Versus Coronary Artery Bypass Surgery Research Articles

Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Patients With Left Main Disease With and Without Diabetes: Findings From a Pooled Analysis of 4 Randomized Clinical Trials.

Diabetes may be associated with differential outcomes in patients undergoing left main coronary revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). The aim of this study was to investigate outcomes in patients with left main disease with and without diabetes randomized to PCI versus CABG. Individual patient data were pooled from 4 trials (SYNTAX [Synergy Between PCI With Taxus and Cardiac Surgery], PRECOMBAT [Premier of Randomized Comparison of Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease], NOBLE [Nordic-Baltic-British Left Main Revascularisation Study], and EXCEL [Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization]) that randomized patients with left main disease to PCI or CABG. Patients were considered suitable for either approach. Patients were categorized by diabetes status. Kaplan-Meier event rates, Cox model hazard ratios, and interactions were assessed. Among 4393 patients, 1104 (25.1%) had diabetes. Patients with diabetes experienced higher rates of 5-year death (158/1104 [Kaplan-Meier rate, 14.7%] versus 297/3289 [9.3%]; P<0.001), spontaneous myocardial infarction (MI; 67/1104 [6.7%] versus 114/3289 [3.7%]; P<0.001), and repeat revascularization (189/1104 [18.5%] versus 410/3289 [13.2%]; P<0.001). Rates of all-cause mortality did not differ after PCI versus CABG in those with (84/563 [15.3%] versus 74/541 [14.1%]; hazard ratio, 1.11 [95% CI, 0.82-1.52]) or without (155/1634 [9.7%] versus 142/1655 [8.9%]; hazard ratio, 1.08 [95% CI, 0.86-1.36; PintHR=0.87) diabetes. Rates of stroke within 1 year were lower with PCI versus CABG in the entire population, with no heterogeneity based on diabetes status (PintHR=0.51). The 5-year rates of spontaneous MI and repeat coronary revascularization were higher after PCI regardless of diabetes status (spontaneous MI: 45/563 [8.9%] versus 22/541 [4.4%] in diabetes and 82/1634 [5.3%] versus 32/1655 [2.1%] in no diabetes, PintHR=0.47; repeat revascularization: 127/563 [24.5%] versus 62/541 [12.4%] in diabetes and 254/1634 [16.3%] versus 156/1655 [10.1%] in no diabetes, PintHR=0.18). For spontaneous MI and repeat revascularization, there were greater absolute risk differences beyond 1 year in patients with diabetes (4.9% and 9.9%) compared with those without (2.1% and 4.3%; PintARD=0.047 and 0.016). In patients with left main disease considered equally suitable for PCI or CABG and with largely low to intermediate SYNTAX scores, diabetes was associated with higher rates of death and cardiovascular events through 5 years. Compared with CABG, PCI resulted in no difference in the risk of death and a lower risk of early stroke regardless of diabetes status, and a higher risk of spontaneous MI and repeat coronary revascularization, with larger late absolute excess risks in patients with diabetes. URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01205776, NCT0146651, NCT00422968, and NCT00114972.

Impact of Incomplete Revascularization After PCI in Left Main Disease: The EXCEL Trial.

