Early and long term results of the Left Main Coronary Artery Stenting LE MANS registry are now published and show that the implantation of a stent in left main disease is feasible, with long term mortality comparing favorably with outcomes of CABG studies.
Investigators also showed that the implantation of a drug-eluting stent significantly decreased the risk of major adverse cardiovascular and cerebral events MACCE and particularly improved survival in patients with distal left main coronary disease.
These findings are encouraging and support the need for long term follow up of patients with unprotected left main coronary artery disease randomized to drug eluting stents or CABG in large trials, write lead investigator Dr Pawel Buszman Medical University of Silesia, Katowice, Poland and colleagues in the report, published August 20, 2009 online in the Journal of the American College of Cardiology.
Commenting on the findings for heartwire, Dr David Kandzari Scripps Clinic, La Jolla, CA said the LE MANS registry report is one of many recent contributions that add to the growing momentum for PCI in left main disease, at least in selected patient populations. Although the data have limitations, including that they are nonrandomized and observational and represent a continuum over a long period of time, which reflects very different techniques and different types of stents, including bare-metal and drug eluting stents, the accumulation of data supports changing the guidelines for left main PCI.
Altogether, I think the LE MANS trials, and many of the other studies, including the ISAR-Left Main study, the SYNTAX left main cohort, and the MAIN COMPARE study published in 2008, contribute to an increasing momentum that is favoring a revision of the existing guidelines for left main PCI, said Kandzari. In particular, the American College of Cardiology and the American Heart Association currently label left main PCI as a class III indication unless patients are considered unsuitable candidates for bypass surgery. I think the level of evidence that we currently have, and notably, even in the absence of a direct randomized trial, is sufficient enough to advance the indication beyond its current level III status.

LE MANS trial and registry
Results of the LE MANS study, a trial comparing PCI vs CABG for left main disease, previously reported by heartwire, suggested that PCI may improve left ventricular ejection fraction to a greater degree than CABG, with similar MACCE free survival at two years. Those results were presented at the TCT 2005 meeting and were published in 2008 in the Journal of the American College of Cardiology.
The LE MANS registry includes 252 patients with unprotected left main coronary artery disease enrolled between March 1997 and February 2008 in three centers in Poland. In 60% of cases, the admission diagnosis was non-ST-segment acute coronary syndrome, and of these patients, 40% had non ST segment-elevation MI. In the majority of cases, direct stenting was the preferred technique, and 36% of patients were implanted with a drug-eluting stent.
After 12 months, angiographically confirmed restenosis was observed in 12% of patients. During long term follow up, which ranged from one to 11 years average 3.8 years, 25% of patients experienced a MACCE and 14% of patients died. The five and 10 year survival rates were 78.1% and 68.9%, respectively, and these rates, say researchers, compare favorably with long term outcomes in the Coronary Artery Surgery Study CASS trial and Duke University database.
Patients treated with drug-eluting stents also had significantly lower MACCE rates than those treated with a bare-metal stent, despite demographic and clinical data favoring the bare metal stent patients. Propensity score matching strengthened the benefit of drug eluting stents over bare-metal stents, report researchers.

Relaxation of the guidelines
In an editorial accompanying the report , Drs Jeffery Moses, Martin Leon, and Gregg Stone Columbia University Medical Center, New York write that certain conclusions can be drawn from the data, the first being that left-main stenting in skilled hands can be performed with low morbidity and mortality with no late catch-up. Second, the data show that drug eluting stents improved clinical outcomes compared with bare metal stents, primarily by reducing the need for repeat revascularizations. Third, they note that the rates of early, late, and very late stent thrombosis were low, despite limited use of antiplatelet therapy, and finally that long-term survival in left main stenting is excellent.
Based upon mounting evidence, there can be little dispute at this juncture that PCI can be offered as a safe alternative to CABG for a significant number of patients with left main disease, particularly nondiabetics without extensive concomitant coronary artery disease, they write.Left main PCI no longer needs to be confined to those patients who adamantly refuse or who are at unacceptably high risk for CABG.
Like Kandzari, Moses, Leon, and Stone believe there is sufficient data to support a relaxation of the ACC AHA guidelines so that left main PCI is no longer a class III indication. How much those guidelines could change is open to interpretation, said Kandzari, but the treatment of ostial and shaft left main disease, given the favorable prognosis with drug eluting stents, could be as high as a IIa indication, whereas as distal bifurcation might be a IIb indication.
To heartwire, Kandzari noted that stent thrombosis of the left main coronary artery is low, possibly because of the large size of the vessels or flow dynamics, and that these data are further supported with evidence from ISAR Left Main, where stent thrombosis was <1% at 30 days and there were no events beyond 30 days. He also noted that the anatomic location of disease in the left main segment is an important predictor of outcomes, with distal bifurcation associated with a higher risk of adverse events, mainly target lesion revascularization, than ostial or shaft disease. And finally, he said that stenosis of the left main appears to most effectively treated with a single stent provisional strategy.
All agreed that what s needed is a multicenter, prospective, randomized, controlled trial comparing drug-eluting stents with CABG in patients with unprotected left main coronary disease. Kandzari said that trial is currently being planned, but there remains some debate as to what end points should be used, particularly whether or not target lesion revascularization should be included in the end point. His opinion, he told heartwire, is that the best end point in a long term trial would be a composite of death, MI, and stroke.
My hope is that this trial would not only demonstrate clinical equivalence between the two strategies for certain left main patients, but equally important, that it would help us define which left main patients are suitable candidates for PCI and which are best treated with a bypass strategy, he said. In other words, it might be that patients with left main and highly complex multivessel disease would be better treated with surgery.