Single versus multiple arterial grafting in diabetic patients at 10 years: the Arterial Revascularization Trial.

AIMS: To evaluate the impact of multiple arterial grafting (MAG) vs. single arterial grafting (SAG) in a post hoc analysis of 10-year outcomes in patients with diabetes mellitus (DM) from the Arterial Revascularization Trial (ART). METHODS AND RESULTS: The primary endpoint was all-cause mortality and the secondary endpoint was a composite of major adverse cardiac events (MACE) at 10-year follow-up. Patients were stratified by diabetes status (non-DM and DM) and grafting strategy (MAG vs. SAG). A total of 3020 patients were included in the analysis; 716 (23.7%) had DM. Overall, 55.8% non-DM patients received MAG and 44.2% received SAG, while 56.6% DM patients received MAG and 43.4% received SAG. The use of MAG compared with SAG was associated with lower 10-year mortality for both non-DM [17.7 vs. 21.0%, adjusted hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.72-1.06] and DM patients (21.5 vs. 29.9%, adjusted HR 0.65, 95% CI 0.48-0.89; P for interaction = 0.12). For both groups, the rate of 10-year MACE was also lower for MAG vs. SAG. Overall, deep sternal wound infections (DSWIs) were uncommon but more frequent in the MAG vs. SAG group in both non-DM (3.3 vs. 2.1%) and DM patients (7.9 vs. 4.8%). The highest rates of DSWI were in insulin-treated patients receiving MAG (9.6 vs. 6.3%, when compared with SAG). CONCLUSION: In this post hoc analysis of the ART, MAG was associated with substantially lower mortality rates at 10 years after coronary artery bypass grafting in patients with DM. Patients with DM receiving MAG had a higher incidence of DSWI, especially if insulin dependent.

Bilateral versus Single Internal-Thoracic-Artery Grafts at 10 Years.

BACKGROUND: Multiple arterial grafts may result in longer survival than single arterial grafts after coronary-artery bypass grafting (CABG) surgery. We evaluated the use of bilateral internal-thoracic-artery grafts for CABG. METHODS: We randomly assigned patients scheduled for CABG to undergo bilateral or single internal-thoracic-artery grafting. Additional arterial or vein grafts were used as indicated. The primary outcome was death from any cause at 10 years. The composite of death from any cause, myocardial infarction, or stroke was a secondary outcome. RESULTS: A total of 1548 patients were randomly assigned to undergo bilateral internal-thoracic-artery grafting (the bilateral-graft group) and 1554 to undergo single internal-thoracic-artery grafting (the single-graft group). In the bilateral-graft group, 13.9% of the patients received only a single internal-thoracic-artery graft, and in the single-graft group, 21.8% of the patients also received a radial-artery graft. Vital status was not known for 2.3% of the patients at 10 years. In the intention-to-treat analysis at 10 years, there were 315 deaths (20.3% of the patients) in the bilateral-graft group and 329 deaths (21.2%) in the single-graft group (hazard ratio, 0.96; 95% confidence interval [CI], 0.82 to 1.12; P=0.62). Regarding the composite outcome of death, myocardial infarction, or stroke, there were 385 patients (24.9%) with an event in the bilateral-graft group and 425 patients (27.3%) with an event in the single-graft group (hazard ratio, 0.90; 95% CI, 0.79 to 1.03). CONCLUSIONS: Among patients who were scheduled for CABG and had been randomly assigned to undergo bilateral or single internal-thoracic-artery grafting, there was no significant between-group difference in the rate of death from any cause at 10 years in the intention-to-treat analysis. Further studies are needed to determine whether multiple arterial grafts provide better outcomes than a single internal-thoracic-artery graft. (Funded by the British Heath Foundation and others; Current Controlled Trials number, ISRCTN46552265 .).

Postoperative Atrial Fibrillation and Long-Term Risk of Stroke After Isolated Coronary Artery Bypass Graft Surgery.

