The use of percutaneous coronary intervention (PCI) for unprotected left main coronary artery stenosis is increasing but it remains unclear whether this approach is non-inferior to coronary artery bypass grafting (CABG). Both the Nordic-Baltic-British left main revascularization study (NOBLE, n=1201) and Evaluation of an everolimus eluting stent versus coronary artery bypass surgery for effectiveness of left main revascularization study (EXCEL, n=1905) randomized patients with severe left main coronary artery stenosis to PCI or CABG to address this question. Though similar, there are important differences in these studies’ design and results. Primary outcomes were defined as all cause death, stroke and non-procedural myocardial infarction (MI) in both trials with the addition of repeat revascularization in NOBLE and post-procedural MI in EXCEL. Other study differences include intended duration of follow up, non-inferiority margins, allowable coronary complexity, and stent type. The prevalence of distal left main stenosis was quite high (~80%) in both trials. In EXCEL, PCI was non-inferior to CABG with respect to the primary composite endpoint at 3 years (15.4% for PCI, 14.7% for CABG, confidence interval (CI) 0.79 to 1.26 while, NOBLE found that PCI was inferior to CABG for the 5-year estimated primary event rate (29% for PCI, 19% for CABG, CI 1.11 to 1.96). Adding repeat revascularization to the primary end-point in EXCEL did not change the finding of non-inferiority between PCI and CABG. All-cause mortality did not differ by treatment in either trial.
The two studies differ substantially but will likely forever be compared if only because they were released simultaneously. Compared to NOBLE, EXCEL enrolled patients with lower SYNTAX scores who received a higher proportion of newer generation drug-eluting stents and reported outcomes over a shorter duration. The inclusion of post-procedure myocardial infartion in the primary outcome in EXCEL (which occurred more frequently in the CABG arm) and the use of first generation stents in NOBLE (which included repeat revascularization, potentially more likely with less refined stents) may account for the disparate findings in the two studies. Their discordant conclusions build on a history in which CABG continues to be the reference standard based on fewer subsequent revascularization events but does not appear to offer a survival advantage. Both trials had difficulty in patient enrollment which resulted in protocol changes, and no new large-scale trials are on the horizon. Thus, it seems unlikely current guidelines for treatment of unprotected left main stenosis with change radically in the near future.
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Authors: Patrick J Goleski, MD and James M McCabe MD