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Background The SYNTAX trial demonstrated negative impact of repeat revascularization (RR) on 5-year outcomes following PCI/CABG in patients with three-vessel(3VD) and/or left main coronary artery disease(LMCAD). We aimed to investigate the impact of RR within 5 years, on 10-year mortality in patients with 3VD and/or LMCAD after PCI/CABG. Methods The SYNTAXES study evaluated the vital status out to 10 years of patients with 3VD and/or LMCAD. Patients were stratified by RR within 5 years and randomized treatment. The association between RR within 5 years and 10-year mortality was assessed. Results A total of 330 out of 1800 patients (18.3%) underwent RR within 5 years. RR occurred more frequently after initial PCI than after initial CABG (25.9% vs. 13.7%, p 0.001). Overall, 10-year mortality was comparable between patients undergoing RR and those not (28.2% vs. 26.1%, adjusted HR: 1.17, 95%CI 0.93–1.48, p = 0.187). In the PCI arm, RR was associated with a trend toward higher 10-year mortality (adjusted HR: 1.29, 95%CI 0.97–1.72, p = 0.075), while in the CABG arm, the trend was opposite (adjusted HR: 0.74, 95%CI 0.46–1.20, p = 0.219). Among patients requiring RR, those who underwent PCI as initial revascularization had a higher risk of 10-year mortality compared to initial CABG (33.5% vs. 17.6%, adjusted HR: 2.09, 95%CI 1.21–3.61, p = 0.008). Conclusion In the SYNTAXES study, RR within 5 years had no impact on 10-year all-cause death in the population overall. Among patients requiring any repeat procedures, 10-year mortality was higher after initial treatment with PCI than after CABG. These exploratory findings should be investigated with larger populations in future studies. Trial registration URL: https://www.clinicaltrials.gov; SYNTAXES Unique identifier: NCT03417050. URL: https://www.clinicaltrials.gov; SYNTAX Unique identifier: NCT00114972. Graphical abstract

ObjectiveWe sought to investigate whether long-term clinical outcomes differ following percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in patients with three-vessel disease (3VD) and lesions in the proximal left anterior descending artery (P-LAD).MethodsThis post-hoc analysis of the Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) Extended Survival study included patients with 3VD who were classified according to the presence or absence of lesions located in the P-LAD. Ten-year all-cause death and 5-year major adverse cardiac or cerebrovascular events (MACCE) were assessed.ResultsAmong 1088 patients with 3VD, 559 (51.4%) had involvement of P-LAD and their 10-year mortality was numerically higher following PCI versus CABG (28.9% vs 21.9%; HR: 1.39, 95% CI 0.99 to 1.95). Although patients without P-LAD lesions had significantly higher 10-year mortality following PCI compared with CABG, there was no evidence of a treatment-by-subgroup interaction (28.8% vs 20.2%; HR: 1.47, 95% CI 1.03 to 2.09, pinteraction=0.837). The incidence of MACCE at 5 years was significantly higher with PCI than CABG, irrespective of involvement of P-LAD (with P-LAD: HR: 1.86, 95% CI 1.36 to 2.55; without P-LAD: HR: 1.54, 95% CI 1.11 to 2.12; pinteraction=0.408). Individualised assessment using the SYNTAX Score II 2020 established that a quarter of patients with P-LAD lesions had significantly higher mortality with PCI than CABG, whereas in the remaining three-quarters CABG had similar mortality.ConclusionsAmong patients with 3VD, the presence or absence of a P-LAD lesion was not associated with any treatment effect on long-term outcomes following PCI or CABG.Trial registration numberSYNTAXES:NCT03417050; SYNTAX:NCT00114972.

Background Creatinine clearance (CrCl) is an independent determinant of mortality in predictive models of revascularisation outcomes for complex coronary artery disease. Aims This study aimed to investigate the impact of preprocedural biological markers on 10-year mortality following coronary revascularisation. Methods The SYNTAX Extended Survival (SYNTAXES) study evaluated the 10-year vital status follow-up of 1,800 patients with de novo three-vessel (3VD) and/or left main coronary artery disease (LMCAD) randomised to include percutaneous or surgical coronary revascularisation. The associations between mortality and preprocedural C-reactive protein (CRP), haemoglobin, HbA1c, CrCl, fasting triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were analysed. Results Out of 1,800 patients, 460 patients died before the 10-year follow-up. CRP, HbA1c and CrCl with threshold values of ≥2 mg/L, ≥6% (42 mmol/mol) and l60 ml/min, respectively, were associated with 10-year all-cause death (adjusted hazard ratio [95% confidence interval]: 1.35 [1.01-1.82], 1.51 [1.16-1.95], and 1.46 [1.07-2.00], respectively). There was no significant interaction between the biological markers on all-cause mortality and the type of revascularisation. Preprocedural lipid markers were not significantly associated with 10-year all-cause death, but the non-use of statins was a determinant factor of worse prognosis (adjusted confidence interval [95% confidence interval]: 1.68 [1.26-2.25]). Conclusions Preprocedural biomarkers, such as CRP and HbA1c, are associated with long-term mortality post revascularisation, regardless of the revascularisation technique. Conventional lipidic biomarkers associated with high-risk of cardiovascular events seem to be effectively mitigated by the long-term use of statins, whereas the non-use of statins was a factor of a worse prognosis, emphasising the importance of pharmacological treatment. Trial registration SYNTAXES ClinicalTrials.gov reference: NCT03417050. SYNTAX ClinicalTrials.gov reference: NCT00114972.

Background The EXCEL trial reported similar five-year rates of the primary composite outcome of death, myocardial infarction (MI), or stroke after percutaneous coronary intervention (PCI) compared with coronary artery bypass grafting (CABG) for treatment of obstructive left main coronary artery disease (LMCAD). Aims We sought to determine whether these outcomes remained consistent regardless of geography of enrolment. Methods We performed a pre-specified subgroup analysis based on regional enrolment. Results Among 1,905 patients randomised to PCI (n=948) or CABG (n=957), 1,075 (56.4%) were recruited at 52 European Union (EU) centres, and 752 (39.5%) were recruited at 67 North American (NA) centres. EU versus NA patients varied according to numerous baseline demographics, anatomy, pharmacotherapy and procedural characteristics. Nonetheless, the relative rates of the primary endpoint after PCI versus CABG were consistent across EU versus NA centres at 30 days and 5 years. However, NA participants had substantially higher late rates of ischaemia-driven revascularisation (IDR) after PCI, driven predominantly by the need for greater target vessel and lesion revascularisation. This culminated in a significant difference in the relative risk of the secondary composite outcome of death, MI, stroke, or IDR at 5 years (pinteraction=0.02). Conclusions In the EXCEL trial, the relative risks for the 30-day and five-year primary composite outcome of death, MI or stroke after PCI versus CABG were consistent irrespective of geography. However, five-year rates of IDR after PCI were significantly higher in NA centres, a finding the Heart Team and patients should consider when making treatment decisions. ClinicalTrials.gov identifier: NCT01205776.