The importance of complete revascularization after percutaneous coronary intervention (PCI) in patients with left main coronary artery disease is uncertain. We investigated the clinical impact of complete revascularization in patients with left main coronary artery disease undergoing PCI in the EXCEL trial (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization). Composite rates of death or myocardial infarction (MI) following PCI during 5-year follow-up were examined in 903 patients based on core laboratory definitions of anatomic and functional complete revascularization, residual SYNTAX score (The Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery), and residual Jeopardy Score (rJS). The risk of death or MI did not vary based on anatomic, functional, or residual SYNTAX score complete revascularization but did differ according to the rJS (5-year rates 17.6%, 19.5%, and 38.9% with rJS 0, 2, and ≥4, respectively; P=0.006). The higher rate of death or MI with rJS≥4 versus rJS≤2 was driven conjointly by increased mortality (adjusted hazard ratio, 2.29 [95% CI, 1.11-4.71]; P=0.02) and spontaneous MI (adjusted hazard ratio, 2.89 [95% CI, 1.17-7.17]; P=0.02). The most common location for untreated severe stenoses in the rJS≥4 group was the left circumflex artery (LCX), and the post-PCI absence, compared with the presence, of any untreated lesion with diameter stenosis ≥70% in the LCX was associated with reduced 5-year rates of death or MI (18.9% versus 35.2%; hazard ratio, 0.48 [95% CI, 0.32-0.74]; P<0.001). The risk was the highest for residual ostial/proximal LCX lesions. Among patients undergoing PCI in EXCEL trial, incomplete revascularization according to the rJS was associated with increased rates of death and spontaneous MI. Post-PCI untreated high-grade lesions in the LCX (especially the ostial/proximal LCX) drove these outcomes. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01205776.

Can Machine Learning Aid the Selectionof Percutaneous vs SurgicalRevascularization?

In patients with 3-vessel coronary artery disease (CAD) and/or left main CAD, individual risk prediction plays a key role in deciding between percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). The aim of this study was to assess whether these individualized revascularization decisions can be improved by applying machine learning (ML) algorithms and integrating clinical, biological, and anatomical factors. In the SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) study, ML algorithms (Lasso regression, gradient boosting) were used to develop a prognostic index for 5-year death, which was combined, in the second stage, with assigned treatment (PCI or CABG) and prespecified effect-modifiers: disease type (3-vessel or left main CAD) and anatomical SYNTAX score. The model's discriminative ability to predict the risk of 5-year death and treatment benefit between PCI and CABG was cross-validated in the SYNTAX trial (n=1,800) and externally validated in the CREDO-Kyoto (Coronary REvascularization Demonstrating Outcome Study in Kyoto) registry (n=7,362), and then compared with the original SYNTAX score II 2020 (SSII-2020). The hybrid gradient boosting model performed best for predicting 5-year all-cause death with C-indexes of 0.78 (95%CI: 0.75-0.81) in cross-validation and 0.77 (95%CI: 0.76-0.79) in external validation. The ML models discriminated 5-year mortality better than the SSII-2020 in the external validation cohort and identified heterogeneity in the treatment benefit of CABG vs PCI. An ML-based approach for identifying individuals who benefit from CABG or PCI is feasible and effective. Implementation of this model in health care systems-trained to collect large numbers of parameters-may harmonize decision making globally. (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; NCT00114972).

Impact of Periprocedural Adverse Events After PCI and CABG on 5-Year Mortality: The EXCEL Trial

BackgroundThe relative risks for different periprocedural major adverse events (MAE) after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) on subsequent mortality have not been described. ObjectivesThe aim of this study was to assess the association between periprocedural MAE occurring within 30 days postprocedure and early and late mortality after left main coronary artery revascularization by PCI and CABG. MethodsIn the EXCEL (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial, patients with left main disease were randomized to PCI vs CABG. The associations between 12 prespecified nonfatal MAE and subsequent 5-year all-cause and cardiovascular death in 1,858 patients were examined using logistic regression. ResultsOne or more nonfatal MAE occurred in 111 of 935 patients (11.9%) after PCI and 419 of 923 patients (45.4%) after CABG (P < 0.0001). Patients with MAE were older and had more baseline comorbidities. Within 5 years, all-cause death occurred in 117 and 87 patients after PCI and CABG, respectively. Experiencing an MAE was a strong independent predictor of 5-year mortality after both PCI (adjusted OR: 4.61; 95% CI: 2.71-7.82) and CABG (adjusted OR: 3.25; 95% CI: 1.95-5.41). These associations were present within the first 30 days and between 30 days and 5 years postprocedure. Major or minor bleeding with blood transfusion ≥2 U was an independent predictor of 5-year mortality after both procedures. Stroke, unplanned revascularization for ischemia, and renal failure were significantly associated with mortality only after CABG. ConclusionsIn the EXCEL trial, nonfatal periprocedural MAE were strongly associated with early and late mortality after both PCI and CABG for left main disease.

