST elevation myocardial infarction (STEMI). Chronic coronary syndrome (CCS), on the other hand, occurs when there are coronary lesions that restrict blood supply to the myocardium despite increases in demand, resulting in angina pectoris, which typically presents as chest discomfort (1). This chronic form of IHD is typically progressive, in which stable atherosclerotic plaque become fully developed and unstable resulting in risk of rupture (2). Reduced coronary blood flow initially causes rapid ischaemic dysfunction and injury which may be reversible or irreversible depending on the site of the coronary obstruction/ischaemic area, magnitude of the reduction in blood flow, duration of insult and the haemodynamic situation and adaptation of the myocardium to prior ischaemic episodes (2). This can lead to sequelae such as heart failure, where the heart is unable to pump effectively, or in failure of the electrical system, causing arrhythmias and sudden death. Additional mechanical complications may include aneurysms, ruptures, and/or valvular dysfunction of the heart (3). IHD has a prevalence of 197.2 million and is the leading cause of death among noncommunicable diseases worldwide, resulting in 9.14million deaths in 2019 alone according to the Global Burden of Disease study 1990-2019 (4). It also accounted for 182 million disability-adjusted life years (DALYs) in the same year (4). Worryingly, projections of the burden of IHD are expected to increase further by 2050 potentially exacerbated by an ageing population and economic disparities globally (5). Diagnosis and management Guidelines for the diagnosis and management of both acute and chronic coronary syndromes have been developed by several bodies including the European Society of Cardiology (ESC) and the American Heart Association (AHA), the former endorsed by the European Association of Cardio-Thoracic Surgery (EACTS)(6, 7). There is broad agreement by these organisations on the overall diagnosis and management of ischaemic heart disease. The diagnosis and management of chronic coronary syndrome will be the focus of the following sections. An initial general clinical evaluation is conducted in patients with suspected CCS. This includes thorough history taking and physical examination to elucidate the symptoms and signs of CCS as well as identification of risk factors. Patients are assessed for the presence and severity of main symptoms of CCS i.e. chest pain/discomfort and exertional dyspnoea. Physical examination of these patients involves measurement of blood pressure, body mass index (BMI) calculation, checking for signs of anaemia, valvular heart disease, left ventricular hypertrophy, arrythmias and the presence of vascular disease elsewhere e.g. the lower limb and carotid arteries. It is also recommended to look for signs of other comorbidities such as diabetes, renal and thyroid disease (6). Basic testing is then performed on these patients which includes a 12-lead ECG, standard biochemical tests, resting echocardiography and, additionally, chest x-ray and pulmonary function testing in selected patients. Of the standard biochemical tests, a lipid profile including LDL-C, full blood count, creatinine with estimation of renal function, HbA1c and/or fasting glucose to assess glycaemic status and thyroid function test are recommended. Other tests such as troponins, NT-proBNP, hs-CRP and/or plasma fibrinogen may be used in a subset of patients (6). Confirmatory testing can be divided into three categories. These are anatomical testing which is CCTA with or without the use CT perfusion imaging, functional imaging which includes stress echocardiography, positron emission tomography (PET) or single photon emission computed tomography (SPECT) myocardial perfusion imaging, cardiac MRI and, lastly, invasive coronary angiography (ICA) with intracoronary pressure measurements (6). Management of patients with CCS starts with the initiation of guideline directed medical therapy (GDMT). The recommendations emphasise focusing on education, lifestyle modifications, and exercise therapy. Specific recommendations include smoking cessation using behavioural and pharmacological strategies, avoiding e-cigarettes and illicit substances, encouraging a healthy weight (BMI 18.5–25) through diet and exercise, and considering pharmacological or surgical interventions for further weight reduction (6). Pharmacological treatment is comprised by a combination of anti-anginal/ischaemic and event prevention medications. The standard approach for antianginal therapy is a stepwise strategy, beginning with first-line drugs such as beta-blockers or CCBs, and potentially adding second-line drugs like nitrates or ivabradine if symptoms persist. Combination therapy may be necessary for patients whose symptoms are not controlled with monotherapy. Medical event-preventing therapies include antithrombotic, lipid-lowering, anti-RAAS (renin–angiotensin–aldosterone system), anti-inflammatory, and metabolic-acting agents (6). Finally, there is a subset of patients with CCS who require coronary revascularisation. Revascularisation for chronic coronary syndromes (CCS) involves coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI), which improve angina-related health status and increase cardiovascular freedom from ischaemia, but do not heal coronary atherosclerosis. Randomised trials suggest CABG offers survival benefits for patients with left main or three-vessel disease, particularly in those with left ventricular (LV) dysfunction, while PCI may benefit cardiovascular survival by preventing myocardial infarctions (MIs). CABG tends to be superior to PCI and medical therapy, especially in patients with diabetes and complex coronary anatomy. While routine revascularisation is debated, it remains valuable for symptom relief in patients with persistent symptoms despite optimal medical therapy (6). Description of the intervention Coronary artery bypass grafting (CABG) has a major role in the management of ischaemic heart disease, particularly in a subset of patients with CCS as mentioned. The myocardium of the heart is supplied by 2 major coronary arteries: the left main coronary artery and the right coronary artery (RCA). The left main coronary artery is usually a short segment that branches into the left anterior descending (LAD) artery and the circumflex artery. The LAD branches further into diagonal branches and the circumflex artery branches into obtuse marginal (OM) branches. The RCA branches into the posterior descending artery (PDA) and the marginal branches (8). CABG involves bypassing atheromatous blockages in the coronary arteries with the use of harvested arterial or venous conduits. This bypass restores blood circulation to the ischemic myocardium, which subsequently improves function, viability, and alleviates anginal symptoms. Generally, there are two types of CABG: on-pump and off-pump. The key difference is that on-pump CABG involves the use of a temporarily arrested heart (cardioplegic arrest) and a cardiopulmonary bypass circuit to maintain organ perfusion during the procedure (8). How the intervention might work The principle behind coronary artery bypass grafting (CABG) is improving perfusion distal to the site of coronary obstruction by means of using grafts/conduits (9). The long-term success of CABG relies on the lasting patency of the grafts used. Graft failure affects a significant proportion of CABG conduits and is a complex, multifactorial occurrence. Graft outcome in CABG is influenced by factors such as the target coronary vessel's characteristics, technical aspects of harvesting as well as grafting, and systemic atherosclerotic risk factors like age, sex, diabetes, hypertension, and dyslipidaemia. Despite this, it is increasingly evident that the intrinsic morphological and functional features associated with the bypass conduit play an important role in its patency. Thus, the choice of conduit used offers an opportunity to influence its long-term patency. The long and short saphenous vein (SV), radial artery (RA), both left and right internal mammary/thoracic (RIMA/RITA/LIMA/LITA) and gastroepiploic artery (GA) are all used at various extents as conduits for grafting (10). The bypass of the left anterior descending (LAD) artery with the left internal mammary/thoracic artery (LIMA/LITA) as a graft is widely recognised as the gold standard, providing the most significant survival benefit. This is partly due to the LIMA eluting nitric oxide into the coronary circulation (11). However, the second-best conduit for CABG remains unclear. Recent reviews of the literature have shown higher mid to long-term patency rates with the use of arterial grafts such as the RA and RIMA/RITA as compared to vein grafts. Despite this, worldwide trends in CABG show that veins remain by far the most common conduit used after the LIMA is grafted to the LAD (12). That being said, the relationship between long term graft patency and clinical outcomes remain unclear with discordant evidence in the literature (10). Why it is important to do this review Even though the first CABG was conducted over six decades ago and its clear benefit for patients with CCS is well established, there still is no consensus on the second-best conduit to be used. As mentioned, there has been some evidence that arterial grafts have better mid- to long-term patency rates compared to their venous counterparts, however, whether or not this translates to improved outcomes is uncertain (10). Recent systematic reviews comparing patency rates and long-term outcomes of different conduits have resulted in conclusions that favour arterial conduits (13-15). However, there has been increasing recognition on the importance of the no-touch harvesting technique for SVGs, which has revealed comparable patency rates to that of the radial artery (14-16). Additionally, long-term outcomes for several large RCTs have been recently published (16-19). These, along with recent RCTs that have not been included in previous reviews provides an opportunity to address a knowledge gap that, as previously explained, has real-world consequences on patient outcomes. Due to the increasing burden of disease caused by IHD, that is only expected increase over the coming decades, we aim perform a thorough review of the existing literature with the ultimate goal of informing clinical practice. OBJECTIVES To compare patency rates and clinical outcomes of patients receiving arterial versus venous conduits in coronary artery bypass grafting (CABG). METHODS Criteria for considering studies for this review Types of studies We included randomised clinical trials from the year 2000 onwards in the English language directly comparing arterial to venous conduits in CABG for assessment of patency rates and/or long-term clinical outcomes. Types of participants We included any adult participants (≥18 years old) undergoing CABG for primary indications i.e. patients with ischaemic heart disease who require CABG. We did not include participants who undergo CABG as a concomitant procedure e.g. valve surgery or acute aortic syndromes. We also excluded trials where only the LIMA/LITA was grafted to the LAD and no other conduits were used. Types of interventions We included studies that directly compare both arms (arterial vs. venous as the second conduit in CABG) that evaluate angiographic patency rates and/or long-term outcomes. Arterial conduits included the radial artery (RA), right internal mammary/thoracic artery (RIMA/RITA) and the gastroepiploic artery (GA). Venous conduits comprised of both the long and short saphenous veins, collectively referred to as saphenous vein grafts (SVG). Types of outcome measures We divided follow-up period into the following categories: Mid-term: ≥5 to <10 years Long-term: ≥10 years Primary outcomes Survival rate (%) Angiographic conduit patency rates (%) Freedom from major adverse cardiac events (MACE) (%), defined as freedom from a composite of cardiac-related death, myocardial infarction, stroke and repeat revascularisation(20), including cardiac event-free survival. Search methods for identification of studies Electronic searches We conducted systematic searches of the following electronic repositories: The Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO) MEDLINE (Ovid MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily and Ovid MEDLINE) Embase Ovid CINAHL, EBSCO (Cumulative Index to Nursing and Allied Health Literature) The following clinical trial registries were also searched: The World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) (who.int/trialsearch) ClinicalTrials.gov (clinicaltrials.gov) Searching other resources We checked reference lists of all included studies and any relevant systematic reviews identified for additional references to trials. We also examined any relevant retraction statements and errata for included studies. We also searched OpenGrey for unpublished studies. Data collection and analysis Selection of studies Results of the search was imported into Covidence Proprietary Software platform. Two review authors independently screened all titles and abstracts identified through the systematic search. Full texts of the studies identified were retrieved by at least one review author. An arbitration process involving a third author was put in place to resolve any disputes that was not resolved through discussion. Studies excluded at the full-text review stage were listed down along with reasons for their exclusion. Additionally, we recorded the selection process in sufficient detail to complete a PRISMA flow diagram. Data extraction and management Data was extracted from selected studies into a data extraction sheet developed within Covidence for this review. Disagreements were resolved via discussion and an arbitration process, as mentioned. One review author transferred all extracted data to STATA (STATA 18). The following information was also extracted into the data extraction sheet: Methods (study design, number of participants, date of study, exclusions after randomisation, losses to follow-up, intention-to-treat analysis, study duration) Demographic characteristics of participants (country, setting, age, ethnicity, sex, inclusion and exclusion criteria) Types of interventions and comparators; we