Aim The aim of this study was to compare long-term all-cause mortality between patients receiving percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) using multiple (MAG) or single arterial grafting (SAG). Methods and results The current study is a post hoc analysis of the SYNTAX Extended Survival Study, which compared PCI with CABG in patients with three-vessel (3VD) and/or left main coronary artery disease (LMCAD) and evaluated survival with ≥10 years of follow-up. The primary endpoint was all-cause mortality at maximum follow-up (median 11.9 years) assessed in the as-treated population. Of the 1743 patients, 901 (51.7%) underwent PCI, 532 (30.5%) received SAG, and 310 (17.8%) had MAG. At maximum follow-up, all-cause death occurred in 305 (33.9%), 175 (32.9%), and 70 (22.6%) patients in the PCI, SAG, and MAG groups, respectively (P Conclusion Our findings suggest that MAG might be the more desirable configuration for CABG to achieve lower long-term all-cause mortality than PCI in patients with 3VD and/or LMCAD. Trial registration Registered on clinicaltrial.gov. SYNTAXES: NCT03417050 (https://clinicaltrials.gov/ct2/show/NCT03417050); SYNTAX: NCT00114972 (https://www.clinicaltrials.gov/ct2/show/NCT00114972).

Background: The significant interaction between major infection and 5-year mortality after percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) for complex coronary artery disease (CAD) was observed previously. However, the very long-term outcomes beyond 5 years remains unclear. Methods and results: This is a subgroup analysis of the SYNTAX Extended Survival (SYNTAXES) trial, which is the extended follow-up of the randomized SYNTAX trial comparing PCI versus CABG in patients with three-vessel disease (3VD) or left-main CAD (LMCAD). Out of 1517 patients enrolled in the SYNTAX trial with available survival status from 5 to 10 years, 140 patients had experienced major infections and survived at 5 years (major infection group). From 5 to 10 years, the mortality of major infection group was 19.8% whereas the mortality of no major infection group was 15.1% (p = 0.157). After the adjustment of other clinical factors, the risk of mortality from 5 to 10 years did not significantly differ between major infection and no major infection groups (HR: 1.10; 95% CI: 0.62–1.96; p = 0.740). When stratified by the presence or absence of periprocedural major infections, defined as a major infection within 60 days after index procedure, there was also no significant difference in 10-year mortality between two groups (30.8% vs. 24.5%; p = 0.057). Conclusions: Despite the initial association between major infections and 5 years mortality, postprocedural major infection was not evident in the 10 years follow-up, suggesting that the impact of major infection on mortality subsided over time beyond 5 years. Trial registration: SYNTAXES ClinicalTrials.gov reference: NCT03417050 SYNTAX ClinicalTrials.gov reference: NCT00114972

Aims The aim of this article was to compare rates of all-cause death at 10 years following coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) in patients with or without diabetes. Methods and results The SYNTAXES study evaluated up to 10-year survival of 1800 patients with three-vessel disease (3VD) and/or left main coronary artery disease (LMCAD) randomized to receive either PCI or CABG in the SYNTAX trial. Ten-year all-cause death according to diabetic status and revascularization strategy was examined. In diabetics (n = 452), the risk of mortality was numerically higher with PCI compared with CABG at 5 years [19.6% vs. 13.3%, hazard ratio (HR): 1.53, 95% confidence interval (CI): 0.96, 2.43, P = 0.075], with the opposite seen between 5 and 10 years (PCI vs. CABG: 20.8% vs. 24.4%, HR: 0.82, 95% CI: 0.52, 1.27, P = 0.366). Irrespective of diabetic status, there was no significant difference in all-cause death at 10 years between patients receiving PCI or CABG, the absolute treatment difference was 1.9% in diabetics (PCI vs. CABG: 36.4% vs. 34.5%, difference: 1.9%, 95% CI: −7.6%, 11.1%, P = 0.551). Among insulin-treated patients (n = 182), all-cause death at 10 years was numerically higher with PCI (47.9% vs. 39.6%, difference: 8.2%, 95% CI: −6.5%, 22.5%, P = 0.227). Conclusions The treatment effects of PCI vs. CABG on all-cause death at 10 years in patients with 3VD and/or LMCAD were similar irrespective of the presence of diabetes. There may, however, be a survival benefit with CABG in patients with insulin-treated diabetes. The association between revascularization strategy and very long-term ischaemic and safety outcomes for patients with diabetes needs further investigation in dedicated trials. Trial registration SYNTAX: ClinicalTrials.gov reference: NCT00114972 and SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050., Graphical Abstract The treatment effects of PCI versus CABG on all-cause death at 10 years in 3VD/LMCAD patients with pharmacologically treated diabetes and insulin-treated diabetes.

Numerous studies have demonstrated a paradoxical association between higher baseline body mass index (BMI) and lower long-term mortality risk after coronary revascularization, known as the “obesity paradox”, possibly relying on the single use of BMI. The current study is a post-hoc analysis of the SYNTAX Extended Survival (SYNTAXES) trial, which is the extended follow-up of the SYNTAX trial comparing percutaneous coronary intervention (PCI) versus coronary artery bypass graft (CABG) in patients with left-main coronary artery disease (LMCAD) or three-vessel disease (3VD). Patients were stratified according to baseline BMI and/or waist circumference (WC). Out of 1,800 patients, 1,799 (99.9%) and 1,587 (88.2%) had available baseline BMI and WC data, respectively. Of those, 1,327 (73.8%) patients had High BMI (≥25 kg/m2), whereas 705 (44.4%) patients had High WC (>102 cm for men or >88 cm for women). When stratified by both BMI and WC, 10-year mortality risk was significantly higher in patients with Low BMI/Low WC (adjusted hazard ratio [HR]: 1.65; 95% confidence interval [CI]: 1.09 to 2.51), Low BMI/ High WC (adjusted HR: 2.74; 95% CI: 1.12 to 6.69), or High BMI/High WC (adjusted HR: 1.59; 95% CI: 1.11 to 2.27) compared to those with High BMI/Low WC. In conclusion, the “obesity paradox” following coronary revascularization would be driven by low long-term mortality risk of the High BMI/Low WC group. Body composition should be assessed by the combination of BMI and WC in the appropriate evaluation of the long-term risk of obesity in patients with LMCAD or 3VD.

Background: The benefit of optimal medical therapy (OMT) on 5-year outcomes in patients with 3-vessel disease and/or left main disease after percutaneous coronary intervention or coronary artery bypass grafting (CABG) was demonstrated in the randomized SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) trial. Objectives: The objective of this analysis is to assess the impact of the status of OMT at 5 years on 10-year mortality after percutaneous coronary intervention or CABG. Methods: This is a subanalysis of the SYNTAXES (Synergy Between PCI With Taxus and Cardiac Surgery Extended Survival) study, which evaluated for up to 10 years the vital status of patients who were originally enrolled in the SYNTAX trial. OMT was defined as the combination of 4 types of medications: at least 1 antiplatelet drug, statin, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and beta-blocker. After stratifying participants by the number of individual OMT agents at 5 years and randomized treatment, a landmark analysis was conducted to assess the association between treatment response and 10-year mortality. Results: In 1,472 patients, patients on OMT at 5 years had a significantly lower mortality at 10 years compared with those on ≤2 types of medications (13.1% vs 19.9%; adjusted HR: 0.470; 95% CI: 0.292-0.757; P = 0.002) but had a mortality similar to those on 3 types of medications. Furthermore, patients undergoing CABG with the individual OMT agents, antiplatelet drug and statin, at 5 years had lower 10-year mortality than those without. Conclusions: In patients with 3-vessel and/or left main disease undergoing percutaneous coronary intervention or CABG, medication status at 5 years had a significant impact on 10-year mortality. Patients on OMT with guideline-recommended pharmacologic therapy at 5 years had a survival benefit. (Synergy Between PCI With Taxus and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]; NCT03417050; Taxus Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972)

