Effectiveness Of Left Main Revascularization 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.

Comparing results of bypass surgery and percutaneous coronary intervention for left main disease by surgical revascularization pump strategy

ObjectiveWe performed a post hoc analysis of the Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial to determine the effect an on-versus off-pump strategy had on outcomes when compared with percutaneous coronary intervention. MethodsAll randomized patients in EXCEL (n = 1905) were included. The outcomes of interest were the primary end point composite of death from any cause, stroke, or myocardial infarction; the composite study end point or ischemia-driven revascularization; and the rate of death from any cause at 5 years. Event rates were based on Kaplan–Meier estimates in time-to-first-event analyses. ResultsPropensity matching resulted in groups of 1142 patients (571 each) for on-pump coronary artery bypass grafting versus percutaneous coronary intervention and 472 patients (236 each) for off-pump coronary artery bypass grafting versus percutaneous coronary intervention. In the on-pump coronary artery bypass grafting versus percutaneous coronary intervention matched groups, the composite end point was similar (18.0% vs 22.1%, P = .19) and the composite end point or ischemia-driven revascularization (23.3% vs 31.0%, P = .01) was lower, and mortality (7.6% vs 11.8%, P = .025) was lower in the on-pump coronary artery bypass grafting group at 5 years. In the off-pump coronary artery bypass grafting versus percutaneous coronary intervention matched groups, the composite end point (19.4% vs 22.2%, P = .47), composite end point or ischemia-driven revascularization (25.9% vs 34.2%, P = .07), and mortality (12.5% vs 14.2%, P = .59) were similar at 5 years. ConclusionsIn the EXCEL trial, on-pump coronary artery bypass grafting was associated with a decreased 5-year rate of the composite outcome of death, stroke, myocardial infarction, or ischemia-driven revascularization, and decreased mortality when compared with percutaneous coronary intervention, whereas outcomes of off-pump coronary artery bypass grafting were similar to percutaneous coronary intervention.

Applicability of the EXCEL Trial Criteria to an All-Comers Real-World Cohort of Unprotected Left Main Percutaneous Coronary Intervention

The Evaluation of XIENCE versus EXCEL (Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial is the largest randomized study comparing percutaneous coronary intervention (PCI) with second-generation drug-eluting stents and bypass surgery in unprotected left main disease (ULMD). Our aim was to assess which proportion of patients from a contemporary all-comer population of ULMD PCI would be eligible for the EXCEL trial and whether these patients show different long-term outcomes than the rest of the ULMD population. A total of 246 consecutive patients underwent ULMD PCI between January 2018 and December 2021 and were retrospectively analyzed. After application of the EXCEL trial inclusion and exclusion criteria, 98 patients (39%) were allocated to the "EXCEL-like" cohort and 148 to the "non-EXCEL-like." Baseline characteristics of the 2 groups were substantially comparable. The mean baseline SYNTAX score was lower in the EXCEL-like patients than the non-EXCEL-like group (20.1 ± 7.1 vs 23.0 ± 11.2, p=0.025), with the latter also showing a higher degree of incomplete revascularization (residual SYNTAX score >8:11% vs 26%, p=0.005). At 1year, the cumulative major adverse cardiovascular and cerebral events rate was 7% for the EXCEL-like and 17% for the non-EXCEL-like patients, respectively (p=0.03). At the last follow-up available, the significant difference in major adverse cardiovascular and cerebral events rate persisted (19% vs 37%, p=0.02) and a significant difference in any unplanned revascularization was also shown (1.5% vs 13%, p=0.04). In conclusion, in a contemporary real-world cohort of ULMD PCI, only a minority of patients could be enrolled in the EXCEL trial; the EXCEL-like patients, in our population, showed less clinical events at long-term follow-up than the cohort of patients who were ineligible for EXCEL, despite comparable baseline cardiovascular profiles; these findings may challenge a broad external applicability of the results of the EXCEL trial in routine clinical activity.

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.

