Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization - EXCEL

Contribution To Literature:

The EXCEL trial showed that PCI with second-generation DES (Xience) is noninferior to CABG for clinical outcomes at 3 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 second-generation 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 Xience everolimus-eluting stents (n = 948) or CABG (n = 957).

  • Total number screened: 2,905
  • Total number of enrollees: 1,905
  • Duration of follow-up: 3 years
  • Mean patient age: 66 years
  • Percentage female: 23%

Inclusion criteria:

  • Unprotected left main coronary artery disease with ≥70% stenosis, or ≥50% to <70% with either: 1) noninvasive evidence of left main ischemia, 2) intravascular ultrasound minimum lumen area ≤6.0 mm2, or 3) fractional flow reserve ≤0.80
  • SYNTAX score ≤32
  • Clinical and anatomic eligibility for both PCI and CABG, as agreed to by the local Heart Team

Exclusion criteria:

  • Prior CABG or left main PCI any time
  • Prior nonleft main PCI within 1 year
  • Need for cardiac surgery other than CABG
  • Inability to tolerate dual antiplatelet therapy for 1 year
  • Creatine kinase-myocardial band > upper limit of normal

Other salient features/characteristics:

  • Diabetics: 29%
  • Prior PCI: 17%
  • Stable angina, 53%; recent myocardial infarction (MI), 15%; unstable angina, 24%
  • Mean left ventricular ejection fraction: 57%
  • SYNTAX scores: low (≤22) for PCI vs. CABG, 32.2% vs. 39.3%; high (≥33), 25.1% vs. 23.4%
  • Distal left main trunk bifurcation lesion: 81%
  • Additional single-vessel disease, 31%; two-vessel disease, 33%; three-vessel disease, 18%
  • PCI arm: IVUS, 77.2%; hemodynamic support, 5.2%; stents per patient, 2.4; stented length, 49.1 mm
  • CABG arm: off-pump, 29.4%; conduits per patient, 2.6; internal mammary artery use, 99%
  • Medication use: aspirin, 99%; statin, 95%; P2Y12 inhibitor for PCI vs. CABG, 97.6% vs. 32.6%; p < 0.001

Principal Findings:

The primary outcome, death, stroke, or MI at 3 years for PCI vs. CABG was 15.4% vs. 14.7%,  p = 0.018 for noninferiority, p = 0.98 for superiority.

  • Death: 8.2% vs. 5.9%, p = 0.11
  • Stroke: 2.3% vs. 2.9%, p = 0.37
  • MI: 8.0% vs. 8.3%, p = 0.64

Secondary outcomes:

  • Death, stroke, or MI at 30 days for PCI vs. CABG: 4.9% vs. 7.9%, p = 0.008
  • Death, stroke, or MI between 30 days and 3 years for PCI vs. CABG: 11.5% vs. 7.9%, p = 0.02
  • Stent thrombosis or graft occlusion at 30 days: 0.3% vs. 1.2%, p = 0.03
  • Ischemia-driven revascularization at 3 years: 12.6% vs. 7.5%, p < 0.0001
  • Stent thrombosis or graft occlusion at 3 years: 0.7% vs. 5.4%, p < 0.001

Quality-of-life assessments: There was no difference in the Seattle Angina Questionnaire frequency between the PCI and CABG arms at 12 months (difference = -0.3, p = 0.63) or 36 months (difference = -0.8, p = 0.21). No differences were noted based on baseline SYNTAX scores at 1 year, but low SYNTAX score patients seemed to do better with CABG at 3 years (p for interaction = 0.03). More patients scored 0 (none) on the Rose Dyspnea Scale at 1 month with PCI than CABG (60% vs. 44%, p < 0.01), but this difference was not significant on subsequent follow-up. Similarly, the Short Form-12 physical summary scale was significantly higher for PCI at 1 month (difference = 8.2, p < 0.01), but similar at 36 months (difference = -0.4, p = 0.5). Clinically significant depression was also lower with PCI at 1 month (8% vs. 19%, p < 0.01) and 12 months (8% vs. 12%, p = 0.03), but similar at 36 months (9% vs. 8%, p = 0.77).

Interpretation:

The results of this important trial indicate that PCI with second-generation DES (Xience) is noninferior to CABG for clinical and functional outcomes at 3 years following revascularization of unprotected left main lesions. As noted earlier, repeat revascularization rates were higher with PCI. Thrombosis (stent vs. graft) rates were lower with PCI than with CABG. 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 actually better with PCI up to 30 days. However, this reversed between 30 days and 3 years, such that outcomes were inferior with PCI compared with CABG beyond this time frame. 

Further longer-term follow-up is awaited. Detailed analysis among patients with pure ostial/shaft left main disease and low SYNTAX scores will be interesting.

References:

Presented by Dr. Suzanne J. Baron at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2017), Denver, CO, October 30, 2017.

Baron SJ, Chinnakondepalli K, Magnuson, EA et al., on behalf of the EXCEL Investigators. Quality of Life After Everolimus-Eluting Stents or Bypass Surgery for Treatment of Left Main Disease. J Am Coll Cardiol 2017;Oct 30:[Epub ahead of print].

Editorial Comment: Mark DB, Patel MR. Patient-Reported Outcomes in Revascularization Decisions for Left Main Disease: Sharing the EXCELlence. J Am Coll Cardiol 2017;Oct 30:[Epub ahead of print].

Stone GW, Sabik JF, Serruys PW, et al., on behalf of the EXCEL Trial Investigators. Everolimus-Eluting Stents or Bypass Surgery for Left Main Coronary Artery Disease. N Engl J Med 2016;375:2223-5.

Editorial: Braunwald E. Treatment of Left Main Coronary Artery Disease. N Engl J Med 2016;375:2284-5.

Presented by Dr. Gregg W. Stone at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2016), Washington, DC, October 31, 2016.


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