Off-pump Versus On-pump Coronary Artery Bypass Grafting in Frail Patients (FRAGILE)

A Multicenter, Prospective, Randomized, Clinical Trial Comparing Off-pump Versus On-pump Coronary Artery Bypass Grafting in Frail Patients

Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina de São Paulo, Hospital Alberto Urquiza Wanderley, Hospital das Clínicas Samuel Libânio, Hospital Samaritano Paulista, Beneficência Portuguesa de São Paulo, Hospital Samaritano Campinas, Instituto Nacional de Cardiologia de Laranjeiras, Pronto-Socorro Cardiológico Universitário de Pernambuco, Mount Sinai Hospital, New York

Frailty is defined as a geriatric syndrome of impaired resiliency to stressors (such as cardiac surgery) that has been delineated recently in the cardiovascular literature. One of the most controversial areas of cardiac surgery has been whether off-pump coronary artery bypass grafting (OPCAB) surgery is superior to conventional on-pump coronary artery bypass grafting (CABG) surgery. There is an ongoing debate about the benefits and disadvantages of OPCAB surgery and we believe that this remains an important technique for the improvement of coronary surgery. The benefits of CABG surgery in frail patients are still undetermined. The aim of this study is to clarify the potential benefit of OPCAB surgery in pre-frail and frail patients by comparing off-pump versus on-pump CABG in these patients.

The FRAGILE protocol is a national multicenter randomized controlled trial (RCT), conducted in 8 Brazilian institutions. The study is already approved by a certified ethics committee. Funding is provided by a grant from São Paulo Research Foundation (FAPESP), which otherwise will not have any role in the conduct of the study nor in the analysis nor in the reporting of data. A confidentiality agreement regarding data use and the data safety will be monitored by an independent monitoring board. All the authors will provide revisions and comments and be testifying for the accuracy and completeness of the report, as well as for the fidelity of the report to the study protocol.

Treatment assignments will be performed in a blinded manner according to a blocked randomization scheme with a block size of ten, stratified according to the participating center.

Pre-frail and frail patients will be randomly assigned to OPCAB after the evaluation of the target vessels by an internet-based, password protected database program. The surgery will be performed as described in the "intervention" section and the patients will be followed up for two years.

Pre-frail and frail patients will be randomly assigned to CABG after the evaluation of the target vessels by an internet-based, password protected database program. The surgery will be performed as described in the "intervention" section and the patients will be followed up for two years.

Surgical access to the heart will be gained through a median sternotomy in all of the patients. In order to reduce the risk of bleeding and transfusions, an absorbable hemostat will be used in the sternal bone marrow. An automatic autotransfusion system will be used to recovery of red blood cells in all patients. Off-pump surgery will be performed with the use of heart stabilizers. Patients will be heparinized with 250 IU/kg intravenously to achieve activated clotting time >200s. The proximal anastomosis will be performed according to our guidelines. The distal anastomosis will be constructed with the help of mechanical stabilizers and cardiac positioner. Intracoronary shunts will be used routinely.

Surgical access to the heart will be gained through a median sternotomy in all of the patients. On-pump surgery will be performed in normothermia, with the use of aortic cross-clamping and cold cardioplegic arrest. Patients will be heparinized with 500 IU/kg to achieve an activated clotting time >480 s. Heparin will be neutralized with 1:1 protamine sulfate. The automatic autotransfusion system will be used just in massive blood loss to recovery the red blood cells. Surgical techniques will be performed according to our guidelines.

Major adverse cardiac and cerebrovascular events after OPCAB and CABG in pre-frail and frail patients

This composite outcome comprises: all cause death, acute myocardial infarction, stroke, renal failure, acute respiratory distress syndrome and bleeding reoperation.

A cluster of symptoms that signals the onset of septic shock, often including a shaking chill, rapid rise in temperature, flushing of the skin, galloping pulse, and alternating rise and fall of the blood pressure.

Physician or advanced practitioner documents the diagnosis in the medical record based on laboratory findings (e.g. positive sputum culture results from transtracheal fluid and/or bronchial washings) and/or radiological evidence (e.g. chest radiograph diagnostic of pulmonary infiltrates).

To evaluate the clinical correlation between the revascularization strategy and the usefulness of the SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery score (SYNTAX score); age, creatinine and ejection fraction score (ACEF score); clinical SYNTAX score; European System for Cardiac Operative Risk Evaluation (EuroSCORE II); The Society of Thoracic Surgeon´s risk model (STS score) and Índice de Predição do INStituto do CORação (InsCor) for prognostic evaluation.

To evaluate the global cognitive status a examination test will be performed included 30 simple questions and tasks in a number of areas (orientation in time and place, repeating and recalling list of words, arithmetic, language use and comprehension, non-verbal memory).

To evaluate the quality of life by the EuroQol-registration, a five domain and a visual analogue scale (VAS). The best state they can imagine is marked by 100 and the worst state marked by 0.

The adjusted amount in US dollars of the total cost of coronary artery bypass surgery for all participating hospitals will be evaluated.

Inclusion criteria: - Participants aged ≥60 years with the indication of myocardial revascularization with ≥2 criteria of frailty by Fried Frailty Criteria, and suitable to undergo either Off-pump or On-pump CABG. Exclusion criteria: - Patients with the indication of angioplasty or another procedure in addition to CABG; patients who underwent an emergency operation (within 24 hours after hospital admission); patients who underwent previous cardiac surgery, even with other approaches than median sternotomy; patients who do not have free, prior and informed consent to participate in this study.

Mejia OAV, Sa MPBO, Deininger MO, Dallan LRP, Segalote RC, Oliveira MAP, Atik FA, Santos MAD, Silva PGMBE, Milani RM, Hueb AC, Monteiro R, Lima RC, Lisboa LAF, Dallan LAO, Puskas J, Jatene FB. Off-pump versus On-pump Coronary Artery Bypass Grafting in Frail Patients: Study Protocol for the FRAGILE Multicenter Randomized Controlled Trial. Braz J Cardiovasc Surg. 2017 Sep-Oct;32(5):428-434. doi: 10.21470/1678-9741-2017-0196.