PCI vs. CABG in the Treatment of Unprotected Left Main Stenosis
PCI vs. CABG in the Treatment of Unprotected Left Main Stenosis
Coronary Artery Bypass Grafting Versus Drug Eluting Stent Percutaneous Coronary Angioplasty
 in the Treatment of Unprotected Left Main Stenosis.

 In a clinical, randomized, 5-year follow-up study to compare essential clinical outcome
 parameters in patients with unprotected left main (LMCA) disease, treated with coronary
 artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) using drug
 eluting stents (DES).

 DES-PCI of unprotected LMCA disease is non-inferior to CABG concerning the 2-year rate of
 death, myocardial infarction, stroke or new revascularization and concerning the 5-year rate
 of death.
Design:

 Randomised open multicentre trial.

 Patients:

 Number 1,200

 Randomisation:

 PCI with DES vs CABG

 Individuals for inclusion will be recruited among the patients referred to the participating
 centers for LMCA treatment. The patients will not be recruited by advertising and will
 receive no honorarium for participation.

 Primary and secondary endpoints will be assessed by an independent endpoint committee (IEC).
 The endpoint committee will consist of experienced cardiac surgeons and cardiologists.

 Follow-up All patients will be seen at the outpatient clinic of the participating centers
 after one month and after 1, 2 ,3 ,4 and 5 years. The outpatient visit may be substituted
 with a telephone contact and subsequent investigation and documentation of possible study
 events (MACCE). Finally, there will be a 10-year registry assessment of total mortality.

 The index angiograms will be assessed by the QCA-laboratories at the Department of
 Cardiology, Aarhus University Hospital, Skejby, Denmark. The left main lesion and the
 non-left main lesions will be described and classified and a SYNTAX SCORE calculated.

 The angiography obtained during the PCI-procedure will be used as index angiography. There
 should be at least two cine-runs before the procedure and after the procedure with the same
 angulations and proceeded by 0.1 mg intracoronary nitroglycerine (documented on the
 angiogram). The diagnostic/guiding catheter should be well visible, near the center of the
 angiogram and filled with dye. The index lesion should be well visible, near the centre of
 the angiogram and shown without foreshortening. There should be an angulation difference
 between the two baseline angiograms of at least 30 degrees. Between the pre and post
 angiograms all balloon inflations and stent implantations should be documented by short
 cine-runs.

 Statistics and data management:

 The statistical analyses will be performed at the Department of Clinical Epidemiology, Aarhus
 University Hospital.

 Analysis population:

 The results will be analyzed according to the intention-to-treat principle, i.e. patients
 randomized to a certain group will be followed and assessed irrespectively of the actual
 treatment. Protocol violations will be noted and the responsible centers notified.

 Sample size calculations:

 Primary endpoint of 2-year MACCE Sample size calculation is based on the combined primary
 endpoint of death, stroke, non-index treatment related MI and new revascularization (PCI or
 CABG) after 2 years.

 The study is planned as a non-inferiority study, where an experimental treatment of a disease
 (E, here PCI) is compared to a standard treatment (S, here CABG). E is not allowed to be more
 than clinically insignificantly inferior to S to be declared non-inferior. Calculations are
 based on the following:

 -  mean follow-up time 24 months

 -  all event curves are exponential

 -  zero dropout

 -  randomization into 2 equally sized groups

 -  α = 0.05 (one-sided)

 -  1- β (power) = 80% The non-inferiority limit is based on a 12 months MACCE rate of 12%
 in the CABG and 16% in the PCI group (the SYNTAX study). With exponential event curves
 (S(t)=exp(-λ*t)) this corresponds to a hazard ratio of 1.36, PCI versus CABG, and, with
 t in months, λ=0.0107 in the CABG group. In continuation if this, the present study uses
 hazard ratio 1.35, E versus S, as limit for non-inferiority, and λ=0.011 to describe
 MACCE in the CABG group. These figures correspond to a 24-month MACCE rate of 30% and
 23% in the PCI and CABG group, respectively.

 The above preconditions and assumptions result in a necessary number of patients in each
 randomization group of 593 (and a total number of events - in both groups - of 275).
 Consequently, 1,186 patients should be randomized.

 By including 600 patients in each group, possible dropouts before follow-up and treatment
 estimation errors are accounted for.

 Data management The study is reported to Danish Data Protection Agency, and the agency's
 guidelines for data management will be followed. Dedicated case record forms will be used and
 faxed to PCI research, Cardiac Cath. Lab., Aarhus University Hospital, Skejby, 8200 Aarhus N,
 Denmark. Data will be stored in an Access database and double data entry will be used as
 quality control. There will be a log of accesses and attempt of accesses. Back-up data and
 original data will be encrypted.

 Monitoring of the study:

 The study will be monitored according to the GCP rules by independent professionals. During
 the study period, monitors will have regular contact to the participating departments to
 ensure that the trial is conducted in compliance with the protocol, GCP and applicable
 regulatory requirements.

 The monitors will ensure that the used products are all right and will review source
 documents for verification of consistency with the data recorded in the CRFs. The monitors
 will also provide information and support to the investigator(s).

 Investigators and other responsible personnel must be available during the monitoring visits,
 audits and inspections and should devote sufficient time to these processes.

 The investigator should provide a CV or equivalent documentation of suitability to be
 responsible for the trial. All investigators and other responsible personnel should be listed
 together with their function in the trial on the signature list.

 Publication:

 Results, positive as well as negative, will be published in an international cardiovascular
 journal. Publication and author issues will be decided by the steering committee on basis of
 general involvement in the study (drafting of protocol, core lab. function, endpoint
 committee membership, etc.) and on number of included patients. Thus, the sequence of authors
 will be determined by the inclusions rates of the participating centres and the most
 including centre will be offered the position as first author.
Inclusion Criteria:

 -  Stable, unstable angina pectoris or ACS.

 -  Significant lesion* of LMCA ostium, mid-shaft and/or bifurcation and with no more than
 three additional non-complex** PCI lesions.

 -  Patient eligible to be treated by CABG and by PCI

 -  Signed informed consent. *Visually assessed diameter stenosis >50% or fractional flow
 reserve <0.80. **Length <25 mm, non-CTO, non-2-stent bifurcation, non-calcified and
 non-tortuous vessel morphology coronary lesion.

 Exclusion Criteria:

 -  ST-elevation infarction within 24 hours.

 -  CABG clearly better treatment option (LMCA stenosis and >3, or complex** additional
 coronary lesions)

 -  Patient is in too high risk for CABG.

 -  Expected survival <1 year.

 -  Allergy to aspirin, clopidogrel or ticlopidine.

 -  Allergy to Biolimus. **Length >25 mm, CTO, 2-stent bifurcation, calcified or tortuous
 vessel morphology coronary lesion.