Departments of Cardiology and Anaesthesia, Critical Care and Pain Medicine, Royal Infirmary of Edinburgh, Little France, Edinburgh EH16 4SA, UK
*Corresponding author. E-mail: a.nimmo{at}ed.ac.uk
In this issue of the British Journal of Anaesthesia, Marcucci and colleagues1 present a case report of prophylactic preoperative coronary stenting in a patient undergoing lung resection. This case was associated with a fatal postoperative myocardial infarct because of in-stent thrombosis, despite waiting 6 weeks between the coronary intervention and surgery as recommended in the ACC/AHA guidelines on perioperative cardiovascular evaluation for non-cardiac surgery.2 The case report appropriately questions the wisdom of prophylactic coronary stenting a few weeks before non-cardiac surgery and suggests the use of alternative strategies to reduce the risk of cardiac complications.
Stenosis and thrombosis
There is no definitive evidence that percutaneous coronary intervention improves prognosis in patients with coronary artery disease except in the context of primary angioplasty for acute myocardial infarction.3 Randomized controlled trials in patients with chronic stable angina have demonstrated that coronary angioplasty is an excellent method of reducing coronary arterial luminal stenoses and anginal symptoms. However, this is at the cost of an excess adverse event rate with a small but significant increase in the future risk of myocardial infarction or death.4 Although such trials were performed before the use of intracoronary stents and glycoprotein IIb/IIIa receptor antagonists became part of standard practice, percutaneous coronary intervention has never been shown to reduce the incidence of myocardial infarction or death in patients with chronic stable angina. Why should the reduction in coronary stenosis not improve the likelihood of avoiding a myocardial infarction?
Severe coronary artery stenoses are not necessarily the lesions responsible for a myocardial infarction. The majority of non-surgical patients who sustain an acute myocardial infarction do not have a history of previous angina. Many patients have a large atherosclerotic plaque burden without apparent coronary arterial luminal encroachment because of the process of arterial or Glagovian remodelling,5 where the artery expands to accommodate the plaque. Luminal stenosis causing haemodynamic flow limitation is a late phenomenon. Clinical angiographic studies have shown that in nearly 90% of acute myocardial infarctions, the culprit lesion encroaches on the lumen by less than 70%.6 This underscores the importance of acute plaque rupture and erosion as the initiating event in acute myocardial infarction and not the functional degree of stenosis.7 Indeed, this pathophysiological process appears to be equally applicable to those patients who sustain a fatal myocardial infarction in the perioperative period. Dawood and colleagues8 found that while most patients dying after a perioperative myocardial infarction did have multivessel coronary artery stenoses, predicting the site of the myocardial infarction based on the severity of stenoses would have been unsuccessful in more than half of the cases, and that evidence of plaque haemorrhage or rupture was present in most cases.
Preoperative prophylactic revascularisation
Should patients with significant coronary artery disease undergo prophylactic coronary artery bypass grafting or percutaneous coronary intervention before non-cardiac surgery? Patients with a severe pattern of coronary disease, such as a critical left main stem stenosis or severe proximal three vessel coronary disease, have a poor prognosis and, irrespective of planned surgery, should be urgently considered for coronary artery bypass surgery. This intervention significantly improves prognosis especially where an exercise test is strongly positive or left ventricular function is impaired.9 In the study by Dawood,8 most of the patients who had a fatal perioperative myocardial infarction had left main stem or three vessel coronary artery disease.
Preoperative percutaneous coronary intervention with angioplasty and stenting, on the other hand, exposes destabilized plaque and coronary stent to the prothrombotic post-operative milieu with potentially catastrophic consequences.10 Whilst the angiographic appearance may have improved, the risk of postoperative coronary thrombosis at the site of intervention may have been increased rather than reduced. As in the case described by Marcucci and colleagues,1 this may be particularly relevant where only short courses of antiplatelet therapies such as clopidogrel are administered. There is increasing evidence that combination antiplatelet therapy with aspirin and clopidogrel has additional benefits beyond the currently used 28-day treatment regimen following elective intracoronary stent implantation. In the CREDO trial,11 aspirin and clopidogrel therapy had benefits for up to 12 months following percutaneous coronary intervention. This suggests that vascular remodelling and repair after percutaneous coronary intervention may take a protracted period of time. This period of remodelling may be further lengthened with the increasing use of drug-eluting stents that inhibit the repair processes in order to prevent neointimal hyperplasia and restenosis. Preoperative coronary stenting converts a stable flow-limiting lesion into a disrupted non-flow limiting lesion with implanted thrombogenic material. This is not a rational approach to preventing perioperative myocardial infarction.