Background: The optimal revascularization strategy for the elderly with complex coronary artery disease remains unclear. Objectives: The goal of this study was to investigate 10-year all-cause mortality, life expectancy, 5-year major adverse cardiac or cerebrovascular events (MACCE), and 5-year quality of life (QOL) after percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) in elderly individuals (>70 years old) with 3-vessel disease (3VD) and/or left main disease (LMD). Methods: In the present pre-specified analysis on age of the SYNTAX Extended Survival study, 10-year all-cause death and 5-year MACCE were compared with Kaplan-Meier estimates and Cox proportional hazards models among elderly or nonelderly patients. Life expectancy was estimated by restricted mean survival time within 10 years, and QOL status according to the Seattle Angina Questionnaire up to 5 years was assessed by linear mixed-effects models. Results: Among 1,800 randomized patients, 575 patients (31.9%) were elderly. Ten-year mortality did not differ significantly between PCI and CABG in elderly (44.1% vs. 41.1%; hazard ratio [HR]: 1.08; 95% confidence interval [CI]: 0.84 to 1.40) and nonelderly patients (21.1% vs. 16.6%; HR: 1.30; 95% CI: 1.00 to 1.69; pinteraction = 0.332). Among elderly patients, 5-year MACCE was comparable between PCI and CABG (39.4% vs. 35.1%; HR: 1.18; 95% CI: 0.90 to 1.56), whereas it was significantly higher in PCI over CABG among nonelderly patients (36.3% vs. 23.0%; HR: 1.69; 95% CI: 1.36 to 2.10; pinteraction = 0.043). There were no significant difference in life expectancy (mean difference: 0.2 years in favor of CABG; 95% CI: −0.4 to 0.7) and 5-year QOL status between PCI and CABG among elderly patients. Conclusions: Elderly patients with 3VD and/or LMD had comparable 10-year all-cause death, life expectancy, 5-year MACCE, and 5-year QOL status irrespective of revascularization mode. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]; NCT03417050) (SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972)

Background: There is a paucity of data regarding the effect of inhibition of the renin-angiotensin system on outcomes after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). We sought to examine long-term outcomes of patients with left main coronary disease (LMCAD) randomized to PCI with fluoropolymer-based cobalt-chromium everolimus-eluting stents or CABG according to treatment at discharge with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) in the large-scale, multicenter, randomized EXCEL trial. Methods: EXCEL randomized 1905 patients with LMCAD of low and intermediate anatomical complexity (visually-assessed SYNTAX score ≤32) to PCI (n = 948) versus CABG (n = 957). Patients were categorized according to whether they were treated with ACEI/ARB at discharge; their outcomes from discharge to 5 years were examined using multivariable logistic regression with an offset for follow-up time. Results: Among 1775 patients discharged alive with known ACEI/ARB treatment status, 896 (50.5%) were treated with one of these agents. Among those treated with ACEI/ARB, the 5-year rate of all-cause death was similar after PCI or CABG (10.7% versus 9.8% respectively, adjOR, 0.94; 95% CI, 0.56-1.57) in contrast to patients not treated with ACEI/ARB (15.0% versus 7.8%, respectively, adjOR, 2.20; 95% CI, 1.32-3.67) (Pinteraction = 0.02). Significant interactions between treatment arm (PCI versus CABG) and ACEI/ARB treatment status were also found for cardiovascular death (Pinteraction = 0.03), ischemia-driven revascularization (Pinteraction = 0.03), target vessel revascularization (Pinteraction = 0.007) and target vessel failure (Pinteraction = 0.0009). Conclusion: In the EXCEL trial, the postdischarge rates of death and revascularization after 5 years were similar after PCI and CABG in patients with LMCAD treated with ACEI/ARB at discharge. In contrast, event rates were higher after PCI versus CABG in those not so treated.

Objectives: We investigated the impact of total stent length (TSL) and average nominal stent diameter (ASD) on 10-year mortality after percutaneous coronary intervention (PCI) in the SYNTAXES trial. Background: TSL and ASD in patients treated with PCI are associated with major adverse cardiovascular events. However, the treatment effect of PCI with extensive and/or small stenting as compared with coronary artery bypass grafting (CABG) for complex coronary artery disease has not been fully evaluated. Methods: Impacts on mortality of extensive stenting defined as TSL >100 mm and small stenting as ASD

Prior studies in patients with noncomplex coronary artery disease have demonstrated the safety of percutaneous coronary intervention (PCI) in the outpatient setting. We sought to examine the outcomes of outpatient PCI in patients with unprotected left main coronary artery disease (LMCAD). In the EXCEL trial, 1905 patients with LMCAD and site-assessed low or intermediate SYNTAX scores were randomized to PCI with everolimus-eluting stents versus coronary artery bypass grafting. The primary end point was major adverse cardiovascular events (MACE; the composite of death, stroke, or myocardial infarction). In this sub-analysis, outcomes at 30 days and 5 years were analyzed according to whether PCI was performed in the outpatient versus inpatient setting. Among 948 patients with LMCAD assigned to PCI, 935 patients underwent PCI as their first procedure, including 100 (10.7%) performed in the outpatient setting. Patients who underwent outpatient compared with inpatient PCI were less likely to have experienced recent myocardial infarction. Distal left main bifurcation disease involvement and SYNTAX scores were similar between the groups. Comparing outpatient to inpatient PCI, there were no significant differences in MACE at 30 days (4.0% vs 5.0% respectively, adjusted OR 0.52 95% CI 0.12 to 2.22; p = 0.38) or 5 years (20.6% vs 22.1% respectively, adjusted OR 0.72, 95% CI 0.40 to 1.29; p = 0.27). Similar results were observed in patients with distal left main bifurcation lesions. In conclusion, in the EXCEL trial, outpatient PCI of patients with LMCAD was not associated with an excess early or late hazard of MACE. These data suggest that outpatient PCI may be safely performed in select patients with LMCAD.

Background: The long-term clinical benefit after percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in patients with total occlusions (TOs) and complex coronary artery disease has not yet been clarified. Objectives: The objective of this analysis was to assess 10-year all-cause mortality in patients with TOs undergoing PCI or CABG. Methods: This is a subanalysis of patients with at least 1 TO in the SYNTAXES (Synergy Between PCI With Taxus and Cardiac Surgery Extended Survival) study, which investigated 10-year all-cause mortality in the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) trial, beyond its original 5-year follow-up. Patients with TOs were further stratified according to the status of TO recanalization or revascularization. Results: Of 1,800 randomized patients to the PCI or CABG arm, 460 patients had at least 1 lesion of TO. In patients with TOs, the status of TO recanalization or revascularization was not associated with 10-year all-cause mortality, irrespective of the assigned treatment (PCI arm: 29.9% vs. 29.4%; adjusted hazard ratio [HR]: 0.992; 95% confidence interval [CI]: 0.474 to 2.075; p = 0.982; and CABG arm: 28.0% vs. 21.4%; adjusted HR: 0.656; 95% CI: 0.281 to 1.533; p = 0.330). When TOs existed in left main and/or left anterior descending artery, the status of TO recanalization or revascularization did not have an impact on the mortality (34.5% vs. 26.9%; adjusted HR: 0.896; 95% CI: 0.314 to 2.555; p = 0.837). Conclusions: At 10-year follow-up, the status of TO recanalization or revascularization did not affect mortality, irrespective of the assigned treatment and location of TOs. The present study might support contemporary practice among high-volume chronic TO-PCI centers where recanalization is primarily offered to patients for the management of angina refractory to medical therapy when myocardial viability is confirmed. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]; NCT03417050; SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972)

