A Clinical Trial of Conservative Versus Routine Invasive Management in Patients with Prior Coronary Artery Bypass Surgery in Patients with a Non-ST Elevation Acute Coronary Syndrome: a Pilot Trial and Registry.

Background: Coronary artery bypass graft (CABG) surgery is commonly performed in the NHS and worldwide based on historical evidence of benefit over medical therapy and more recent evidence of benefit over percutaneous coronary intervention (PCI). According to the national audit data from the Society of Cardiothoracic Surgeons and the British Cardiovascular Intervention Society, over 1 million CABG operations have been performed in the UK, with 20,000 - 25,000 operations performed annually since 1994. Although the number of isolated CABG operations performed annually has fallen slightly (e.g. 17,822 in 2010), CABG combined with valve surgery has increased. Since the 5 year survival rate after CABG is approximately 90%, several hundred thousand patients with prior CABG are likely alive in the UK. However, occlusive vein graft disease affects around 10% of patients within 12 months of surgery and affects at least two thirds of patients by 10 years. Furthermore, disease in the native coronary arteries may also deteriorate. Consequently, even though vein graft occlusion may initially be subclinical, angina eventually recurs in most patients with repeat revascularisation (almost always by PCI) required in nearly two thirds of patients by 12 years. Furthermore, when PCI is performed in these patients clinical outcomes in the longer term are poor because of restenosis.

Given the large number of CABG survivors in the UK, and the complexities of their clinical management, their cardiac morbidity and mortality is an increasing challenge in NHS hospitals.

Chest pain is the commonest reason for hospital admission in the UK and more than 1 in 10 hospital admissions with suspected acute myocardial infarction (MI) have a history of prior CABG and non-ST elevation acute coronary syndrome (NSTE-ACS) patients with prior CABG spend more time in hospital than those without a history of CABG. According to the Myocardial Ischaemia National Audit Project (MINAP), 47,162 patients were admitted with an NSTE-ACS in England and Wales during 2009/2010 including approximately 5000 patients with prior CABG. The median 30-day death rate of all NSTE-ACS patients in the UK in 2009/2010 was approximately 7.5% and clinical outcomes in CABG patients are much worse than in patients without prior CABG. However, since prior CABG status is not an independent predictor of mortality, the prognostic determinants are multifactorial and strongly influenced by age and co-morbidity.

There is an important lack of evidence to inform clinical decision making in symptomatic CABG patients hospitalised with NSTE-ACS. Firstly, most clinical trials of treatment strategies in ACS have excluded patients with prior CABG. The pivotal clinical trials which specifically compared invasive versus conservative management in unstable coronary syndromes, including Thrombolysis in Myocardial Infarction (TIMI) IIIb, Fragmin during Instability in Coronary Artery Disease (FRISC) II, Treat Angina With Aggrastat and Determine the Cost of Therapy With an Invasive or Conservative Strategy (TACTICS)-TIMI 18, and Randomized Intervention Treatment of Angina (RITA) 3, excluded patients with prior CABG, meaning evidence is lacking on which treatment strategy is most appropriate in this patient group. In the absence of trial data, guidelines for clinicians are based on observational studies, a subgroup analysis and expert opinion (level of evidence C). According to the UK National Institute of Clinical Excellence (NICE) Clinical Guideline 94, "in the absence of more research, consensus expert opinion is the best that can be achieved." Although CABG patients with acute ischaemia are often managed invasively, angiography commonly does not lead to revascularisation. PCI, or even repeat CABG, is technically challenging, complications are common and longer term outcomes are poor. This is especially the case for repeat PCI in vein grafts. Overall, invasive management of patients with prior CABG is technically challenging and health outcomes are influenced by the effectiveness of the procedure and complications (safety). Procedural success is harder to achieve because of advanced native coronary and graft disease and co-morbidity meaning the procedure is less often a success and the risks of complications and adverse events (e.g. stroke) are three-four fold higher than average. Since the internal mammary graft is almost always patent, redo surgery is rarely performed because sternotomy may damage the mammary graft (which can be a life-threatening complication) and current guidelines recommend PCI unless the mammary graft is occluded.

The effectiveness of a routine invasive approach in every-day clinical practice, which is the approach of many clinicians, is called into question because acute and long term outcomes are much worse than in patients without prior CABG. PCI in redo CABG carries a four-fold higher risk of death compared to the index procedure and complications associated with PCI include bleeding, stroke and contrast nephropathy. Redo CABG confers a much higher risk than percutaneous coronary intervention (PCI). Overall, increased age and co-morbidity are common and key drivers of long-term outcome. Outcomes after PCI in vein grafts or native vessel disease are poor. For example, in Wales, of 161 patients who had PCI after CABG, adverse cardiac events occurred in 14% of them by 13 months (mainly related to repeat PCI (12%). In the UK overall, of 33,652 PCIs performed in 1999/2000, 907 (2.7%) were performed in patients with prior CABG. Only 1 in 10 procedures were reported as successful and 1.3% and 1.0% of patients experienced in-hospital MI or death. Ten years on (2009/2010), 8.4% of all patients undergoing PCI had a history of prior CABG and procedure-related outcomes remained disappointingly similar (1 in 10 procedures unsuccessful, in-hospital death rate (1.0%), 30-day mortality 1.5%).