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The Great Left Main Debate
Interventionalists and surgeons sound off on the viability of PCI for the treatment of left main disease.
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The discussion about whether PCI is a viable alternative to CABG in patients with left main CAD continues with current evidence suggesting it might be in a subset of patients who have a less severe form of the disease or who are at high risk for surgery.
A currently enrolling trial, EXCEL, which will be the largest to directly compare the two treatments for left main CAD, could further clarify the issue. If PCI is proven as safe and effective as CABG for certain patients, it could mean that fewer patients with left main CAD need to be exposed to the risks of surgery.
“Current evidence and guidelines would suggest that PCI with drug-eluting stents is a reasonable option in the short- to intermediate-term for patients with simple left main disease or for patients who are poor candidates for bypass surgery,” said David J. Cohen, MD, MSc, director of cardiovascular research, Saint Luke’s Mid America Heart Institute, Kansas City, Mo., and an Editorial Board member for Cardiology Today’s Intervention. “In general, most serious outcomes, including death and MI, appear quite comparable between the two strategies in these populations, although there is some evidence that PCI is less likely to result in stroke, whereas CABG is clearly associated with less need for repeat revascularization procedures.”
Lessons from SYNTAX
Patients with left main CAD were a subset of the SYNTAX trial that compared PCI using the Taxus paclitaxel-eluting stent (PES; Boston Scientific) with CABG. There were 750 patients with left main CAD in an overall pool of 1,800.
Michael J. Mack
“In this subgroup analysis of the SYNTAX trial, which is considered hypothesis-generating only [since it did not achieve its primary endpoint], it appears as if low complexity left main disease [SYNTAX score <33] may do as well with PCI as with CABG,” said Michael J. Mack, MD, medical director of cardiovascular surgery for the Baylor Health Care System and director of cardiovascular research at The Heart Hospital Baylor, Plano, Texas. These findings served as the basis for the design of the EXCEL Trial. However, currently, he said, “There are no other direct-comparison nor randomized trial data available until we learn the results of EXCEL.”
For patients with a more complex form of the disease, however, it has been a different story.
Joanna Chikwe
“Three-year follow-up data from the SYNTAX trial showed trends in all-cause mortality, cardiac death, MI and repeat revascularization that favored CABG in the first year of follow-up, continuing through the second and third year,” said Joanna Chikwe, MD, associate professor of cardiothoracic surgery, Mount Sinai Hospital, New York. “Significantly higher cardiac death rates were reported in the PCI arm compared with the CABG arm, primarily in those patients with left main stem disease and greater lesion complexity. These data support the recommendation for CABG over PCI in patients with left main disease and high complexity lesions (SYNTAX scores ≥33) or intermediate complexity scores (23-32).”
In Europe, there are guidelines that assist doctors in determining which left main patients are candidates for PCI, said Alaide Chieffo, MD, San Raffaele Scientific Institute, Milan, Italy. “Guidelines take into consideration the lesion location in the left main as well as the extent of disease in coronary arteries,” she said. “Current European guidelines state that unprotected left main PCI has an indication Class IIa in patients with isolated or one-vessel disease with left main ostium/shaft involvement. Indeed, left main PCI has an indication Class IIb in cases of isolated or one-vessel disease with left main distal bifurcation involvement or two- or three-vessel disease and a SYNTAX score ≤32. In patients with two- or three-vessel disease, SYNTAX score ≥33 PCI for unprotected left main coronary artery lesions has a Class IIIb indication.”
Other Telling Trials
A smaller study, LE MANS, which included 105 patients with left main CAD, found that rates of MACCE after 1 year were about the same for patients treated with PCI as for those who received CABG.
The randomized PRECOMBAT trial compared PCI (n=300) with CABG (n=300) in patients with unprotected left main CAD and concluded that PCI with sirolimus-eluting stents was noninferior to CABG with respect to MACCE. However, the study’s investigators cautioned that the results cannot be considered clinically directive because the trial was underpowered and the noninferiority margin was wide.
Chikwe agreed with the conclusions of the investigators and added that bias may have been introduced into the study because the PCI group received routine surveillance angiography and the CABG group did not.
Figure. Left main disease associated with chronic occlusion of the right coronary artery (RCA), left anterior descending artery (LAD) and circumflex artery (Circ); EuroSCORE 13, SYNTAX score 72. Panel A: Total occlusion of RCA in the middle segment. Panel B: Severe stenosis of left main involving both LAD and Circ; total occlusion of LAD and Circ and severe stenosis of a large first diagonal branch. Panel C: RCA after stenting provides collateral flow to LAD. Panel D: Wiring of LAD, diagonal branch and ramus. Panel E: Stenting of left main, LAD and first diagonal branch.
Images: Careggi Hospital, Division of Cardiology, Florence, Italy
Possible Insights from EXCEL
The EXCEL trial — a large study comparing PCI with Xience Prime and Xience V everolimus-eluting stents (EES, Abbott Vascular) with CABG in 2,600 left main CAD patients who are suitable for either treatment — is under way and could produce more conclusive results. According to Cohen, the trial should provide much more definitive data on the outcomes of PCI vs. CABG for patients with left main disease, including a broad array of secondary outcomes such as quality of life and health economics. The primary endpoints of the trial are death, MI or stroke after 3 years.