Clearly, where there is genuine concern that the extent and severity of coronary disease is likely to produce major haemodynamic compromise or widespread and profound myocardial ischaemia during perioperative stress, consideration should be given to coronary revascularization. However, such haemodynamic ischaemia and instability is usually encountered in patients with left main stem or severe three-vessel disease, which would normally mandate bypass surgery.
Perioperative prophylactic medical therapy
Patients with cardiovascular disease have a high cardiovascular event rate and should receive secondary preventative therapy. Current evidence supports the use of aspirin,12 statin,13 14 and angiotensin converting enzyme inhibitor15 therapy. There is also compelling evidence to support the use of beta-blockers, especially in patients who have recently sustained a myocardial infarction,16 or have heart failure.17 18
These drugs should be considered for all patients with coronary, cerebral, or peripheral vascular disease. In addition to its role in reducing long-term cardiovascular events, drug therapy may be very important in reducing perioperative cardiac complications in at risk patients undergoing major non-cardiac surgery. Much of the evidence for the use of perioperative drug therapy comes from studies in patients having vascular surgerya group at particularly high risk of cardiac complications.
Beta blockers
The proven secondary preventative benefits of beta-blocker therapy in non-surgical patients are limited to patients with heart failure or after myocardial infarction. However, randomized trials in at risk patients having non-cardiac surgery19 and high-risk patients having vascular surgery20 have supported the use of perioperative beta-blockade. In Poldermans study of patients with positive preoperative stress echocardiography who underwent elective abdominal aortic surgery or infrainguinal arterial reconstruction, there was a 10-fold reduction in the combined rate of cardiac death and non-fatal myocardial infarction in the beta-blocker group.20 An observational study by Boersma and colleagues21 of over 1000 patients screened for inclusion in Poldermans study concluded that beta-blockers were beneficial both in patients with low and high clinical risk scores. Unless there is a clear contraindication, perioperative beta-blocker therapy should be given to all patients who are to have vascular surgery of the type studied by Poldermansand perhaps to most patients with cardiovascular disease who are to undergo major non-cardiac surgery. In the absence of clearly reversible obstructive airways disease, this should also include patients with chronic obstructive pulmonary disease. The secondary preventative benefits of beta-blocker therapy are equally important in patients with chronic obstructive pulmonary disease22 and beta-blockers were not considered to be contraindicated because of reactive airways disease in any of the patients reported by Boersma.21
Withdrawal of chronic beta-blocker therapy may have serious adverse effects.2325 It is important that beta-blocker therapy is maintained perioperatively in at risk patients and a rebound withdrawal syndrome must be avoided. Beta-blockers may be given intravenously during or after surgery in patients unable to take oral drugs.
Statins
Hydroxymethylglutaryl coenzyme A (HMGCoA) reductase inhibitor or statin therapy is associated with major benefits in patients with vascular disease. These benefits are now recognized to occur not only in patients with coronary artery disease, but also in patients with peripheral vascular disease, cerebrovascular disease, and those with multiple risk factors.14 26 Moreover, the recent Heart Protection Study14 has redefined the criteria for commencing statin therapy. In high-risk populations, statin therapy produces major morbidity and mortality benefits in patients with normal serum cholesterol concentrations (less than 5.0 mmol litre1) that would not have merited therapy according to previous guidelines. These benefits may, in part, relate to the stabilization of the atherosclerotic plaque surface and cap, making plaque rupture less likely and enhancing plaque remodelling. Indeed, recurrent myocardial ischaemia and cardiovascular event rates are reduced when statins are used early following an acute coronary syndrome.27 28
Recently, it has been suggested that statins may have a role in preventing perioperative events. In a case control study, the perioperative mortality of patients undergoing vascular surgery was reduced in those receiving statin therapy.29 This benefit was substantial with an adjusted odds ratio for perioperative mortality among statin users as compared with non-users of 0.22 (95% confidence interval 0.100.47). This intriguing finding needs to be assessed in a prospective randomized controlled trial. However, all patients with vascular disease should be established on a statin, given the powerful evidence provided by the Heart Protection Study,14 and statin therapy may be even more critical in the perioperative period.
