David J McCormack MFSTEd FRCSEd (CTh) Advanced Clinical Fellow Cardiothoracic Journal Club ROOBY Trial (Veterans Affairs Randomised On/Off Bypass) David J McCormack MFSTEd FRCSEd (CTh) Advanced Clinical Fellow

What proportion of Waikato patients is ROOBY applicable to? 5% 20% 50% 90%

Off-Pump Proposed Advantages Off-Pump Proposed Challenges No aortic cannulation No atrial cannulation No cross-clamping No blood-plastic interface No cardioplegia K+ load fluid load coronary air embolism No risk of bypass machine failure -> air embolism Less cost Less equipment Less staff Needs skilled staff Technically more difficult Not all coronary arteries easily reached by technique Potential for MI without cardioplegia Incomplete revascularisation more frequent. Worse long-term graft patency Proposed neuropsychological benefit not shown in trial Difficult in diffuse disease or small artery disease

Hypothesis or objective ‘We hypothesised there would be no difference between the on-pump and off-pump procedures for the two primary outcomes’ Primary Outcomes Major morbidity and mortality at 1 month Major morbidity and mortality at 1 year Secondary Outcomes Completeness of revascularisation 1-year graft patency Neuropsychological test scores

Methods – Study Design The ROOBY trial was a controlled, single-blind, randomized trial conducted from February 2002 through May 2008 at 18 VA medical centres. Participating surgeons were required to document that they had performed at least 20 off-pump CABG surgeries, including some in which complete revascularization was performed for all vascular territories of the heart. The pre-study off-pump experience of the surgeons averaged 120 cases (median, 50). Sixteen sites had training programs in which cardiothoracic trainees (postgraduate year 6 to 10) were designated before randomization as the primary surgeon or first assistant surgeon. Postoperatively, enrolled patients were followed every 2 months for up to 1 year.

Methods – Inclusion Criteria Patients undergoing isolated CABG surgery Scheduled or elective procedures

Methods – Exclusion Criteria Any clinically significant valve disease (i.e., moderate, moderate-to-severe, or severe valve disease). Requiring immediate surgery. Small target vessels (<1.1 mm in internal diameter) or diffuse coronary disease. Clinical reservations of the surgical team regarding patients with risk-factor profiles that predisposed them to an extremely high risk of an adverse event. The inability or unwillingness of the patient to provide consent.

Methods – Randomisation While in the preoperative holding area, patients underwent randomization. Automated central telephone system in a blocked randomization scheme. Assignments of the patients were balanced for each attending surgeon.

Methods – Surgical Details A standard median sternotomy was performed in all patients. Mandatory use of stabilisation device for off-pump surgery. Conversion from the assigned procedure to the other procedure was performed when clinically necessary

Methods – Primary Endpoints Short-term composite end point (<30d / discharge) death reoperation new mechanical support cardiac arrest, coma, Stroke renal failure requiring dialysis Long-term composite end point (30d – 1y) death from any cause nonfatal myocardial infarction repeat revascularization “Composite end points were selected for feasibility and fiscal reasons”

Methods – Secondary Endpoints Completeness of revascularization (determined by the number of graft s performed as compared with the number planned) Graft patency at 1 year Scores on a battery of neuropsychological tests which were performed preoperatively and 1 year post- operatively.

Methods – Statistical Analysis Power calculation indicated a sample size of 2200 patients Two-tailed continuity-corrected chi-square test. P value of 0.05 to indicate statistical significance for primary end points, Power of 0.80, a 10% rate of loss to follow-up, and the ability to detect a reduction of 40% in the rate of the primary 1-year composite end point in the off-pump group as compared with the expected 8% rate in the on-pump group. This sample size also allowed the detection of a 30% reduction in the primary short-term composite endpoint from the expected 14% rate in the on-pump group.

Methods – Statistical Analysis The two primary end points – continuity corrected chi square tests. Study-centre effects – Mantel–Haenszel chi-square tests. Baseline characteristic and secondary outcomes were compared with the use of chi-square techniques and t-tests as appropriate. Log-rank tests with On-Pump versus Off-Pump Coronary-Artery Bypass Surgery Kaplan–Meier curves were used to report time to death.

Results Consort Diagram

Results – Baseline Characteristics

Results – Baseline Characteristics

Results – Baseline Characteristics

Results – Primary Endpoints

Results – Primary Endpoints

Results – Primary Endpoints

Results – Secondary Enpoints

Results – Secondary Endpoints

Results – Secondary Endpoints Less grafts performed in off-pump group. More patients ‘undergrafted’ in off-pump group.

Conclusion Our trial did not show any overall advantage to the use of the off-pump as compared with the on-pump cardiac surgical approach for coronary bypass. Instead, there was a consistent trend toward better outcomes in patients undergoing the conventional on- pump CABG technique. This including better 1-year composite outcomes and 1-year patency rates. No significant differences between the off-pump and the on-pump techniques were identified in neuropsychological outcomes or the use of major resources.

Strengths of the study Prospective, controlled, randomised and blinded trial. Large multicentre trial. Achieved sufficient patients to power study. Impressive angiographic follow up Good clinical follow up rate (XX %)

Limitations of the study Surgical intervention not performed by experts. Minimum of 20 cases with some cases grafting all coronary territories. Self documentation of experience (expertise). Residents cases included. Large cohort of patients excluded Limited description of 3282 excluded patients (44% of eligible patients) Limited applicability to our local cohort. No standard operation in either limb.

Limitations of the study No description of reason for cross over Off-pump -> on-pump (12.4%) On-pump -> off-pump (3.6%) Historic study CORONARY Trial On/Off Trial Cologne Metanlysis GOPCABE

General Discussion Points Landmark paper – largely negative for off-pump. Less grafts per patient in off-pump surgery (2.9 vs 3.0). What level of experience should be required? Should resident cases be performed? Intention to treat analysis not used.

What proportion of Waikato Patients is ROOBY applicable to? 5% 20% 50% 90%