Cost-Effectiveness of Percutaneous Coronary Intervention Versus Bypass Surgery for Patients With Left Main Disease: Results From the EXCEL Trial.

The EXCEL trial (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) demonstrated in patients with left main coronary artery disease, no significant difference between coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) with everolimus-eluting stents for the composite end point of death, stroke, or myocardial infarction at 5 years. However, all-cause mortality at 5 years was higher with PCI. Long-term cost-effectiveness of these 2 strategies has heretofore not been evaluated. From 2010 to 2014, 1905 patients with left main coronary artery disease were randomized to CABG (n=957) or PCI (n=948). Costs ($2019) were assessed over 5 years using resource-based costing and Medicare reimbursement rates. Health utilities were assessed using the EuroQOL 5-dimension questionnaire. Five-year EXCEL data in combination with US lifetables were used to develop a Markov model to evaluate lifetime cost-effectiveness. An incremental cost-effectiveness ratio <$50 000 per quality-adjusted life year (QALY) gained was considered highly cost-effective. Index revascularization procedure costs were $4,850/patient higher with CABG, and total costs for the index hospitalization were $17 610/patient higher with CABG ($32 297 versus $19 687, P<0.001). Cumulative 5-year costs were $20 449/patient higher with CABG. CABG was projected to increase lifetime costs by $21 551 while increasing quality-adjusted life expectancy by 0.49 QALYs, yielding an incremental cost-effectiveness ratio of $44 235/QALY. In a post hoc sensitivity analysis using mortality hazard ratios from a meta-analysis of all randomized CABG versus PCI in left main disease trials, the gain associated with CABG was 0.08 to 0.14 QALYs, resulting in an incremental cost-effectiveness ratio of $139 775 to $232 710/QALY gained. Based on data from the EXCEL trial, CABG is an economically attractive revascularization strategy compared with PCI over a lifetime horizon for patients with significant left main coronary artery disease. However, this conclusion is sensitive to the long-term mortality rates with the 2 strategies, and CABG is no longer highly cost-effective when substituting the pooled treatment effect from the 4 major PCI versus CABG trials for left main disease. URL: https://www. gov; Unique identifier: NCT01205776.

Predicted and Observed Mortality at 10Years in Patients With Bifurcation Lesions intheSYNTAX Trial.

Percutaneous coronary intervention (PCI) of bifurcation lesions is associated with higher rates of adverse events, and currently it is unclear whether PCI or coronary artery bypass grafting (CABG) is the safer treatment for these patients at very long-term follow-up. The aim of this study was to investigate the impact of bifurcation lesions on individual predicted and observed all-cause 10-year mortality in the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) trial. In the SYNTAXES (SYNTAX Extended Survival) study, 10-year observed and individual predicted mortality derived from the SYNTAX score 2020 (SS-2020) was compared between patients with≥1 bifurcation (n=1,300) and those with no bifurcations (n=487). Among patients treated with PCI, patients with >1 bifurcation lesion compared with those without bifurcation lesions had a significantly higher risk for all-cause death (19.8% vs 30.1%; HR: 1.55; 95%CI: 1.12-2.14; P=0.007), whereas following CABG, mortality was similar in patients with and those without bifurcation lesions (23.3% vs 23.0%; HR: 0.81; 95%CI: 0.59-1.12; P=0.207; Pinteraction=0.006). In PCI patients, a 2-stent vs a 1-stent technique was associated with higher mortality (33.3% vs 25.9%; HR: 1.51; 95%CI: 1.06-2.14; P=0.021). According to the SS-2020, among those with≥1 bifurcation, there was equipoise for all-cause mortality between PCI and CABG in 2 quartiles of the population, whereas CABG was superior to PCI in the 2 remaining quartiles. Bifurcation lesions require special attention from the heart team, considering the higher 10-year all-cause mortality associated with PCI. Careful evaluation of bifurcation lesion complexity and calculation of individualized 10-year prognosis using the SS-2020 may therefore be helpful in decision making. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES], NCT03417050; Taxus Drug-Eluting StentVersus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX], NCT00114972).