BACKGROUND: Postoperative atrial fibrillation (pAF) after coronary artery bypass grafting is a common complication. Whether pAF is associated with an increased risk of cerebrovascular accident (CVA) remains uncertain. We investigated the association between pAF and long-term risk of CVA by performing a post hoc analysis of 10-year outcomes of the ART (Arterial Revascularization Trial). METHODS: For the present analysis, among patients enrolled in the ART (n=3102), we excluded those who did not undergo surgery (n=25), had a history of atrial fibrillation (n=45), or had no information on the incidence of pAF (n=9). The final population consisted of 3023 patients, of whom 734 (24.3%) developed pAF with the remaining 2289 maintaining sinus rhythm. Competing risk and Cox regression analyses were used to investigate the association between pAF and the risk of CVA. RESULTS: At 10 years, the cumulative incidence of CVA was 6.3% (4.6%-8.1%) versus 3.7% (2.9%-4.5%) in patients with pAF and sinus rhythm, respectively. pAF was an independent predictor of CVA at 10 years (hazard ratio, 1.53 [95% CI, 1.06-2.23]; P=0.025) even when CVAs that occurred during the index admission were excluded from the analysis (hazard ratio, 1.47 [95% 1.02-2.11]; P=0.04). CONCLUSIONS: Patients with pAF after coronary artery bypass grafting are at higher risk of CVA. These findings challenge the notion that pAF is a benign complication.

Randomized Trial of Bilateral versus Single Internal-Thoracic-Artery Grafts.

BACKGROUND: The use of bilateral internal thoracic (mammary) arteries for coronary-artery bypass grafting (CABG) may improve long-term outcomes as compared with the use of a single internal-thoracic-artery plus vein grafts. METHODS: We randomly assigned patients scheduled for CABG to undergo single or bilateral internal-thoracic-artery grafting in 28 cardiac surgical centers in seven countries. The primary outcome was death from any cause at 10 years. The composite of death from any cause, myocardial infarction, or stroke was a secondary outcome. Interim analyses were prespecified at 5 years of follow-up. RESULTS: A total of 3102 patients were enrolled; 1554 were randomly assigned to undergo single internal-thoracic-artery grafting (the single-graft group) and 1548 to undergo bilateral internal-thoracic-artery grafting (the bilateral-graft group). At 5 years of follow-up, the rate of death was 8.7% in the bilateral-graft group and 8.4% in the single-graft group (hazard ratio, 1.04; 95% confidence interval [CI], 0.81 to 1.32; P=0.77), and the rate of the composite of death from any cause, myocardial infarction, or stroke was 12.2% and 12.7%, respectively (hazard ratio, 0.96; 95% CI, 0.79 to 1.17; P=0.69). The rate of sternal wound complication was 3.5% in the bilateral-graft group versus 1.9% in the single-graft group (P=0.005), and the rate of sternal reconstruction was 1.9% versus 0.6% (P=0.002). CONCLUSIONS: Among patients undergoing CABG, there was no significant difference between those receiving single internal-thoracic-artery grafts and those receiving bilateral internal-thoracic-artery grafts with regard to mortality or the rates of cardiovascular events at 5 years of follow-up. There were more sternal wound complications with bilateral internal-thoracic-artery grafting than with single internal-thoracic-artery grafting. Ten-year follow-up is ongoing. (Funded by the British Heart Foundation and others; ART Current Controlled Trials number, ISRCTN46552265 .).

Associations Between Adding a Radial Artery Graft to Single and Bilateral Internal Thoracic Artery Grafts and Outcomes: Insights From the Arterial Revascularization Trial.

BACKGROUND: Whether the use of the radial artery (RA) can improve clinical outcomes in coronary artery bypass graft surgery remains unclear. The ART (Arterial Revascularization Trial) was designed to compare survival after bilateral internal thoracic artery (BITA) over single left internal thoracic artery (SITA). In the ART, a large proportion of patients (≈20%) also received an RA graft instead of a saphenous vein graft (SVG). We aimed to investigate the associations between using the RA instead of an SVG to supplement SITA or BITA grafts and outcomes by performing a post hoc analysis of the ART. METHODS: Patients enrolled in the ART (n=3102) were classified on the basis of conduits actually received (as treated). The analysis included 2737 patients who received an RA graft (RA group; n=632) or SVG only (SVG group; n=2105) in addition to SITA or BITA grafts. The primary end point was the composite of myocardial infarction, cardiovascular death, and repeat revascularization at 5 years. Propensity score matching and stratified Cox regression were used to compare the 2 strategies. RESULTS: Myocardial infarction, cardiovascular death, and repeat revascularization cumulative incidence was 2.3% (95% confidence interval [CI], 1.1-3.4), 3.5% (95% CI, 2.1-5.0), and 4.4% (95% CI, 2.8-6.0) in the RA group and 3.4% (95% CI, 2.0-4.8), 4.0% (95% CI, 2.5-5.6), and 7.6% (95% CI, 5.5-9.7) in the SVG group, respectively. The composite end point was significantly lower in the RA group (8.8%; 95% CI, 6.5-11.0) compared with the SVG group (13.6%; 95% CI, 10.8-16.3; P=0.005). This association was present when an RA graft was used to supplement both SITA and BITA grafts (interaction P=0.62). CONCLUSIONS: This post hoc ART analysis showed that an additional RA was associated with lower risk for midterm major adverse cardiac events when used to supplement SITA or BITA grafts. CLINICAL TRIAL REGISTRATION: URL: https://www.situ.ox.ac.uk/surgical-trials/art. Unique identifier: ISRCTN46552265.