list all treatment groups, even if they are not used in the review. Outcomes measured and reported, measurement tools and scales, measurement time points Assessment of risk of bias included studies Two review authors independently assessed the risk of bias of all included studies using the latest Cochrane risk of bias tool (RoB-2) described in the Cochrane Handbook of Systematic Reviews of Interventions (21). The risk of bias in the following domains was judged to be low, high, or unclear. Random sequence generation. Allocation concealment. Blinding of participants and personnel. Blinding of outcome assessment. Incomplete outcome data. Selective outcome reporting. Other sources of bias. Measures of treatment effect Data will be analysed in accordance with the Cochrane Handbook of Systematic Reviews of Interventions(21). Continuous data Our outcomes of interest contained no continuous data, thus, this was not used in our pooled analysis of studies. Dichotomous data We analysed dichotomous data as risk ratios with 95% confidence intervals , as well as the trial sequential analysis-adjusted confidence intervals. Unit of analysis issues We planned to use the individual patient as the unit of analysis. For cross-over trials, we planned to follow the guidance in the Cochrane Handbook for Systematic Reviews of Interventions (21) which states that cross-over trials should include data from the first phase to avoid period effect or carry-over effect. Lastly, for multi-arm studies, we combined arms into groups, where appropriate, to create a single pair-wise comparison. Dealing with missing data We recorded missing data for each included study. When possible, we performed all analyses using an intention to-treat approach and used STATA to calculate missing standard deviations using other data from the trial, such as CI, based on methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions (21). Assessment of heterogeneity We visually investigated forest plots to assess heterogeneity. We then assessed the presence of statistical heterogeneity by the Chi 2 test (threshold P < 0.10) and measure the quantities of heterogeneity using the I 2 and H 2 statistic. Where substantial heterogeneity was identified, we reported it and explored possible causes. Data synthesis We conducted statistical analyses using STATA (STATA 18). We used the random-effect model to synthesise data as it was reasonable to assume that trials would have a significant clinical heterogeneity. We planned to report narratively instead of performing meta-analysis if we identified considerable clinical, methodological, or statistical heterogeneity, however this was not found. Subgroup analysis and investigation of heterogeneity We planned to perform the following subgroup analyses on our outcomes if we had high heterogeneity: According to type of conduit used (SVG, RIMA/RITA, GA, RA) Conduit configuration According to coronary artery target/territory for grafting (LAD, LCx, RCA) According to harvesting technique (no-touch vs conventional) However, we did not identify substantial heterogeneity (I 2 greater than 50%). Sensitivity analysis We planned to repeat the meta-analyses including high-quality trials only. Trials would have been classified as high quality if they were judged to be at low risk of bias for sequence generation, allocation concealment, and blinding of outcome assessment. However, due to the limited number of high-quality studies we did not perform repeat meta-analyses. Summary of findings and assessment of certainty of the evidence The following outcomes (mid- and long-term) were assessed for certainty of evidence using GRADEpro software ((https://gradepro.org/)) for the comparison arterial versus venous conduits: Survival rate (%) Angiographic conduit patency rates (%) Freedom from major adverse cardiac events (MACE) (%), defined as freedom from a composite of cardiac-related death, myocardial infarction, stroke and repeat revascularisation(20), including cardiac event-free survival. We followed the methods described by the Cochrane Handbook for Systematic Reviews of Interventions to assign one of four levels of certainty - high, moderate, low, or very low based on risk of bias, directness of the evidence, consistency of results, precision of the estimates, and risk of publication bias(21). We justified all decisions to downgrade the certainty of the evidence in the results narrative. RESULTS Description of studies Results of the search Search of electronic databases revealed 8461 reports. After deduplication and automated removal of ineligible studies (n=3292), 5168 reports were screened in the title and abstract phase. Of these reports, 5090 were assessed as not relevant and 78 full texts were obtained. At the full text review stage, 67 were excluded and 11 studies met our inclusion criteria (Tuore et al. 2021 (22), Gaudino et al. 2005 (23), Dreifaldt et al. 2021 (16), Petrovic et al. 2015 (24), Kim et al. 2018 (25), Collins et al. 2008 (26), Buxton and Hayward et al. 2013, 2020 (19, 27), Deb et al. 2012 (28), Goldman et al. 2022 (17), Damgaard et al. 2015 (29), Myers et al. 2000 (30). We also identified four ongoing studies (CTRI/2020/09/027692 (31), UMIN000039746 (32), CTRI/2021/06/034072 (33), ACTRN12622000552785 (34). See Figure 1. Included studies We included 11 studies in our review. All studies included were randomised controlled trials (RCTs). Two trials (Dreifaldt et al. (16), Deb et al. (28)), were crossover RCTs, whereby conduits were randomised to coronary target vessels and patients received both the study and control conduit. For these studies, the only outcome data extracted was conduit patency (%). These 11 studies contained a total sample size of 2848 participants. Studies were conducted from 1990 to 2011 in North America, Europe, Asia, Australia, and North Africa. See Table 1: Characteristics of included studies. Table 1: Characteristics of included studies Study ID Study Design Population (Sample Size) Intervention and Comparator Outcomes Key Results Toure et al. (2021) Randomised controlled trial 50 CABG patients Radial artery vs saphenous vein grafts Mid-term (5-year) conduit patency RA had significantly higher 5-year patency than SVG Gaudino et al. (2005) Randomised controlled trial 120 CABG patients, 60 with in-stent restenosis, 60 control RA vs RITA vs SVG Mid-term survival and conduit patency No difference in survival. RA/RITA grafts had superior patency in both arms Dreifaldt et al. (2021) Randomised controlled trial (crossover) 108 CABG patients No-touch SVG vs RA (randomised to coronary target) Mid-term (8-year) conduit patency No-touch SVG comparable to RA in long-term patency Petrovic et al. (2015) Randomised controlled trial 200 CABG patients RA vs SVG as second conduit Mid-term (8-year) survival, MACE Similar survival and MACE in both arms Kim et al. (2018) Randomised controlled trial 224 CABG patients RA vs RITA vs SVG (Y-composite) Mid-term (8-year) patency, MACE Comparable outcomes; SV had slightly lower MACE Collins et al. (2008) Randomised controlled trial 142 CABG patients RA vs SVG 5-year conduit patency No difference in survival. RA had significantly better patency Buxton and Hayward et al. (2013, 2020) Randomised controlled trial (RAPCO) 225 CABG patients RA vs SVG Mid-term (5.5-6 years) and long-term (10-year) survival and patency RA superior to SVG in survival and patency Deb et al. (2012) Randomised controlled trial (RAPS)- (crossover) 529 CABG patients RA vs SVG (randomised to coronary target) Mid-term (7.7 years) patency RA had higher patency than SVG Goldman et al. (2022) Multicentre randomised controlled trial 757 first-time elective CABG patients RA vs SVG Long-term (17.95 years) survival RA had higher survival but not statistically significant Damgaard et al. (2015) Randomised controlled trial (CARRPO) 331 CABG patients RA+RITA vs SVG Mid-term (5.7-6.6 years) survival, patency, MACE Similar survival, patency and MACE Myers et al. (2000) Randomised controlled trial 162 patients RITA vs SVG Mid-term (5-year) survival and MACE Comparable survival and MACE Participants The mean age of participants in the included studies was 61.9 (56.7-72.9) years old with 17.9% of them being female. Of note, Buxton and Hayward et al. (19, 27), only recruited patients aged ≥70 (≥60 if diabetic) in their RA vs SV arm. Demographic data was not available for 1 study (Toure et al. (22)). Criteria for participant inclusion in all studies were adult patients undergoing primary isolated CABG with two or more graftable coronary arteries (at least one after LIMA to LAD). All studies only included patients with an ejection fraction (EF) greater than 35%, with the exception of Kim et al. (25), which allowed an EF of at least 25% and only recruited patients scheduled for off-pump CABG (OPCAB) for both arms. Gaudino et al. (23) only recruited patients with in-stent restenosis in one arm of their trial. Degree of stenosis of the target coronary vessels was at least 70% for all studies, apart from Dreifaldt et al. (16) and Damgaard et al. (29), where it was at least 50%. The studies excluded participants that had contraindications for conduit harvesting or where conduits were unavailable e.g. positive Allen’s test/abnormal doppler, history of Reynaud’s/vasculitis, bilateral varicose veins, amputation, previous thoracic surgery/radiotherapy. Studies also excluded patients with varying degrees of renal impairment and allergy to contrast media. Patients with concurrent illness e.g. malignancy that resulted in expected survival of <5 years were also excluded. Myers et al. (30) excluded patients with insulin dependent diabetes. Interventions The interventions in all included studies were the use of either an arterial (RA/RITA) or venous (SV) conduit to bypass a non-LAD coronary target/territory. Two of the studies included, Damgaard et al. (29) and Myers et al. (30), had participants receive only arterial (total arterial) or only venous conduits to the non-LAD coronary target/territory. In all other studies, participants could receive either additional SVs or a conduit of the surgeon’s choice to other non-study (3 rd , 4 th , 5 th ) coronary targets. In two of these studies, participants received both an arterial and a venous conduit either to the left or right coronary territories and acted as their own control (crossover RCTs). The primary outcome for both these studies was conduit patency. For three of the included studies (Toure et al. (22), Collins et al. (26), Goldman et al. (17)) it is unclear if participants were allowed to receive a different conduit type for the non-study coronary targets. In five studies, (Dreifaldt et al. (16), Petrovic et al. (24), Collins et al. (26), Buxton and Hayward et al. (19, 27), Goldman et al. (17)), conduit configuration was aortocoronary. A combination of aortocoronary and sequential grafting was used in Damgaard et al. (29) whilst participants in Myers et al. (30) had aortocoronary configuration in the SV group and sequential in the RITA group. In Kim et al. (25), Y-composite grafts were used for all participants in this purely OPCAB study. Graft configuration data was not available for three studies (Toure et al. (22), Gaudino et al. (23), Deb et al. (28)). In only one study (Dreifaldt et al. (16)), a no-touch harvesting technique was used to harvest the SV. Outcomes reported and relevant to this review Outcomes relevant to this review are survival, conduit patency rates and freedom from MACE. For the outcomes of survival and freedom from MACE, all studies used either follow-up visits, phone calls, hospital/national databases/registries, or a combination of these modalities to report outcomes. For studies reporting conduit patency rates, conventional coronary angiography was used exclusively for all apart from four studies. Toure et al. (22) and Dreifaldt et al. (16) used computed tomography (CT) angiography for all participants whilst Deb et al. (28) and Kim et al. (25) offered it to patients who did not consent to or withdrew consent for conventional angiography. Angiography studies were reviewed by at least two independent reviewers with expertise in the field in all cases. Where rates of survival, conduit patency and freedom from MACE data was not explicitly reported, these were calculated from the available data. The follow-up periods of interest in this review are mid-term (≥5 to <10 years) and long-term (≥10 years). Long-term outcome data was only available for two studies (Buxton and Hayward et al. (19, 27), Goldman et al. (17)), with the former having both mid-term and long-term outcome data for all three primary outcomes of interest i.e. survival, conduit patency rate and freedom from MACE and the later only reporting survival. Mid-term survival was also available for a further six studies (Gaudino et al. (23), Petrovic et al. (24), Kim et al, Collins et al. (26), Damgaard et al. (29), Myers et al. (30)). Conduit patency rates were reported by a further seven studies (Toure et al. (22), Gaudino et al. (23), Dreifaldt et al. (16), Kim et al. (25), Collins et al. (26), Deb et al. (28), Damgaard et al. (29)). Freedom from MACE was reported by four other studies (Petrovic et al. (24), Kim et al. (25), Damgaard et al. (29), Myers et al. (30). Ongoing studies We identified four ongoing studies (CTRI/2020/09/027692 (31), UMIN000039746 (32), CTRI/2021/06/034072 (33), ACTRN12622000552785 (34)). Excluded studies At full-text review stage, sixty-seven studies were excluded. The most prevalent reasons for exclusion were wrong study design or wrong intervention. Risk of bias in included studies Risk of bias for all included studies are summarised in Figure 2 and 3. The most prevalent risk of bias was that of observer bias for the outcome of conduit patency. Reviewers of the angiography study, even if blinded, would be able to ascertain conduit type when assessing for patency which introduces bias in the “measurement of outcome” domain. For studies reporting survival and freedom from MACE, we found that all studies, apart from, Damgaard et al. (29) and Myers et al. (30), either allowed for additional arterial or venous conduits to be used to graft the other non-study coronary targets/territories, usually RCA, as part of their protocol or did not provide information regarding these additional bypasses. Therefore, this represented performance bias due to this confounding factor and these studies were judged to have some concerns. Effects of intervention Survival Mid-term survival was reported by seven studies (Gaudino et al. (23), Petrovic et al. (24), Kim et al. (25), Collins et al. (26), Buxton and Hayward et al. (19, 27), Damgaard et al. (29) and Myers et al. (30)). Mean mid-term survival (%) across these studies was 92.1% (±4.7) for arterial versus 92.2% (±5.3) for venous conduits. Pooled analysis showed no difference in midterm survival between arterial and venous conduits (log risk-ratio 0.00, 95% confidence interval -0.03-0.03; P= 0.95; Analysis 1). There was very low heterogeneity across studies (I 2 =0.01%, H 2 =1.00) Long-term survival was reported by only two studies (Buxton and Hayward et al. (19, 27) and Goldman et al. (17)). Mean long-term survival was 62.6% (±22.4) for arterial versus 50.3% (±21.1) for venous conduits. Pooled analysis showed a trend towards increased survival for the arterial group (log risk ratio 0.23, 95% confidence interval 0.09-0.37, P< 0.001; Analysis 2). There was low to moderate heterogeneity across these two studies (I 2 =26.1%, H 2 =1.35). The substantial difference in mean long-term survival in these two studies can be explained by their duration of follow up. Mean follow-up duration for Buxton and Hayward et al. was 10-years whilst for Goldman et al. it was 17.95 years. Certainty evidence was deemed to be “moderate” (downgraded one point) using the GRADE criteria due to the risk of performance bias. Conduit patency Mid-term conduit patency was reported by eight studies (Toure et al. (22), Gaudiono et al. (23), Dreifaldt et al. (16), Kim et al.