• SCAI Statement on EACTS Response to EXCEL Trial Investigation

    December 10, 2019

    This week, leaders of the European Association for Cardiothoracic Surgery (EACTS) withdrew their support for European practice guidelines that endorse the use of coronary stents in many patients with left main coronary artery disease. EACTS leadership claims the results of the EXCEL randomized clinical trial1 were misleading because the protocol definition of myocardial infarction (MI), based on the SCAI definition of MI2, did not align with the Third Universal Definition of MI3 developed collaboratively by the European Society of Cardiology, the American College of Cardiology, the American Heart Association, and World Health Foundation. These definitions differ in the recommended biomarker measurements and thresholds for adjudicating a peri-procedural MI. EACTS leaders further expressed concern that mortality rates were greater among stent-treated patients in EXCEL, and suggested that the trial leadership was not forthcoming about this observation.

    The authors of the EXCEL trial preferred the SCAI definition of MI because it is based on the best available evidence linking biomarker abnormalities to subsequent mortality in large clinical trials, avoids ascertainment bias, and uses the same criteria for PCI and bypass surgery4. The SCAI definition has been used in multiple clinical trials because it avoids the pitfall of tabulating MI events that are small enough to have little clinical impact. Instead, the SCAI definition permits assessment of MI events that are likely to be clinically relevant.

    Cumulative event curves for all-cause death for the two treatment groups in EXCEL were superimposable for the first 18 months after treatment, but separated from 18 to 36 months.  Even though the difference was not statistically important at 3 years1, it raised concerns that death rates would rise further for PCI-treated patients.  For this reason, the recent publication of 5 year follow-up for EXCEL patients in the New England Journal of Medicine5 was welcomed. The paper shows that all-cause mortality remains higher for PCI-treated patients (13% versus 9.9%), but no difference in definite cardiovascular death was observed (5% versus 4.5%).  The powered composite endpoint of death, stroke, or MI was not different at 3 or 5 years of follow up.

    SCAI respectfully disagrees with EACTS regarding EXCEL. While all-cause mortality is an important endpoint to follow, the EXCEL trial was neither designed nor powered to assess differences in this endpoint.  Lethal differences in treatment effectiveness would be expected to manifest as differences in cardiovascular death rates; while this was also an unpowered observation, the lack of any difference in definite cardiovascular death at 5 years is reassuring. SCAI endorses the guidelines in Europe and the United States that support use of coronary stents for treatment of left main coronary artery disease in appropriately selected patients.

    1. Stone GW, Sabik JF, Simonton CA, et al.  Everolimus-eluting stents of bypass surgery for left main coronary artery disease.  New Engl J Med 2016;375:2223-35.
    2. Moussa ID, Klein LW, Shah B, et al. Consideration of a new definition of clinically relevant myocardial infarction after coronary revascularization: an expert consensus document from the Society for Cardiovascular Angiography and Interventions (SCAI).  J Am Coll Cardiol 2013;62:1563-70.
    3. Thygesen K, Alpert JS, Jaffe AS. et al. Third universal definition of myocardial infarction.  Eur Heart J 2012;33:2551-67.
    4. Moussa ID, Stone GW. Myocardial infarction after percutaneous coronary intervention and coronary artery bypass grafting surgery.  Time for a unifying definition.  JACC: Cardiovasc Interv 2017;10:1508-10.
    5. Stone GW, Kappetein AP, Sabik JF, et al. Five year outcomes after PCI or CABG for left main coronary artery disease. New Engl J Med 2019;381:1820-30.

     

    Read the response from the EXCEL Investigators