Finding the evidence for pulmonary metastasectomy in colorectal cancer: the PulMicc trial.

The PulMiCC trial is a randomized controlled trial testing the effect on survival of pulmonary metastasectomy in patients with colorectal cancer. In stage 1 of the trial patients with treated primary colorectal cancer metastatic to the lungs are invited to consent for protocol-based evaluation of their suitability for metastasectomy. The evaluation is as in current practice and includes PET/CT. A decision for or against metastasectomy may be based on the opinion of the clinicians and the preference of the patient. If there is uncertainty the patient is invited to consent to have the treatment arm assigned by randomization in stage 2 of PulMiCC. More than 300 patients have entered stage 1 and more than 70 are in stage 2.

Minimal clinically important differences in patient-reported outcomes after coronary artery bypass surgery in the arterial revascularization trial.

OBJECTIVES: This article identifies minimal clinically important differences (MCIDs) in quality of life (QoL) measures among patients who had coronary artery bypass grafting (CABG) and were enrolled in the arterial revascularization trial (ART). METHODS AND RESULTS: The European Quality of Life-5 Dimensions (EQ-5D) and the Short Form Health Survey 36-Item (SF-36) physical component (PC) and mental component (MC) scores were recorded at baseline, 5 years and 10 years in ART. The MCIDs were calculated as changes in QoL scores anchored to 1-class improvement in the New York Heart Association functional class and Canadian Cardiovascular Society scale at 5 years. Cox proportional hazard models were used to evaluate associations between MCIDs and mortality. Patient cohorts were examined for the SF-36 PC (N = 2671), SF-36 MC (N = 2815) and EQ-5D (N = 2943) measures, respectively. All QoL scores significantly improved after CABG compared to baseline. When anchored to the New York Heart Association, the MCID at 5 years was 17 (95% confidence interval: 17-20) for SF-36 PC, 14 (14-17) for the SF-36 MC and 0.12 (0.12-0.15) for EQ-5D. Using the Canadian Cardiovascular Society scale as an anchor, the MCID at 5 years was 15 (15-17) for the SF-36 PC, 12 (13-15) for the SF-36 MC and 0.12 (0.11-0.14) for the EQ-5D. The MCIDs for SF-36 PC and EQ-5D at 5 years were associated with a lower risk of mortality at the 10-year follow-up point after surgery. CONCLUSIONS: MCIDs for CABG patients have been identified. These thresholds may have direct clinical applications in monitoring patients during follow-up and in designing new trials that include QoL as a primary study outcome. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN46552265.

Influence of diabetes and obesity on ten-year outcomes after coronary artery bypass grafting in the arterial revascularisation trial.

