Randomized Trial of Stents versus BypassSurgery for Left Main Coronary Artery

DiseaseSeung Park, Young-Hak Kim, Duk-Woo Park, et.al.

n engl j med 364;18

Dr.Ravi Prakash Moderator –Dr Roopa Salwan

INTRODUCTION

• Recent registry and sub-study results have shown that percutaneous coronary intervention (PCI) is safe and effective in patients with unprotected left main coronary artery (ULMCA) stenosis.

• However, due to the lack of randomized clinical trials, the comparability of PCI with coronary artery bypass graft (CABG) remains uncertain.

PRECOMBAT Trial Premier of Randomized Comparison of Bypass Surgery versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease

• DESIGN: a prospective, randomized clinical trial

• OBJECTIVE: To compare PCI with sirolimus-eluting stents and CABG surgery for optimal revascularization of patients with ULMCA stenosis.

• PRINCIPAL INVESTIGATOR Seung-Jung Park, MD, PhD, Asan Medical Center,

Seoul, Korea

PATIENT FLOW

CABG registry N=335

PCI registry N=475

Medication registry N=44

Assigned CABGN=300

Assigned PCIN=300

Treated CABGN=248

Treated PCIN=51

Treated medicalN=1

Treated CABGN=24

Treated PCIN=276

Treated medicalN=0

1-year follow-upN=296

1-year follow-upN=298

1-year follow-up

CABG registry N=310PCI registry N=457

Medication registry N=41

Randomized CohortN=600

2-year follow-upN=266

2-year F/UN=270

2-year follow-up

CABG registry N=259PCI registry N=289

Medication registry N=39

Enrolled Patients (N=1454)

MAJOR INCLUSION CRITERIA

• 18 years of age.

• Significant de novo ULMCA stenosis (>50%)

• Left main lesion and lesions outside ULMCA (if

present) potentially comparably treatable with PCI

and CABG.

• Objective evidence of ischemia or ischemic

symptom with angina or NSTEMI

MAJOR EXCLUSION CRITERIA

• Any contraindication to dual antiplatelet therapy• Any previous PCI within 1 year• Previous CABG• Chronic total occlusion > 1 • AMI within 1 week• Shock or LV EF < 30%• Planned surgery• Disabling stroke• Other comorbidity, such as CRF, liver disease, etc

STUDY PROCEDURES

• Sirolimus-eluting Cypher stent for all lesions• Strong recommendation of IVUS-guidance• Other adjunctive devices at the operator’s discretion• Use of LIMA to LAD anastomosis• Off- or on-pump surgery at the operator’s discretion• Dual antiplatelet therapy at least for 6 months after

PCI• Standard medical treatment after PCI and CABG

FOLLOW-UP• Clinical follow-up at 30 days and 6, 9, and 12

months via clinic visit or telephone interview.• Routine angiographic follow-up at 8-10 months after

PCI.• Ischemia-guided angiographic follow-up after CABG.• Retrospective SYNTAX score measurement in the

Core Lab, CVRF, Seoul, Korea

PRIMARY END POINT• A composite of major adverse cardiac or

cerebrovascular events (MACCE) for the 12-month period after randomization including

– Death from any cause– Myocardial infarction (MI)– Stroke– Ischemia-driven target vessel revascularization (TVR)

POWER CALCULATION• A non-inferiority margin : 7%• A one-sided type I error rate : 0.05• Power : 80% • Assumption : a total of 572 patients (286 per group) • A final sample size : 600 patients (300 per group)

assuming 5% of loss

RESULTS

The baseline clinical characteristics of the PCI and CABG groups were similar.

Mean age of participants- 62 years 76.5% were men. The baseline angiographic characteristics of

thetwo groups were also similar.

PROCEDURAL CHARACTERISTICS OF THE STUDY GROUPS

.Complete revascularization 68.3% in the PCI group 70.3% in the CABG group (P = 0.60). Duration of the hospital stay after the procedure 8.4±14.5 days in the CABG group 3.1±5.8 days in the PCI group (P<0.001). At the time of discharge, patients in the PCI group more consistently received medications.Follow-up angiography at 8 to 10 months performed more frequently in the PCI group

PROCEDURAL CHARACTERISATION

PROCEDURAL CHARACTERISATION

TRIAL END POINT

median follow-up period was 24.0 months in both the PCI and CABG groups.

The primary end point of major adverse cardiac or cerebrovascular events at 12 months

occurred in 26 patients assigned to PCI 20 patients assigned to CABG

DEATH FROM ANY CAUSE

MYOCARDIAL INFARCTION

STROKE

TARGET VESSEL REVASCULARISATION

INFERENCE No significant between-group differences in the cumulative

incidence rates of the individual components of the primary end point .

2-year rate of ischemia-driven target-vessel revascularization was significantly

lower in the CABG group than in the PCI group.

There was no significant differences between the PCI and CABG groups in the registry cohort with respect to the rates of most of the major trial end points at 1 or 2 years.

The exception was the end point of ischemia-driven target-vessel revascularization, which occurred significantly more frequently in

PCI group.

DISCUSSION: COMPARISON WITH SYNTAX TRIAL

PRECOMBAT SYNTAXLower CV or

cerebrovascular event rate.

Lower in stent thrombosis

Pt. had less complex coronary lesions & clinical settings.

Mean SYNTAX score=25Mean EUROSCORE=2.7Better device &

techniqueAsian population

Higher event rateEvent rate similar in

PCI/CABGMean SYNTAX score=30Mean EUROSCORE=3.8US & European

population

LIMITATIONS OF THE STUDY

Underpowered study due to low event rateWide inferiority margin of 7% point, so

findings can not be considered clinically directive.

Relatively high rate of cross over between PCI & CABG group.

2 yr follow up period may not be enough for comparison.

Restricted sample size. Difficult to extrapolate.

CONCLUSION

At 1 yr, rate of CV or cerebrovascular events are similar in PCI & CABG groups .

Meets the pre-specified criteria on non-inferiority of PCI to CABG.

However due to low power and wide inferiority margin of trial, findings can not be considered as clinically directive.

Thanks