A study design to assess the safety and efficacy of on-pump versus off-pump coronary bypass grafting: the ROOBY trial

Abstract

Background Since the late 1960s, coronary artery bypass graft (CABG-only) procedures were traditionally performed using a heart-lung machine on an arrested heart (on-pump). Over the past decade, an increasing number CABG-only procedures were performed on a beating heart (off-pump). Advocates of the off-pump approach expect to reduce many of the adverse side effects related to using the heart-lung machine, while advocates for the on-pump procedure raise concerns related to graft patency rates and long-term event-free survival for the off-pump technique.

Purpose The U.S. Department of Veteran Affairs (VA) Cooperative Studies Program funded a randomized, multicenter clinical trial comparing the clinical and resourcerelated outcomes following on-pump versus off-pump techniques for veterans undergoing a non-emergent CABG-only procedure. The planning committee was faced with several critically important challenges to assure feasibility of study costs and required sample size; generalizability to non-VA surgical practices; and comparability of clinically meaningful results. These challenges are discussed.

Methods This study is a prospective, randomized, multicenter, single blinded (patient) clinical trial that compares on-pump and off-pump techniques for veterans requiring non-emergent CABG-only procedures. There will be 2200 patients randomized at 17 VA Medical Centers when the five-year recruitment period ends on 15 April 2007. There are two primary objectives: a short-term objective to assess the immediate impact of the two techniques on 30-day mortality/morbidity and a long-term objective to assess one-year mortality/morbidity. Major secondary outcomes are one-year graft patency rates and change in neuropsychological assessments from baseline to one year. All patients are assessed at 30 days post-surgery or discharge from the hospital, whichever is latest, and at one-year post-surgery.

Results During planning, several key issues had to be decided. These included 1) choosing primary objectives: a short-term (30-day) and a long-term (one-year) objective were chosen; 2) choosing primary outcome measures: composite measures were selected to ensure sufficient end-points; 3) standardization of surgical techniques: minimal standardization required but guidelines and continuing discussions on both techniques provided; 4) establishing criteria for surgeons and residents for participation: surgeons required to have completed 20 off-pump procedures prior to doing study procedures and residents, in presence of study surgeon, capable of doing either procedure; 5) identifying metrics of cognitive dysfunction sensitive to treatment: a neuropshychologist hired who centrally monitors cognitive functioning testing; and 6) blinding participants of surgical procedure: attempt to blind participants.

Limitations Areas of concern are whether all surgeons sufficiently experienced on the off-pump procedure, should residents have been allowed to do study surgeries, should techniques have been standardized more and were the best neurocognitive tests selected.

Conclusion The study design presented allows for a balanced and fair assessment of the on-pump and off-pump CABG procedures across a diversity of clinical outcomes and resource use metrics. Its results have the potential to influence clinical cardiac surgical practice in the future.

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References

American Heart Association. Heart disease and stroke statistics – 2005 update.

Weiland AP , Walker WE . Physiologic principles and clinical sequelae of Cardiopulmonary bypass . Clin Aspects Cardiac Surgery 1986; 15: 34–39 .

Spencer FC , Galloway AC , Colvin SB . Surgical management of coronary artery disease and bypass grafting for coronary artery disease. In Sabiston DC , Spencer FC eds. Surgery of the chest, Vol. II. W.B. Saunders Company , 1996.

Favaloro RG. Saphenous vein autograft replacement of severe segmental coronary artery occlusion . Ann Thoracic Surg 1968; 5: 334–339 .

Smith PLC. The cerebral consequences of coronary artery bypass surgery . Ann R Coll Surg Engl 1988; 70: 212–216 .

Taylor KM. Brain damage during cardiopulmonary bypass . Ann Thorac Surg 1998; 65: S20–S26 .

Savageau JA , Stanton BA , Jenkins CD , Frater RW . Neuropsychological dysfunction following elective cardiac operation. II. A six-month assessment . J Thorac Cardiovasc Surg 1982; 84: 595–600 .

Taylor KM. Central nervous system effects of cardiopulmonary bypass . Ann Thorac Surg 1998; 66: S20–S24 .

Picone AL , Lutz CJ , Finck C et al. Multiple sequential insults causing post-pump syndrome . Ann Thorac Surg 1999; 67: 978–985 .

10.

Edmunds Jr LH. Inflammatory response to cardiopulmonary bypass . Ann Thorac Surg 1998; 66: S12–S16 .

11.

Gill IS , Higginson LA , Maharajh GS , Keon WJ . Early and follow-up angiography in minimally invasive coronary bypass without mechanical stabilization . Ann Thor Surg 2000; 69: 56–60 .

12.

Goldman S. Saphenous vein graft patency 1 year after coronary artery bypass surgery and effects of anti-platelet therapy. Results of a Veterans Administration Cooperative Study . Circulation, 1989; 80: 1190–1197 .

13.

Grover FL , Hammermeister KE , Burchfield C et al. Initial report of the veterans administration preoperative risk assessment study for cardiac surgery . Ann Thorac Surg 1990; 50: 12–28 .

14.

Sellke FW , DiMaio JM , Caplan LR et al. for the American Heart Association. Comparing on-pump and off-pump coronary artery bypass grafting: numerous studies but few conclusions: a scientific statement from the American Heart Association council on cardiovascular surgery and anesthesia in collaboration with the interdisciplinary working group on quality of care and outcomes research . Circ 2005; 111: 2858–2864 .

15.