Aims To evaluate the impact of various smoking status on 10-year all-cause mortality and to examine a relative treatment benefit of coronary artery bypass grafting (CABG) vs. percutaneous coronary intervention (PCI) according to smoking habits. Methods and results The SYNTAX Extended Survival study evaluated vital status up to 10 years in 1800 patients with de novo three-vessel disease and/or left main coronary artery disease randomized to CABG or PCI in the SYNTAX trial. In the present analysis, patients were divided into three groups (current, former, or never smokers), and the primary endpoint of 10-year all-cause mortality was assessed according to smoking status. Smoking status was available in 1793 (99.6%) patients at the time of randomization, of whom 363 were current smokers, 798 were former smokers, and 632 were never smokers. The crude rates of 10-year all-cause mortality were 29.7% in current smokers, 25.3% in former smokers, and 25.9% in never smokers (Log-rank P = 0.343). After adjustment for imbalances in baseline characteristics, current smokers had a significantly higher risk of 10-year all-cause mortality than never smokers [adjusted hazard ratio (aHR): 2.29; 95% confidence interval (CI): 1.60–3.27; P Conclusion Current smokers had a higher adjusted risk of 10-year all-cause mortality, whereas former smokers did not. The treatment effect of CABG vs. PCI did not differ significantly according to smoking status. Clinical trial registration SYNTAX: ClinicalTrials.gov reference: NCT00114972; SYNTAX Extended Survival. ClinicalTrials.gov reference: NCT03417050.

Objective It remains unclear how often coronary revascularization is necessary after aortic valve interventions, either by surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement. However, these data are relevant for treatment and prosthesis choice. The authors sought to analyze the incidence and characteristics of coronary revascularization after SAVR during follow-up. Methods Of 2256 patients undergoing isolated SAVR between 1987 and 2015, 420 patients (mean age 56.9 ± 15.5 years, 66.9% male) were followed at the Erasmus Medical Center. Incidence, predictors, and characteristics of coronary revascularization were analyzed. Cumulative incidence of revascularization was assessed using a competing risk approach. Results Mean follow-up after SAVR was 17.2 years (total of 4541 patient-years). A total of 24 patients underwent 28 procedures of revascularization. The cumulative incidence of revascularization after SAVR was 0.5%, 2.2%, 4.1%, and 6.9% at 1, 5, 10, and 20 years, respectively. The linearized rate of revascularization was 6.2 per 1000 patient-years. Percutaneous coronary intervention was the most common revascularization method (64%; N = 18/28). Revascularization before SAVR (N = 36/420; of whom 27 percutaneous coronary intervention) was an independent predictor of revascularization during follow-up (hazard ratio, 6.6; 95% confidence interval, 2.6-17.1; P Conclusions After SAVR, the rate of coronary revascularization was 6.9% (N = 24/420) at 20-year follow-up. Patients were at particular risk if they had undergone previous revascularization before SAVR. These data may furthermore be relevant to the transcatheter aortic valve replacement population.

Background: The poorer prognosis of coronary artery disease in females compared with males is related mainly to differences in baseline characteristics. In the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) trial, the effect of treatment with percutaneous coronary intervention (PCI) versus coronary artery bypass grafting surgery (CABG) on mortality at 5 years differed significantly between females and males; however, the optimal revascularization beyond 5 years according to sex has not been evaluated. Objectives: The aim of this study was to investigate the impact of sex on mortality and sex-treatment interaction at 10 years. Methods: The SYNTAXES (SYNTAX Extended Survival) study evaluated vital status up to 10 years in 1,800 patients with de novo 3-vessel and/or left main coronary artery disease randomized to treatment with PCI or CABG in the SYNTAX trial. All-cause death at 10 years was separately evaluated in female and male patients with complex coronary artery disease. Results: Of 1,800 patients, 402 (22.3%) were female and 1,398 (77.7%) were males. Females had a higher 10-year mortality rate compared with males (32.8% vs. 24.7%; log-rank p = 0.002), but female sex was not an independent predictor of mortality (adjusted hazard ratio: 1.02; 95% confidence interval: 0.76 to 1.36). Mortality at 10 years tended to be lower after CABG than after PCI, with a similar treatment effect for female and male patients (adjusted hazard ratio for females: 0.90 [95% confidence interval: 0.54 to 1.51]; adjusted hazard ratio for males: 0.76 [95% confidence interval: 0.56 to 1.02]; p for interaction = 0.952). Conclusions: Female sex was not an independent predictor of mortality at 10 years in patients with complex coronary artery disease. The interaction between sex and treatment with PCI or CABG that was observed at 5 years was no longer present at 10 years. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES], NCT03417050; SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX], NCT00114972)

Aims Indexed effective orifice area (EOAi) charts are used to determine the likelihood of prosthesis–patient mismatch (PPM) after aortic valve replacement (AVR). The aim of this study is to validate whether these EOAi charts, based on echocardiographic normal reference values, can accurately predict PPM. Methods and results In the PERIcardial SurGical AOrtic Valve ReplacemeNt (PERIGON) Pivotal Trial, 986 patients with aortic valve stenosis/regurgitation underwent AVR with an Avalus valve. Patients were randomly split (50:50) into training and test sets. The mean measured EOAs for each valve size from the training set were used to create an Avalus EOAi chart. This chart was subsequently used to predict PPM in the test set and measures of diagnostic accuracy (sensitivity, specificity, and negative and positive predictive value) were assessed. PPM was defined by an EOAi ≤0.85 cm2/m2, and severe PPM was defined as EOAi ≤0.65 cm2/m2. The reference values obtained from the training set ranged from 1.27 cm2 for size 19 mm up to 1.81 cm2 for size 27 mm. The test set had an incidence of 66% of PPM and 24% of severe PPM. The EOAi chart inaccurately predicted PPM in 30% of patients and severe PPM in 22% of patients. For the prediction of PPM, the sensitivity was 87% and the specificity 37%. For the prediction of severe PPM, the sensitivity was 13% and the specificity 98%. Conclusion The use of echocardiographic normal reference values for EOAi charts to predict PPM is unreliable due to the large proportion of misclassifications.

The incidence, recurrence rate, and prognostic significance of atrial fibrillation or flutter (AF) following hospital discharge after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for left main coronary artery disease (LMCAD) are unknown. We sought to determine the 3-year incidence and clinical impact of postdischarge AF in patients with LMCAD treated with PCI or CABG. In the EXCEL trial, 1,905 patients with LMCAD were randomized to PCI versus CABG. We analyzed the occurrence of postdischarge AF through 3 years and its time-adjusted association with adverse outcomes. A total of 1,802 patients without AF at baseline comprised the study cohort. Within 3 years, 227 episodes of AF occurred (29 [12.8%] in the PCI arm and 198 [87.2%] in the CABG arm, p