10-Year All-Cause Mortality Following Percutaneous or Surgical Revascularization inPatientsWithHeavyCalcification.

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). Limited data are available on very long term outcomes in patients with HCLs according to the mode of revascularization. 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). 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). 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).

Impact of Optimal Medical Therapy on 10-Year Mortality After Coronary Revascularization

BackgroundThe 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. ObjectivesThe 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. MethodsThis 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. ResultsIn 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. ConclusionsIn 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)

10-Year Follow-Up After Revascularization in Elderly Patients With Complex Coronary Artery Disease

BackgroundThe optimal revascularization strategy for the elderly with complex coronary artery disease remains unclear. ObjectivesThe 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). MethodsIn 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. ResultsAmong 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. ConclusionsElderly 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)

White blood cell count and clinical outcomes after left main coronary artery revascularization: insights from the EXCEL trial.

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). 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). 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. 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.

TCTAP A-017 Long-term Outcomes of Percutaneous Coronary Intervention Versus Coronary Artery Bypass Surgery in Elderly Patients with Multivessel and/or Left Main Coronary Artery Disease and Diabetes Mellitus: A Systematic Review and Meta-analysis

TCTAP A-017 Long-term Outcomes of Percutaneous Coronary Intervention Versus Coronary Artery Bypass Surgery in Elderly Patients with Multivessel and/or Left Main Coronary Artery Disease and Diabetes Mellitus: A Systematic Review and Meta-analysis

Mortality 10 Years After Percutaneous or Surgical Revascularization in Patients With Total Coronary Artery Occlusions

BackgroundThe 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. ObjectivesThe objective of this analysis was to assess 10-year all-cause mortality in patients with TOs undergoing PCI or CABG. MethodsThis 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. ResultsOf 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). ConclusionsAt 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)

Fallacies and Possible Remedies of the SYNTAX Score.

Quite a few studies have revealed the clinical values regarding the outcome predictions in the cohort of the Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) trial and decision-making with the SYNTAX score. The Evaluation of Xience Everolimus-Eluting Stent Versus Coronary Artery Bypass Surgery for Effectiveness of Left-Main Revascularization (EXCEL) and Nordic-Baltic-British left main revascularization (NOBLE) studies are the largest international randomized studies so far, comparing percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) in the treatment of left main coronary artery disease. Unfortunately, both studies failed to validate the value of the SYNTAX score in the selection of revascularization strategies for patients with coronary artery diseases (CAD).. This scenario prompted us to reconsider the inherent fallacies of the SYNTAX score in its derivation. We pointed out eight fallacies for the SYNTAX score in this paper. A recently developed Coronary Artery Tree description and Lesion EvaluaTion (CatLet) score, available at http://www.catletscore.com, a novel angiographic scoring system, could be the remedies for the SYNTAX score.

Impact of Peri-Procedural Myocardial Infarction on Outcomes After Revascularization

