Intervention in left main coronary artery disease
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Tarek Nafee, M.D. [2]
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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). [1]
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).[2]
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.[3]
Left Main Disease Clinical Trials
Synopsis
| Clinical Trial | Year | Sample Size (N) | Patient Population | Follow-up Period | Primary Endpoint | PCI Intervention | CABG Intervention | Post-procedural Anti-platelet Therapy Balanced Between Treatment arms? | Main Study Finding | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary graft artery used | Off pump procedure | Aspirin | P2Y12 inhibitors | ||||||||||
| 1 month | 12 months | 1 month | 12 months | ||||||||||
| SYNTAX[4] | 2005 to 2007 | ~1800 patients | Stable angina, Unstable angina, Atypical chest pain, Candidates for PCI or CABG | 5 years | Death, MI, Stroke or repeat revascularization | 57% Plaxitaxel Stent, 24% BMS, 19% other DES | Not reported.
internal mammary artery preferred. |
15% off-pump procedure | NR† | NR† | NR† | NR† | No significant difference in primary outcome was found between treatment groups. PCI associated with lower risk of stroke, but higher risk of revascularization. Highest tercile of SYNTAX scores benefit more from CABG. |
| PRECOMBAT[5] | 2004 to 2009 | ~600 patients | Stable angina, ACS, candidates for PCI or CABG | 5 years | Death, MI, Stroke, or target vessel revascularization | Sirolimus DES | 93.8% internal mammary artery | 63.8% off-pump procedure | ✓ | ✓ | ✘ | ✘ | No significant difference in the occurrence of the primary endpoint. |
| EXCEL[2] | 2010 to 2014 | ~2000 patients | Stable angina, ACS, SYNTAX score <33, candidates for PCI or CABG | 3 years | Death, MI, or Stroke | Everolimus DES | 98.8% internal mammary artery | 29.4% off-pump procedure | ✓ | ✓ | ✘ | ✘ | PCI with everolimus-eluting stents was noninferior to CABG. |
| NOBLE[1] | 2008 to 2015 | ~1200 patients | Stable angina, ACS, candidates for PCI or CABG | 5 years | Death, MI, Stroke, or revascularization | Biolimus DES | 94% internal mammary artery | 16% off-pump procedure | CABG might provide a better clinical outcome for treatment of left main coronary artery disease than PCI. | ||||
†NR=Not Reported
SYNTAX Trial
Visit the SYNTAX page for details about this trial.[4]
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.[5]
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.[2][3]
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.[1]
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. [6][3]
References
- ↑ 1.0 1.1 1.2 Mäkikallio T, Holm NR, Lindsay M, Spence MS, Erglis A, Menown IB; et al. (2016). "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. doi:10.1016/S0140-6736(16)32052-9. PMID 27810312.
- ↑ 2.0 2.1 2.2 Stone GW, Sabik JF, Serruys PW, Simonton CA, Généreux P, Puskas J; et al. (2016). "Everolimus-Eluting Stents or Bypass Surgery for Left Main Coronary Artery Disease". N Engl J Med. doi:10.1056/NEJMoa1610227. PMID 27797291.
- ↑ 3.0 3.1 3.2 Braunwald E (2016). "Treatment of Left Main Coronary Artery Disease". N Engl J Med. doi:10.1056/NEJMe1612570. PMID 27797298.
- ↑ 4.0 4.1 Morice MC, Serruys PW, Kappetein AP, Feldman TE, Ståhle E, Colombo A; et al. (2014). "Five-year outcomes in patients with left main disease treated with either percutaneous coronary intervention or coronary artery bypass grafting in the synergy between percutaneous coronary intervention with taxus and cardiac surgery trial". Circulation. 129 (23): 2388–94. doi:10.1161/CIRCULATIONAHA.113.006689. PMID 24700706.
- ↑ 5.0 5.1 Ahn JM, Roh JH, Kim YH, Park DW, Yun SC, Lee PH; et al. (2015). "Randomized Trial of Stents Versus Bypass Surgery for Left Main Coronary Artery Disease: 5-Year Outcomes of the PRECOMBAT Study". J Am Coll Cardiol. 65 (20): 2198–206. doi:10.1016/j.jacc.2015.03.033. PMID 25787197.
- ↑ Campos CM, Christiansen EH, Stone GW, Serruys PW (2015). "The EXCEL and NOBLE trials: similarities, contrasts and future perspectives for left main revascularisation". EuroIntervention. 11 Suppl V: V115–9. doi:10.4244/EIJV11SVA26. PMID 25983143.