(25), Collins et al. (26), Bexton and Hayward et al. (19, 27), Deb et al. (28), Damgaard et al. (29)). Mean mid-term conduit patency was 91.3% (±4.1) for arterial versus 82.8% (±8.8) for venous conduits. Pooled analysis is in favour of arterial conduits (log risk-ratio 0.06, 95% confidence interval 0.02-0.11, P=0.01; Analysis 3). These studies show moderate heterogeneity (I 2 =41.6%, H 2 =1.71). This may be due to the differences in the intervention whereby Kim et al. (5) used a Y-composite/sequential graft configuration for both arterial and venous conduits based on the LITA and is the only study to perform CABG entirely off-pump. Damgaard et al. (29) used a combination of aortocoronary and sequential grafting for their conduits. All other studies used a more conventional aortocoronary graft configuration, apart from Toure et al.(22), Gaudino et al. (23) and Deb et al. (28), where graft configuration is unknown. Long-term conduit patency was only reported by Buxton and Hayward et al. (19, 27). Patency rates were higher for arterial versus venous conduits, 85.0% vs 71.4% (log risk-ratio 0.17, 95% confidence interval 0.03-0.31; Analysis 4). Using the GRADE criteria, certainty of evidence for both mid and long-term conduit patency was “low” (downgraded two points) due to risk of observer bias, moderate heterogeneity in the mid-term studies and the presence of only one study with a relatively small sample size reporting on long-term conduit patency. Freedom from MACE Mid-term freedom from MACE was reported by five studies (Petrovic et al. (24), Kim et al.(25), Buxton and Hayward et al. (19, 27), Damgaard et al. (29), Myers et al. (30)). Mean mid-term freedom from MACE was 83.2% (±13.7) in the arterial group and 82.9 (±13.8). Pooled analysis showed no difference between arterial and venous groups (log risk-ratio 0.00, 95% confidence interval -0.04-0.05, P=0.48; Analysis 5). There was low heterogeneity between the five studies (I 2 =10.81%, H 2 =1.12). Only one study reported long-term freedom from MACE (Buxton and Hayward et al. (19, 27)). There was a higher rate of freedom from MACE in the arterial group (86.7%) compared the venous group (83.0%), however this did not reach statistical significance (log risk-ratio 0.04, 95% confidence interval -0.07-0.15). As with survival, certainty evidence for mid-term freedom from MACE was deemed to be “moderate” (downgraded one point) using the GRADE criteria due to the risk of performance bias. For long-term freedom from MACE, we also deemed it to have the same risk of bias with the additional factor of the evidence coming from only one study. Thus, we judged the certainty of evidence to be “low” (downgraded two points). DISCUSSION Summary of main results The main objective of this study was to compare both conduit patency and clinical outcomes of arterial versus venous conduits in CABG. Eight of the included studies reported on survival (mid-term=7, long-term=2), with one study reporting both mid-term and long-term survival. We deemed the certainty of the evidence to be “moderate” due the risk of performance bias i.e. participants were allowed to receive a different conduit type to the other non-study coronary targets or no information was available in six of the eight studies. There was no difference in mid-term survival between the two groups. However, arterial conduits did show a trend for greater survival in the long-run. This is backed up by two of the studies that were pooled for long-term survival analysis. Participants in the arterial arm of Goldman et al. (17), followed up for 17.95 years, showed a greater difference in survival versus the venous arm compared to their counterparts in Buxton and Hayward et al. (19, 27), who were followed up for 10 years. Additionally, the later study only enrolled participants aged >70 years in their RA vs SV arm further accounting for this difference. This principle of delayed or long-term benefit is also thought to apply to conduit patency and freedom from MACE of arterial versus venous conduits. Our analysis of patency rates showed a modest difference in favour of arterial conduits from the eight studies reporting mid-term, and the one study reporting long-term patency rates. However, certainty of this evidence was deemed to be “low” as there was moderate heterogeneity in the mid-term studies and all studies had a risk of observer bias. Outcome assessors, like that of angiogram reviewers who are unable to be fully blinded, always risked introducing bias. At present, conventional coronary angiography remains the gold-standard for evaluating and grading conduit patency and it is unlikely this source of bias can be eliminated. Results from long-term conduit patency was obtained from only one study and thus, we are unable to draw strong conclusions about both mid and long-term conduit patency. Similar to survival, freedom from MACE analysis showed no difference in midterm freedom from MACE and suggests a minimal benefit of arterial conduits in long-term freedom from MACE that failed to reach statistical significance in the pooled studies. This outcome also carries the same performance bias as survival which resulted in downgrading of the certainty to “moderate” for the mid-term group and “low” for the long-term group. Overall completeness and applicability of evidence Our comprehensive search of the literature did result in one other study from the Chinese clinical trial registry that could have been included. But it was unclear if this trial had been completed (ChiCTR-TRC-13003294 (35)). We attempted to contact the listed authors of this trial; however, they did not respond which resulted in this trial being excluded at the full-text review stage under the label “Authors uncontactable.” Mid-term survival was consistently reported across seven studies, with minimal heterogeneity and “moderate” certainty. However, long-term survival data were limited to only two studies with differing follow-up durations (10 and 17.95 years), thereby reducing the precision of pooled estimates despite a statistically significant effect favouring arterial conduits. This limits the generalisability of the long-term survival findings and introduces uncertainty about their consistency across broader populations and practice settings. Conduit patency was more thoroughly reported, particularly at mid-term follow-up, with eight studies contributing data. The observed benefit of arterial conduits was statistically significant but modest, and the moderate heterogeneity, largely attributable to variations in the intervention, should temper the interpretation. Long-term patency data were restricted to a single study, limiting the strength of inference and applicability, especially in diverse surgical contexts. Overall, the evidence for conduit patency was judged to be of “low” certainty, due to the aforementioned risk of bias, heterogeneity and the limited scope of long-term data. Data on mid-term freedom from MACE were available from five studies with low heterogeneity and moderate certainty. However, similar to survival and patency outcomes, the evidence for long-term freedom from MACE was sparse, being derived from a single study with imprecise effect estimates. This significantly limits the robustness and applicability of the evidence for long-term event prevention. Importantly, several studies lacked granular detail on key methodological factors such as conduit configuration, completeness of revascularization, and use of additional conduits which introduced performance bias, all of which may influence outcomes. Additionally, observer bias remains a concern in several studies, reliant on subjective assessments of conduit patency. In summary, while the evidence base is moderately complete for mid-term outcomes, particularly for survival and conduit patency. It is notably weaker for long-term endpoints and for MACE outcomes overall. The findings are most applicable to relatively young, low-risk, surgical populations in whom complete revascularization was technically feasible. Extrapolation to higher-risk cohorts or to practices using alternative graft configurations, off-pump CABG and non-conventional harvesting techniques should be done with caution. Further high-quality, long-term studies are warranted to definitively determine the comparative efficacy of arterial and venous conduits in contemporary CABG practice. Potential biases in the review process Several potential sources of bias may have influenced the review process, despite efforts to adhere to rigorous methodological standards. First, although a comprehensive literature search was conducted across multiple databases, there is a risk of publication bias, particularly given the tendency for studies with positive findings to be more likely published. We attempted to mitigate this by searching grey literature and trial registries; however, it is possible that some relevant unpublished data were not identified. Secondly, the risk of selection bias in the study inclusion process was minimised by having two reviewers independently screen titles and abstracts. Nevertheless, the subjective nature of study selection may introduce some degree of reviewer bias, particularly in cases where reporting was unclear or where study eligibility was borderline. Any discrepancies were resolved through discussion or consultation with a third reviewer, but the potential for subtle biases in judgement remains. Third, heterogeneity in study designs, patient populations, the interventions themselves, and outcome definitions posed challenges in data synthesis. Although we used a random-effects model for all of our outcomes and conducted sensitivity analyses, the pooling of data across diverse clinical contexts may introduce confounding. For instance, studies varied in their definitions of MACE and in whether outcomes were reported on a per-patient or per-graft basis. Finally, while risk of bias assessments and GRADE evaluations were applied systematically, these tools involve a degree of subjectivity. Observer bias were frequent concerns in the included studies, particularly in angiographic interpretation. Overall, while every effort was made to minimise bias at each stage of the review process, some degree of systematic and interpretative bias is unavoidable. These limitations should be considered when interpreting the findings of this review. Agreements or disagreements with other studies or reviews Our findings are broadly consistent with the recent meta-analyses by Ding et al. (2025) (36) and Gaudino et al. (2019, 2020) (13) (37), which support the superiority of arterial conduits over saphenous vein grafts in CABG. Ding et al. (36) demonstrated improved survival with multiple arterial grafting compared to single arterial strategies, aligning with our observation of a trend toward enhanced long-term survival in the arterial group, although our review did not stratify by number of arterial grafts. Gaudino et al.(13), in their landmark individual participant data meta-analysis, found that radial artery grafts were associated with significantly lower rates of death, myocardial infarction, and repeat revascularization over a 10-year period, which corroborates our finding of superior long-term outcomes with arterial conduits, albeit with more limited data and lower certainty. Gaudino et al.