AIMS: Diabetes and obesity are common conditions which can influence outcomes after coronary artery bypass graft (CABG) surgery. The aim of this study was to evaluate the influence of diabetes and obesity, and their interactions, on ten-year outcomes following CABG. METHODS AND RESULTS: Patients enrolled in the Arterial Revascularisation Trial (ART) were stratified by diabetes and obesity at baseline. Diabetes was further stratified into insulin and non-insulin dependent. The primary outcome was all-cause mortality at 10 years of follow-up. Secondary outcomes were the composite of all-cause mortality, myocardial infarction or stroke at 10 years, and sternal wound complications at 6 months follow-up. A total of 3096 patients were included in the analysis (24% with diabetes, 30% with obesity). Patients in the "diabetes/no obesity" group had a higher risk of all-cause mortality following CABG (adjusted hazard ratio [aHR] 1.33, 95% confidence interval [CI] 1.08-1.64, p = 0.01) compared to the reference group of "no diabetes/no obesity". No excess risk was observed in the "no diabetes/obesity" or "diabetes/obesity" groups. Patients with insulin dependent diabetes had a significantly higher ten-year mortality risk compared to no diabetes (aHR 1.85, 95% CI 1.41-2.44, p = 0.00). Patients in the "diabetes/no obesity" and "diabetes/obesity groups" had a higher risk of sternal wound complications (HR 2.29, 95% CI 1.39-3.79, p < 0.001 and HR 3.21, 95% CI 1.89-5.45, p < 0.001 respectively). The composite outcome results were consistent with the mortality results. CONCLUSION: Diabetes, especially insulin dependent diabetes, is associated with a higher ten-year mortality risk after CABG, in contrast to obesity which does not appear to increase long term mortality compared to non-obese. The interaction between diabetes and obesity shows an apparent "protective" effect of obesity irrespective of diabetes on mortality. Both conditions are associated with a higher risk of post-operative sternal wound infections.

Coronary artery bypass grafting using bilateral internal thoracic arteries in patients with diabetes and obesity: A systematic review and meta-analysis.

Background: Patients with diabetes and obesity are at higher risk of adverse long-term outcomes following coronary artery bypass grafting. The use of bilateral internal thoracic arteries (BITA) can potentially offer survival benefit in higher risk patients compared to single internal thoracic artery (SITA), but BITA is not routinely used due to lack of clear evidence of efficacy and concerns over sternal wound complications. Methods: Medline, Embase and the Cochrane Library were searched for studies comparing the efficacy and safety of BITA and SITA grafting in patients with diabetes and obesity. Meta-analysis of mortality and sternal wound complications was performed. Results: We identified eight observational and ten propensity matched studies, and one RCT, comparing BITA and SITA which included patients with diabetes (n = 19,589); two propensity matched studies and one RCT which included patients with obesity (n = 6,972); mean follow up was 10.5 and 11.3 years respectively. Meta-analysis demonstrated a mortality reduction for BITA compared to SITA in patients with diabetes (risk ratio [RR] 0.79; 95% confidence interval [CI] 0.70-0.90; p = 0.0003). In patients with obesity there was a non-significant reduction in mortality in the BITA group (RR 0.73, 95% CI 0.47-1.12; p = 0.15). There was a significantly higher rate of sternal wound complications following BITA observed in patients with diabetes (RR 1.53, 95% CI 1.23-1.90; p = 0.0001) and obesity (RR 2.24, 95% CI 1.63-3.07; p < 0.00001). Conclusions: BITA is associated with better long-term survival in patients with diabetes. The effects of BITA grafting in patients with obesity are uncertain. BITA is associated with higher rates of sternal wound complications compared to SITA in both patients with diabetes and obesity.

Association between sternal wound complications and 10-year mortality following coronary artery bypass grafting.

OBJECTIVE: To evaluate the association between sternal wound complications (SWC) and long-term mortality in the Arterial Revascularization Trial. METHODS: Participants in the Arterial Revascularization Trial were stratified according to the occurrence of postoperative SWC. The primary outcome was all-cause mortality at long-term follow-up. The secondary outcome was major adverse cardiovascular events. RESULTS: Three thousand one hundred two patients were included in the analysis; the median follow-up was 10 years. 115 patients (3.7%) had postoperative SWC: 85 (73.9%) deep sternal wound infections and 30 (26.1%) sterile SWC that required sternal reconstruction. Independent predictors of SWC included diabetes (odds ratio [OR], 2.77; 95% CI, 1.79-4.30; P < .001), female sex (OR, 2.73; 95% CI, 1.71-4.38; P < .001), prior stroke (OR, 2.59; 95% CI, 1.12-5.98; P = .03), chronic obstructive pulmonary disease (OR, 2.44; 95% CI, 1.60-3.71; P < .001), and use of bilateral internal thoracic artery (OR, 1.70; 95% CI, 1.12-2.59; P = .01). Postoperative SWC was significantly associated with long-term mortality. The Kaplan-Meier survival estimate was 91.3% at 5 years and 79.4% at 10 years in patients without SWC, and 86.1% and 64.3% in patients with SWC (log rank P < .001). The rate of major adverse cardiovascular events was also higher among patients who had SWC (n = 51 [44.3%] vs 758 [25.4%]; P < .001). Using multivariable analysis, the occurrence of SWC was independently associated with long-term mortality (hazard ratio, 1.81; 95% CI, 1.30-2.54; P < .001). CONCLUSIONS: In the Arterial Revascularization Trial, postoperative SWC although uncommon were significantly associated with long-term mortality.