Marc P. Sakwa
“We are curious to see what the results will be for the short and long term,” said Marc P. Sakwa, MD, chief of cardiovascular surgery at Beaumont Hospital, Royal Oak, Mich., and co-principal investigator of the EXCEL site at Beaumont. “If there is some efficacy with stenting certain patients, we may want to consider doing a less invasive approach on them. But right now, most articles suggest that surgery is the ‘gold standard.’” He added that it may be necessary to use PCI in patients who will not be able to tolerate surgery or as a “last-ditch effort” on patients for whom all other treatments have failed, and the EXCEL trial could shed some light on how safe and effective PCI might be for those patients.
He noted that because randomized trials tend to focus on lower-risk and lower-complexity patients, the EXCEL study should show some success for patients who had PCI, but that will not necessarily mean PCI is the best option for all, or even most, left main CAD patients.
David Antoniucci, MD, cardiologist, Careggi Institute, Florence, Italy, and Cardiology Today’s Intervention Editorial Board member, agreed. “The ongoing EXCEL trial will focus mainly in low-surgical-risk patients and low-coronary-anatomy complexity, and it is easy to predict at least equivalence between the two revascularization strategies in this subset of patients,” he said.
Inherent Limitations
It is possible that no matter how stent technology develops in the coming years, PCI might never become an alternative for CABG in complex left main CAD cases, because of the nature of the procedure.
David J. Cohen
“Stenting only works where stents are placed,” Cohen said. “Since coronary disease is an inherently systemic condition that affects all the coronary arteries and segments, once patients have extensive multivessel disease, it may be difficult to predict where the next coronary event will arise. In that case, in addition to aggressive medical therapy, the more extensive revascularization afforded by CABG may be an advantage. When patients have extensive three-vessel CAD, focal treatment with DES simply does not seem to prevent as many events in the short- to intermediate-term as a more extensive revascularization that is possible with CABG.”
Another obstacle for PCI is the risk for restenosis. This is particularly an issue at the origin of the circumflex coronary artery in patients with distal bifurcation disease, Cohen said. However, DES have a significantly lower restenosis rate than bare-metal stents, and newer-generation DES have a better rate than older generations, so the rate could improve further as DES technology advances.
Even accounting for future developments in DES, some physicians do not expect the paradigm for treating left main CAD to change significantly.
“There has never been a mortality benefit demonstrated with any stent,” Mack said. “Newer stents result in lower restenosis, but there is no evidence yet of any other improved outcomes.”
Chikwe said some progress with PCI could be made if future generations of DES reduce stent thrombosis.
David Antoniucci
“If the incidence and mortality of stent thrombosis, which accounted for 11 deaths out of 36 patients that experienced this complication in the SYNTAX study, can be reduced by newer-generation stents, then the event-free survival benefit of CABG may become less significant in these patient groups,” she said. She added that stent thrombosis remains one of the largest obstacles to progress in treating left main CAD with PCI, along with poor outcomes in patients with diabetes and the need for patients to comply completely with antiplatelet therapy after the procedure.
Antoniucci noted that at least one-third of patients with left main CAD also have chronic total occlusion, which PCI is not an appropriate treatment option for at this time. “The goal should be a complete revascularization in all patients,” he said. “Thus, considering that at least one-third of patients with left main disease have CTO, PCI should approach this type of lesion.”
Future Outlook for PCI
Technological advancements have brought some progress for PCI in the setting of left main CAD. A paper published in October 2012 in the Journal of the American College of Cardiology found that EES had several tangible clinical benefits over PES in patients with unprotected left main CAD, and suggested that the SYNTAX trial would have produced better results had it used EES instead of PES. It analyzed patients in the ULMD Florence registry, 224 of whom received PES and 166 of whom received EES. MACCE after 1 year was observed in 20.4% of patients with PES vs. 10.2% of those with EES. Likewise, the rate of target vessel failure after 1 year was 19.3% in PES patients and 7.8% in EES patients, while the restenosis rates were 5.2% in the EES group and 15.4% in the PES group. Patients in this study had a mean EuroSCORE of 5.8, CTOs were treated routinely and a complete revascularization was achieved in more than 70% of cases.
For that and other reasons, Chieffo finds an encouraging future for PCI as a treatment of left main CAD. “New-generation DES, a larger use of adjunctive tools such as IVUS and fractional flow reserve, as well as the use of more effective antiplatelet therapy, will help to achieve better results and extend our indications,” she said. – by Erik Swain
Disclosure: Cohen reports receiving research grant support from Abbott Vascular, Boston Scientific and Medtronic, and consulting fees from Abbott Vascular and Medtronic. Antoniucci, Chieffo, Chikwe, Mack and Sakwa report no relevant financial disclosures.