Objectives The aim of this study was to investigate the incidence and impact on mortality of repeat revascularization after index percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) for left main coronary artery disease (LMCAD). Background The impact on mortality of the need of repeat revascularization following PCI or CABG in patients with unprotected LMCAD is unknown. Methods All patients with LMCAD and site-assessed low or intermediate SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) scores randomized to PCI (n = 948) or CABG (n = 957) in the EXCEL (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial were included. Repeat revascularization events were adjudicated by an independent clinical events committee. The effect of repeat revascularization on mortality through 3-year follow-up was examined in time-varying Cox regression models. Results During 3-year follow-up, there were 346 repeat revascularization procedures among 185 patients. PCI was associated with higher rates of any repeat revascularization (12.9% vs. 7.6%; hazard ratio: 1.73; 95% confidence interval: 1.28 to 2.33; p = 0.0003). Need for repeat revascularization was independently associated with increased risk for 3-year all-cause mortality (adjusted hazard ratio: 2.05; 95% confidence interval: 1.13 to 3.70; p = 0.02) and cardiovascular mortality (adjusted hazard ratio: 4.22; 95% confidence interval: 2.10 to 8.48; p Conclusions In the EXCEL trial, repeat revascularization during follow-up was performed less frequently after CABG than PCI and was associated with increased mortality after both procedures. Reducing the need for repeat revascularization may further improve long-term survival after percutaneous or surgical treatment of LMCAD. (EXCEL Clinical Trial; NCT01205776)

The prognostic impact of resting heart rate (RHR) following revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in patients with left main coronary artery disease (LMCAD) is unknown. We aimed to assess the effect of RHR at discharge on 3-year cardiovascular outcomes following PCI and CABG for LMCAD. In the EXCEL trial, 1,905 patients with LMCAD were randomized to PCI with everolimus-eluting stents versus CABG. RHR was measured at discharge following the index hospitalization. The principal outcome measure was the composite endpoint of death, myocardial infarction (MI) or stroke at 3 years. Among 1,303 patients in sinus rhythm with available ECGs, the median (IQR) discharge RHR was 72 (62to 81) bpm. Median discharge RHR was higher after CABG versus PCI (78 [IQR 70 to 86] versus 65 [IQR 59 to 74] bpm, p0.0001). At 3 years, 107 patients (8.2%) had a primary composite endpoint event including 61 patients (4.7%) who died. By multivariable analysis, discharge RHR assessed as a continuous variable (per 5 bpm) was an independent predictor at 3 years of the primary composite endpoint of death, MI, or stroke (hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.06 to 1.25, p = 0.0006); the secondary composite endpoint of death, MI, stroke, or ischemia-driven revascularization at 3 years (HR 1.12, 95% CI 1.05 to 1.19, p = 0.0007); all-cause mortality (HR 1.18, 95% CI 1.07 to 1.31, p = 0.002); and cardiovascular death (HR 1.16, 95% CI 1.00 to 1.33, p = 0.046). No significant interactions were present between RHR and treatment with PCI versus CABG for the primary (p

Background The Cardiac Surgical Societies Valve Labeling Task Force consensus document acknowledged inconsistent sizing and labeling of prosthetic heart valves. This study compared the labeled size, internal diameter, and hemodynamics of different surgical and transcatheter valve types implanted into the same size annulus, measured by preprocedural computed tomography (CT). Methods Patients were retrospectively sorted into 3 CT annular diameter size groups: small (less than 23 mm), medium (23 to less than 26 mm), and large (26 mm or greater). Surgical valves were sorted into 4 categories based on tissue and design: (stentless porcine, standard stented bovine, wraparound stented bovine, and stented porcine). Comparisons were made within the surgical types and with a transcatheter valve. Echocardiograms were independently assessed and CTs were centrally measured. Results We analyzed 726 surgical and 923 transcatheter valve paired data sets. Among the various valve types implanted into the same size CT annulus, there were significant differences regarding size, internal diameter, and hemodynamics within all 3 size groups. Root enlargement procedures occurred in 1.2% with no differences across valve types or size groups. Transcatheter valve hemodynamics were similar to stentless valves and were significantly better than all stented valves. There was no difference in hemodynamics between the 2 bovine stented valve types, and stented porcine valves were inferior to all valve types. Conclusions This study documents that prosthetic heart valve sizing and labeling inconsistencies exist. Use of preoperative CT annular dimensions is the most accurate method to compare size, internal diameter, and hemodynamics of bioprosthetic aortic valves because it compares values among various valve types implanted into the same size annulus.

Objectives The aim of this study was to report the 2-year results of the SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) trial and confirm the interim Bayesian analysis. Background Transcatheter aortic valve replacement (TAVR) with a self-expanding valve was noninferior to surgery in patients with severe aortic stenosis and intermediate operative risk using Bayesian statistical methods. Novel Bayesian designs have been used to shorten the time to primary endpoint analysis in randomized clinical trials, although the predictive value of Bayesian analysis compared with frequentist approaches remains debated. Methods The SURTAVI trial randomized 1,660 patients. An interim analysis was performed 1 year after the 1,400th patient was treated to estimate the primary 2-year endpoint of all-cause mortality or disabling strokes for all patients. Results The Kaplan-Meier rate for the complete 2-year primary endpoint was 12.7% in the TAVR group and 12.6% in the surgery group (0.0% difference; 95% confidence interval: −3.4% to 3.5%), compared with 12.6% with TAVR and 14.0% with surgery (−1.4% difference; Bayesian credible interval: −5.2% to 2.3%) in the interim Bayesian analysis. A comparison of individual clinical, hemodynamic, and quality-of-life endpoints using Bayesian and frequentist methods found no significant differences. Conclusions The complete analysis of all patients with aortic stenosis at intermediate risk for surgery in the SURTAVI trial confirmed the noninferiority, with respect to the frequency of all-cause mortality or disabling stroke, of TAVR to surgery, as determined in the interim Bayesian analysis. Follow-up will extend out to 10 years.

Objectives: The aim of this study was to assess 10-year all-cause mortality in patients with heavily calcified lesions (HCLs) undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Background: Limited data are available on very long term outcomes in patients with HCLs according to the mode of revascularization. Methods: This substudy of the SYNTAXES (Synergy Between PCI With Taxus and Cardiac Surgery Extended Survival) study assessed 10-year all-cause mortality according to the presence of HCLs within lesions with >50% diameter stenosis and identified during the calculation of the anatomical SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score among 1,800 patients with the 3-vessel disease and/or left main disease randomized to PCI or CABG in the SYNTAX trial. Patients with HCLs were further stratified according to disease type (3-vessel disease or left main disease) and assigned treatment (PCI or CABG). Results: The 532 patients with ≥1 HCL had a higher crude mortality rate at 10 years than those without (36.4% vs 22.3%; HR: 1.79; 95% CI: 1.49-2.16; P < 0.001). After adjustment, an HCL remained an independent predictor of 10-year mortality (HR: 1.36; 95% CI: 1.09-1.69; P = 0.006). There was a significant interaction in mortality between treatment effect (PCI and CABG) and the presence or absence of HCLs (Pinteraction = 0.005). In patients without HCLs, mortality was significantly higher after PCI than after CABG (26.0% vs 18.8%; HR: 1.44; 95% CI: 0.97-1.41; P = 0.003), whereas in those with HCLs, there was no significant difference (34.0% vs 39.0%; HR: 0.85; 95% CI: 0.64-1.13; P = 0.264). Conclusions: At 10 years, the presence of an HCL was an independent predictor of mortality, with a similar prognosis following PCI or CABG. Whether HCLs require special consideration when deciding the mode of revascularization beyond their current contribution to the anatomical SYNTAX score deserves further evaluation. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES], NCT03417050; SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX], NCT00114972)

