Nordic–Baltic–British Left Main Revascularisation Study - NOBLE

Contribution To Literature:

The NOBLE trial showed that PCI with biodegradable polymer DES (biolimus) is inferior to CABG for clinical outcomes at 5 years following revascularization of unprotected left main lesions.

Description:

The goal of the trial was to compare outcomes following coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) with biolimus drug-eluting stents (DES) in patients with unprotected left main disease.

Study Design

Patients were randomized in a 1:1 fashion to either PCI with Biolimus DES (n = 592) or CABG (n = 592).

  • Total number of enrollees: 1,184
  • Duration of follow-up: 5 years
  • Mean patient age: 66.2 years
  • Percentage female: 22%

Inclusion criteria:

  • Significant left main lesion
  • Visually assessed stenosis diameter ≥50% or fractional flow reserve ≤0.80
  • Located in the ostium, mid-shaft, or bifurcation
  • No more than three additional noncomplex lesions
  • Local interventional cardiologists and cardiac surgeons determined that equivalent revascularization could be achieved with CABG or PCI

Exclusion criteria:

  • Additional nonleft main complex lesions
  • Chronic total occlusions
  • Bifurcation lesions requiring two stent techniques
  • Calcified or tortuous vessel morphology
  • ST-elevation infarction within 24 hours
  • Being considered too high-risk for CABG or PCI
  • Expected survival of <1 year

Other salient features/characteristics:

  • Percentage with diabetes: 15%
  • Stable angina, 80%; acute coronary syndrome, 18%
  • Mean left ventricular ejection fraction: 60%
  • SYNTAX scores: median, 22.5; low (≤22), 51.8%; high (≥33), 8.6%
  • Distal left main trunk bifurcation lesion: 81%
  • PCI arm: Post-PCI intravascular ultrasound, 74%; total stented length in left main, 24 mm
  • CABG arm: Off-pump, 16%; arterial graft use, 95%

Principal Findings:

The primary outcome, death, myocardial infarction (MI), stroke, or repeat revascularization for PCI vs. CABG, was 28.9% vs. 19.1%, p = 0.0066.

  • Death: 11.6% PCI vs. 9.5% CABG, p = 0.77
  • Nonprocedural MI: 6.9% PCI vs. 1.9% CABG, p = 0.004
  • Stroke: 4.9% PCI vs. 1.7% CABG, p = 0.07
  • Repeat revascularization: 16.2% PCI vs. 10.4% CABG, p = 0.03; target lesion revascularization: 12% vs. 8%, p = 0.14; de novo lesion revascularization: 6% vs. 3%, p = 0.018
  • Results for primary outcome: similar across SYNTAX score terciles

Secondary outcomes for PCI vs. CABG:

  • Stent thrombosis or graft occlusion: 3% vs. 4%, p = 0.22
  • 30-day mortality: 0.34% vs. 1.2%, p = 0.09
  • 30-day stroke: 0% vs. 0.7%, p = 0.04

Interpretation:

The results of this important trial indicate that PCI with a biolimus DES is inferior to CABG for clinical outcomes at 5 years following revascularization of unprotected left main lesions. Nonprocedural MI, stroke, and revascularization were higher with PCI. Thrombosis (stent vs. graft) rates were similar between the two arms. As expected, adverse clinical events were not uniformly distributed from a temporal standpoint between the two arms. The hazard was highest with CABG in the first 30 days, and clinical outcomes were somewhat better with PCI up to 30 days. However, this reversed between 30 days and 5 years, such that outcomes were inferior with PCI compared with CABG beyond this time frame. The results of this trial are in discordance with the larger EXCEL trial, which showed noninferiority between PCI and CABG for left main lesions.

The event rates in this trial are higher in the PCI arm than those noted in the EXCEL trial, despite enrolling a lower-risk population (80% stable angina, median SYNTAX score 22.5). It is unclear if this is due to the different stents used in the two trials – biolimus DES with biodegradable polymer in the NOBLE trial, and Xience durable polymer everolimus-eluting stents (EES) in the EXCEL trial, although in the NEXT and COMPARE II trials, clinical outcomes were generally similar between biolimus and EES. Differences between the two trials (and their differing conclusions) will need to be investigated further.

References:

Mäkikallio T, Holm NR, Lindsay M, et al., on behalf of the NOBLE Study Investigators. Percutaneous coronary angioplasty versus coronary artery bypass grafting in treatment of unprotected left main stenosis (NOBLE): a prospective, randomised, open-label, non-inferiority trial. Lancet 2016;Oct 31:[Epub ahead of print].

Presented by Dr. Evald H. Christiansen at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2016), Washington, DC, October 31, 2016.

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Aortic Surgery, Interventions and Coronary Artery Disease

Keywords: Cardiac Surgical Procedures, Coronary Artery Bypass, Coronary Artery Bypass, Off-Pump, Coronary Artery Disease, Drug-Eluting Stents, Myocardial Infarction, Percutaneous Coronary Intervention, Polymers, Myocardial Revascularization, Stents, Stroke, Thrombosis, Transcatheter Cardiovascular Therapeutics


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