New clinical trial evaluates choice of treatment for left main coronary disease

The development of coronary artery bypass graft (CABG) in 1967 and percutaneous coronary intervention (PCI) in 1977 were seminal events in the evolution of the treatment of coronary artery disease (CAD). Multiple clinical trials in the intervening years have helped to clarify appropriate utilization of each approach.

Meanwhile, improvements in anesthesia, operative technique and postoperative care, as well as technological advances in percutaneous systems, have resulted in reduced hospital stays and improved outcomes and durability for both procedures.

"However, these advances challenge the medical community to continually reevaluate the safety, efficacy and indications for these treatment modalities," according to Richard C. Daly, M.D., a cardiovascular surgeon at Mayo Clinic in Rochester, Minn.

Traditionally, individuals with significant stenosis of the left main (LM) coronary artery were treated with CABG rather than PCI due to:

  • The large area of myocardium at risk
  • The dire consequences of abrupt periprocedural closure
  • Concerns regarding durability of PCI

The introduction of drug-eluting stents, and now second-generation drug-eluting stents, has prompted re-examination of the possible role of PCI for some patients with LM disease. There is now evidence to suggest that PCI with drug-eluting stents may be appropriate treatment for some patients with LM disease, especially when the total burden of coronary disease is not high.

SYNTAX

Although the randomized Synergy Between PCI With TAXUS and Cardiac Surgery (SYNTAX) trial found that PCI with the first generation of paclitaxel-eluting stents in patients with three-vessel and LM disease was inferior to CABG for the composite primary endpoint of death, myocardial infarction (MI), stroke or revascularization at one year, a post hoc analysis suggested that subgroups with low anatomic SYNTAX scores had similar outcomes with PCI compared to CABG.

COMPARE

Second-generation drug-eluting stents have been shown to demonstrate lower restenosis and stent thrombosis rates than first-generation stents. The Comparison of the everolimus eluting XIENCE-V stent with the paclitaxel eluting TAXUS LIBERTÉ stent in all-comers (COMPARE) trial was a single-center, real-world prospective randomized study conducted in the Netherlands comparing the clinical performance of paclitaxel- and everolimus-eluting stents.

  • The rate of major adverse events (all death, nonfatal MI and target vessel revascularization) was significantly higher in the paclitaxel group than in the everolimus group at one year (9.1 percent vs, 6.2 percent; p = 0.023) and two years (13.7 percent vs. 9.0 percent; p = 0.0016).
  • The everolimus group also had lower rates of stent thrombosis at one year (2.6 percent vs. 0.7 percent; p = 0.002) and two years (3.9 percent vs. 0.9 percent; p = 0.0001), primarily due to a reduction in early stent thrombosis.

However, only 2 percent of the patients in this trial had unprotected LM stenting.

EXCEL

Mayo Clinic in Rochester is participating in the Evaluation of XIENCE PRIME™ Everolimus Eluting Stent System (EECSS) or XIENCE V® EECSS Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) Clinical Trial, which will clarify the role of second-generation drug-eluting stents for LM disease.

The EXCEL Clinical Trial will randomize 2,600 patients at 165 sites globally; 1,300 will receive stenting, and 1,300 will undergo CABG. In addition to clinical endpoints, the study will evaluate quality-of-life scores and analyze procedural and follow-up costs for the full study period.

For information about enrolling a patient in the EXCEL Clinical Trial at Mayo Clinic in Rochester, contact study coordinators Mary E. Peterson (507-255-4080) or Deborah A. Rolbiecki (507-255-5027).

Main inclusion criteria

  • Unprotected LMCA disease with angiographic stenosis ≥ 70 percent requiring revascularization as assessed by both interventional cardiologist and cardiac surgeon or
  • Unprotected LMCA disease with angiographic stenosis ≥ 50 percent but < 70 percent requiring revascularization as assessed by both interventional cardiologist and cardiac surgeon and one of the following:
    • Noninvasive evidence of ischemia referable to a LM lesion
    • IVUS MLA ≤ 6.0 mm2
    • FFR ≤ 0.80

or

  • Significant LM equivalent disease: ostial lesions of LAD and CFX ≥ 70 percent, OR
  • One or both of the ostial LAD and CFX lesions ≥ 50 percent and < 70 percent and one of the following:
    • Noninvasive evidence of ischemia
    • IVUS MLA ≤ 4.0 mm2
    • FFR ≤ 0.80
  • Clinical and anatomic eligibility for both PCI and CABG
  • Silent ischemia, stable angina, unstable angina, or recent MI

Main exclusion criteria

  • Prior PCI LM at any time
  • Prior CABG at any time
  • Prior PCI any coronary artery within past year
  • Need for other cardiac surgery
  • Need for any other surgery within next year
  • Inability to tolerate dual antiplatelet therapy for at least one year
  • Noncardiac comorbidities with life expectancy of ≤ three years
  • Other investigational studies
  • Pregnancy

Trial endpoints

Primary endpoints

  • Composite all-cause mortality, MI, CVA at three years

Secondary endpoints

  • All-cause mortality, MI, CVA at 30 days
  • Unplanned revascularization within three years
  • Quality-of-life measures and treatment costs for the full follow-up period