Washington, DC -The first modern-day, randomized controlled study to compare unprotected left main stenting with CABG for left main disease indicates that an interventional strategy is not only feasible but may be safer [1]. The LE MANS study, presented here at the TCT 2005 meeting by Dr Pawel Buszman, showed left main stenting to improve left ventricular ejection fraction (LVEF) and decrease risk of major adverse cardiac and noncardiac events compared with CABG. Of note, target vessel revascularization (TVR) and mortality rates were no different between the two groups.

Dr Pawel Buszman

Buszman and colleagues randomized 52 patients to PCI and 53 patients to CABG with the aim of assessing LVEF, functional capacity, and angina status after 12 months—the primary end point of the study—as well as the secondary end points of major adverse cardiac events (MACE), hospital length of stay, survival, and any major adverse events (MAEs), defined as any MACE, procedure-related infection, bleeding, or renal or respiratory insufficiency.

In total, left internal mammary artery (LIMA) grafts were used in 79% of the CABG patients; in the PCI group, drug-eluting stents (DES) were used in 35% of patients. As Buszman explained during the late-breaking session today, the decision was made to use a DES only in vessels that were smaller than 3.8 mm in diameter.

Clear differences in LVEF

Strikingly, for a trial with such low numbers, change in LVEF at 12 months was significantly different between the two groups, with PCI patients experiencing a significant increase in LVEF, from about 55% to 60%, while LVEF in CABG patients remained more or less unchanged. Angina status and treadmill stress test at follow-up were similar between the two groups.

In terms of the secondary end points, rates of death, AMI, stroke, repeat revascularization, or heart failure at 30 days were no different between the two groups but, when combined (as specified by the MACE end point), were significantly more common among the CABG-treated patients. MAEs were also significantly higher, driven by the higher MACE rate, as well as a statistically different rate of infections and complications in the CABG-treated patients. Between 30 days and 12 months, however, no further statistically significant differences were seen between the two groups. Hospital stay, not surprisingly, was almost twice as long in the CABG-treated patients. TVR rates over the first 12 months postprocedure were similar between the two groups.

LE MANS outcomes

Outcomes	CABG, n (%)	PCI, n (%)	p
Any MACE (<30 days)	9 (20.7)	2 (3.8)	0.028
Any MAE (<30 days)	19 (35.8)	3 (5.8)	0.0001
Any MACE (30 d-12 mo)	11 (20)	11 (21)	NS

In an interview with heartwire, Buszman and a colleague, Dr Radoslaw Stefan (San Antonio Heart Institute, TX), pointed out that the improvement in LV function is a new and important finding, particularly since reduced LV function is often an indication for surgical revascularization over PCI. As well, other surgery studies have not necessarily included or have underestimated information on infections, bleeding, pericardial effusions, and renal function. "We don't see any of that after left main stenting," Stefan said.

Dr Antonio Colombo (EMO Centro Cuore Columbus, Milan, Italy), the scheduled discussant for LE MANS, called the trial a "good initial study."

He quibbled with some features of the trial design, including the decision to not use drug-eluting stents in all patients. " I would have liked for the sake of cleanness that every patient got a drug-eluting stent, but I don't think this is an important point."

He also took issue with the fact that Buszman did not clarify whether TVR was angiographically or clinically driven and with the use of LVEF as a primary end point.

"This is not a standard end point, and it is also hard to be blinded in a patient who has had a sternotomy," Colombo said. "This may be something to keep in mind for the future; maybe this is an important end point and we should think progressively."

Colombo also reminded the audience that the risks of CABG for left main disease are not negligible and include the risk of MI, less gain in ejection fraction, increased stroke, and death in the early postoperative period.

"I always smile when people tell me there is a risk of 1% of late stent thrombosis [with drug-eluting stents] and I say, decide: do you want to die early or late?" he quipped.

More randomized clinical trial data in the works

During a press conference, Buszman pointed out that while the ACC/AHA guidelines stipulate that PCI is not indicated for left main disease, the technology and methods for left main stenting have evolved very quickly. Nevertheless, he said, "We need two randomized clinical trials to change the guidelines showing that PCI is at least equal to CABG. I hope that LE MANS will be the first one, and others are coming soon, such as the SYTNAX trial."

As well, the multicenter, international COMBAT trial, randomizing 1000 patients to either a Cypher stent or surgery for left main disease, is poised to receive the FDA's stamp of approval, permitting it to start enrolling patients in 2006.