1127 APPLICABILITY OF THE EXCEL TRIAL CRITERIA IN AN ALL-COMERS REAL-WORLD POPULATION OF UNPROTECTED LEFT MAIN PCI

Abstract Background The Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial is the largest randomized trial comparing percutaneous coronary intervention (PCI) with 2nd generation drug eluting stents (DES) and bypass surgery in unprotected left main disease (ULMD). Our aim was to assess which proportion of patients from a contemporary all-comers population of ULMD-PCI would be eligible for the EXCEL trial and whether these patients showed different short- and long-term outcomes than the rest of the population. Methods and results A total of 246 consecutive patients that underwent ULMD-PCI between January 2018 and December 2021, were retrospectively analyzed. After application of the EXCEL trial inclusion ed exclusion criteria, 98 patients (38.9%) were allocated in the "Excel-like" cohort and 148 in the "Non-Excel-like". Baseline characteristics of the two groups were substantially comparable. Mean baseline Syntax Score (SS) was significantly lower in the "Excel-like" patients (Excel 20.1 ± 7.1 VS Non-Excel 23.0 ± 11.2; p-value = 0.025) than the "Non-Excel-like" group with the latter showing also a higher degree of incomplete revascularization (rSS &amp;gt;8: Excel 11.2%.VS Non-Excel 25.7%; p-value 0.005). At 1 year the cumulative major adverse cardiovascular and cerebral events (MACCEs) rates were 7.2% and 17.2% for the "Excel-like" and "Non-Excel-like" patients respectively (Log-rank p-value = 0.03). At last follow-up available the significant difference in MACCEs rate persisted (Excel 19.3%, VS Non-Excel 37%, Log-rank p-value 0.02) and a significant difference in any unplanned revascularization was also shown (Excel 1.5% VS Non-Excel 12.6%; p-value 0.04). Conclusions in a contemporary real-world cohort of ULMD-PCI only a minority of the patients could be enrolled in the EXCEL trial. This cohort of patients showed a more extensive revascularization and less clinical events at long-term follow-up despite comparable burden of cardiovascular risk factors and atherosclerotic coronary disease. These findings "challenge" the external applicability of the results of the Excel trial in the routine clinical activity.

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.

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.

Therapeutic Options for Left Main, Left Main Equivalent, and Three-Vessel Disease.

Patients with left main, left main equivalent, and three-vessel coronary artery disease (CAD) represent an overlapping spectrum of patients with advanced CAD that is associated with an adverse prognosis. Guideline-directed medical therapy is a necessary but often insufficient treatment option, as such patients frequently need mechanical revascularization by either coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). In patients with advanced CAD presenting with acute myocardial infarction, PCI, of course, is the preferred treatment option. For stable patients with advanced CAD, CABG surgery remains the standard of care. However, observations from the SYNergy between Percutaneous Coronary Intervention with TAXus and Cardiac Surgery (SYNTAX) trial suggest that PCI may be a useful alternative in patients with three-vessel disease with a low SYNTAX score as well as in patients with left main disease and a low or intermediate SYNTAX score. In the subset of patients with diabetes mellitus, the Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease trial unequivocally demonstrated the superiority of CABG surgery in improving outcomes. The findings of the recently published Everolimus-Eluting Stent System versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization and Nordic-Baltic-British Left Main Revascularization study trials point to a favorable role for PCI in certain low-to-moderate risk patients with left main stem disease.

Implications of Alternative Definitions of Peri-Procedural Myocardial Infarction After Coronary Revascularization

BackgroundVarying definitions of procedural myocardial infarction (PMI) are in widespread use. ObjectivesThis 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. MethodsThe pre-specified protocol definition of PMI (PMIProt) required a large elevation of creatine kinase-MB (CK-MB), with identical threshold for both procedures. The Third Universal Definition of MI (types 4a and 5) (PMIUD) required lesser biomarker elevations but with supporting evidence of myocardial ischemia, different after PCI and CABG. For the PMIUD, troponins were used preferentially (available in 49.5% of patients), CK-MB otherwise. The multivariable relationship between each PMI type and 5-year mortality was determined. ResultsPMIProt occurred in 34 of 935 (3.6%) patients after PCI and 56 of 923 (6.1%) patients after CABG (difference −2.4%; 95% confidence interval [CI]: −4.4% to −0.5%; p = 0.015). The corresponding rates of PMIUD were 37 (4.0%) and 20 (2.2%), respectively (difference 1.8%; 95% CI: 0.2% to 3.4%; p = 0.025). Both PMIProt and PMIUD were associated with 5-year cardiovascular mortality (adjusted hazard ratio [HR]: 2.18 [95% CI: 1.13 to 4.23] and 2.87 [95% CI: 1.44 to 5.73], respectively). PMIProt was associated with a consistent hazard of cardiovascular mortality after both PCI and CABG (pinteraction = 0.86). Conversely, PMIUD was strongly associated with cardiovascular mortality after CABG (adjusted HR: 11.94; 95% CI: 4.84 to 29.47) but not after PCI (adjusted HR: 1.14; 95% CI: 0.35 to 3.67) (pinteraction = 0.004). Results were similar for all-cause mortality and with varying PMIUD biomarker definitions. Only large biomarker elevations (CK-MB ≥10× upper reference limit and troponin ≥70× upper reference limit) were associated with mortality. ConclusionsThe rates of PMI after PCI and CABG vary greatly with different definitions. In the EXCEL trial, the pre-specified PMIProt was associated with similar hazard after PCI and CABG, whereas PMIUD was strongly associated with mortality after CABG but not after PCI. (EXCEL Clinical Trial [EXCEL]; NCT01205776)