BackgroundNumerous definitions for peri-procedural myocardial infarction (PMI) following percutaneous coronary intervention (PCI) and coronary bypass grafting (CABG) surgery exist. ObjectivesThe purpose of this study was to investigate the PMI rates according to various definitions, their clinically relevant association with all-cause mortality at 10 years, and their impact on composite endpoints at 5 years in the SYNTAXES (Synergy between PCI with Taxus and Cardiac Surgery Extended Survival) trial. MethodsPMI was classified as a myocardial infarction occurring within 48 h of the procedure according to definitions of the SYNTAX (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries), ISCHEMIA (International Study Of Comparative Health Effectiveness With Medical And Invasive Approaches), and EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trials; the Fourth Universal Definition of MI; and the Society for Cardiovascular Angiography and Interventions (SCAI). Of the 1,800 patients enrolled, 1,652 with creatine kinase and/or creatine kinase-myocardial band (CK-MB) post-procedure were included. The association between PMI and mortality was analyzed by Cox regression. ResultsPMI rates according to the SYNTAX and Fourth Universal Definition of MI, both of which required CK-MB elevation and electrocardiographic evidence of permanent myocardial damage, were 2.7% and 3.0%, respectively, in the PCI arm versus 2.4% and 2.1%, respectively, in the CABG arm. PMI rates according to the SCAI or EXCEL definition were higher in the PCI (5.7%) and CABG (16.5%) arms. PMIs according to the SYNTAX and Fourth Universal Definition of MI were more strongly associated with mortality than EXCEL and SCAI PMIs defined by isolated enzyme elevation when CK-MB was more than 10 times ULN. The impact of these “enzyme-driven events” on time-to-event curves and the composite endpoints was greater in the surgical cohort. PMIs after PCI were associated with 10-year mortality regardless of definition, whereas their impact on mortality after CABG was limited to 1 year. ConclusionsThe rates of PMI are highly dependent on their definition, which affects time-to-event curves, composite endpoints, and their lethal prognostic relevance. (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)

Sex Differences in All-Cause Mortality in the Decade Following Complex Coronary Revascularization

BackgroundThe 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. ObjectivesThe aim of this study was to investigate the impact of sex on mortality and sex-treatment interaction at 10 years. MethodsThe 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. ResultsOf 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). ConclusionsFemale 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)

Bayesian Interpretation of the EXCEL Trial and Other Randomized Clinical Trials of Left Main Coronary Artery Revascularization

Patients with left main coronary artery disease have improved outcomes with coronary revascularization compared with medical therapy, but the choice of optimal revascularization technique is unresolved. To use bayesian methods to analyze the risk differences for patients with left main coronary artery disease randomized to treatment with coronary artery bypass surgery (CABG) compared with those randomized to percutaneous coronary intervention (PCI) in recent randomized clinical trials (RCTs). A systematic review using the PubMed database with the query string "(left main disease) and (PCI or CABG) and (5-year follow-up) and (clinical trial)" identified all RCTs from January 1996 to January 2020 comparing CABG to PCI for treatment of patients with left main coronary artery disease and with 5-year follow-up data. With the use of bayesian methods, the largest and most publicized RCT (EXCEL; Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization; 2019) was reanalyzed (1) as an isolated entity using noninformative priors and (2) in the context of previous knowledge using informative priors derived from similar trials. Published aggregate data were used with assignments from each trial following the original intention-to-treat principle. Combining EXCEL data with varying levels of prior information using Bayes theorem provided final (posterior) probability distributions for primary and secondary outcomes. A composite end point of death, nonfatal myocardial infarction, and stroke was the primary EXCEL outcome and was accordingly the primary outcome for this reanalysis. Secondary analyses were performed for isolated all-cause mortality and for the composite outcome along with repeated revascularization procedures. When EXCEL data were analyzed using the originally stated noninferiority design, the 5-year primary outcome difference reported (2.8%; 95% CI, -0.9% to 6.5%) exceeded the predefined 4.2% noninferiority margin; thus, the null hypothesis of PCI inferiority could not be rejected. By contrast, the present bayesian analysis of the EXCEL primary outcome estimated 95% probability that the 5-year primary outcome difference was increased with PCI compared with CABG and 87% probability that this difference was greater than 1 extra event per 100 patients treated. Bayesian analyses also suggested 99% probability that EXCEL total mortality was increased with PCI and 94% probability that this absolute difference exceeded 1 extra deaths per 100 treated. A systematic review identified 3 other RCTs that studied the same question. The incorporation of this prior knowledge reduced the estimated probability of any excess mortality with PCI to 85%. For the secondary composite end point, which also included repeated revascularizations, there were estimated probabilities of 98% for at least 4 extra events and of 90% for at least 5 extra events per 100 patients treated with PCI. Bayesian analysis assisted in RCT data interpretation and specifically suggested, whether based on EXCEL results alone or on the totality of available evidence, that PCI was associated with inferior long-term results for all events, including mortality, compared with CABG for patients with left main coronary artery disease.