(37) again, using a network meta-analysis, further reinforced the advantages of arterial grafts, showing that both radial artery and right internal thoracic artery conferred better long-term results than venous grafts, a conclusion consistent with our data, though our review did not directly compare different arterial types. Together, these studies complement and validate the patterns observed in our review, while also highlighting the evolving consensus in favour of arterial revascularisation. This echoes previous large observational data that that report a higher survival for those receiving total arterial revascularisation in the long run compared to a single arterial (LITA/LIMA) plus additional venous conduits (18, 38, 39) and supports the long held theory that the benefits from arterial grafting are most pronounced in younger patients who have a greater time horizon (40). Although the evidence in favour of arterial revascularisation is growing, an authoritative expert review endorsed by the European Association for Cardio‑Thoracic Surgery (EACTS) and The Society of Thoracic Surgeons (STS) in 2023, warns against a one size fits all approach and surgeons must be aware of the nuances of conduit selection (41). Conduit selection must be individualised based on factors such as patient age, comorbidities, coronary anatomy, surgical risk, and surgeon expertise. CONCLUSIONS This systematic review synthesised mid- and long-term outcomes for arterial versus venous conduits in coronary artery bypass grafting (CABG), focusing on survival, conduit patency, and freedom from major adverse cardiac events (MACE). The findings suggest that while mid-term outcomes are comparable between conduit types in terms of survival and freedom from MACE, arterial conduits, demonstrate superior patency at mid-term follow-up. Limited long-term data suggest a potential survival advantage and better conduit durability with arterial grafts, although the evidence remains incomplete and subject to methodological limitations. Implications for Practice The consistent patency advantage observed with arterial grafts at mid-term, coupled with a trend towards improved long-term survival, supports the selective use of arterial conduits beyond the left internal mammary artery (LIMA), particularly in younger patients and those with longer life expectancy. However, given the modest absolute differences in clinical endpoints and the limited long-term evidence, the decision to use additional arterial grafts should be individualised, considering patient comorbidities, target vessel anatomy, surgical expertise, and institutional practices. The routine use of arterial conduits as second or third grafts may not be universally warranted but should remain an important option in the armamentarium of modern surgical revascularisation. Implications for Research There is a clear need for further high-quality, long-term studies comparing arterial and venous conduits, particularly beyond 10 years of follow-up. Future research should aim to stratify outcomes by surgical approach (conduit configuration, minimally invasive/robotic surgery vs conventional, on- vs off-pump, no-touch vs. conventional conduit harvesting), and patient subgroups, including those with diabetes, renal impairment, or advanced age. Through our search we discovered one promising study, with two of its trial sites included in our ongoing studies (UMIN000039746 (32) CTRI/2021/06/034072 (33)) . This is the “Randomized comparison of the clinical outcome of single versus multiple arterial grafts: the ROMA trial,” which is a large, international RCT currently enrolling participants (42). Large, pragmatic trials with sufficient follow-up duration, like the ROMA trial, are required to definitively determine the long-term clinical benefit of expanded arterial graft use in CABG. Standardisation of outcome reporting, including consistent definitions for MACE and conduit patency, and uniform follow-up intervals, would enhance comparability across studies. Additionally, with the advent of artificial intelligence (AI), specifically machine learning, observer bias may be eliminated through the use of validated, robust, AI powered angiographic adjudication. 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Expert systematic review on the choice of conduits for coronary artery bypass grafting: endorsed by the European Association for Cardio-Thoracic Surgery (EACTS) and The Society of Thoracic Surgeons (STS). The Journal of Thoracic and Cardiovascular Surgery. 2023;166(4):1099-114. Gaudino M, Alexander JH, Bakaeen FG, Ballman K, Barili F, Calafiore AM, 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(6):1031-40. Analysis Analysis 1 to 6 are available in the Supplementary Files section. Additional Declarations The authors declare no competing interests. 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2","display":"","copyAsset":false,"role":"figure","size":18055,"visible":true,"origin":"","legend":"\u003cp\u003eRisk of bias graph\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8050782/v1/804cd5eafef006e17f926f22.png"},{"id":95507758,"identity":"d5caa44f-4743-4715-aa05-3327fb3a7dac","added_by":"auto","created_at":"2025-11-10 06:39:09","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":117317,"visible":true,"origin":"","legend":"\u003cp\u003eRisk of bias summary\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8050782/v1/080a57d9bb6a9d151b6d2b9a.png"},{"id":95654283,"identity":"f22b3bf1-6831-4a48-8915-3a1830dc4a6f","added_by":"auto","created_at":"2025-11-11 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Since the primary pathophysiological issue in ischemic myocardium is insufficient blood flow, ischemia is linked not only to a lack of oxygen but also to a decrease in nutrient availability and an impaired removal of metabolic waste products (1). In the vast majority of patients with IHD, myocardial ischemia is caused by a decrease in coronary blood flow, typically resulting from atherosclerotic coronary artery disease (1). IHD manifestations are dependent on duration, severity, and the onset or acuity of the ischaemic episodes (1). These can broadly be classified into acute coronary syndromes (ACS) and chronic coronary syndrome/disease.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eACS results from a sudden critical reduction in coronary blood flow causing a spectrum of clinical conditions with varying degrees of severity ranging from unstable angina to ST elevation myocardial infarction (STEMI). Chronic coronary syndrome (CCS), on the other hand, occurs when there are coronary lesions that restrict blood supply to the myocardium despite increases in demand, resulting in angina pectoris, which typically presents as chest discomfort (1). This chronic form of IHD is typically progressive, in which stable atherosclerotic plaque become fully developed and unstable resulting in risk of rupture (2). Reduced coronary blood flow initially causes rapid ischaemic dysfunction and injury which may be reversible or irreversible depending on the site of the coronary obstruction/ischaemic area, magnitude of the reduction in blood flow, duration of insult and the haemodynamic situation and adaptation of the myocardium to prior ischaemic episodes (2). This can lead to sequelae such as heart failure, where the heart is unable to pump effectively, or in failure of the electrical system, causing arrhythmias and sudden death. Additional mechanical complications may include aneurysms, ruptures, and/or valvular dysfunction of the heart (3).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIHD has a prevalence of 197.2 million and is the leading cause of death among noncommunicable diseases worldwide, resulting in 9.14million deaths in 2019 alone according to the Global Burden of Disease study 1990-2019 (4). It also accounted for 182 million disability-adjusted life years (DALYs) in the same year (4). Worryingly, projections of the burden of IHD are expected to increase further by 2050 potentially exacerbated by an ageing population and economic disparities globally (5).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eDiagnosis and management\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGuidelines for the diagnosis and management of both acute and chronic coronary syndromes have been developed by several bodies including the European Society of Cardiology (ESC) and the American Heart Association (AHA), the former endorsed by the European Association of Cardio-Thoracic Surgery (EACTS)(6, 7). There is broad agreement by these organisations on the overall diagnosis and management of ischaemic heart disease. The diagnosis and management of chronic coronary syndrome will be the focus of the following sections.\u003c/p\u003e\n\u003cp\u003eAn initial general clinical evaluation is conducted in patients with suspected CCS. This includes thorough history taking and physical examination to elucidate the symptoms and signs of CCS as well as identification of risk factors. Patients are assessed for the presence and severity of main symptoms of CCS i.e. chest pain/discomfort and exertional dyspnoea. Physical examination of these patients involves measurement of blood pressure, body mass index (BMI) calculation, checking for signs of anaemia, valvular heart disease, left ventricular hypertrophy, arrythmias and the presence of vascular disease elsewhere e.g. the lower limb and carotid arteries. It is also recommended to look for signs of other comorbidities such as diabetes, renal and thyroid disease (6).\u003c/p\u003e\n\u003cp\u003eBasic testing is then performed on these patients which includes a 12-lead ECG, standard biochemical tests, resting echocardiography and, additionally, chest x-ray and pulmonary function testing in selected patients. Of the standard biochemical tests, a lipid profile including LDL-C, full blood count, creatinine with estimation of renal function, HbA1c and/or fasting glucose to assess glycaemic status and thyroid function test are recommended. Other tests such as troponins, NT-proBNP, hs-CRP and/or plasma fibrinogen may be used in a subset of patients (6).\u003c/p\u003e\n\u003cp\u003eConfirmatory testing can be divided into three categories. These are anatomical testing which is CCTA with or without the use CT perfusion imaging, functional imaging which includes stress echocardiography, positron emission tomography (PET) or single photon emission computed tomography (SPECT) myocardial perfusion imaging, cardiac MRI and, lastly, invasive coronary angiography (ICA) with intracoronary pressure measurements (6).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eManagement of patients with CCS starts with the initiation of guideline directed medical therapy (GDMT). The recommendations emphasise focusing on education, lifestyle modifications, and exercise therapy. Specific recommendations include smoking cessation using behavioural and pharmacological strategies, avoiding e-cigarettes and illicit substances, encouraging a healthy weight (BMI 18.5\u0026ndash;25) through diet and exercise, and considering pharmacological or surgical interventions for further weight reduction (6).\u003c/p\u003e\n\u003cp\u003ePharmacological treatment is comprised by a combination of anti-anginal/ischaemic and event prevention medications. The standard approach for antianginal therapy is a stepwise strategy, beginning with first-line drugs such as beta-blockers or CCBs, and potentially adding second-line drugs like nitrates or ivabradine if symptoms persist. Combination therapy may be necessary for patients whose symptoms are not controlled with monotherapy. Medical event-preventing therapies include antithrombotic, lipid-lowering, anti-RAAS (renin\u0026ndash;angiotensin\u0026ndash;aldosterone system), anti-inflammatory, and metabolic-acting agents (6).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFinally, there is a subset of patients with CCS who require coronary revascularisation. Revascularisation for chronic coronary syndromes (CCS) involves coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI), which improve angina-related health status and increase cardiovascular freedom from ischaemia, but do not heal coronary atherosclerosis. Randomised trials suggest CABG offers survival benefits for patients with left main or three-vessel disease, particularly in those with left ventricular (LV) dysfunction, while PCI may benefit cardiovascular survival by preventing myocardial infarctions (MIs). CABG tends to be superior to PCI and medical therapy, especially in patients with diabetes and complex coronary anatomy. While routine revascularisation is debated, it remains valuable for symptom relief in patients with persistent symptoms despite optimal medical therapy (6).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eDescription of the intervention\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCoronary artery bypass grafting (CABG) has a major role in the management of ischaemic heart disease, particularly in a subset of patients with CCS as mentioned. The myocardium of the heart is supplied by 2 major coronary arteries: the left main coronary artery and the right coronary artery (RCA). The left main coronary artery is usually a short segment that branches into the left anterior descending (LAD) artery and the circumflex artery. The LAD branches further into diagonal branches and the circumflex artery branches into obtuse marginal (OM) branches. The RCA branches into the posterior descending artery (PDA) and the marginal branches (8).\u003c/p\u003e\n\u003cp\u003eCABG involves bypassing atheromatous blockages in the coronary arteries with the use of harvested arterial or venous conduits. This bypass restores blood circulation to the ischemic myocardium, which subsequently improves function, viability, and alleviates anginal symptoms. Generally, there are two types of CABG: on-pump and off-pump. The key difference is that on-pump CABG involves the use of a temporarily arrested heart (cardioplegic arrest) and a cardiopulmonary bypass circuit to maintain organ perfusion during the procedure (8).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eHow the intervention might work\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe principle behind coronary artery bypass grafting (CABG) is improving perfusion distal to the site of coronary obstruction by means of using grafts/conduits (9). The long-term success of CABG relies on the lasting patency of the grafts used. Graft failure affects a significant proportion of CABG conduits and is a complex, multifactorial occurrence. Graft outcome in CABG is influenced by factors such as the target coronary vessel\u0026apos;s characteristics, technical aspects of harvesting as well as grafting, and systemic atherosclerotic risk factors like age, sex, diabetes, hypertension, and dyslipidaemia. Despite this, it is increasingly evident that the intrinsic morphological and functional features associated with the bypass conduit play an important role in its patency. Thus, the choice of conduit used offers an opportunity to influence its long-term patency. The long and short saphenous vein (SV), radial artery (RA), both left and right internal mammary/thoracic (RIMA/RITA/LIMA/LITA) and gastroepiploic artery (GA) are all used at various extents as conduits for grafting (10).