Pulmonary metastasectomy in colorectal cancer: the PulMiCC trial.

PulMiCC (Pulmonary Metastasectomy in Colorectal Cancer) is a randomised controlled trial funded by Cancer Research UK. Patients with a history of resected colorectal cancer who are found to have pulmonary metastases are first registered for evaluation and, if subsequently eligible for the trial, they are invited to be randomly allocated to 'active monitoring' or 'active monitoring with pulmonary metastasectomy'. The clinical outcomes are overall survival, relapse-free survival, lung function and patient-reported quality of life.

Prognostic factors of 10-year mortality after coronary artery bypass graft surgery: a secondary analysis of the arterial revascularization trial.

OBJECTIVES: The objective of this investigation was to determine the preoperative prognostic factors of long-term (10-year) mortality in patients treated with isolated coronary artery bypass graft surgery in the arterial revascularization trial (ART). METHODS: A post hoc analysis of the ART was conducted. Cumulative 10-year mortality was estimated using the Kaplan-Meier method. Prospectively collected preoperative data were used to determine the prognostic factors of 10-year all-cause mortality in patients who participated in the ART (Cox proportional hazards model). RESULTS: A total of 3102 patients who participated in the ART were included in the analysis. Ten-year follow-up was completed in 3040 patients (98%). A total of 644 patients (20.8%) had died by 10 years. Preoperative factors that were identified as statistically significant predictors of 10-year mortality in the multivariable analysis (all P ≤ 0.01) were: left ventricular ejection fraction, atrial fibrillation, age, diabetes, prior cerebrovascular event (stroke or transient ischaemic attack), serum creatinine and smoking status. The following variables were significantly associated in univariable models but did not retain significance in the multivariable model for mortality: non-Caucasian ethnicity, hypertension, peripheral vascular disease, chronic obstructive pulmonary disease and prior myocardial infarction. CONCLUSIONS: Independent predictors of 10-year mortality in the ART were multifactorial. Several key independent predictors of 10-year mortality in the ART were identified including: heart function, renal function, cerebrovascular disease, age, atrial fibrillation, smoking status and diabetes. Understanding which preoperative variables influence long-term outcome after coronary artery bypass grafting may help to target treatments to those at higher risk to reduce mortality.

Cost-effectiveness of bilateral vs. single internal thoracic artery grafts at 10 years.

AIMS: Using bilateral internal thoracic arteries (BITAs) for coronary artery bypass grafting (CABG) has been suggested to improve survival compared to CABG using single internal thoracic arteries (SITAs) for patients with advanced coronary artery disease. We used data from the Arterial Revascularization Trial (ART) to assess long-term cost-effectiveness of BITA grafting compared to SITA grafting from an English health system perspective. METHODS AND RESULTS: Resource use, healthcare costs, and quality-adjusted life years (QALYs) were assessed across 10 years of follow-up from an intention-to-treat perspective. Missing data were addressed using multiple imputation. Incremental cost-effectiveness ratios were calculated with uncertainty characterized using non-parametric bootstrapping. Results were extrapolated beyond 10 years using Gompertz functions for survival and linear models for total cost and utility. Total mean costs at 10 years of follow-up were £17 594 in the BITA arm and £16 462 in the SITA arm [mean difference £1133 95% confidence interval (CI) £239 to £2026, P = 0.015]. Total mean QALYs at 10 years were 6.54 in the BITA arm and 6.57 in the SITA arm (adjusted mean difference -0.01 95% CI -0.2 to 0.1, P = 0.883). At 10 years, BITA grafting had a 33% probability of being cost-effective compared to SITA, assuming a cost-effectiveness threshold of £20 000. Lifetime extrapolation increased the probability of BITA being cost-effective to 51%. CONCLUSIONS: BITA grafting has significantly higher costs but similar quality-adjusted survival at 10 years compared to SITA grafting. Extrapolation suggests this could change over lifetime.