May 2020 at a glance: ischaemic heart failure and sex-related differences.

Almost half of patients with heart failure (HF) had an ischaemic aetiology.1 However, HF occurrence in patients with chronic coronary syndrome is unclear. During a 5-year follow-up, Parma et al.2 observed a 16.4% incidence of cardiovascular death, HF hospitalization and new-onset HF (primary endpoint) in patients with chronic coronary syndrome without history of HF. Hospitalization for HF and new-onset HF occurred in 2.8% and 11.6% of patients, respectively. Malik et al.3 showed that the risk of developing HF at 5 years after the diagnosis of diabetes is low in patients without ischaemic heart disease (IHD) or end-stage renal disease (ESRD) (4%), intermediate (8-12%) in diabetic subjects with IHD or ESRD, and high (20%) in those with diabetes complicated by both IHD and ESRD. Sama et al.4 performed a network analysis to recognize pathophysiological pathways distinguishing ischaemic from non-ischaemic HF. They identified six pathways, related to inflammation, endothelial dysfunction superoxide production, coagulation, and atherosclerosis, and five key network proteins, acid phosphatase 5, epidermal growth factor receptor, insulin-like growth factor binding protein-1, plasminogen activator urokinase receptor, and secreted phosphoprotein 1, as specific for ischaemic HF and potential targets for specific treatment. The role of coronary revascularization in asymptomatic patients with HF of ischaemic aetiology remains debated.5 A comprehensive review showing the pathophysiology and diagnosis of this condition, as well as the role of coronary revascularization, is reported in this issue.6 Thuijs et al.7 performed a pre-specified analysis from the Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial. They found no differences in the composite of death, stroke, or myocardial infarction at 3 years in patients stratified by left ventricular ejection fraction (LVEF) and treated by percutaneous vs. surgical revascularization of the left main coronary artery. However, patients with reduced LVEF had worse outcomes compared to the others. Whether indications for implantable cardioverter-defibrillator (ICD) therapy after acute myocardial infarction should be merely based on LVEF is debated.8 Docherty et al.9 developed and validated a risk model to predict the occurrence of sudden cardiac death early and up to 2 years after myocardial infarction. Including simple variables, this score could easily identify patients who may benefit from ICD therapy. Fudim et al.10 noted that 1-year mortality after ICD implantation, for primary or secondary prevention, increased with increasing age reaching an incidence of 32% in the oldest patients (median age 82 years). This confirms the importance of a careful selection of ICD candidates in order to avoid futility. Treatment of ischaemic HF with mesenchymal stem cells is an area of active research.11 Mathiesen et al.11 reported the long-term results of the Autologous Mesenchymal Stromal Cell Therapy in Heart Failure (MCS-HF) trial, a 2:1 randomized double-blind trial comparing intramyocardial injections of autologous mesenchymal stromal cells (MSCs) vs. placebo in patients with ischaemic HF. They found a significant reduction in left ventricular end-systolic volume in the treatment compared to the placebo arm. Also LVEF, stroke volume and myocardial mass improved after MCS injection. Studies exploring the efficacy of heterologous MCSs in ischaemic HF are ongoing.12 Sex-related differences in HF biomarkers are known.13 Suthahar et al.14 reviewed sex-specific differences and the interaction with obesity. Rossello et al.15 conducted a patient-level meta-analysis including three randomized trials comparing the effect of mineralocorticoid receptor antagonists (MRA) and placebo. Women differ from men in their clinical features and event rates. However, no sex-specific impact of MRA on cardiovascular mortality and HF hospitalization was noted. Interestingly, sex, and namely male sex, was an independent predictor of MRA non-use in a recent large survey.16

Mortality After Repeat Revascularization Following PCI or CABG for Left Main Disease: The EXCEL Trial