Background: Prior studies have reported an association between elevated white blood cell count (WBCc) and worse clinical outcomes after coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI). We assessed the prognostic impact of WBCc in patients undergoing revascularization for left main coronary artery disease (LMCAD). Methods: In Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL), 1905 patients with LMCAD and low or intermediate SYNTAX scores were randomized to PCI with everolimus-eluting stents versus CABG. The 1895 patients with baseline WBCc available were grouped in tertiles of WBCc (mean 5.6 ± 0.8, 7.5 ± 0.5, and 10.1 ± 1.6 × 109/L). Results: Five-year rates of the primary endpoint (death, myocardial infarction or stroke) were similar across increasing WBCc tertiles (21.2, 18.9, and 21.6%; P = 0.46). Individual components of the primary endpoint, Bleeding Academic Research Consortium (BARC) 3-5 bleeding, stent thrombosis or graft occlusion and ischemia-driven revascularization were all similar across WBCc tertiles. By multivariable analysis, WBCc as a continuous variable was not an independent predictor of adverse events (hazard radio per 1 × 109/L: 1.02; 95% CI, 0.97-1.08; P = 0.43). Results were consistent in the PCI and CABG arms individually. Conclusion: There was no association between baseline WBCc and 30-day or 5-year clinical outcomes after PCI or CABG. The absence of a clear incremental increase in events with increasing WBCc in the current analysis indicates that WBCc should not routinely be used as a prognostic marker or to guide revascularization decisions in patients with LMCAD.

Background Coronary bypass artery grafting (CABG) has a higher procedural risk of stroke than percutaneous coronary intervention (PCI), but may offer better long-term survival. The optimal revascularization strategy for patients with prior cerebrovascular disease (CEVD) remains unclear. Methods and results The SYNTAXES study assessed the vital status out to 10 year of patients with three-vessel disease and/or left main coronary artery disease enrolled in the SYNTAX trial. The relative efficacy of PCI vs. CABG in terms of 10 year all-cause death was assessed according to prior CEVD. The primary endpoint was 10 year all-cause death. The status of prior CEVD was available in 1791 (99.5%) patients, of whom 253 patients had prior CEVD. Patients with prior CEVD were older and had more comorbidities (medically treated diabetes, insulin-dependent diabetes, metabolic syndrome, peripheral vascular disease, chronic obstructive pulmonary disease, impaired renal function, and congestive heart failure), compared with those without prior CEVD. Prior CEVD was an independent predictor of 10 year all-cause death (adjusted HR: 1.35; 95% CI: 1.04–1.73; p = 0.021). Patients with prior CEVD had a significantly higher risk of 10 year all-cause death (41.1 vs. 24.1%; HR: 1.92; 95% CI: 1.54–2.40; p -interaction = 0.624). Conclusion Prior CEVD was associated with a significantly increased risk of 10 year all-cause death which was similar in patients treated with PCI or CABG. These results do not support preferential referral for PCI rather than CABG in patients with prior CEVD. Trial registration: SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050. Graphic abstract

Background: For patients with severe aortic stenosis and coronary artery disease, the completely percutaneous approach to aortic valve replacement and revascularization has not been compared with the standard surgical approach. Methods: The prospective SURTAVI trial (Safety and Efficiency Study of the Medtronic CoreValve System in the Treatment of Severe, Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement) enrolled intermediate-risk patients with severe aortic stenosis from 87 centers in the United States, Canada, and Europe between June 2012 and June 2016. Complex coronary artery disease with SYNTAX score (Synergy Between PCI with Taxus and Cardiac Surgery Trial) >22 was an exclusion criterion. Patients were stratified according to the need for revascularization and then randomly assigned to treatment with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR). Patients assigned to revascularization in the TAVR group underwent percutaneous coronary intervention, whereas those in the SAVR group had coronary artery bypass grafting. The primary end point was the rate of all-cause mortality or disabling stroke at 2 years. Results: Of 1660 subjects with attempted aortic valve implants, 332 (20%) were assigned to revascularization. They had a higher Society of Thoracic Surgeons risk score for mortality (4.8±1.7% versus 4.4±1.5%; P P P =0.62), or between TAVR and SAVR (11.9%; 95% CI, 9.5–14.7 versus 12.3%; 95% CI, 9.8–15.4; P =0.76). Conclusions: For patients at intermediate surgical risk with severe aortic stenosis and noncomplex coronary artery disease (SYNTAX score ≤22), a complete percutaneous approach of TAVR and percutaneous coronary intervention is a reasonable alternative to SAVR and coronary artery bypass grafting. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01586910.

The prognostic impact of high-sensitivity C-reactive protein (CRP) levels in patients with left main coronary artery disease (LMCAD) treated with percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) is unknown. We sought to determine the effect of elevated baseline CRP levels on the 3-year outcomes after LMCAD revascularization and to examine whether CRP influenced the relative outcomes of PCI versus CABG.In the EXCEL trial, patients with LMCAD and Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) scores ≤32 were randomized to PCI versus CABG. The primary composite outcome of death, myocardial infarction (MI), or stroke was analyzed according to baseline CRP levels.Among 999 patients with available CRP levels, median CRP was 3.10 mg/L (interquartile range 1.12-6.40 mg/L). The rate of the primary composite end point of death, MI, or stroke at 3 years steadily increased with greater baseline CRP levels. The adjusted relationship between the 3-year composite rate of death, MI, or stroke and baseline CRP modeled as a continuous log-transformed variable demonstrated steadily increasing event rates with greater CRP levels (adjusted hazard ratio, 1.26, 95% CI 1.10-1.44, P = .0008). Similarly, patients with CRP ≥10 mg/L had a 3-fold higher risk of the 3-year primary end point compared to patients with lower CRP levels (adjusted hazard ratio 2.92, 95% CI 1.88-4.54, P.0001). The association between an elevated CRP level and the adjusted 3-year risk of the primary composite end point did not differ according to revascularization strategy (PIn patients with LMCAD undergoing revascularization, elevated baseline CRP levels were strongly associated with subsequent death, MI, and stroke at 3 years, irrespective of the mode of revascularization. Further studies are warranted to determine whether anti-inflammatory therapies may improve the prognosis of high-risk patients with LMCAD following revascularization.

Objectives There is a paucity of data on the effect of baseline lipid-lowering therapy (LLT) in patients undergoing revascularization for left main (LM) coronary artery disease (CAD). We compared outcomes for patients with LMCAD randomized to percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) according to the presence of baseline LLT in the EXCEL trial. Patients and methods The EXCEL trial randomized 1905 patients with LMCAD and SYNTAX scores up to 32 to PCI with everolimus-eluting stents versus CABG. Patients were categorized according to whether they were medically treated with LLT at baseline, and their outcomes were examined using multivariable Cox proportional hazards regression. The primary endpoint was a composite of death, stroke, or myocardial infarction at 3 years. Results Among 1901 patients with known baseline LLT status, 1331 (70.0%) were medically treated with LLT at baseline. There were no significant differences between the PCI and CABG groups in the 3-year rates of the primary endpoint in patients with versus without baseline LLT (Pinteraction = 0.62). Among patients with baseline LLT, the 3-year rate of ischemia-driven revascularization was higher after PCI compared with CABG (13.7 vs. 5.3%; adjusted hazard ratio = 2.97; 95% confidence interval: 1.95–4.55; P < 0.0001), in contrast to patients without baseline LLT (9.8 vs. 12.1%; adjusted hazard ratio = 0.79; 95% confidence interval: 0.47–1.33; P = 0.39) (Pinteraction = 0.0003). Conclusion In the EXCEL trial, 3-year major adverse event rates after PCI versus CABG for LMCAD were similar and consistent in patients with and without LLT at baseline; however, revascularization during follow-up was more common after PCI compared with CABG in patients with baseline LLT, but not in those without baseline LLT. Coron Artery Dis 30:143–149 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