Effect of total arterial grafting in the Arterial Revascularization Trial.

OBJECTIVES: The Arterial Revascularization Trial (ART) was designed to compare 10-year survival in bilateral versus single internal thoracic artery grafts. The intention-to-treat analysis has showed comparable outcomes between the 2 groups but an explanatory analysis suggested that those receiving 2 or more arterial grafts had better survival. Whether the exclusive use of arterial grafts provide further benefit is unclear. METHODS: We performed an exploratory analysis of the ART based on conduits actually received (as-treated principle). From ART cohort, only patients receiving at least 3 grafts were included. The final population consisted of 1084, 1010, and 390 patients in the single arterial graft (SAG) group, in the multiple arterial graft (MAG) group (2 or more arterial grafts with additional saphenous veins) and total arterial graft (TAG) group (3 or more arterial grafts only) respectively. Inverse probability of treatment weighting was used for comparison. RESULTS: When compared with the SAG group, there was a significant trend toward a reduction of 10-year mortality in the MAG and TAG group (test for trend P = .02). The TAG group was associated with the lowest risk of late mortality (hazard ratio, 0.68; 95% confidence interval, 0.48-0.96; P = .03) and with a significant risk reduction of the composite of death/myocardial infarction/stroke and repeat revascularization (hazard ratio, 0.71; 95% confidence interval, 0.53-0.94; P = .02). CONCLUSIONS: When compared with SAG, both MAG and TAG represent valuable strategies to improve clinical outcomes following coronary artery bypass grafting but TAG can potentially provide further benefit.

Randomized trial to compare bilateral vs. single internal mammary coronary artery bypass grafting: 1-year results of the Arterial Revascularisation Trial (ART).

AIMS: Observational data suggest that the use of bilateral internal mammary arteries (BIMA) during coronary artery bypass graft surgery provides superior revascularization to a single internal mammary artery (SIMA), but concerns about safety have prevented the widespread use of BIMA. The Arterial Revascularisation Trial (ART) is a randomized trial of BIMA vs. SIMA, with a primary outcome of survival at 10 years. This paper reports mortality, morbidity, and resource use data at 1 year. METHODS AND RESULTS: Coronary artery bypass graft patients were enrolled in 28 hospitals in seven countries. Three thousand one hundred and two patients were randomly assigned to SIMA (n = 1554) or BIMA (n = 1548). The mean number of grafts was 3 for both groups. Forty per cent of the SIMA procedures and 42% of the BIMA were performed off-pump. Mortality at 30 days was 18 of 1548 (1.2%) for SIMA and 19 of 1537 (1.2%) for BIMA, and at 1 year was 36 of 1540 (2.3%) and 38 of 1529 (2.5%), respectively. The rates of stroke, myocardial infarction, and repeat revascularization were all ≤2% at 1 year and similar between the two groups. Sternal wound reconstruction was required in 0.6 and 1.9% of the SIMA and BIMA groups, respectively. CONCLUSION: Data from ART demonstrate similar clinical outcomes for SIMA and BIMA at 1 year but BIMA grafts are associated with a small absolute increase (1.3%) in the need for sternal wound reconstruction. The results suggest that the use of BIMA grafts is feasible on a routine basis. The 10-year results of the ART will confirm whether BIMA grafting results in lower mortality and the need for repeat intervention. TRIAL REGISTRATION: Controlled-trials.com (ISRCTN46552265).

Ten-year outcomes after off-pump versus on-pump coronary artery bypass grafting: Insights from the Arterial Revascularization Trial.

