Left Main Interventions: A NOBLE Effort, but How and In Whom Do We EXCEL?

Presented at the 15th Biennial International Andreas Gruentzig Society Meeting, February 3-7, 2019

Program Agenda               Faculty Disclosures              Vendor Acknowledgment


10.2 / IAGS 2019
Session 10: Coronary Session 3

Left Main Interventions: A NOBLE Effort, but How and in Whom Do We EXCEL?
Problem Presenter: Theodore A. Bass, MD

 

Statement of the problem or issue

The cardiovascular community has debated the optimal role of percutaneous coronary intervention (PCI) in the treatment of patients presenting with left main coronary artery (LMCA) disease for over a decade. Interventional catheter-based treatment of LMCA stenosis was strongly discouraged after initial experience in the era of balloon angioplasty resulted in unfavorable outcomes in several reported cases. However, as technology has advanced, PCI has evolved into a safe and effective treatment option for an expanding population of patients with complex coronary disease. This has renewed interventional interest in unprotected LMCA PCI.

 

Gaps in knowledge

Many of the technical and procedural challenges involving left main coronary PCI have been well addressed. The optimal use of adjunctive imaging, improved stent technologies and expanding operator experience with LMCA bifurcation lesions has resulted in improved procedural outcomes. Comparing early registry data with subsequent more recent randomized trial clinical outcomes, we see that procedural safety has continually improved. There are, however, gaps in our knowledge that still involve some incompletely resolved issues. The most compelling of these issues has to do with patient selection criteria in patients who are also candidates for possible surgical revascularization. United States and European guidelines have some differences regarding their respective recommendations. These differences mostly involve the quantity and complexity of coronary disease that would favor a stronger evidence-based surgical recommendation. There is a clear and consistent signal that patients with more severe coronary artery disease require more repeat revascularization when treated with a PCI strategy than with a surgical bypass strategy. The latest available NCDR data suggests that unprotected LMCA represents roughly 1% of all PCIs performed in the United States. It is reasonable to assume that a significant percentage of these patients were at high surgical risk and may not have been candidates for coronary artery bypass surgery (CABG).

 

Possible solutions and future directions

Two interesting randomized clinical trials published in the last several years shed further light on the optimal revascularization strategy for patients with LMCA disease. The EXCEL (Everolimus-Eluting Stents or Bypass Surgery for Left Main Coronary Artery Disease) trial concluded that patients with LMCA disease and less complex CAD (low to intermediate SYNTAX scores by site assessment) did as well (non- inferior) when treated by PCI versus CABG, using a 3-year clinical endpoint of death, MI or stroke. Very shortly following this publication, NOBLE (percutaneous coronary angioplasty versus coronary bypass grafting in treatment of unprotected left main stenosis: a prospective randomized, open label non-inferiority trial) reported that the composite major adverse cerebrovascular and cardiac events (MACCE; death from any cause, non-procedural MI, repeat revascularization, and stroke) at 3-year follow-up favored a surgical revascularization strategy. Why do these two similar RCTs send what appear to be conflicting signal, and how does this affect current interventional practice?

Some baseline differences exist comparing the United States and European EXCEL trial with the exclusively European NOBLE trial. The trials used different coronary stents. In addition, there were some minor baseline differences in the study populations comparing both trials. However, the major reason for the seemingly contradictory signals involves the use of different primary composite endpoints, most notably the inclusion of revascularization in the NOBLE trial but not in the EXCEL trial. Review of individual clinical endpoints, including death, cardiovascular death, spontaneous MI, procedural MI, stroke, and revascularization, demonstrate little outcome differences when comparing both trials. The disadvantage of more subsequent repeat revascularizations noted for patients treated with a PCI strategy versus CABG is well known, and expectedly was a potent driver of the PCI inferiority signal noted in the NOBLE trial.

Why has unprotected LMCA PCI not caught on in the United States and are our current Guidelines still relevant regarding this area? What are the factors influencing physician and patient decision-making involving the choice of a coronary revascularization strategy in this population when both options might be reasonable? Patient preference, quality of life concerns, patient age, and uncertainties about the optimal long-term clinical follow-up strategies may all play a role in this decision-making. Is there a need for further clinical randomized studies or will future practice be best defined by subsequent large registry derived data?