Antiplatelet therapy
Perioperative antiplatelet therapy presents both benefits and risks. Through their mechanisms of action, all antiplatelet agents may be associated with an increased bleeding risk. This is the case for both aspirin and clopidogrel, and in particular their combination. Both of these agents cause prolonged antiplatelet actions as a result of irreversible platelet enzyme or receptor inhibition. The bleeding risks can be reduced by withdrawal of antiplatelet therapy but this may be associated with an increased perioperative cardiac event rate. There have been no randomized studies of antiplatelet drugs in non-cardiac surgery but, when a decision analysis model was used to examine the effect of continuing aspirin perioperatively in patients having peripheral vascular surgery,30 it was concluded that perioperative mortality would be reduced. It is usual in the UK to continue an antiplatelet drug perioperatively in patients having vascular surgery.31 Aspirin may be given after surgery by the nasogastric, rectal or i.v. route in patients unable to take oral drugs.
In the CURE trial,32 withdrawal of clopidogrel 5 days before coronary artery bypass surgery appeared to reduce the risk of postoperative bleeding in patients on combination aspirin and clopidogrel therapy for an acute coronary syndrome. Therefore, where operative bleeding risks are high, withdrawal of clopidogrel 5 days before surgery would appear to be appropriate in patients on combination therapy.
Antithrombin therapy
Subcutaneous heparin is commonly given perioperatively to reduce the risk of deep vein thrombosis and pulmonary embolism. However, heparin may also have a beneficial effect on the incidence of coronary artery thrombosis. A randomized trial in patients undergoing elective abdominal aortic aneurysm repair found that the administration of i.v. heparin during surgery reduced the incidence of fatal perioperative myocardial infarction.33 Low dose s.c. heparin has been shown to reduce hypercoagulability after elective abdominal aortic surgery.34
ACE inhibition
Patients with vascular disease or diabetes mellitus should be maintained on angiotensin converting enzyme inhibitor therapy. Benefit was initially demonstrated in patients with heart failure or recent myocardial infarction but major morbidity and mortality benefits have now been demonstrated in patients with vascular disease and normal left ventricular function.15 These benefits extend to patients with diabetes mellitus where there is the added advantage of a reduction in progression to microalbuminuria. ACE inhibitors have anti-ischaemic actions with a 20% relative reduction for myocardial infarction.15 35
The balance of benefits and risks of ACE inhibition in the perioperative period is uncertain. Inhibition of both the sympathetic nervous system with a beta-blocker and the renin-angiotensin system with an ACE inhibitor removes the major protective reflexes for intravascular volume regulation and homeostasis. Such combination therapy may result in a greater risk of hypotension and may necessitate more detailed and invasive haemodynamic monitoring and more frequent intervention. In the presence of ACE inhibition, acute renal failure can be precipitated by hypotension, hypovolaemia, radiocontrast, or NSAID administration.36
Conclusions
We believe that there is rarely a need for preoperative prophylactic percutaneous coronary intervention in patients with stable angina who are to undergo major non-cardiac surgery. Indeed, such a strategy is more likely to be harmful than beneficial. Instead, perioperative drug therapy should be used to prevent the induction of plaque instability, acute coronary thrombosis, and myocardial infarction. Patients with severe left main stem or three-vessel coronary artery disease should be considered for surgical revascularization.
Where surgery within weeks of percutaneous coronary intervention is unavoidable, protracted antiplatelet therapy, statin, and beta-blocker therapy should be given, and perioperative heparin administration should be considered. Postoperative cardiac complications should be anticipated and the patient should be admitted to a critical care area after surgery.
Declaration of interest
Dr Newbys salary is funded by the British Heart Foundation and he holds or has held research or educational grants from Bristol-Myers Squibb, Pfizer, and Johnson & Johnson.
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