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)

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)

Off-pump versus on-pump bypass surgery for left main coronary artery disease (EXCEL study) - is experience the unknown variable?

A post hoc analysis of the Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) data compared off-pump coronary artery bypass (OPCAB) technique with conventional coronary artery bypass grafting (CABG). It was reported that OPCAB was associated with lower rate of revascularization especially in the inferolateral wall and carried increased risk of 3-year all-cause mortality compared to on-pump CABG. However, the study does not provide any information on the experience of participating surgeons which is a key determinant of outcomes in OPCAB surgery. In the absence of this key variable, the extrapolation and applicability of this finding to the wider surgical practice, especially in countries like India and Japan, may not be accurate.

Off-Pump Versus On-Pump Bypass Surgery for Left Main Coronary Artery Disease

BackgroundConcerns remain for a greater risk of incomplete revascularization and reduced survival with off-pump coronary artery bypass grafting (CABG) surgery compared with on-pump surgery particularly in patients with left main disease and extensive underlying myocardial ischemia. ObjectivesThis study sought to compare outcomes following off-pump versus on-pump surgery for left main disease by performing a post hoc analysis from the multicenter, randomized EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial. MethodsThe EXCEL trial was designed to compare percutaneous coronary intervention with everolimus-eluting stents versus CABG in patients with left main disease. CABG was performed with or without cardiopulmonary bypass (on-pump vs. off-pump surgery) according to the discretion of the operator. The 3-year outcomes in the off-pump and on-pump groups were compared using inverse probability of treatment weighting (IPTW) for treatment effect estimation. ResultsAmong 923 CABG patients, 652 and 271 patients underwent on-pump and off-pump surgery, respectively. Despite a similar extent of disease, off-pump surgery was associated with a lower rate of revascularization of the left circumflex coronary artery (84.1% vs. 90.0%; p = 0.01) and right coronary artery (31.1% vs. 40.6%; p = 0.007). After IPTW adjustment for baseline differences, off-pump surgery was associated with a significantly increased risk of 3-year all-cause death (8.8% vs. 4.5%; hazard ratio: 1.94; 95% confidence interval: 1.10 to 3.41; p = 0.02) and a nonsignificant difference in the risk for the composite endpoint of death, myocardial infarction, or stroke (11.8% vs. 9.2%; hazard ratio: 1.28; 95% confidence interval: 0.82 to 2.00; p = 0.28). ConclusionsAmong patients with left main disease treated with CABG in the EXCEL trial, off-pump surgery was associated with a lower rate of revascularization of the coronary arteries supplying the inferolateral wall and an increased risk of 3-year all-cause death compared with on-pump surgery.

