After EXCEL and NOBLE, New Meta-analysis Revisits PCI vs Surgery for Unprotected Left Main CAD

In the wake of the EXCEL and NOBLE studies, a new meta-analysis has shown PCI with drug-eluting stents and CABG surgery to be equally safe means of revascularization for patients with unprotected left main coronary artery disease.

In the five studies with 4,594 patients included in the meta-analysis, there was no significant difference seen for the primary composite safety endpoint of all-cause mortality, MI, and stroke between PCI and surgery. In terms of the secondary effectiveness endpoint, which included repeat coronary revascularization along with the safety endpoint, treatment favored CABG surgery (OR 1.36; 95% CI 1.18-1.58), although the benefit was not seen in the first year.

Overall, patients with left main coronary disease treated with PCI had a significantly increased risk of repeat revascularization compared with CABG surgery (OR 1.85; 95% CI 1.53-2.23).

“Revascularization of [unprotected left main coronary artery] stenosis is frequently performed for prognostic gain, because CABG has been shown in randomized trials to improve survival when compared with optimal medical therapy,” according to lead investigator Nitesh Nirlekar, MBBS (Monash University, Victoria, Australia). “Thus, it is imperative when considering alternate revascularization strategies, such as PCI, that the treatment offered does not confer deleterious outcomes.”

These data, say the researchers, suggest PCI with DES for unprotected left main coronary artery disease is “not harmful and should be considered an acceptable revascularization option.”

The analysis, recently published online in Circulation: Cardiovascular Interventions, included PRECOMBAT, SYNTAX, EXCEL, NOBLE, and a 2011 German randomized comparison of PCI with sirolimus-eluting stents versus CABG in patients with left main stenosis. Follow-up in the trials varied, with 60-month data available from PRECOMBAT, SYNTAX, and NOBLE; 36-month results from EXCEL; and just 1-year data available from the German study.

The researchers caution that PCI is not without risk and that a suboptimal intervention can have “profound implications” for the patient. They point out that short- and long-term clinical outcomes are better when the procedure is performed at high-volume centers by experienced physicians.

Need for Longer-Term Data Still

Azeem Latib, MD (San Raffaele Scientific Institute, Milan, Italy), who was not involved in the analysis, told TCTMD that EXCEL and NOBLE, albeit mainly EXCEL, reinforced what a lot of European operators have been doing in clinical practice: selective PCI for unprotected left main disease in patients with low-to-intermediate SYNTAX scores. He noted that while NOBLE went in the wrong direction—the trial showed a higher rate of major adverse cardiac and cerebrovascular events at 5 years with PCI compared with CABG surgery—there were some differences between the two trials, such as the stents and endpoints used.

In contrast with NOBLE, EXCEL was a positive study, showing that patients with low- or intermediate-SYNTAX scores treated with an everolimus-eluting metallic stent (Xience, Abbott Vascular) had comparable rates of death, stroke, or MI at 3 years when compared with patients treated with CABG surgery. Investigators saw more periprocedural MI and STEMI in the CABG-treated patients at 30 days.

“EXCEL is really going to be the one that people remember, that will have an impact on clinical practice, although I would like to see longer-term results on EXCEL,” said Latib. “I would like to see longer-term data, just to be sure there are no surprises.”

An “editor’s perspective” was published in the journal alongside the study by Nirlekar et al, although it does not specifically address the meta-analysis. In it, Davide Capodanno, MD (University of Catania, Italy), and Theodore Bass, MD (University of Florida College of Medicine, Jacksonville), dissect the existing data and clinical guidelines for revascularization of unprotected left main coronary artery disease. In particular they focus on similarities and dissimilarities between EXCEL and NOBLE, both of which were reported by TCTMD at TCT 2016 in Washington, DC, in October.

Capodanno and Bass point out that in the EXCEL trial, clinical sites underestimated the SYNTAX score compared with the core-lab assessment, leading to the enrollment of patients with high scores who should have been excluded from the trial—who in the end made up about one-third of the cohort. In addition, the SYNTAX score in EXCEL did not differentiate clinical outcomes of PCI versus CABG.

As a result, the editorialists question whether the current guidelines for revascularization of left main disease, which are based on SYNTAX scores, are valid. Based on the latest data, namely EXCEL, Capodanno and Bass suggest PCI could become a class I indication for selected patients, a recommendation that is now supported by stronger evidence. Presently, CABG is gold-standard for treatment of left main disease, but US and European guidelines do provide various recommendations, with varying degrees of support, for certain patients with unprotected left main coronary disease.