ObjectivesThe 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). BackgroundThe impact on mortality of the need of repeat revascularization following PCI or CABG in patients with unprotected LMCAD is unknown. MethodsAll 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. ResultsDuring 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 < 0.0001) consistently after both PCI and CABG (pint = 0.85 for both endpoints). Although target vessel revascularization and target lesion revascularization were both associated with an increased risk for mortality, target vessel non–target lesion revascularization and non–target vessel revascularization were not. ConclusionsIn 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)

Insulin resistance and the severity of coronary artery disease based on obesity status in stable-angina patients: A cross-sectional analysis

The evaluation of coronary artery disease (CAD) concerning the metabolic status and body mass index (BMI) is poorly studied. This study was designed to observe the relationship between insulin resistance (IR) and the severity of CAD on the basis of the metabolic and phenotypic status in stable-angina patients. A cross-sectional study was conducted on 532 patients with stable angina and coronary angiogram was done to diagnose the CAD for all. Determination of metabolic obesity was done using the National Cholesterol Education Program-Adult Treatment Panel III criteria. Phenotypic obesity was defined as BMI ≥ 25 kg/m2. Homeostasis model assessment IR in correlation with the severity of CAD was measured using SYNTAX (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries) Score. The average age of the patients was 57.58 ± 10.40 years, and 69.4% were males. Out of 532 subjects, 51.3% were hypertensive, 14.5% were smokers, 29.1% consumed alcohol, 49.3% were metabolically obese, and 50% were phenotypically obese. Increase in IR increased the risk of severity of CAD in metabolically obese subjects (OR = 2.51, p = 0.048). In the phenotypically obese group, the relationship between IR and the severity of CAD was not statistically significant (OR = −2.19, p = 0.08). The study concludes that the increased IR increases the risk of severity of CAD in metabolically obese subjects.

Contemporary Outcomes Following Coronary Artery Bypass Graft Surgery for Left Main Disease

BackgroundAlthough results of percutaneous coronary intervention (PCI) have been steadily improving, whether surgical outcomes have improved over time is not fully elucidated. ObjectivesThis study sought to compare the current outcomes of patients undergoing coronary artery bypass grafting (CABG) with prior surgical results, in the context of randomized trials including the left main (LM) coronary artery stem. MethodsThe authors performed a propensity-matched analysis of patients randomized to CABG in the SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) (enrollment period 2005 to 2007) and EXCEL (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) (enrollment period 2010 to 2014) trials. All patients had left main (LM) disease with or without multivessel disease. Adjustment was based on 15 clinical and angiographic variables, including anatomic SYNTAX score, with a 2:1 ratio for the EXCEL and SYNTAX trials, collectively analyzing 909 subjects (n = 580 and n = 329, respectively). The primary endpoint was the composite of all-cause death, myocardial infarction (MI), stroke, or ischemia-driven revascularization at 3 years. ResultsBaseline characteristics, anatomic SYNTAX score, number and types of grafts, and duration of hospitalization for the procedures were similar in both groups. CABG procedures in the EXCEL compared with the SYNTAX trial were more often off-pump (29.6% vs. 15.4%; p < 0.001), and guideline-directed medical therapies were used more frequently in the EXCEL surgical cohort. The primary endpoint occurred in 14.0% and 20.9% (p = 0.008) of patients in the EXCEL and SYNTAX trials, respectively. With the exception of MI (4.1% vs. 3.7%), all nonhierarchical events tended to contribute to the improved outcomes in the more recent trial: all-cause death (5.5% vs. 8.5%), stroke (3.1% vs. 5.1%), and ischemia-driven revascularization (7.1% vs. 9.4%) in the EXCEL and SYNTAX trials, respectively. ConclusionsOver a 5- to 7-year period, significant improvement in event-free survival after surgical revascularization for LM disease at 3 years was noted between the SYNTAX and EXCEL trials, consistent with improving results with cardiac surgery over time. (Synergy Between PCI With Taxus and Cardiac Surgery [SYNTAX]; NCT00114972; Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization [EXCEL]; NCT01205776)