NOBLE Trial Compares PCI and CABG to Treat Left Main Coronary Artery Disease

October 31, 2016—NOBLE, the Nordic–Baltic–British Left Main Revascularization study, found that despite similar mortality, the 5-year risk of major adverse events was higher after percutaneous coronary intervention (PCI) compared to coronary artery bypass graft surgery (CABG) for the treatment of unprotected left main coronary artery disease (CAD). The study was reported at TCT 2016, the 28th annual Transcatheter Cardiovascular Therapeutics scientific symposium in Washington, DC, and simultaneously published online by Timo Mäkikallio, MD, et al in The Lancet.

According to TCT, NOBLE is a prospective, randomized, open-label, clinical, noninferiority trial. The study was conducted at 36 sites in Latvia, Estonia, Lithuania, Germany, Norway, Sweden, Finland, United Kingdom, and Denmark. Eligible patients had stable angina pectoris, unstable angina pectoris or non–ST-segment elevation myocardial infarction (MI). The primary endpoint was major adverse cardiac or cerebrovascular events (MACCE)—a composite of all-cause mortality, nonprocedural MI, any repeat coronary revascularization, and stroke.

The original primary endpoint in the NOBLE trial was evaluation of noninferiority of PCI to CABG assessed by MACCE at 2-year follow-up in the complete study cohort. Because of lower than expected endpoint rates, the primary endpoint assessment was ultimately changed to a median follow-up of 3 years.

As summarized in the TCT press release, a total of 1,201 patients were randomized 1:1 to PCI (598) or CABG (603), with 592 patients in each arm who entered analysis by intention to treat. Kaplan-Meier 5-year estimates of MACCE were 28.9% (121 events) for PCI and 19.1% (81 events) for CABG (hazard ration [HR], 1.48; 95% confidence interval [CI], 1.11–1.96), exceeding the limit for noninferiority and demonstrating superiority of CABG over PCI (P = .0066). As-treated estimates were 28.1% versus 19.2% (HR, 1.55; 95% CI, 1.18–2.04; P = .0015). 

Comparing PCI with CABG, 5-year estimates were 11.6% versus 9.5% (HR, 1.07; 95% CI, 0.67–1.72; P = .7701) for all-cause mortality; 6.9% versus 1.9% (HR, 2.88; 95% CI, 1.4–5.9; P = .004) for nonprocedural myocardial infarction; 16.2% versus 10.4% (HR, 1.5l; 95% CI, 1.04–2.17; P = .0315) for any revascularization; and 4.9% versus 1.7% (HR, 2.25; 95% CI, 0.93–5.48; P = .0731) for stroke.

In the TCT announcement, the NOBLE lead investigator Evald H. Christiansen, MD, commented, “Our findings of similar mortality but higher rates of MI and repeat revascularization in patients undergoing PCI compared to CABG are consistent with previous studies of coronary revascularization in patients with left main CAD. However, the low mortality following treatment in both groups demonstrates that modern revascularization techniques can lead to excellent survival in stable left main CAD patients. Further, the increased rates of nonprocedural MI, repeat revascularization, and stroke associated with PCI are important considerations in selecting the optimal treatment for individual patients.”