OBJECTIVES Percutaneous coronary intervention (PCI) is often favoured over coronary artery bypass grafting (CABG) surgery for revascularization in patients with chronic obstructive pulmonary disease (COPD). We studied whether COPD affected clinical outcomes according to revascularization in the Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial, in which PCI with everolimus-eluting stents was non-inferior to CABG for the treatment of patients with left main coronary artery disease and low or intermediate SYNTAX scores. METHODS Patients with a history of COPD were propensity score matched to those without COPD. Outcomes at 30 days and 3 years in both groups were compared in patients randomized to PCI versus CABG. RESULTS COPD status was available for 1901 of 1905 randomized patients (99.8%), 148 of whom had COPD (7.8%). Propensity score matching yielded 135 patients with COPD and 675 patients without COPD. Patients with COPD had higher 3-year rates of the primary composite end point of death, myocardial infarction or stroke (31.7% vs 14.5%, P

To assess the safety and efficacy of using vascular closure devices (VCDs) in percutaneous coronary intervention (PCI) for left main coronary artery disease (LM-CAD).VCDs provide rapid hemostasis for patients undergoing PCI with transfemoral access (TFA); however, the safety and efficacy of VCDs continues to be debated.We analyzed data from the EXCEL trial in patients with LM-CAD in whom PCI was performed via TFA with vs without VCD. The primary endpoint was a composite of death, myocardial infarction (MI), or stroke. Bleeding Academic Research Consortium (BARC) type 2-5 bleeding at 30 days was also assessed. Propensity-score matching analysis was used.Among 694 patients with LM-CAD undergoing TFA-PCI, 423 (61.0%) received VCDs (collagen plug, 320 [75.7%]; suture mediated, 55 [13.0%]; others, 48 [11.3%]). Patients with and without VCD use had similar 30-day rates of BARC type 2-5 bleeding (5.0% vs 6.7%, respectively; P=.30) and BARC type 3-5 bleeding (2.1% vs 3.7%, respectively; P=.20). There were no significant differences in the rates of death, MI, or stroke in patients with and without VCD use at 30 days (4.7% vs 4.1%, respectively; P=.74) or at 5 years (20.3% vs 24.2%, respectively; P=.16). These results were similar after adjustment.In the EXCEL trial, LM-CAD PCI via TFA using VCD was associated with similar 30-day rates of bleeding and comparable early and late major adverse cardiovascular events compared with manual compression.

Background: Ten-year all-cause death according to incomplete (IR) versus complete revascularization (CR) has not been fully investigated in patients with 3-vessel disease and left main coronary artery disease undergoing percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG). Methods: The SYNTAX Extended Survival study (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES]) evaluated vital status up to 10 years in patients who were originally enrolled in the SYNTAX trial. In the present substudy, outcomes of the CABG CR group were compared with the CABG IR, PCI CR, and PCI IR groups. In addition, in the PCI cohort, the residual SYNTAX score (rSS) was used to quantify the extent of IR and to assess its association with fatal late outcome. The rSS of 0 suggests CR, whereas a rSS>0 identifies the degree of IR. Results: IR was more frequently observed in patients with PCI versus CABG (56.6% versus 36.8%) and more common in those with 3-vessel disease than left main coronary artery disease in both the PCI arm (58.5% versus 53.8%) and the CABG arm (42.8% versus 27.5%). Patients undergoing PCI with CR had no significant difference in 10-year all-cause death compared with those undergoing CABG (22.2% for PCI with CR versus 24.3% for CABG with IR versus 23.8% for CABG with CR). In contrast, those with PCI and IR had a significantly higher risk of all-cause death at 10 years compared with CABG and CR (33.5% versus 23.7%; adjusted hazard ratio, 1.48 [95% CI, 1.15–1.91]). When patients with PCI were stratified according to the rSS, those with a rSS≤8 had no significant difference in all-cause death at 10 years as the other terciles (22.2% for rSS=0 versus 23.9% for rSS>0–4 versus 28.9% for rSS>4–8), whereas a rSS>8 had a significantly higher risk of 10-year all-cause death than those undergoing PCI with CR (50.1% versus 22.2%; adjusted hazard ratio, 3.40 [95% CI, 2.13–5.43]). Conclusions: IR is common after PCI, and the degree of incompleteness was associated with 10-year mortality. If it is unlikely that complete (or nearly complete; rSS Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00114972. URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03417050.

Aims To evaluate the impact of chronic obstructive pulmonary disease (COPD) on 10-year all-cause death and the treatment effect of CABG versus PCI on 10-year all-cause death in patients with three-vessel disease (3VD) and/or left main coronary artery disease (LMCAD) and COPD. Methods Patients were stratified according to COPD status and compared with regard to clinical outcomes. Ten-year all-cause death was examined according to the presence of COPD and the revascularization strategy. Results COPD status was available for all randomized 1800 patients, of whom, 154 had COPD (8.6%) at the time of randomization. Regardless of the revascularization strategy, patients with COPD had a higher risk of 10-year all-cause death, compared with those without COPD (43.1% vs. 24.9%; hazard ratio [HR]: 2.03; 95% confidence interval [CI]: 1.56–2.64; p p = 0.858), whereas among those without COPD, CABG had a significantly lower risk of 10-year all-cause death (22.7% vs. 27.1%; HR: 0.81; 95% CI: 0.67–0.99, p = 0.041). There was no significant differential treatment effect of CABG versus PCI on 10-year all-cause death between patients with and without COPD (pinteraction = 0.544). Conclusions COPD was associated with a higher risk of 10-year all-cause death after revascularization for complex coronary artery disease. The presence of COPD did not significantly modify the beneficial effect of CABG versus PCI on 10-year all-cause death. Trial registration: SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050 Graphic abstract

Aims To investigate the impact of established cardiovascular disease (CVD) on 10-year all-cause death following coronary revascularization in patients with complex coronary artery disease (CAD). Methods The SYNTAXES study assessed vital status out to 10 years of patients with complex CAD enrolled in the SYNTAX trial. The relative efficacy of PCI versus CABG in terms of 10-year all-cause death was assessed according to co-existing CVD. Results Established CVD status was recorded in 1771 (98.3%) patients, of whom 827 (46.7%) had established CVD. Compared to those without CVD, patients with CVD had a significantly higher risk of 10-year all-cause death (31.4% vs. 21.7%; adjusted HR: 1.40; 95% CI 1.08–1.80, p = 0.010). In patients with CVD, PCI had a non-significant numerically higher risk of 10-year all-cause death compared with CABG (35.9% vs. 27.2%; adjusted HR: 1.14; 95% CI 0.83–1.58, p = 0.412). The relative treatment effects of PCI versus CABG on 10-year all-cause death in patients with complex CAD were similar irrespective of the presence of CVD (p-interaction = 0.986). Only those patients with CVD in ≥ 2 territories had a higher risk of 10-year all-cause death (adjusted HR: 2.99, 95% CI 2.11–4.23, p Conclusions The presence of CVD involving more than one territory was associated with a significantly increased risk of 10-year all-cause death, which was non-significantly higher in complex CAD patients treated with PCI compared with CABG. Acceptable long-term outcomes were observed, suggesting that patients with established CVD should not be precluded from undergoing invasive angiography or revascularization. Trial registration SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050. Graphic abstract

