Unprotected left main coronary artery disease is one of the most severe forms of coronary artery disease and requires a revascularisation strategy aimed at reducing morbidity and mortality and limiting the occurrence of cardiovascular events. Traditionally, two treatment options have been available: coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI).
Although previous studies have reported a higher incidence of spontaneous myocardial infarction among patients treated with PCI, this has not translated into increased mortality compared with CABG, leaving uncertainty regarding potential differences between the two strategies over the long term. In addition, the development of second-generation drug-eluting stents (DES), together with the introduction of newer technologies such as intravascular ultrasound (IVUS), has helped optimise stent implantation and improve procedural outcomes in carefully selected patients.
Against this background, the NOBLE trial aimed to provide evidence on the long-term outcomes of PCI with newer-generation DES compared with CABG in patients with significant unprotected left main coronary artery disease, with follow-up extending to 10 years.
The trial initially enrolled 1201 patients with significant unprotected left main coronary artery stenosis between December 2008 and January 2015 at 36 hospitals across nine European countries. Eligible patients had either chronic or acute coronary syndrome, a life expectancy of more than 1 year, and left main coronary artery stenosis ≥50% or fractional flow reserve ≤0.80. Patients with ST-elevation myocardial infarction within the preceding 24 hours were excluded, as were those considered at excessively high risk for either revascularisation strategy or those with additional complex coronary lesions. Importantly, all patients were assessed by a multidisciplinary Heart Team, which determined that both PCI and CABG were feasible treatment options.
Participants were randomly assigned in a 1:1 ratio to PCI (598 patients) or CABG (603 patients). After the initial losses to follow-up, the intention-to-treat population comprised 592 patients in each group. Mean age was 66.2 years, and 22% of participants were women. Median follow-up reached 10 years, with vital status available for 98% of participants.
The primary outcome was 10-year all-cause mortality, assessed using Kaplan–Meier estimates and Cox proportional hazards models. Prespecified subgroup analyses were also performed according to age, sex, diabetes, SYNTAX score, distal left main coronary artery bifurcation lesions, and acute or chronic coronary syndrome. In addition, a Bayesian sensitivity analysis was conducted to assess the robustness of the findings.
At 10 years, all-cause mortality was 23% in the PCI group and 25% in the CABG group, with no statistically significant difference between the two strategies (HR = 0.93; 95% CI = 0.74–1.18; 𝑝 = .56). Similarly, no significant differences in mortality were observed during either the 0–5-year or 5–10-year periods after revascularisation. The relative effect of either strategy also did not differ according to SYNTAX score, supporting an individualised approach to revascularisation in each patient.
The subgroup analysis is particularly noteworthy because it suggested a possible advantage of PCI among patients presenting with acute coronary syndrome. However, the authors emphasise that this finding should be interpreted cautiously because of the limited size of this subgroup and the consequent increased likelihood that the observed difference may have occurred by chance.
𝗖𝗢𝗠𝗠𝗘𝗡𝗧𝗔𝗥𝗬:
The main contribution of the NOBLE trial, in my view, extends beyond the finding that long-term mortality was similar, with no statistically significant difference between PCI and CABG. Its results should also be interpreted within the technological context in which the trial was conducted.
One of the key considerations when interpreting these findings is the substantial evolution of PCI since enrolment in the trial began. Newer-generation stents and the increasingly widespread use of IVUS are now integral to the treatment of many patients with complex left main coronary artery lesions and have contributed to improved procedural optimisation. It is therefore reasonable to consider that advances in interventional cardiology may favourably influence contemporary PCI outcomes.
Another important lesson from this study is the value of a multidisciplinary Heart Team approach. The choice between PCI and CABG should not depend solely on coronary anatomy or lesion complexity, but should also incorporate the patient’s clinical profile, institutional expertise, comorbidities, and individual preferences. These factors remain essential when selecting the most appropriate revascularisation strategy.
Future studies including patients with ST-elevation myocardial infarction and assessing medium- and long-term outcomes would also be of interest. Such evidence could help determine whether the findings of NOBLE can be extrapolated to a clinically different and higher-risk population.
𝗥𝗘𝗙𝗘𝗥𝗘𝗡𝗖𝗘:
Holck EN, Holm NR, Hildick-Smith D, Lindsay MM, Spence MS, Erglis A, et al. Percutaneous coronary intervention versus coronary artery bypass grafting for unprotected left main stenosis: 10-year final results from the randomised, open-label, non-inferiority NOBLE trial. Lancet. 2026 Apr 4;407(10536):1374-1382. doi: 10.1016/S0140-6736(26)00205-9. PMID: 41936368.