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe bypass of the left anterior descending (LAD) artery with the left internal mammary/thoracic artery (LIMA/LITA) as a graft is widely recognised as the gold standard, providing the most significant survival benefit. This is partly due to the LIMA eluting nitric oxide into the coronary circulation (11). However, the second-best conduit for CABG remains unclear. Recent reviews of the literature have shown higher mid to long-term patency rates with the use of arterial grafts such as the RA and RIMA/RITA as compared to vein grafts. Despite this, worldwide trends in CABG show that veins remain by far the most common conduit used after the LIMA is grafted to the LAD (12). That being said, the relationship between long term graft patency and clinical outcomes remain unclear with discordant evidence in the literature (10).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eWhy it is important to do this review\u0026nbsp;\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEven though the first CABG was conducted over six decades ago and its clear benefit for patients with CCS is well established, there still is no consensus on the second-best conduit to be used. As mentioned, there has been some evidence that arterial grafts have better mid- to long-term patency rates compared to their venous counterparts, however, whether or not this translates to improved outcomes is uncertain (10). Recent systematic reviews comparing patency rates and long-term outcomes of different conduits have resulted in conclusions that favour arterial conduits (13-15). However, there has been increasing recognition on the importance of the no-touch harvesting technique for SVGs, which has revealed comparable patency rates to that of the radial artery (14-16).\u003c/p\u003e\n\u003cp\u003eAdditionally, long-term outcomes for several large RCTs have been recently published (16-19). These, along with recent RCTs that have not been included in previous reviews provides an opportunity to address a knowledge gap that, as previously explained, has real-world consequences on patient outcomes. Due to the increasing burden of disease caused by IHD, that is only expected increase over the coming decades, we aim perform a thorough review of the existing literature with the ultimate goal of informing clinical practice.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eOBJECTIVES\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo compare patency rates and clinical outcomes of patients receiving arterial versus venous conduits in coronary artery bypass grafting (CABG).\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e\u003cstrong\u003eCriteria for considering studies for this review\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTypes of studies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe included randomised clinical trials from the year 2000 onwards in the English language directly comparing arterial to venous conduits in CABG for assessment of patency rates and/or long-term clinical outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTypes of participants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe included any adult participants (\u0026ge;18 years old) undergoing CABG for primary indications i.e. patients with ischaemic heart disease who require CABG. We did not include participants who undergo CABG as a concomitant procedure e.g. valve surgery or acute aortic syndromes. We also excluded trials where only the LIMA/LITA was grafted to the LAD and no other conduits were used.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTypes of interventions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe included studies that directly compare both arms (arterial vs. venous as the second conduit in CABG) that evaluate angiographic patency rates and/or long-term outcomes. Arterial conduits included the radial artery (RA), right internal mammary/thoracic artery (RIMA/RITA) and the gastroepiploic artery (GA). Venous conduits comprised of both the long and short saphenous veins, collectively referred to as saphenous vein grafts (SVG).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTypes of outcome measures\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe divided follow-up period into the following categories:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eMid-term:\u0026nbsp;\u0026ge;5 to\u0026nbsp;\u0026lt;10 years\u003c/li\u003e\n \u003cli\u003eLong-term:\u0026nbsp;\u0026ge;10 years\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003ePrimary outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eSurvival rate (%)\u003c/li\u003e\n \u003cli\u003eAngiographic conduit patency rates (%)\u003c/li\u003e\n \u003cli\u003eFreedom from major adverse cardiac events (MACE) (%), defined as freedom from a composite of cardiac-related death, myocardial infarction, stroke and repeat revascularisation(20), including cardiac event-free survival. \u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eSearch methods for identification of studies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eElectronic searches\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe conducted systematic searches of the following electronic repositories:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eThe Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO)\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eMEDLINE (Ovid MEDLINE Epub Ahead of Print, In-Process \u0026amp; Other Non-Indexed Citations, Ovid MEDLINE Daily and Ovid MEDLINE)\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eEmbase Ovid\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eCINAHL, EBSCO (Cumulative Index to Nursing and Allied Health Literature)\u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThe following clinical trial registries were also searched:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eThe World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) (who.int/trialsearch)\u003c/li\u003e\n \u003cli\u003eClinicalTrials.gov (clinicaltrials.gov)\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eSearching other resources\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe checked reference lists of all included studies and any relevant systematic reviews identified for additional references to trials. We also examined any relevant retraction statements and errata for included studies. We also searched OpenGrey for unpublished studies.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData collection and analysis\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSelection of studies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eResults of the search was imported into Covidence Proprietary Software platform. Two review authors independently screened all titles and abstracts identified through the systematic search. Full texts of the studies identified were retrieved by at least one review author. An arbitration process involving a third author was put in place to resolve any disputes that was not resolved through discussion. Studies excluded at the full-text review stage were listed down along with reasons for their exclusion. Additionally, we recorded the selection process in sufficient detail to complete a PRISMA flow diagram.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData extraction and management\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData was extracted from selected studies into a data extraction sheet developed within Covidence for this review. Disagreements were resolved via discussion and an arbitration process, as mentioned. One review author transferred all extracted data to STATA (STATA 18). The following information was also extracted into the data extraction sheet:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eMethods (study design, number of participants, date of study, exclusions after randomisation, losses to follow-up, intention-to-treat analysis, study duration)\u003c/li\u003e\n \u003cli\u003eDemographic characteristics of participants (country, setting, age, ethnicity, sex, inclusion and exclusion criteria)\u003c/li\u003e\n \u003cli\u003eTypes of interventions and comparators; we list all treatment groups, even if they are not used in the review.\u003c/li\u003e\n \u003cli\u003eOutcomes measured and reported, measurement tools and scales, measurement time points\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eAssessment of risk of bias included studies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTwo review authors independently assessed the risk of bias of all included studies using the latest Cochrane risk of bias tool (RoB-2) described in the Cochrane Handbook of Systematic Reviews of Interventions (21). The risk of bias in the following domains was judged to be low, high, or unclear.\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eRandom sequence generation.\u003c/li\u003e\n \u003cli\u003eAllocation concealment.\u003c/li\u003e\n \u003cli\u003eBlinding of participants and personnel.\u003c/li\u003e\n \u003cli\u003eBlinding of outcome assessment.\u003c/li\u003e\n \u003cli\u003eIncomplete outcome data.\u003c/li\u003e\n \u003cli\u003eSelective outcome reporting.\u003c/li\u003e\n \u003cli\u003eOther sources of bias.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eMeasures of treatment effect\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData will be analysed in accordance with the Cochrane Handbook of Systematic Reviews of Interventions(21).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContinuous data\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur outcomes of interest contained no continuous data, thus, this was not used in our pooled analysis of studies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDichotomous data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe analysed dichotomous data as risk ratios with 95% confidence intervals\u003cem\u003e,\u003c/em\u003e as well as the trial sequential analysis-adjusted confidence intervals.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eUnit of analysis issues\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe planned to use the individual patient as the unit of analysis.\u003c/p\u003e\n\u003cp\u003eFor cross-over trials, we planned to follow the guidance in the Cochrane Handbook for Systematic Reviews of Interventions (21) which states that cross-over trials should include data from the first phase to avoid period effect or carry-over effect.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLastly, for multi-arm studies, we combined arms into groups, where appropriate, to create a single pair-wise comparison.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDealing with missing data\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe recorded missing data for each included study. When possible, we performed all analyses using an intention to-treat approach and used STATA to calculate missing standard deviations using other data from the trial, such as CI, based on methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions (21).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAssessment of heterogeneity\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe visually investigated forest plots to assess heterogeneity. We then assessed the presence of statistical heterogeneity by the Chi\u003csup\u003e2\u003c/sup\u003e test (threshold \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.10) and measure the quantities of heterogeneity using the \u003cem\u003eI\u003c/em\u003e\u003csup\u003e2\u003c/sup\u003e and H\u003csup\u003e2\u003c/sup\u003e statistic.\u003c/p\u003e\n\u003cp\u003eWhere substantial heterogeneity was identified, we reported it and explored possible causes.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData synthesis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe conducted statistical analyses using STATA (STATA 18). We used the random-effect model to synthesise data as it was reasonable to assume that trials would have a significant clinical heterogeneity. We planned to report narratively instead of performing meta-analysis if we identified considerable clinical, methodological, or statistical heterogeneity, however this was not found.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSubgroup analysis and investigation of heterogeneity\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe planned to perform the following subgroup analyses on our outcomes if we had high heterogeneity:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eAccording to type of conduit used (SVG, RIMA/RITA, GA, RA)\u003c/li\u003e\n \u003cli\u003eConduit configuration\u003c/li\u003e\n \u003cli\u003eAccording to coronary artery target/territory for grafting (LAD, LCx, RCA)\u003c/li\u003e\n \u003cli\u003eAccording to harvesting technique (no-touch vs conventional)\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eHowever, we did not identify substantial heterogeneity (I\u003csup\u003e2\u003c/sup\u003e greater than 50%).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSensitivity analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe planned to repeat the meta-analyses including high-quality trials only. Trials would have been classified as high quality if they were judged to be at low risk of bias for sequence generation, allocation concealment, and blinding of outcome assessment. However, due to the limited number of high-quality studies we did not perform repeat meta-analyses.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSummary of findings and assessment of certainty of the evidence\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe following outcomes (mid- and long-term) were assessed for certainty of evidence using GRADEpro software ((https://gradepro.org/)) for the comparison arterial versus venous conduits:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eSurvival rate (%)\u003c/li\u003e\n \u003cli\u003eAngiographic conduit patency rates (%)\u003c/li\u003e\n \u003cli\u003eFreedom from major adverse cardiac events (MACE) (%), defined as freedom from a composite of cardiac-related death, myocardial infarction, stroke and repeat revascularisation(20), including cardiac event-free survival.