Percutaneous coronary angioplasty versus coronary artery bypass grafting in treatment of unprotected left main stenosis (NOBLE): a prospective, randomised, open-label, non-inferiority trial

Summary

Background

Coronary artery bypass grafting (CABG) is the standard treatment for revascularisation in patients with left main coronary artery disease, but use of percutaneous coronary intervention (PCI) for this indication is increasing. We aimed to compare PCI and CABG for treatment of left main coronary artery disease.

Methods

In this prospective, randomised, open-label, non-inferiority trial, patients with left main coronary artery disease were enrolled in 36 centres in northern Europe and randomised 1:1 to treatment with PCI or CABG. Eligible patients had stable angina pectoris, unstable angina pectoris, or non-ST-elevation myocardial infarction. Exclusion criteria were ST-elevation myocardial infarction within 24 h, being considered too high risk for CABG or PCI, or expected survival of less than 1 year. The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE), a composite of all-cause mortality, non-procedural myocardial infarction, any repeat coronary revascularisation, and stroke. Non-inferiority of PCI to CABG required the lower end of the 95% CI not to exceed a hazard ratio (HR) of 1·35 after up to 5 years of follow-up. The intention-to-treat principle was used in the analysis if not specified otherwise. This trial is registered with ClinicalTrials.gov identifier, number NCT01496651.

Findings

Between Dec 9, 2008, and Jan 21, 2015, 1201 patients were randomly assigned, 598 to PCI and 603 to CABG, and 592 in each group entered analysis by intention to treat. Kaplan-Meier 5 year estimates of MACCE were 28% for PCI (121 events) and 18% for CABG (80 events), HR 1·51 (95% CI 1·13–2·00), exceeding the limit for non-inferiority, and CABG was significantly better than PCI (p=0·0044). As-treated estimates were 28% versus 18% (1·48, 1·11–1·98, p=0·0069). Comparing PCI with CABG, 5 year estimates were 11% versus 9% (1·08, 0·67–1·74, p=0·84) for all-cause mortality, 6% versus 2% (2·87, 1·40–5·89, p=0·0040) for non-procedural myocardial infarction, 15% versus 10% (1·50, 1·04–2·17, p=0·0304) for any revascularisation, and 5% versus 2% (2·20, 0·91–5·36, p=0·08) for stroke.

Interpretation

The findings of this study suggest that CABG might be better than PCI for treatment of left main stem coronary artery disease.

Funding

Biosensors, Aarhus University Hospital, and participating sites.

Introduction

Treatment of unprotected left main coronary artery disease with percutaneous coronary intervention (PCI) has increased rapidly during the past decade, following the favourable results of randomised trials1, 2, 3, 4 and observational registry studies comparing PCI and coronary artery bypass grafting (CABG).5, 6, 7, 8, 9 At present, both options are used to treat left main coronary artery disease.¹⁰ Present guidelines recommend PCI in patients with left main coronary artery disease and coronary pathology favourable to PCI (ie, in the absence of complex and diffuse lesions).¹⁰ The guidelines are based primarily on the prespecified and powered subgroup of 705 patients with left main coronary artery disease in the SYNTAX trial,11, 12 which compared PCI and the drug-eluting Taxus stent with CABG in patients with three-vessel or left main coronary artery disease. The guidelines also refer to the findings of the randomised trials LE MANS (100 patients),¹ PRECOMBAT (600 patients),² and Boudriot and colleagues (201 patients)³ trials, which included patients with left main coronary artery stenosis. In the randomised trials, the non-inferiority margin was wide, because of relatively small patient sample sizes, and thus the trials were not powered to definitively determine the best treatment for unprotected left main coronary artery disease.

In the NOBLE trial, we postulated that PCI with drug-eluting stents would produce non-inferior clinical results compared with CABG in revascularisation of 1200 patients with unprotected left main coronary artery stenosis.

Research in context

Evidence before this study

We searched PubMed for randomised trials comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in the treatment of left main coronary artery disease with the search terms “percutaneous coronary intervention”, “coronary artery bypass operation”, “coronary artery bypass grafting”, “randomised”, or “randomized”, published after the introduction of drug-eluting stents between Jan 1, 2003, and Sept 1, 2016. We identified four randomised trials. Three trials were underpowered for clinical endpoints and in the SYNTAX trial, only 705 patients with left main coronary artery disease were included. Although, the randomised trials suggested that PCI was a valid alternative to CABG, we found a need for further documentation with a large randomised trial.

Added value of this study

Our findings of similar mortality but higher rates of myocardial infarction and repeat revascularisation in patients with left main coronary artery disease undergoing PCI compared with CABG are consistent with previous randomised studies. With 1201 patients included in our study the increased rates of major adverse cardiac or cerebrovascular events (MACCE) associated with PCI beyond 1 year became significant, and confirm findings from a meta-analysis also showing increased MACCE after PCI at 5 years. In contrast with the SYNTAX trial, our study suggested that patients with left main coronary artery disease had inferior outcome after PCI compared with CABG, irrespective of coronary lesion complexity assessed with the SYNTAX score.

Implications of all the available evidence

Despite similar mortality, the 5-year risk of MACCE is higher after PCI compared with CABG for treatment of unprotected left main coronary artery disease.