Coronary artery complexity: the importance of patient selection

The Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) Trial has been the first randomized clinical trial comparing percutaneous coronary intervention (PCI) (using first-generation DES) and CABG in ULM. Comparable 12-month-major adverse cardiovascular and cerebrovascular events (MACCE) were reported in both groups (16% PCI versus 14 % CABG, p=0.44). For the first time in the SYNTAX trial a novel scoring system, the Syntax score, has been validated in order to predict outcomes . In either low or intermediate baseline Syntax score, MACCE outcomes at 1 year were comparable between PCI and CABG. Conversely, in the higher terciles, patients treated by PCI presented a significant higher incidence of MACCE as compared to CABG. This difference was mostly led by an increased incidence of repeat revascularization in the PCI group and was a measure of the extension of CAD in this subgroup of patients . Similar outcomes were documented at five years follow-up .

The importance of device selection

At the beginning of percutaneous revascularization era, plain balloon angioplasty was attempted also on ULM, with unacceptable high rates of restenosis and early mortality . The adoption of bare metal stent (BMS) rejuvenated interest in PCI for ULM with reduction of acute procedural complications (e.g., recoil, abrupt closure, or dissection): procedural and short-term results were acceptable with, however, an excessive rate of in-stent restenosis and needing of repeat revascularization .

The introduction of first-generation DES, with a remarkable reduction of restenosis and repeat revascularization, allowed a spreading of percutaneous revascularization of ULM with good angiographic and clinical outcomes , which were confirmed in randomized trial against CABG .

Recently, two randomized trials evaluated second-generation DES compared to CABG in the treatment of ULM: the Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial and the percutaneous coronary angioplasty versus coronary artery bypass grafting in treatment of unprotected left main stenosis (NOBLE) trial . According to the results of the SYNTAX, only patients with low to intermediate Syntax score were enrolled in the EXCEL trial. At a median follow up of 3 years, PCI with second generation DES was non-inferior to CABG with respect to the rate of the composite end point of death, stroke, or myocardial infarction. However, the rate of repeat revascularization was greater in the PCI group (12.6% vs 7.5%, p<0.001). Of note only 24.8% of the patients in CABG group had a complete arterial revascularization not significantly different from what was reported from SYNTAX and despite the protocol recommendation to aim for complete arterial revascularization. Indeed, in the NOBLE trial, the primary end point was a composite of major adverse cardiac and cerebrovascular event (MACCE: death from any cause, non-procedural myocardial infarction, repeat revascularization or stroke), with the main hypothesis of PCI being non-inferior to CABG at 3-years follow-up. Patients treated with PCI had a significantly higher incidence of MACCE than surgical-treated patients (29% vs 19%, p=0.006) led by a higher incidence of repeat revascularization (16% vs 10%, p=0.032).

However, as recently demonstrated by Capodanno et al there is an important difference in the prognostic role between repeat revascularization and the other MACCE like death, myocardial infarction and stroke: arguably it may be more comparable to numerous other adverse outcomes such as bleeding, renal failure, or atrial fibrillation .

Current data confirm that PCI with current second-generation DES can be an affordable strategy for ULM revascularization, with freedom from death, myocardial infarction and cerebrovascular accident comparable to CABG in a population with low to intermediate Syntax score, at the price of a slight higher incidence of repeat revascularization.

The importance of device selection

At the beginning of percutaneous revascularization era, plain balloon angioplasty was attempted also on ULM, with unacceptable high rates of restenosis and early mortality . The adoption of bare metal stent (BMS) rejuvenated interest in PCI for ULM with reduction of acute procedural complications (e.g., recoil, abrupt closure, or dissection): procedural and short-term results were acceptable with, however, an excessive rate of in-stent restenosis and needing of repeat revascularization .

The introduction of first-generation DES, with a remarkable reduction of restenosis and repeat revascularization, allowed a spreading of percutaneous revascularization of ULM with good angiographic and clinical outcomes , which were confirmed in randomized trial against CABG .

Recently, two randomized trials evaluated second-generation DES compared to CABG in the treatment of ULM: the Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial and the percutaneous coronary angioplasty versus coronary artery bypass grafting in treatment of unprotected left main stenosis (NOBLE) trial . According to the results of the SYNTAX, only patients with low to intermediate Syntax score were enrolled in the EXCEL trial. At a median follow up of 3 years, PCI with second generation DES was non-inferior to CABG with respect to the rate of the composite end point of death, stroke, or myocardial infarction. However, the rate of repeat revascularization was greater in the PCI group (12.6% vs 7.5%, p<0.001). Of note only 24.8% of the patients in CABG group had a complete arterial revascularization not significantly different from what was reported from SYNTAX and despite the protocol recommendation to aim for complete arterial revascularization. Indeed, in the NOBLE trial, the primary end point was a composite of major adverse cardiac and cerebrovascular event (MACCE: death from any cause, non-procedural myocardial infarction, repeat revascularization or stroke), with the main hypothesis of PCI being non-inferior to CABG at 3-years follow-up. Patients treated with PCI had a significantly higher incidence of MACCE than surgical-treated patients (29% vs 19%, p=0.006) led by a higher incidence of repeat revascularization (16% vs 10%, p=0.032).

However, as recently demonstrated by Capodanno et al there is an important difference in the prognostic role between repeat revascularization and the other MACCE like death, myocardial infarction and stroke: arguably it may be more comparable to numerous other adverse outcomes such as bleeding, renal failure, or atrial fibrillation .

Current data confirm that PCI with current second-generation DES can be an affordable strategy for ULM revascularization, with freedom from death, myocardial infarction and cerebrovascular accident comparable to CABG in a population with low to intermediate Syntax score, at the price of a slight higher incidence of repeat revascularization.