\u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eWe followed the methods described by the Cochrane Handbook for Systematic Reviews of Interventions to assign\u003cem\u003e\u0026nbsp;\u003c/em\u003eone of four levels of certainty - high, moderate, low, or very low\u003cem\u003e\u0026nbsp;\u003c/em\u003ebased on risk of bias, directness of the evidence, consistency\u003cem\u003e\u0026nbsp;\u003c/em\u003eof results, precision of the estimates, and risk of publication\u003cem\u003e\u0026nbsp;\u003c/em\u003ebias(21). We justified all decisions to downgrade the\u003cem\u003e\u0026nbsp;\u003c/em\u003ecertainty of the evidence in the results narrative. \u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003cstrong\u003eDescription of studies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults of the search\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSearch of electronic databases revealed 8461 reports. After deduplication and automated removal of ineligible studies (n=3292), 5168 reports were screened in the title and abstract phase. Of these reports, 5090 were assessed as not relevant and 78 full texts were obtained. At the full text review stage, 67 were excluded and 11 studies met our inclusion criteria (Tuore et al. 2021 (22), Gaudino et al. 2005 (23), Dreifaldt et al. 2021 (16), Petrovic et al. 2015 (24), Kim et al. 2018 (25), Collins et al. 2008 (26), Buxton and Hayward et al. 2013, 2020 (19, 27), Deb et al. 2012 (28), Goldman et al. 2022 (17), Damgaard et al. 2015 (29), Myers et al. 2000 (30). We also identified four ongoing studies (CTRI/2020/09/027692 (31), UMIN000039746 (32), CTRI/2021/06/034072 (33), ACTRN12622000552785 (34). See Figure 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIncluded studies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe included 11 studies in our review. All studies included were randomised controlled trials (RCTs). Two trials (Dreifaldt et al. (16), Deb et al. (28)), were crossover RCTs, whereby conduits were randomised to coronary target vessels and patients received both the study and control conduit. For these studies, the only outcome data extracted was conduit patency (%). These 11 studies contained a total sample size of 2848 participants. Studies were conducted from 1990 to 2011 in North America, Europe, Asia, Australia, and North Africa. See Table 1: Characteristics of included studies.\u003c/p\u003e\n\u003cp\u003eTable 1: Characteristics of included studies\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy ID\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStudy Design\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePopulation (Sample Size)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntervention and Comparator\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOutcomes\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eKey Results\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eToure et al. (2021)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eRandomised controlled trial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e50 CABG patients\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eRadial artery vs saphenous vein grafts\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eMid-term (5-year) conduit patency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eRA had significantly higher 5-year patency than SVG\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGaudino et al. (2005)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eRandomised controlled trial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e120 CABG patients, 60 with in-stent restenosis, 60 control\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eRA vs RITA vs SVG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eMid-term survival and conduit patency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eNo difference in survival. RA/RITA grafts had superior patency in both arms\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDreifaldt et al. (2021)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eRandomised controlled trial (crossover)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e108 CABG patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eNo-touch SVG vs RA (randomised to coronary target)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eMid-term (8-year) conduit patency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eNo-touch SVG comparable to RA in long-term patency\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePetrovic et al. (2015)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eRandomised controlled trial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e200 CABG patients\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eRA vs SVG as second conduit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eMid-term (8-year) survival, MACE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eSimilar survival and MACE in both arms\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eKim et al. (2018)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eRandomised controlled trial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e224 CABG patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eRA vs RITA vs SVG (Y-composite)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eMid-term (8-year) patency, MACE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eComparable outcomes; SV had slightly lower MACE\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCollins et al. (2008)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eRandomised controlled trial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e142 CABG patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eRA vs SVG\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e5-year conduit patency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eNo difference in survival. RA had significantly better patency\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBuxton and Hayward et al. (2013, 2020)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eRandomised controlled trial (RAPCO)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e225 CABG patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eRA vs SVG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eMid-term (5.5-6 years) and long-term (10-year) survival and patency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eRA superior to SVG in survival and patency\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDeb et al. (2012)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eRandomised controlled trial (RAPS)- (crossover)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e529 CABG patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eRA vs SVG (randomised to coronary target)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eMid-term (7.7 years) patency\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eRA had higher patency than SVG\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGoldman et al. (2022)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eMulticentre randomised controlled trial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e757 first-time elective CABG patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eRA vs SVG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eLong-term (17.95 years) survival\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eRA had higher survival but not statistically significant\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDamgaard et al. (2015)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eRandomised controlled trial (CARRPO)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e331 CABG patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eRA+RITA vs SVG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eMid-term (5.7-6.6 years) survival, patency, MACE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eSimilar survival, patency and MACE\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMyers et al. (2000)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eRandomised controlled trial\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003e162 patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eRITA vs SVG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eMid-term (5-year) survival and MACE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 16.6667%;\"\u003e\n \u003cp\u003eComparable survival and MACE\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eParticipants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe mean age of participants in the included studies was 61.9 (56.7-72.9) years old with 17.9% of them being female. Of note, Buxton and Hayward et al. (19, 27), only recruited patients aged\u0026nbsp;\u0026ge;70 (\u0026ge;60 if diabetic)\u0026nbsp;in their RA vs SV arm. Demographic data was not available for 1 study (Toure et al.\u0026nbsp;(22)). Criteria for participant inclusion in all studies were adult patients undergoing primary isolated CABG with two or more graftable coronary arteries (at least one after LIMA to LAD). All studies only included patients with an ejection fraction (EF) greater than 35%, with the exception of Kim et al.\u0026nbsp;(25), which allowed an EF of at least 25% and only recruited patients scheduled for off-pump CABG (OPCAB) for both arms. Gaudino et al.\u0026nbsp;(23)\u0026nbsp;only recruited patients with in-stent restenosis in one arm of their trial. Degree of stenosis of the target coronary vessels was at least 70% for all studies, apart from Dreifaldt et al.\u0026nbsp;(16)\u0026nbsp;and Damgaard et al.\u0026nbsp;(29), where it was at least 50%.\u003c/p\u003e\n\u003cp\u003eThe studies excluded participants that had contraindications for conduit harvesting or where conduits were unavailable e.g. positive Allen\u0026rsquo;s test/abnormal doppler, history of Reynaud\u0026rsquo;s/vasculitis, bilateral varicose veins, amputation, previous thoracic surgery/radiotherapy. Studies also excluded patients with varying degrees of renal impairment and allergy to contrast media. Patients with concurrent illness e.g. malignancy that resulted in expected survival of \u0026lt;5 years were also excluded. Myers et al. (30) excluded patients with insulin dependent diabetes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInterventions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe interventions in all included studies were the use of either an arterial (RA/RITA) or venous (SV) conduit to bypass a non-LAD coronary target/territory. Two of the studies included, Damgaard et al. (29) and Myers et al. (30), had participants receive only arterial (total arterial) or only venous conduits to the non-LAD coronary target/territory. In all other studies, participants could receive either additional SVs or a conduit of the surgeon\u0026rsquo;s choice to other non-study (3\u003csup\u003erd\u003c/sup\u003e, 4\u003csup\u003eth\u003c/sup\u003e, 5\u003csup\u003eth\u003c/sup\u003e) coronary targets. In two of these studies, participants received both an arterial and a venous conduit either to the left or right coronary territories and acted as their own control (crossover RCTs). The primary outcome for both these studies was conduit patency. For three of the included studies (Toure et al. (22), Collins et al. (26), Goldman et al. (17)) it is unclear if participants were allowed to receive a different conduit type for the non-study coronary targets. In five studies, (Dreifaldt et al. (16), Petrovic et al. (24), Collins et al. (26), Buxton and Hayward et al. (19, 27), Goldman et al. (17)), conduit configuration was aortocoronary. A combination of aortocoronary and sequential grafting was used in Damgaard et al. (29) whilst participants in Myers et al. (30) had aortocoronary configuration in the SV group and sequential in the RITA group. In Kim et al. (25), Y-composite grafts were used for all participants in this purely OPCAB study. Graft configuration data was not available for three studies (Toure et al. (22), Gaudino et al. (23), Deb et al. (28)). In only one study (Dreifaldt et al. (16)), a no-touch harvesting technique was used to harvest the SV.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOutcomes reported and relevant to this review\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOutcomes relevant to this review are survival, conduit patency rates and freedom from MACE. For the outcomes of survival and freedom from MACE, all studies used either follow-up visits, phone calls, hospital/national databases/registries, or a combination of these modalities to report outcomes. For studies reporting conduit patency rates, conventional coronary angiography was used exclusively for all apart from four studies. Toure et al. (22) and Dreifaldt et al. (16) used computed tomography (CT) angiography for all participants whilst Deb et al. (28) and Kim et al. (25) offered it to patients who did not consent to or withdrew consent for conventional angiography. Angiography studies were reviewed by at least two independent reviewers with expertise in the field in all cases. Where rates of survival, conduit patency and freedom from MACE data was not explicitly reported, these were calculated from the available data.\u003c/p\u003e\n\u003cp\u003eThe follow-up periods of interest in this review are mid-term (\u0026ge;5 to\u0026nbsp;\u0026lt;10 years) and long-term (\u0026ge;10 years). Long-term outcome data was only available for two studies (Buxton and Hayward et al. (19, 27), Goldman et al. (17)), with the former having both mid-term and long-term outcome data for all three primary outcomes of interest i.e. survival, conduit patency rate and freedom from MACE and the later only reporting survival. Mid-term survival was also available for a further six studies (Gaudino et al. (23), Petrovic et al. (24), Kim et al, Collins et al. (26), Damgaard et al. (29), Myers et al. (30)). Conduit patency rates were reported by a further seven studies (Toure et al. (22), Gaudino et al. (23), Dreifaldt et al. (16), Kim et al. (25), Collins et al. (26), Deb et al. (28), Damgaard et al. (29)). Freedom from MACE was reported by four other studies (Petrovic et al. (24), Kim et al. (25), Damgaard et al. (29), Myers et al. (30).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOngoing studies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe identified four ongoing studies (CTRI/2020/09/027692 (31), UMIN000039746 (32), CTRI/2021/06/034072 (33), ACTRN12622000552785 (34)).