Secrets of Success in Unprotected Left Main Intervention: Patient and Lesion Selection

Madan Sharma, MD and Yerem Yeghiazarians, MD
Madan Sharma, MD and Yerem Yeghiazarians, MD

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.



1. Chaitman BR, Fisher LD, Bourassa MG, et al. Effect of coronary bypass surgery on survival patterns in subsets of patients with left main coronary artery disease. Report of the collaborative Study in Coronary Artery Surgery (CASS). Am J Cardiol 1981;48:765–777.

2. O’Keefe JH Jr, Hartzler GO, Rutherford BD, et al. Left main coronary angioplasty: Early and late results of 127 acute and elective procedures. Am J Cardiol 1989;64:144 –147.

3. Takagi T, Stankovic G, Finci L, et al. Results and long-term predictors of adverse clinical events after elective percutaneous interventions on unprotected left main coronary artery. Circulation 2002;106:698–702.

4. Silvestri M, Barragan P, Sainsous J, et al. Unprotected left main coronary artery stenting: Immediate and medium-term outcomes of 140 elective procedures. J Am Coll Cardiol 2000;35:1543–1550.

5. Lopez JJ, Ho KK, Stoler RC, et al. Percutaneous treatment of protected and unprotected left main coronary stenoses with new devices: Immediate angiographic results and intermediate-term follow-up. J Am Coll Cardiol 1997;29:345–352.

6. Black A, Cortina R, Bossi I, et al. Unprotected left main coronary artery stenting: Correlates of midterm survival and impact of patient selection. J Am Coll Cardiol 2001;37:832–838.

7. Park SJ, Park SW, Hong MK, et al. Stenting of unprotected left main coronary artery stenoses: Immediate and late outcomes. J Am Coll Cardiol 1998;31:37–42.

8. Tan WA, Tamai H, Park SJ, et al. for the ULTIMA Investigators. Long-term clinical outcomes after unprotected left main trunk percutaneous revascularization in 279 patients. Circulation 2001;104:1609–1614.

9. Moses JW, Leon MB, Popma JJ, et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 2003;349:1315–1323.

10. Stone GW, Ellis SG, Cox DA, et al. A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease. N Engl J Med 2004;350:221–231.

11. Stone GW, Ellis SG, Cox DA, et al, TAXUS-IV Investigators. One-year clinical results with the slow-release, polymer-based, paclitaxel-eluting Taxus stent: The TAXUS-IV trial. Circulation 2004;109:1942–1947.

12. Schofer J, Shluter M, Gershlick AH, et al. Sirolimus-eluting stents for treatment of patients with long atherosclerotic lesions in small coronary arteries: Double-blind, randomized controlled trial (E-SIRIUS). Lancet 2003;362:1093–1099.

13. Schampaert E, Cohen EA, Schlüter M, et al. The Canadian study of the sirolimuseluting stent in the treatment of patients with long de novo lesions in small native coronary arteries (C-SIRIUS). J Am Coll Cardiol 2004;43:1110 –1115.

14. Powell BD, Rihal CS, Bell MR, et al Anticipated impact of drug-eluting stents on referral patterns for coronary artery bypass graft surgery: A population-based angiographic analysis. Mayo Clin Proc 2004;79:769–772.

15. Lee MS, Kapoor N, Jamal F, et al. Comparison of coronary artery bypass surgery with percutaneous coronary intervention with drug-eluting stents for unprotected left main coronary artery disease. J Am Coll Cardiol 2006;47:864–870.

16. Price MJ, Cristea E, Sawhney N, et al. Serial angiographic follow-up of sirolimuseluting stents for unprotected left main coronary artery revascularization. J Am Coll Cardiol 2006;47:871–877.

17. Park SJ, Kim YH, Lee BK, et al. Sirolimus-eluting stent implantation for unprotected left main coronary artery stenosis. Comparison with bare metal stent implantation. J Am Coll Cardiol 2005;45:351–356.

18. Chieffo A, Stankovic G, Bonizzoni E, et al. Early and mid-term results of drug-eluting stent implantation in unprotected left main. Circulation 2005;111:791–795.

19. Valgimigli M, Van Mieghem CA, Ong AT, et al. Short- and long-term clinical outcome after drug-eluting stent implantation for the percutaneous treatment of left main coronary artery disease: Insights from the Rapamycin-Eluting and taxus-Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH and T-SEARCH) registries. Circulation 2005;111:1383–1389.

20. Nashef SA, Roques F, Michel P, et al. European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac Surg 1999;16:9–13.

21. Singh M, Rihal C, Selzer F, et al. Validation of Mayo Clinic Risk adjustment model for inhospital complications after percutaneous coronary interventions, using the National Heart, Lung, and Blood Institute Dynamuc Registry. J Am Coll Cardiol 2003;42:1722–1728.

22. Park SJ, Park SW, Hong MK, et al. Long-term (three-year) outcomes after stenting of unprotected left main coronary artery stenosis in patients with normal left ventricular function. Am J Cardiol 2003;91:12–16.

23. Chieffo A, Stankovic G, Bonizzoni E, et al. Results and long-term predictors of adverse clinical events after elective percutaneous interventions on unprotected left main coronary artery. Circulation 2002;106:698–702.

24. Valgimigli M, Malagutti P, Rodriguez-Granillo GA, et al. Distal left main coronary disease is a major predictor of outcome in patients undergoing percutaneous intervention in the drug-eluting stent era: An integrated clinical and angiographic analysis based on the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) and Taxus-Stent Evaluated At Rotterdam Cardiology Hospital (TSEARCH) Registry. J Am Coll Cardiol 2006;47:1530–1537.

25. Steigen TK, Maeng M, Wiseth R, et al. Randomized study on simple versus complex stenting of coronary artery bifurcation lesions. The Nordic Bifurcation Study. Circulation 2006;114:1955–1961.

26. Vecchio S, Chechi T, Vittori G, et al. Outlook of drug-eluting stent implantation for unprotected left main disease: Insights on long-term clinical predictors. J Invasive Cardiol 2007:19:381-187.