Benetti FJ , Naselli G , Wood M , Geffner L . Direct myocardial revascularization without extracorporeal circulation: experience in 700 patients . Chest 1991; 100: 312–316 .

16.

Buffolo E , Summo H , Aguiar LF , Teles CA , Branco JN . Myocardial revascularization in patients 70 years of age and older without the use of extracorporeal circulation . Am J Geriatr Cardiol 1997; 6: 7–15 .

17.

Arom KV , Flavin TF , Emery RW , Kshettry VR , Janey PA , Petersen RJ . Safety and efficacy of off-pump coronary artery bypass grafting . Ann Thorac Surg 2000; 69: 704–710 .

18.

Cartier R , Brann S , Dagenais F , Martineau R , Coutrier A . Systematic off-pump coronary artery revascularization in mulitvessel disease: experience of three hundred cases . Jour Thorac and Cardiovasc Surg 2000; 119: 221–229 .

19.

Bergsland J , Hasnan S , Lewin AN , Bhayana J , Lajos T , Salerno T . Coronary artery bypass grafting without cardiopulmonary bypass – an attractive alternative in high risk patients . European Jour Cardio-Vascular Surgery 1997; 11: 876–880 .

20.

Bergsland J , Hasnan S , Lewin AN , Lajos T , Salerno T . Elimination of cardiopulmonary bypass: a prime goal in reoperative coronary artery bypass surgery . European Jour Cardio-Vascular Surgery 1998; 14: 59–63 .

21.

Bredee JJ , Jansen EWL . Coronary artery bypass grafting without cardiopulmonary bypass . Current Opin Cardiol 1998; 13: 476–482 .

22.

Buffolo E , de Andrade JCS , Branco J , Teles CA , Aguiar LF , Gomes WJ . Coronary artery bypass grafting without cardiopulmonary bypass . Ann Thorac Surg 1996; 61: 63–66 .

23.

Buffolo E , Gerola LR . Coronary artery bypass grafting without cardiopulmonary bypass through sternotomy and minimally invasive procedure . International Jour Cardiol 1997; 62: S89–S93 .

24.

Calafiore AM , Teodori G , Giammarco GD et al. Multiple arterial conduits without cardiopulmonary bypass: early angiographic results . Ann Thorac Surg 1999; 67: 450–456 .

25.

Hammermeister KE , Johnson R , Marshall G , Grover FL . Continuous assessment and improvement in quality of care . Ann Surg 1994; 219: 281–290 .

26.

Kazis LE , Perlin J , Skinner K , Rogers WH . Health status and outcomes of veterans: report of change scores. 1999 Large Health Survey of Veteran Enrollees. Office of Quality and Performance. Veterans Health Administration, 2000.

27.

Kazis LE , Skinner K , Rogers WH et al. Health status and outcomes of veterans: physical and mental component summary scores (Veterans SF-36). 1998 National Survey of Ambulatory Care Patients. Office of Quality and Performance. Veterans Health Administration, 1999.

28.

Spertus JA , Winder JA , Dewhurst TA , Deyo RA , Fihn SD . Monitoring the quality of life in patients with coronary artery disease . Am J Cardiol 1994; 74: 1240–1244 .

29.

Massimo AM , Gu YJ , Boonstra PW , Grandjean JG , van Oeveren W , Ebels T . Procoagulant activity after off-pump coronary operation: is the current anticoagulation adequate? Ann Thorac Surg 1999; 67: 1370–1375 .

30.

Croughwell ND , Newman MF , Blumenthal JA et al. Jugular bulb saturation and cognitive dysfunction after cardiopulmonary bypass . Ann Thorac Surg 1994; 58: 1702–1708 .

31.

Khatri P , Babyak M , Clancy C et al. Perception of cognitive function in older adults following coronary artery bypass surgery . Health Psychol 1999; 18: 301–306 .

32.

Murkin JM , Baird DL , Martzke JS , Adams SJ , Lok P . Long-term neurological and neuropsychological outcome 3 years after coronary artery bypass surgery . Anesth Analg 1996; 82: S1–S515 .

33.

Newman MF , Kirchner JL , Phillips-Bute B et al. Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery . N Engl J Med 2001; 344: 227–233 .

34.

Pugsley W , Klinger L , Paschalis C , Treasure T , Harrison M , Newman S . The impact of Microemboli during cardiopulmonary bypass on neuropsychological functioning . Stroke 1994; 25: 1393–1399 .

35.

Wechsler D. Wechsler adult intelligence scale, 3rd edition. The Psychological Corporation , 1997.

36.

Reitan RM , Wolfson D . The Halstead-Reitan neuropsychological test battery. Neurospychological Press , 1985.

37.

Goodglass H , Kaplan E . The assessment of aphasia and related disorders. Lea & Febiger , 1983.

38.

Kozora E , Cullum CM . Qualitative features of clock drawing in normal aging and Alzheimer's disease . Assessment 1994; 1: 179–188 .

39.

Beck AT , Steer RA . Beck depression inventory manual. Psychological Corporation , 1987.

40.

Wijeysundera DN , Beattie WS , Djaiani G et al. Off-pump coronary artery surgery for reducing mortality and morbidity: Meta-analysis of randomized and observational studies . J Am Coll Cardiol 2005; 46: 872–882 .

41.

Fitzgibbon GM , Kafka HP , Leach AJ et al. Coronary bypass graft fate and patient outcome: angiographic follow-up of 5,065 grafts related to survival and reoperation in 1388 patients during 25 years . J Am Coll Cardiol 1996; 28: 616–626 .