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eExcluded studies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAt full-text review stage, sixty-seven studies were excluded. The most prevalent reasons for exclusion were wrong study design or wrong intervention.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRisk of bias in included studies\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRisk of bias for all included studies are summarised in Figure 2 and 3. The most prevalent risk of bias was that of observer bias for the outcome of conduit patency. Reviewers of the angiography study, even if blinded, would be able to ascertain conduit type when assessing for patency which introduces bias in the \u0026ldquo;measurement of outcome\u0026rdquo; domain. For studies reporting survival and freedom from MACE, we found that all studies, apart from, Damgaard et al. (29) and Myers et al. (30), either allowed for additional arterial or venous conduits to be used to graft the other non-study coronary targets/territories, usually RCA, as part of their protocol or did not provide information regarding these additional bypasses. Therefore, this represented performance bias due to this confounding factor and these studies were judged to have some concerns.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEffects of intervention\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSurvival\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMid-term survival was reported by seven studies (Gaudino et al. (23), Petrovic et al. (24), Kim et al. (25), Collins et al. (26), Buxton and Hayward et al. (19, 27), Damgaard et al. (29) and Myers et al. (30)). Mean mid-term survival (%) across these studies was 92.1% (\u0026plusmn;4.7) for arterial versus 92.2% (\u0026plusmn;5.3) for\u0026nbsp;venous conduits. Pooled analysis showed no difference in midterm survival between arterial and venous conduits (log risk-ratio 0.00, 95% confidence interval -0.03-0.03; P= 0.95; Analysis 1). There was very low heterogeneity across studies (I\u003csup\u003e2\u003c/sup\u003e=0.01%, H\u003csup\u003e2\u003c/sup\u003e=1.00)\u003c/p\u003e\n\u003cp\u003eLong-term survival was reported by only two studies (Buxton and Hayward et al. (19, 27) and Goldman et al. (17)). Mean long-term survival was 62.6% (\u0026plusmn;22.4) for arterial versus 50.3% (\u0026plusmn;21.1) for venous conduits. Pooled analysis showed a trend towards increased survival for the arterial group (log risk ratio 0.23, 95% confidence interval 0.09-0.37, P\u0026lt; 0.001; Analysis 2). There was low to moderate heterogeneity across these two studies (I\u003csup\u003e2\u003c/sup\u003e=26.1%, H\u003csup\u003e2\u003c/sup\u003e=1.35). The substantial difference in mean long-term survival in these two studies can be explained by their duration of follow up. Mean follow-up duration for Buxton and Hayward et al. was 10-years whilst for Goldman et al. it was 17.95 years. Certainty evidence was deemed to be \u0026ldquo;moderate\u0026rdquo; (downgraded one point) using the GRADE criteria due to the risk of performance bias.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConduit patency\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMid-term conduit patency was reported by eight studies (Toure et al. (22), Gaudiono et al. (23), Dreifaldt et al. (16), Kim et al.(25), Collins et al. (26), Bexton and Hayward et al. (19, 27), Deb et al. (28), Damgaard et al. (29)). Mean mid-term conduit patency was 91.3% (\u0026plusmn;4.1) for arterial versus 82.8% (\u0026plusmn;8.8) for venous conduits. Pooled analysis is in favour of arterial conduits (log risk-ratio 0.06, 95% confidence interval 0.02-0.11, P=0.01; Analysis 3). These studies show moderate heterogeneity (I\u003csup\u003e2\u003c/sup\u003e=41.6%, H\u003csup\u003e2\u003c/sup\u003e=1.71). This may be due to the differences in the intervention whereby Kim et al.\u0026nbsp;(5)\u0026nbsp;used a Y-composite/sequential graft configuration for both arterial and venous conduits based on the LITA and is the only study to perform CABG entirely off-pump. Damgaard et al.\u0026nbsp;(29)\u0026nbsp;used a combination of aortocoronary and sequential grafting for their conduits. All other studies used a more conventional aortocoronary graft configuration, apart from Toure et al.(22), Gaudino et al.\u0026nbsp;(23)\u0026nbsp;and Deb et al.\u0026nbsp;(28), where graft configuration is unknown. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLong-term conduit patency was only reported by Buxton and Hayward et al. (19, 27). Patency rates were higher for arterial versus venous conduits, 85.0% vs 71.4% (log risk-ratio 0.17, 95% confidence interval 0.03-0.31; Analysis 4). Using the GRADE criteria, certainty of evidence for both mid and long-term conduit patency was \u0026ldquo;low\u0026rdquo; (downgraded two points) due to risk of observer bias, moderate heterogeneity in the mid-term studies and the presence of only one study with a relatively small sample size reporting on long-term conduit patency.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFreedom from MACE\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMid-term freedom from MACE was reported by five studies (Petrovic et al. (24), Kim et al.(25), Buxton and Hayward et al. (19, 27), Damgaard et al. (29), Myers et al. (30)). Mean mid-term freedom from MACE was 83.2% (\u0026plusmn;13.7) in the arterial group and 82.9 (\u0026plusmn;13.8). Pooled analysis showed no difference between arterial and venous groups (log risk-ratio 0.00, 95% confidence interval -0.04-0.05, P=0.48; Analysis 5). There was low heterogeneity between the five studies (I\u003csup\u003e2\u003c/sup\u003e=10.81%, H\u003csup\u003e2\u003c/sup\u003e=1.12).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOnly one study reported long-term freedom from MACE (Buxton and Hayward et al. (19, 27)). There was a higher rate of freedom from MACE in the arterial group (86.7%) compared the venous group (83.0%), however this did not reach statistical significance (log risk-ratio 0.04, 95% confidence interval -0.07-0.15). As with survival, certainty evidence for mid-term freedom from MACE was deemed to be \u0026ldquo;moderate\u0026rdquo; (downgraded one point) using the GRADE criteria due to the risk of performance bias. For long-term freedom from MACE, we also deemed it to have the same risk of bias with the additional factor of the evidence coming from only one study. Thus, we judged the certainty of evidence to be \u0026ldquo;low\u0026rdquo; (downgraded two points).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003e\u003cstrong\u003eSummary of main results\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe main objective of this study was to compare both conduit patency and clinical outcomes of arterial versus venous conduits in CABG. Eight of the included studies reported on survival (mid-term=7, long-term=2), with one study reporting both mid-term and long-term survival. We deemed the certainty of the evidence to be \u0026ldquo;moderate\u0026rdquo; due the risk of performance bias i.e. participants were allowed to receive a different conduit type to the other non-study coronary targets or no information was available in six of the eight studies. There was no difference in mid-term survival between the two groups. However, arterial conduits did show a trend for greater survival in the long-run. This is backed up by two of the studies that were pooled for long-term survival analysis. Participants in the arterial arm of Goldman et al. (17), followed up for 17.95 years, showed a greater difference in survival versus the venous arm compared to their counterparts in Buxton and Hayward et al. (19, 27), who were followed up for 10 years. Additionally, the later study only enrolled participants aged \u0026gt;70 years in their RA vs SV arm further accounting for this difference.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis principle of delayed or long-term benefit is also thought to apply to conduit patency and freedom from MACE of arterial versus venous conduits. Our analysis of patency rates showed a modest difference in favour of arterial conduits from the eight studies reporting mid-term, and the one study reporting long-term patency rates. However, certainty of this evidence was deemed to be \u0026ldquo;low\u0026rdquo; as there was moderate heterogeneity in the mid-term studies and all studies had a risk of observer bias. Outcome assessors, like that of angiogram reviewers who are unable to be fully blinded, always risked introducing bias. At present, conventional coronary angiography remains the gold-standard for evaluating and grading conduit patency and it is unlikely this source of bias can be eliminated. Results from long-term conduit patency was obtained from only one study and thus, we are unable to draw strong conclusions about both mid and long-term conduit patency.\u003c/p\u003e\n\u003cp\u003eSimilar to survival, freedom from MACE analysis showed no difference in midterm freedom from MACE and suggests a minimal benefit of arterial conduits in long-term freedom from MACE that failed to reach statistical significance in the pooled studies. This outcome also carries the same performance bias as survival which resulted in downgrading of the certainty to \u0026ldquo;moderate\u0026rdquo; for the mid-term group and \u0026ldquo;low\u0026rdquo; for the long-term group.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eOverall completeness and applicability of evidence\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur comprehensive search of the literature did result in one other study from the Chinese clinical trial registry that could have been included. But it was unclear if this trial had been completed (ChiCTR-TRC-13003294 (35)). We attempted to contact the listed authors of this trial; however, they did not respond which resulted in this trial being excluded at the full-text review stage under the label \u0026ldquo;Authors uncontactable.\u0026rdquo;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMid-term survival was consistently reported across seven studies, with minimal heterogeneity and \u0026ldquo;moderate\u0026rdquo; certainty. However, long-term survival data were limited to only two studies with differing follow-up durations (10 and 17.95 years), thereby reducing the precision of pooled estimates despite a statistically significant effect favouring arterial conduits. This limits the generalisability of the long-term survival findings and introduces uncertainty about their consistency across broader populations and practice settings.\u003c/p\u003e\n\u003cp\u003eConduit patency was more thoroughly reported, particularly at mid-term follow-up, with eight studies contributing data. The observed benefit of arterial conduits was statistically significant but modest, and the moderate heterogeneity, largely attributable to variations in the intervention, should temper the interpretation. Long-term patency data were restricted to a single study, limiting the strength of inference and applicability, especially in diverse surgical contexts. Overall, the evidence for conduit patency was judged to be of \u0026ldquo;low\u0026rdquo; certainty, due to the aforementioned risk of bias, heterogeneity and the limited scope of long-term data.\u003c/p\u003e\n\u003cp\u003eData on mid-term freedom from MACE were available from five studies with low heterogeneity and moderate certainty. However, similar to survival and patency outcomes, the evidence for long-term freedom from MACE was sparse, being derived from a single study with imprecise effect estimates. This significantly limits the robustness and applicability of the evidence for long-term event prevention.\u003c/p\u003e\n\u003cp\u003eImportantly, several studies lacked granular detail on key methodological factors such as conduit configuration, completeness of revascularization, and use of additional conduits which introduced performance bias, all of which may influence outcomes. Additionally, observer bias remains a concern in several studies, reliant on subjective assessments of conduit patency.\u003c/p\u003e\n\u003cp\u003eIn summary, while the evidence base is moderately complete for mid-term outcomes, particularly for survival and conduit patency. It is notably weaker for long-term endpoints and for MACE outcomes overall. The findings are most applicable to relatively young, low-risk, surgical populations in whom complete revascularization was technically feasible. Extrapolation to higher-risk cohorts or to practices using alternative graft configurations, off-pump CABG and non-conventional harvesting techniques should be done with caution. Further high-quality, long-term studies are warranted to definitively determine the comparative efficacy of arterial and venous conduits in contemporary CABG practice.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePotential biases in the review process\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSeveral potential sources of bias may have influenced the review process, despite efforts to adhere to rigorous methodological standards. First, although a comprehensive literature search was conducted across multiple databases, there is a risk of publication bias, particularly given the tendency for studies with positive findings to be more likely published. We attempted to mitigate this by searching grey literature and trial registries; however, it is possible that some relevant unpublished data were not identified.\u003c/p\u003e\n\u003cp\u003eSecondly, the risk of selection bias in the study inclusion process was minimised by having two reviewers independently screen titles and abstracts. Nevertheless, the subjective nature of study selection may introduce some degree of reviewer bias, particularly in cases where reporting was unclear or where study eligibility was borderline. Any discrepancies were resolved through discussion or consultation with a third reviewer, but the potential for subtle biases in judgement remains.\u003c/p\u003e\n\u003cp\u003eThird, heterogeneity in study designs, patient populations, the interventions themselves, and outcome definitions posed challenges in data synthesis. Although we used a random-effects model for all of our outcomes and conducted sensitivity analyses, the pooling of data across diverse clinical contexts may introduce confounding. For instance, studies varied in their definitions of MACE and in whether outcomes were reported on a per-patient or per-graft basis.