Despite advances in percutaneous coronary intervention techniques over the last two decades, the unprotected left main has largely remained the domain of cardiovascular surgery. The subset of patients with left main disease in the Collaborative Study in Coronary Artery Surgery (CASS) study demonstrated superior outcomes with bypass surgery as compared with medical therapy.1 While percutaneous intervention of the unprotected left main artery has been reported as early as in the late 1980s, initial results with balloon angioplasty of the left main were poor, with 1-year mortality approaching 30%.2 Coronary stenting clearly improved both acute results and restenosis rates as compared to balloon angioplasty, however, repeat revascularization rates remained high at 25–30%.3–8 With the advent of drug-eluting stents (DES), clinical restenosis rates have significantly dropped for most lesion types,9–13 but similar restenosis rates and clinical outcomes have not been consistently noted with unprotected left main stenting.14–25
In this issue of the Journal, Vecchio et al have described the safety, feasibility and mid-term outcomes of patients undergoing DES implantation for unprotected left main coronary artery (LMCA) stenosis.26 The study enrolled 114 consecutive patients with de novo unprotected LMCA stenosis, and after successful PCI with DES in all enrolled patients (35% sirolimus and 65% paclitaxel stents), followed them over a mean period of 17.1 ± 9.1 months. The primary endpoint of the study was the occurrence of major adverse cardiovascular events (MACE). The inclusion criteria were symptomatic LMCA disease or documented myocardial ischemia and angiographic documentation of ≥ 50% stenosis. It should be noted, however, that patients were preselected based on “suitable” anatomy for stenting, patient’s and physician’s preference for PCI and contraindications to surgery. The mean age was 75 years. Seventy-four percent of the enrolled patients were males and 29% had diabetes. Only 30% of the cases were elective for stable angina, whereas the remainder was urgent or emergent. The majority of patients in this study with non-ostial left main disease had distal/bifurcation disease as compared to mid-portion left main stenosis (61% vs. 9%).
Debulking coronary procedures were used in only 1.8% of the patients and intravascular ultrasound (IVUS) guidance in 7.9%. Intra-aortic balloon pump support was needed in 28% of patients. The mean stent diameter was 3.1 ± 0.3 mm, with an average of 1.2 ± 0.4 stents per lesion. Direct stenting was performed in 11.4% and postdilatation performed in 55.3% of patients. A variety of strategies were used in bifurcation lesions, with provisional T-stenting being the most common (63%). Final kissing-balloon inflations in distal lesions were performed in 94% of those patients. All patients received heparin to achieve an activated clotting time (ACT) > 250 seconds, however glycoprotein IIb/IIIa inhibitors were used in 40% of patients and their use was left to the physician’s discretion. All patients received aspirin 100 mg/day indefinitely, a loading dose of clopidogrel, followed by 75 mg/day for at least 9 months.
The in-hospital mortality rate was 3.5%. The overall MACE rate was 14.9%. An analysis of events out-of-hospital over the follow-up period revealed an overall mortality rate of 7.9%, with 3.5% cardiac-related deaths. Target lesion revascularization was performed in 7.9% of patients, and the incidence of stent thrombosis was 0.9%. Most of the angiographic restenosis was in-stent restenosis within the LMCA (63%), though in an additional 25% of cases, angiographic restenosis also involved the circumflex ostia. The overall restenosis rate was 7% in the cases in which follow-up angiography was performed. Notably, patients presenting with acute coronary syndromes were more likely to experience death, and all-cause mortality for non-ostial disease was more common in the dying patients (p = 0.05). MACE was more common in patients with mid or distal LMCA stenosis (p = 0.054).
While the study separates outcomes based on lesion location, i.e., ostial versus non-ostial, the number of patients with left main shaft disease was small (8.8% of total), and likely the outcomes in non-ostial disease were driven by distal disease (61% of total). As noted in earlier studies, distal left main disease remains a predictor of poor outcomes regardless of the choice of bifurcation strategy.15–19 Angiographic follow up was performed in only 40% of the patients in this study, and an argument could be made for protocol-mandated angiography in all patients in similar studies. Restenosis in this location is not a benign entity, and other studies of unprotected left main stenting have reiterated the importance of follow-up angiography.3–8,15–19
To further assess risk for the patients in this study, the Euroscore was used to stratify the surgical risk of death at 30 days, while the Mayo Clinic risk score was used to stratify the risk of in-hospital complications.20,21 The Euroscore system considers patient-related variables such as age, extracardiac arteriopathy, renal function and left ventricular ejectionfraction; the Mayo Clinic Risk score considers five clinical variables (including age, congestive heart failure, New York Heart Association Functional Class > III, urgent/emergent PCI, chronic renal disease and preprocedural cardiogenic shock), and three angiographic variables (LMCA disease, multivessel disease and presence of thrombus in any lesion). Notably, Vecchio et al report that all non-surviving patients had a high Euroscore > 6.26 Survival analysis demonstrated that patients with a Euroscore < 11 had significantly improved survival rates over those with higher scores. As the authors point out, the Mayo Clinic Scoring system did not separate out the survivors from the non-survivors, possibly because this scoring system does not consider specific patient features such as left ventricular function that may affect long-term outcome in these patients.
In summary, the study addresses the questions on unprotected left main stenting that have been raised in other studies on the same issue.15–19,22–24 Left main stenting is becoming a relatively safe and feasible procedure as technology evolves, albeit with meticulous attention to lesion location and patient selection. Outcomes in this study were poor in patients with distal left main disease and those with acute coronary syndrome as their initial presentation. Systems of risk stratification (i.e.,Euroscore) could be factored in the decision-making process in patient selection, since all non-survivors in this study were classified as high risk by Euroscore criteria. As such, in the subset of patients with non-bifurcation left main disease who are nondiabetic and have stable angina as their presentation, unprotected left main stenting in “suitable” anatomy may be a therapeutic option and may lead to clinical outcomes similar to or better than coronary artery bypass grafting surgery (CABG). Future randomized clinical trials will shed more light on outcomes, both clinical and angiographic, with unprotected left main stenting. Additionally, bifurcation lesion management is evolving, and with the development of dedicated bifurcation stents as well as biodegradable stent technology, restenosis rates in the distal left main location may well diminish in the future. Until such data are available, a recommendation cannot be made for routine unprotected left main stenting as an alternative to CABG for all patients with left main disease. Until then, unprotected left main stenting can certainly be considered in patients who are not surgical candidates due to comorbidities. However, these patients would then probably fall into the highrisk group, thereby negating to some extent the good outcomes noted with meticulous patient selection. If unprotected left main stenting is performed, we would recommend the use of intraprocedural IVUS, chronic dual antiplatelet therapy and follow-up angiography at the very least 3 months and 9 months after PCI. It goes without saying that these patients will, of course, need close long-term clinical follow up.
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