Outcomes of left main revascularization in patients with acute coronary syndromes and stable ischemic heart disease: Analysis from the EXCEL trial

Prompt revascularization is often required in acute coronary syndromes (ACS), whereas stable ischemic heart disease (SIHD) may allow for more measured procedural planning. Whether the acuity of presentation preferentially affects outcomes after coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in patients with left main coronary artery disease (LMCAD) is unknown. We investigated whether the acuity of presentation discriminated patients who derived a differential benefit from PCI versus CABG in the randomized Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial. We used multivariable Cox models to assess the interaction between the acuity of presentation, type of revascularization and outcomes in patients with low or intermediate SYNTAX scores enrolled in EXCEL. At baseline, 1151 patients (60.7%) presented with SIHD and 746 patients (39.3%) presented with an ACS. The acuity of presentation was not associated with the primary endpoint of all-cause death, MI, or stroke at 3 years (multivariable adjusted hazard ratio [HR] 0.94; 95% CI 0.70-1.26, P = .64). The primary endpoint rate was similar in patients assigned to PCI versus CABG whether they presented with SIHD (adjusted HR 1.04; 95% CI 0.73-1.48]) or with ACS (HR 0.82; 95% CI 0.54-1.26) (Pinteraction = .34). The acuity of presentation did not predict outcomes in patients with LMCAD undergoing revascularization, nor did it discriminate patients who derive greater event-free survival from PCI versus CABG.

Bypass Surgery or Stenting for Left Main Coronary Artery Disease in Patients With Diabetes

BackgroundThe randomized EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial reported a similar rate of the 3-year composite primary endpoint of death, myocardial infarction (MI), or stroke in patients with left main coronary artery disease (LMCAD) and site-assessed low or intermediate SYNTAX scores treated with percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). Whether these results are consistent in high-risk patients with diabetes, who have fared relatively better with CABG in most prior trials, is unknown. ObjectivesIn this pre-specified subgroup analysis from the EXCEL trial, the authors sought to examine the effect of diabetes in patients with LMCAD treated with PCI versus CABG. MethodsPatients (N = 1,905) with LMCAD and site-assessed low or intermediate CAD complexity (SYNTAX scores ≤32) were randomized 1:1 to PCI with everolimus-eluting stents versus CABG, stratified by the presence of diabetes. The primary endpoint was the rate of a composite of all-cause death, stroke, or MI at 3 years. Outcomes were examined in patients with (n = 554) and without (n = 1,350) diabetes. ResultsThe 3-year composite primary endpoint was significantly higher in diabetic compared with nondiabetic patients (20.0% vs. 12.9%; p < 0.001). The rate of the 3-year primary endpoint was similar after treatment with PCI and CABG in diabetic patients (20.7% vs. 19.3%, respectively; hazard ratio: 1.03; 95% confidence interval: 0.71 to 1.50; p = 0.87) and nondiabetic patients (12.9% vs. 12.9%, respectively; hazard ratio: 0.98; 95% confidence interval: 0.73 to 1.32; p = 0.89). All-cause death at 3 years occurred in 13.6% of PCI and 9.0% of CABG patients (p = 0.046), although no significant interaction was present between diabetes status and treatment for all-cause death (p = 0.22) or other endpoints, including the 3-year primary endpoint (p = 0.82) or the major secondary endpoints of death, MI, or stroke at 30 days (p = 0.61) or death, MI, stroke, or ischemia-driven revascularization at 3 years (p = 0.65). ConclusionsIn the EXCEL trial, the relative 30-day and 3-year outcomes of PCI with everolimus-eluting stents versus CABG were consistent in diabetic and nondiabetic patients with LMCAD and site-assessed low or intermediate SYNTAX scores.(Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization [EXCEL]; NCT01205776)

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)

Impact of chronic obstructive pulmonary disease on prognosis after percutaneous coronary intervention and bypass surgery for left main coronary artery disease: an analysis from the EXCEL trial.

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. 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. 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 < 0.0001), death (17.1% vs 7.5%, P = 0.0005) and myocardial infarction (18.3% vs 7.3%, P < 0.0001), but not stroke (3.3% vs 2.9%, P = 0.84). There were no statistically significant interactions in the relative risks of PCI versus CABG for the primary composite end point in patients with and without COPD at 30 days [hazard ratio (HR) 0.39, 95% confidence interval (CI) 0.12-1.21 vs HR 0.55, 95% CI 0.29-1.06; Pinteraction = 0.61] or at 3 years (HR 0.85, 95% CI 0.46-1.56 vs HR 1.28, 95% CI 0.84-1.94; Pinteraction = 0.27). In the EXCEL trial, COPD was independently associated with poor prognosis after left main coronary artery disease revascularization. The relative risks of PCI versus CABG at 30 days and 3 years were consistent in patients with and without COPD. http://www.clinicaltrials.gov; NCT01205776.