\u003c/p\u003e\n\u003cp\u003eFinally, while risk of bias assessments and GRADE evaluations were applied systematically, these tools involve a degree of subjectivity. Observer bias were frequent concerns in the included studies, particularly in angiographic interpretation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOverall, while every effort was made to minimise bias at each stage of the review process, some degree of systematic and interpretative bias is unavoidable. These limitations should be considered when interpreting the findings of this review.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAgreements or disagreements with other studies or reviews\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur findings are broadly consistent with the recent meta-analyses by Ding et al. (2025) (36) and Gaudino et al. (2019, 2020) (13) (37), which support the superiority of arterial conduits over saphenous vein grafts in CABG. Ding et al. (36) demonstrated improved survival with multiple arterial grafting compared to single arterial strategies, aligning with our observation of a trend toward enhanced long-term survival in the arterial group, although our review did not stratify by number of arterial grafts. Gaudino et al.(13), in their landmark individual participant data meta-analysis, found that radial artery grafts were associated with significantly lower rates of death, myocardial infarction, and repeat revascularization over a 10-year period, which corroborates our finding of superior long-term outcomes with arterial conduits, albeit with more limited data and lower certainty. Gaudino et al.(37) again, using a network meta-analysis, further reinforced the advantages of arterial grafts, showing that both radial artery and right internal thoracic artery conferred better long-term results than venous grafts, a conclusion consistent with our data, though our review did not directly compare different arterial types. \u0026nbsp;Together, these studies complement and validate the patterns observed in our review, while also highlighting the evolving consensus in favour of arterial revascularisation.\u003c/p\u003e\n\u003cp\u003eThis echoes previous large observational data that that report a higher survival for those receiving total arterial revascularisation in the long run compared to a single arterial (LITA/LIMA) plus additional venous conduits (18, 38, 39) and supports the long held theory that the benefits from arterial grafting are most pronounced in younger patients who have a greater time horizon (40).\u003c/p\u003e\n\u003cp\u003eAlthough the evidence in favour of arterial revascularisation is growing, an authoritative expert review endorsed by the European Association for Cardio‑Thoracic Surgery (EACTS) and The Society of Thoracic Surgeons (STS) in 2023, warns against a one size fits all approach and surgeons must be aware of the nuances of conduit selection (41). Conduit selection must be individualised based on factors such as patient age, comorbidities, coronary anatomy, surgical risk, and surgeon expertise.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eThis systematic review synthesised mid- and long-term outcomes for arterial versus venous conduits in coronary artery bypass grafting (CABG), focusing on survival, conduit patency, and freedom from major adverse cardiac events (MACE). The findings suggest that while mid-term outcomes are comparable between conduit types in terms of survival and freedom from MACE, arterial conduits, demonstrate superior patency at mid-term follow-up. Limited long-term data suggest a potential survival advantage and better conduit durability with arterial grafts, although the evidence remains incomplete and subject to methodological limitations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eImplications for Practice\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe consistent patency advantage observed with arterial grafts at mid-term, coupled with a trend towards improved long-term survival, supports the selective use of arterial conduits beyond the left internal mammary artery (LIMA), particularly in younger patients and those with longer life expectancy. However, given the modest absolute differences in clinical endpoints and the limited long-term evidence, the decision to use additional arterial grafts should be individualised, considering patient comorbidities, target vessel anatomy, surgical expertise, and institutional practices. The routine use of arterial conduits as second or third grafts may not be universally warranted but should remain an important option in the armamentarium of modern surgical revascularisation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eImplications for Research\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere is a clear need for further high-quality, long-term studies comparing arterial and venous conduits, particularly beyond 10 years of follow-up. Future research should aim to stratify outcomes by surgical approach (conduit configuration, minimally invasive/robotic surgery vs conventional, on- vs off-pump, no-touch vs. conventional conduit harvesting), and patient subgroups, including those with diabetes, renal impairment, or advanced age. Through our search we discovered one promising study, with two of its trial sites included in our ongoing studies (UMIN000039746 (32) CTRI/2021/06/034072 (33)) . This is the \u0026ldquo;Randomized comparison of the clinical outcome of single versus multiple arterial grafts: the ROMA trial,\u0026rdquo; which is a large, international RCT currently enrolling participants (42).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eLarge, pragmatic trials with sufficient follow-up duration, like the ROMA trial, are required to definitively determine the long-term clinical benefit of expanded arterial graft use in CABG. Standardisation of outcome reporting, including consistent definitions for MACE and conduit patency, and uniform follow-up intervals, would enhance comparability across studies. Additionally, with the advent of artificial intelligence (AI), specifically machine learning, observer bias may be eliminated through the use of validated, robust, AI powered angiographic adjudication. Our final word on arterial versus venous conduits in CABG is that venous conduits still hold a vital place on the frontline of coronary revascularisation. With higher quality evidence, arterial conduits may redraw the map of long-term coronary revascularisation.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSteenbergen C, Frangogiannis NG. Chapter 36 - Ischemic Heart Disease. In: Hill JA, Olson EN, editors. Muscle. Boston/Waltham: Academic Press; 2012. p. 495-521.\u003c/li\u003e\n\u003cli\u003eHeusch G. Myocardial ischemia/reperfusion: Translational pathophysiology of ischemic heart disease. Med. 2024;5(1):10-31.\u003c/li\u003e\n\u003cli\u003eFishbein GA, Fishbein MC, Buja LM. Chapter 7 - Myocardial Ischemia and Its Complications. In: Buja LM, Butany J, editors. Cardiovascular Pathology (Fourth Edition). San Diego: Academic Press; 2016. p. 239-70.\u003c/li\u003e\n\u003cli\u003eSafiri S, Karamzad N, Singh K, Carson-Chahhoud K, Adams C, Nejadghaderi SA, et al. Burden of ischemic heart disease and its attributable risk factors in 204 countries and territories, 1990-2019. 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American Association for Thoracic Surgery, International Coronary Congress; 21/08/2015; New York, N.Y, USA2015.\u003c/li\u003e\n\u003cli\u003eMyers WO, Berg R, Ray JF, Douglas-Jones JWE, Maki HS, Ulmer RH, et al. All-artery multigraft coronary artery bypass grafting with only internal throracic arteries possible and safe: A randomized trial. Surgery. 2000;128(4):650-9.\u003c/li\u003e\n\u003cli\u003eCtri. Evaluation of outcomes of arterial grafts to one versus two or more vessels during heart bypass surgery in diabetic patients. 2020.\u003c/li\u003e\n\u003cli\u003eUmin. Randomized comparison of the clinical Outcome of single versus Multiple Arterial grafts. 2020.\u003c/li\u003e\n\u003cli\u003eCtri. The study is to determine the effect and outcomes of single vs multiple arterial revascularization for patients undergoing coronary artery bypass surgery. 2021.\u003c/li\u003e\n\u003cli\u003eActrn. Multiple Arterial Revascularization versus Single in a patients with coronary artery disease. 2022.\u003c/li\u003e\n\u003cli\u003eChi CT. Outcomes of total arterial revascularization with skeletonized bilateral internal mammary artery: a prospective randomized trial. 2013.\u003c/li\u003e\n\u003cli\u003eDing Q, Zhu Q, Lu L, Cheng X, Ge M. Comparison of multiple arterial grafts vs. single arterial graft in coronary artery bypass surgery: a systematic review and meta-analysis. Frontiers in Cardiovascular Medicine. 2025;Volume 12 - 2025.\u003c/li\u003e\n\u003cli\u003eGaudino M, Lorusso R, Rahouma M, Abouarab A, Tam DY, Spadaccio C, et al. Radial Artery Versus Right Internal Thoracic Artery Versus Saphenous Vein as the Second Conduit for Coronary Artery Bypass Surgery: A Network Meta‐Analysis of Clinical Outcomes. Journal of the American Heart Association. 2019;8(2):e010839.\u003c/li\u003e\n\u003cli\u003eMomin A, Ranjan R, Valencia O, Jacques A, Lim P, Fluck D, et al. Long Term Survival Benefits of Different Conduits Used in Coronary Artery Bypass Graft Surgery- A Single Institutional Practice Over 20 Years. J Multidiscip Healthc. 2024;17:1505-12.\u003c/li\u003e\n\u003cli\u003eRocha RV, Tam DY, Karkhanis R, Nedadur R, Fang J, Tu JV, et al. Multiple Arterial Grafting Is Associated With Better Outcomes for Coronary Artery Bypass Grafting Patients. Circulation. 2018;138(19):2081-90.\u003c/li\u003e\n\u003cli\u003eGaudino M, Benedetto U, Fremes S, Biondi-Zoccai G, Sedrakyan A, Puskas JD, et al. Radial-Artery or Saphenous-Vein Grafts in Coronary-Artery Bypass Surgery. New England Journal of Medicine. 2018;378(22):2069-77.\u003c/li\u003e\n\u003cli\u003eGaudino M, Bakaeen FG, Sandner S, Aldea GS, Arai H, Chikwe J, et al. Expert systematic review on the choice of conduits for coronary artery bypass grafting: endorsed by the European Association for Cardio-Thoracic Surgery (EACTS) and The Society of Thoracic Surgeons (STS). 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Eur J Cardiothorac Surg. 2017;52(6):1031-40.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Analysis","content":"\u003cp\u003eAnalysis 1 to 6 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Royal College of Surgeons in Ireland","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"cardiothoracic surgery, coronary artery bypass grafting, arterial, venous, conduit, graft, CABG, revascularisation","lastPublishedDoi":"10.21203/rs.3.rs-8050782/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8050782/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cu\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003c/u\u003e\u003cbr\u003e\nCoronary artery bypass grafting (CABG) remains a cornerstone of treatment for patients with multivessel coronary artery disease. While the use of the left internal mammary artery (LIMA) to the left anterior descending artery is the standard of care, the optimal choice of additional conduits—arterial versus venous—remains a subject of ongoing debate.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003e\u003cstrong\u003eObjectives:\u003c/strong\u003e\u003c/u\u003e\u003cbr\u003e\nTo compare mid- and long-term conduit patency, survival, and freedom from major adverse cardiac events (MACE) between arterial and venous conduits in CABG.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003c/u\u003e\u003cbr\u003e\nWe conducted a systematic review and meta-analysis of randomized controlled trials from 2000 onwards comparing arterial and venous conduits for non-LAD targets in CABG. Primary outcomes were mid- and long-term survival, angiographic patency, and freedom from MACE. Studies were appraised for risk of bias using RoB-2 and evidence certainty was evaluated using GRADE.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/u\u003e\u003cbr\u003e\nEleven RCTs including 2,848 participants were analyzed. Mid-term survival did not differ between arterial and venous conduits (log risk ratio 0.00; 95% CI -0.03 to 0.03). Long-term survival showed a modest benefit for arterial conduits (log risk ratio 0.23; 95% CI 0.09 to 0.37; \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001). Arterial conduits demonstrated higher mid-term patency (log risk ratio 0.06; 95% CI 0.02 to 0.11; \u003cem\u003eP\u003c/em\u003e=0.01), and long-term patency data from a single study also favoured arterial grafts. Freedom from MACE was similar at mid-term (log risk ratio 0.00; 95% CI -0.04 to 0.05), while long-term data suggested a small, non-significant advantage for arterial grafts. Certainty of evidence ranged from moderate to low, primarily due to observer and performance bias and limited long-term data.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e\u003c/u\u003e\u003cbr\u003e\nArterial conduits offer superior mid-term patency and show a trend toward improved long-term survival, supporting their selective use beyond the LIMA-LAD graft. However, given the modest clinical differences and low-certainty long-term data, venous conduits continue to play an essential role in CABG. Further large-scale, high-quality trials are needed to define the optimal conduit strategy in contemporary surgical practice.\u003c/p\u003e","manuscriptTitle":"Arterial versus venous conduits in coronary artery bypass grafting: a systematic review with meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-10 06:38:43","doi":"10.21203/rs.3.rs-8050782/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e360b8c3-bdf9-4101-a548-8395715a4fa2","owner":[],"postedDate":"November 10th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":57574401,"name":"Cardiothoracic Surgery"}],"tags":[],"updatedAt":"2025-11-10T06:38:44+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-10 06:38:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8050782","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8050782","identity":"rs-8050782","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}