Background The SYNTAX Extended Survival (SYNTAXES) study is an investigator-driven extension of follow-up of the SYNTAX trial, which was a non-inferiority trial that compared percutaneous coronary intervention (PCI) using first-generation paclitaxel-eluting stents with coronary artery bypass grafting (CABG) in patients with de-novo three-vessel and left main coronary artery disease. The SYNTAXES study is the first randomized trial that reported the complete 10-year data on all-cause death in patients with complex coronary artery disease. Purpose Patients with coronary artery disease (CAD) and concomitant diabetes mellitus (DM) or chronic kidney disease (CKD) are more susceptible to major adverse cardiovascular and cerebrovascular events. However, to date, the long-term prognosis and which revascularization strategy was associated with better clinical outcomes for patients with complex coronary artery disease and concomitant with DM and CKD have not been documented. Methods In this sub-analysis of the SYNTAXES trial, a total of 1,638 patients were classified into four subgroups according to the DM and CKD status: DM−/CKD− (n=999, 60.1%), DM+/CKD− (n=323, 19.7%), DM−/CKD+ (n=231, 14.1%), and DM+/CKD+ (n=85, 5.2%). The treatment effects of PCI and CABG were analyzed in each subgroup. The primary endpoint was all-cause death at 10 years. Results Compared with the DM−/CKD− patients, patients with DM+/CKD+ were older, more often had a history of stroke, hypertension, heart failure, and were more frequently presented with total occlusion, bifurcation lesion and three-vessel disease. At 10 years, patients with DM+/CKD+ had a 3.94-fold higher incidence of all-cause mortality compared with DM−/CKD− individuals (54.1% versus 18.9%, 95% CI [2.85–5.44]). Patients with DM−/CKD+ (38.1%, HR 2.36; 95% CI [1.83–5.44]) or DM+/CKD− (28.2%, HR 1.61; 95% CI [1.26–2.07]) had intermediate risk profile. For DM+/CKD+ patients, compared with PCI, those who underwent CABG were associated with lower incidence of all-cause mortality (64.3% versus 44.2%, adjusted HR 0.52; 95% CI [0.27–0.99], p=0.047, pinteraction=0.443). The number of needed-to-treat to reduce mortality for CABG was 12. Conclusion In the SYNTAX population, patients with DM and CKD are at markedly increased risk of long-term mortality rate compared with patients one or neither of these risk factors. For patients with both comorbidities, CABG was associated with better clinical outcome compared with PCI. These findings should be interpreted as hypothesis-generating. Figure 1. Kaplan-Meier curves showing the clinical events according to treatment and DM/CKD status. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Boston Scientific Corporation

Varying definitions of procedural myocardial infarction (PMI) are in widespread use.This study sought to determine the rates and clinical relevance of PMI using different definitions in patients with left main coronary artery disease randomized to percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) surgery in the EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial.The pre-specified protocol definition of PMI (PMIPMIThe rates of PMI after PCI and CABG vary greatly with different definitions. In the EXCEL trial, the pre-specified PMI

Objectives: We examined outcomes according to lesion preparation strategy (LPS) in patients with left main coronary artery (LMCA) percutaneous coronary intervention (PCI) in the EXCEL trial. Background: The optimal LPS for LMCA PCI is unclear. Methods: We categorized LPS hierarchically (high to low) as: (a) rotational atherectomy (RA); (b) cutting or scoring balloon (CSB); (c) balloon angioplasty (BAL); and d) direct stenting (DIR). The primary endpoint was 3-year MACE; all-cause death, stroke, or myocardial infarction. Results: Among 938 patients undergoing LMCA PCI, RA was performed in 6.0%, CSB 9.5%, BAL 71.3%, and DIR 13.2%. In patients treated with DIR, BAL, CSB, and RA, respectively, there was a progressive increase in SYNTAX score, LMCA complex bifurcation, trifurcation or calcification, number of stents, and total stent length. Any procedural complication occurred in 10.4% of cases overall, with the lowest rate in the DIR (7.4%) and highest in the RA group (16.1%) (ptrend =.22). There were no significant differences in the 3-year rates of MACE (from RA to DIR: 17.9%, 20.2%, 14.5%, 14.7%; p =.50) or ischemia-driven revascularization (from RA to DIR: 16.8%, 10.8%, 12.3%, 14.2%; p =.65). The adjusted 3-year rates of MACE did not differ according to LPS. Conclusions: The comparable 3-year outcomes suggest that appropriate lesion preparation may be able to overcome the increased risks of complex LMCA lesion morphology.

OBJECTIVES The SYNTAX score II (SSII) was developed from the SYNTAX trial to predict the 4-year all-cause mortality after left main or multivessel disease revascularization and to facilitate the decision-making process. The SSII provides the following treatment recommendations: (i) coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) (equipoise risk), (ii) CABG preferred (excessive risk for PCI) or (iii) PCI preferred (excessive risk for CABG). We sought to externally validate SSII and to investigate the impact of not abiding by the SSII recommendations in the randomized EXCEL trial of PCI versus CABG for left main disease. METHODS The calibration plot of predicted versus observed 4-year mortality was constructed from individual values of SSII in EXCEL. To assess overestimation versus underestimation of predicted mortality risk, an optimal fit regression line with slope and intercept was determined. Prospective treatment recommendations based on SSII were compared with actual treatments and all-cause mortality at 4 years. RESULTS SSII variables were available from EXCEL trial in 1807/1905 (95%) patients. For the entire cohort, discrimination was possibly helpful (C statistic = 0.670). SSII-predicted all-cause mortality at 4 years overestimated the observed mortality, particularly in the highest-risk percentiles, as confirmed by the fit regression line [intercept 2.37 (1.51–3.24), P = 0.003; slope 0.67 (0.61–0.74), P CONCLUSIONS In the EXCEL trial of patients with left main disease, the SSII-predicted 4-year mortality overestimated the 4-year observed mortality with a possibly helpful discrimination. Non-compliance with SSII CABG treatment recommendations (i.e. randomized to PCI) was associated with higher 4-year all-cause mortality.

Cigarette smoking is a well-known risk factor for coronary artery disease (CAD). However, the impact of smoking on outcomes after coronary revascularization, especially in patients with left main CAD (LMCAD) is less well understood. The EXCEL trial randomized 1,905 patients with LMCAD and visually assessed low or intermediate anatomical complexity (SYNTAX score ≤32) to PCI with everolimus-eluting stents or CABG. Patients were categorized according to smoking status (current, former, or never), and their outcomes at 5 years were compared by logistic regression with follow-up time included as a log-transformed offset variable. The primary endpoint was a composite of death, myocardial infarction, or stroke. Among 1893 patients with known smoking status at baseline, 416 (22%) were current smokers and 774 (41%) were former smokers. The crude rates of the primary endpoint were 19.5% for never smokers, 20.5% for former smokers (p = 0.61 vs never smokers), and 23.1% for smokers (p = 0.15 vs never smokers). Compared with never smokers, the adjusted risk of the primary endpoint was higher for current smokers (adjOR 1.82, 95% confidence interval [CI] 1.126 to 2.63; p = 0.001), but not for former smokers (adjOR 1.00, 95% CI 0.75 to 1.33, p = 0.10). The relative efficacy of PCI versus CABG for the 5-year primary endpoint was similar irrespective of smoking status (Pinteraction = 0.22). In conclusion, current smokers in the EXCEL trial had a higher adjusted 5-year risk of the primary composite endpoint of death, myocardial infarction, or stroke than never smokers, whereas former smokers were not at increased risk. Active smoking was a risk factor after LMCAD revascularization irrespective of revascularization method.