OBJECTIVE: We performed a post hoc analysis of the Arterial Revascularization Trial to compare 10-year outcomes after off-pump versus on-pump surgery. METHODS: Among 3102 patients enrolled, 1252 (40% of total) and 1699 patients received off-pump and on-pump surgery (151 patients were excluded because of other reasons); 2792 patients (95%) completed 10-year follow-up. Propensity matching and mixed-effect Cox model were used to compare long-term outcomes. Interaction term analysis was used to determine whether bilateral internal thoracic artery grafting was a significant effect modifier. RESULTS: One thousand seventy-eight matched pairs were selected for comparison. A total of 27 patients (2.5%) in the off-pump group required conversion to on-pump surgery. The off-pump and on-pump groups received a similar number of grafts (3.2 ± 0.89 vs 3.1 ± 0.8; P = .88). At 10 years, when compared with on-pump, there was no significant difference in death (adjusted hazard ratio for off-pump, 1.1; 95% confidence interval, 0.84-1.4; P = .54) or the composite of death, myocardial infarction, stroke, and repeat revascularization (adjusted hazard ratio, 0.92; 95% confidence interval, 0.72-1.2; P = .47). However, off-pump surgery performed by low volume off-pump surgeons was associated with a significantly lower number of grafts, increased conversion rates, and increased cardiovascular death (hazard ratio, 2.39; 95% confidence interval, 1.28-4.47; P = .006) when compared with on-pump surgery performed by on-pump-only surgeons. CONCLUSIONS: The findings showed that in the Arterial Revascularization Trial, off-pump and on-pump techniques achieved comparable long-term outcomes. However, when off-pump surgery was performed by low-volume surgeons, it was associated with a lower number of grafts, increased conversion, and a higher risk of cardiovascular death.

Association of Age With 10-Year Outcomes After Coronary Surgery in the Arterial Revascularization Trial.

BACKGROUND: The association of age with the outcomes of bilateral internal thoracic arteries (BITAs) versus single internal thoracic arteries (SITAs) for coronary bypass grafting (CABG) remains to be determined. OBJECTIVES: The purpose of this study was to evaluate the association between age and BITA versus SITA outcomes in the Arterial Revascularization Trial. METHODS: The primary endpoints were all-cause mortality and a composite of major adverse events, including all-cause mortality, myocardial infarction, or stroke. Secondary endpoints were bleeding complications and sternal wound complications up to 6 months after surgery. Multivariable fractional polynomials analysis and log-rank tests were used. RESULTS: Age did not affect any of the explored outcomes in the overall BITA versus SITA comparison in the intention-to-treat analysis and in the analysis based on the number of arterial grafts received. However, when the intention-to-treat analysis was restricted to the populations of patients between age 50 and 70 years, younger patients in the BITA arm had a significantly lower incidence of major adverse events (p = 0.03). CONCLUSIONS: Our results suggest that BITA may improve long-term outcome in younger patients, although more randomized data are needed to confirm this hypothesis.

Comparison of Long-term Clinical Outcomes of Skeletonized vs Pedicled Internal Thoracic Artery Harvesting Techniques in the Arterial Revascularization Trial.

Importance: Recent evidence has suggested that skeletonization of the internal thoracic artery (ITA) is associated with worse clinical outcomes in patients undergoing coronary artery bypass surgery (CABG). Objective: To compare the long-term clinical outcomes of skeletonized and pedicled ITA for CABG. Design, Setting, and Participants: The Arterial Revascularization Trial (ART) was a 2-group, multicenter trial comparing the use of a bilateral ITA vs a single ITA for CABG at 10 years. Patients in the ART trial were stratified by ITA harvesting technique: skeletonized vs pedicled. Data were collected from June 2004 to December 2017, and data were analyzed from June to July 2021. Interventions: In this analysis, the 10-year clinical outcomes were compared between patients who received skeletonized vs pedicled ITAs. Main Outcomes and Measures: The primary outcome was all-cause mortality. The secondary outcomes were a composite of major adverse cardiac events (MACE) including all-cause mortality, myocardial infarction, and repeated revascularization and a composite including MACE and sternal wound complication (SWC). Cox regression and propensity score matching were used. Results: Of 2161 included patients, 295 (13.7%) were female, and the median (interquartile range) age was 65.0 (58.0-70.0) years. At 10 years, the risk of all-cause mortality was not significantly different between the pedicled and skeletonized groups (hazard ratio [HR], 1.12; 95% CI, 0.92-1.36; P = .27). However, the long-term risks of the secondary outcomes were significantly higher in the skeletonized group compared with the pedicled group (MACE: HR, 1.25; 95% CI, 1.06-1.47; P = .01; MACE and SWC: HR, 1.22; 95% CI, 1.05-1.43; P = .01). The difference was not seen when considering only patients operated on by surgeons who enrolled 51 patients or more in the trial (MACE: HR, 1.07; 95% CI, 0.82-1.39; P = .62; MACE and SWC: HR, 1.04; 95% CI, 0.80-1.34; P = .78). Conclusions and Relevance: While the long-term survival of patients was not different between groups, the rate of adverse cardiovascular events was consistently higher in the skeletonized group and the difference was associated with surgeon-related factors. Further evidence on the outcome of skeletonized ITA is needed.

