Intervention in left main coronary artery disease
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# Overview
Left main coronary artery stenosis is associated with poor patient outcomes secondary to ischemia of the large area of the myocardium which it supplies. Traditionally, CABG was indicated for left main disease. The SYNTAX trial demonstrated non-inferiority of PCI to CABG in a subgroup of patients with low to intermediate SYNTAX score. This clinical trial suggests a possible indication for a PCI option for the treatment of left main disease. Subsequently, the PRECOMBAT trial was conducted to compare the two interventions. In 2016, two large trials results were published (EXCEL trial and NOBLE trial) addressing the comparison of CABG and PCI in patients with left main disease in this particular subgroup of interest with low to intermediate SYNTAX scores.
The 5-year NOBLE trial results reported event rates of 29% in the primary endpoint (Major Adverse Cardiovascular or Cerebrovascular Events) in the PCI group compared to 19% in the CABG group (HR: 1.45; p=0.0066); 12% vs. 9% in all-cause mortality (HR: 1.07, p=0.77); and 5% vs. 2% in stroke (HR:2.25, p=0.073). 
The 3-year EXCEL trial results reported non-inferiority of PCI with a 15.4% vs. 14.7% occurrence of the primary endpoint of MACCE (HR:1.00, p=0.02) between PCI and CABG, respectively. In terms of superiority, 3 year results demonstrate a PCI vs. CABG event rate of  2.3% vs. 2.9% in stroke (HR:0.77, p=0.37), and 8.2% vs. 5.9% in all-cause mortality (HR:1.34, p=0.11). At 30 days, the EXCEL trial demonstrate a statistically significant reduction in MACCE (HR:0.61, p<0.001) with PCI; however, a non-significant reduction in stroke(HR:0.50, p=0.15) and all-cause mortality (HR:0.90, p=0.82).
The variability in the results of the latest two trials (NOBLE and EXCEL) is a topic of much discussion. The complexity of left main disease, type of stent, complexity of disease in other vessels, and duration of follow up may affect results. Additionally, the effect of the anti-platelet treatments administered post-operatively, as well as the variability in the specific CABG procedures performed by the surgeon may contribute to the variability in the results.

# Left Main Disease Clinical Trials

## Synopsis
NR=Not Reported

## SYNTAX Trial
Visit the SYNTAX page for details about this trial.

## PRECOMBAT Trial
The PRECOMBAT trial was the first clinical trial primarily evaluating MTOR drug eluding stents compared to CABG in the treatment of left main disease. The study found no significant difference in the primary endpoints between patients treated with PCI and patients treated with CABG through 5 years. This study was underpowered, thus results of this trial should be interpreted with caution.

## EXCEL Trial
The EXCEL trial was well-powered to evaluate the interventions in patients with low to intermediate SYNTAX scores. It was a large, multinational trial in the U.S. and international sites. The results show that everolimus-eluting stents were noninferior to CABG in the management of left main disease at 3 years. Additionally, the trial found that in the first 30 days, PCI was associated with less complications and a lower incidence of the primary endpoint, a finding attributed to the higher rate of complications in the post-operative period in patients undergoing CABG. Results of the 5-year follow up are expected in 2017.

## NOBLE Trial
The NOBLE trial was also well-powered to evaluate the interventions in patients with low to intermediate SYNTAX scores. It was a large, multinational trial mainly performed in the E.U. The 5-year results suggest that CABG may provide a better clinical outcome for the treatment of left main disease compared to PCI. This trial did not evaluate the rate of complications in the 30-day post-operative period.

# Conclusion and Future Perspectives
The variability in the results of the latest two trials (NOBLE and EXCEL) is a topic of much discussion. The complexity of left main disease, type of stent, complexity of disease in other vessels, and duration of follow up may affect results. Additionally, the effect of the anti-platelet treatments administered post-operatively, as well as the variability in the specific CABG procedures performed by the surgeon may contribute to the variability in the results. Additionally, the different populations (geographically) may represent a variability in local treatment practices that may have affected patient outcomes. The duration of follow up was not uniform across the trials (5 years vs. 3 years) and may have resulted in varying results. More trials are needed utilizing more uniform interventions in both groups to evaluate the efficacy of one treatment over the other in left main coronary artery disease.