Pulmonary Metastasectomy versus Continued Active Monitoring in Colorectal Cancer (PulMiCC): a multicentre randomised clinical trial.

BACKGROUND: Lung metastasectomy in the treatment of advanced colorectal cancer has been widely adopted without good evidence of survival or palliative benefit. We aimed to test its effectiveness in a randomised controlled trial (RCT). METHODS: Multidisciplinary teams in 13 hospitals recruited participants with potentially resectable lung metastases to a multicentre, two-arm RCT comparing active monitoring with or without metastasectomy. Other local or systemic treatments were decided by the local team. Randomisation was remote and stratified by site with minimisation for age, sex, primary cancer stage, interval since primary resection, prior liver involvement, the number of metastases, and carcinoembryonic antigen level. The central Trial Management Group were blind to patient allocation until completion of the analysis. Analysis was on intention to treat with a margin for non-inferiority of 10%. RESULTS: Between December 2010 and December 2016, 65 participants were randomised. Characteristics were well-matched in the two arms and similar to those in reported studies: age 35 to 86 years (interquartile range (IQR) 60 to 74); primary resection IQR 16 to 35 months previously; stage at resection T1, 2 or 3 in 3, 8 and 46; N1 or N2 in 31 and 26; unknown in 8. Lung metastases 1 to 5 (median 2); 16/65 had previous liver metastases; carcinoembryonic antigen normal in 55/65. There were no other interventions in the first 6 months, no crossovers from control to treatment, and no treatment-related deaths or major adverse events. The Hazard ratio for death within 5 years, comparing metastasectomy with control, was 0.82 (95%CI 0.43, 1.56). CONCLUSIONS: Because of poor and worsening recruitment, the study was stopped. The small number of participants in the trial (N = 65) precludes a conclusive answer to the research question given the large overlap in the confidence intervals in the proportions still alive at all time points. A widely held belief is that the 5-year absolute survival benefit with metastasectomy is about 35%: 40% after metastasectomy compared to < 5% in controls. The estimated survival in this study was 38% (23-62%) for metastasectomy patients and 29% (16-52%) in the well-matched controls. That is the new and important finding of this RCT. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT01106261. Registered on 19 April 2010.

Five-year costs from a randomised comparison of bilateral and single internal thoracic artery grafts.

BACKGROUND: The use of bilateral internal thoracic arteries (BITA) for coronary artery bypass grafting (CABG) may improve survival compared with CABG using single internal thoracic arteries (SITA). We assessed the long-term costs of BITA compared with SITA. METHODS: Between June 2004 and December 2007, 3102 patients from 28 hospitals in seven countries were randomised to CABG surgery using BITA (n=1548) or SITA (n=1554). Detailed resource use data were collected from the initial hospital episode and annually up to 5 years. The associated costs of this resource use were assessed from a UK perspective with 5 year totals calculated for each trial arm and pre-selected patient subgroups. RESULTS: Total costs increased by approximately £1000 annually in each arm, with no significant annual difference between trial arms. Cumulative costs per patient at 5-year follow-up remained significantly higher in the BITA group (£18 629) compared with the SITA group (£17 480; mean cost difference £1149, 95% CI £330 to £1968, p=0.006) due to the higher costs of the initial procedure. There were no significant differences between the trial arms in the cost associated with healthcare contacts, medication use or serious adverse events. CONCLUSIONS: Higher index costs for BITA were still present at 5-year follow-up mainly driven by the higher initial cost with no subsequent difference emerging between 1 year and 5 years of follow-up. The overall cost-effectiveness of the two procedures, to be assessed at the primary endpoint of the 10-year follow-up, will depend on composite differences in costs and quality-adjusted survival. TRIAL REGISTRATION NUMBER: ISRCTN46552265.