Coronary Revascularization before Noncardiac Surgery
【关键词】 Revascularization,
The evaluation of cardiac risk before noncardiac surgical procedures and interventions aimed toward reducing that risk have become an integral part of the contemporary practice of medicine. In the nonoperative setting, it is generally accepted that the pathophysiology of acute myocardial infarction is usually due to the disruption of a vulnerable coronary-artery plaque followed by coronary-artery thrombosis. Histopathological analyses of coronary arteries in patients who had a fatal myocardial infarction soon after noncardiac surgery have confirmed this pathophysiology, with evidence of an unstable plaque present in more than half of patients.1
An association between fatal perioperative myocardial infarction and advanced left main coronary artery disease, severe three-vessel disease, or both is also common. Perioperative activation of neurohumoral pathways, an increase in catecholamine levels, a reduction in endogenous levels of tissue plasminogen activator, an increase in shear stress in association with platelet activation, and possibly coronary spasm have been postulated to be mechanisms leading to plaque disruption and subsequent coronary-artery occlusion. However, some patients appear to have a myocardial infarction without ST-segment elevation, perhaps caused primarily by periods of prolonged ischemia as a result of perioperative stresses that occur in the presence of severe fixed coronary-artery obstruction.
Previous studies have shown that patients at increased risk for perioperative events can be identified on the basis of simple clinical markers (e.g., angina pectoris, previous myocardial infarction, diabetes mellitus, previous heart failure, renal insufficiency, poor functional capacity, or high-risk surgery) available at the time of the initial evaluation.2,3 The addition of noninvasive and invasive testing further improves the accuracy of risk stratification.4 Applying the lessons learned from risk stratification to the care of patients, in an attempt to reduce risk, has been a challenge, particularly in light of the large numbers of patients who currently undergo noncardiac surgery and the variable risks.
There is today overwhelming agreement that aggressive medical management to provide myocardial protection in the perioperative state is a central element in reducing the risk of adverse clinical events. In a landmark clinical trial, patients undergoing noncardiac surgery who had or were at risk for coronary artery disease were randomly assigned to receive atenolol intravenously before and immediately after surgery and orally thereafter for the duration of hospitalization or to receive placebo.5 A significant reduction in the incidence of perioperative ischemia was observed among the patients who received atenolol. This reduction was associated with a lower mortality in the atenolol group six months after hospital discharge (0 percent, vs. 8 percent in the placebo group; P<0.001), after one year of follow-up (3 percent vs. 14 percent, P=0.005), and after two years of follow-up (10 percent vs. 21 percent, P=0.02). The lower mortality was predominantly due to a reduction in deaths from cardiac causes during the first six to eight months after noncardiac surgery.
Poldermans et al., in the Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography (DECREASE) trial, investigated the use of the beta-blocker bisoprolol in high-risk patients referred for vascular surgery.6 In that study, the group treated with bisoprolol had a significant reduction in the incidence of death from cardiac causes as compared with patients receiving standard care (3.4 percent vs. 17 percent, P=0.02) and a significant reduction in the incidence of nonfatal myocardial infarction (0 percent vs. 17 percent, P<0.001).
The benefits of beta-blockers in these two studies are consistent with the proposed cascade of events that occur when sympathetic activation is triggered by perioperative stresses. Interrupting this cascade, even for a short period of time, might have long-term benefits.
More recently, a large body of data have been reported that support the pleiotropic and antiinflammatory effects of statins, which promote the stabilization of potentially vulnerable coronary plaques and a reduction in adverse coronary events. In particular, the prehospital or preprocedure use of statins has been found to be associated with reductions in the incidence of in-hospital death in patients with acute coronary syndromes, of periprocedural myocardial infarction after percutaneous coronary intervention, and of perioperative mortality in patients undergoing major noncardiac vascular surgery.7 Although no large, randomized clinical trials have been completed to confirm the efficacy of statins in these settings, the strong association shown in large observational studies supports the inclusion of statins in the perioperative management of patients with known or strongly suspected coronary artery disease who are undergoing noncardiac surgery.
The role of preoperative coronary revascularization in patients being evaluated before noncardiac surgery has been controversial for several decades. The limited size and number of observational studies and the absence of randomized clinical trials have resulted in uncertainty concerning the benefits and risks of preoperative coronary revascularization for the purpose of improving perioperative and longer-term coronary outcomes.
In this issue of the Journal, McFalls et al. report the results of the Coronary Artery Revascularization Prophylaxis trial.8 Patients with clinically significant, stable coronary artery disease who were scheduled for elective vascular operations at 18 Veterans Affairs medical centers were randomly assigned to undergo coronary revascularization (percutaneous coronary intervention or coronary-artery bypass grafting, 258 patients) or medical therapy alone (252 patients). Medical therapy was optimized in both groups, with 84 percent of patients in the revascularization group and 86 percent of those who did not undergo revascularization receiving beta-blockers, 54 percent in both groups receiving statins, and 70 percent and 76 percent, respectively, receiving aspirin. Patients with a stenosis of the left main coronary artery of at least 50 percent, a left ventricular ejection fraction of less than 20 percent, and severe aortic stenosis were excluded from randomization. The majority of patients enrolled had single-vessel or two-vessel disease. After vascular surgery, there were no differences between the two groups in the incidence of myocardial infarction or in-hospital mortality. At a median follow-up of 2.7 years, the mortality was 22 percent in the revascularization group and 23 percent in the no-revascularization group.
Although the randomized study by McFalls et al. was underpowered to detect differences in event rates in high-risk subgroups, the study design and the clinical question answered put the study at the very top of the list of clinically relevant studies in this field. The results should be interpreted in light of its design, the exclusion criteria, and the ancillary therapies. If one carefully screens candidates for vascular surgery and excludes patients with symptoms of unstable coronary disease, left main coronary artery disease, aortic stenosis, or severe left ventricular dysfunction, and if one provides excellent perioperative medical treatment to those remaining, then coronary revascularization does not appear to provide an additional benefit in reducing the incidence of perioperative death or myocardial infarction. The results mirror those of other randomized clinical trials in the nonoperative setting that have shown that elective coronary revascularization in "low risk" patients who have stable coronary artery disease does not provide a survival benefit and does not reduce the risk of late myocardial infarction as compared with excellent medical and preventive therapies.
However, the issue of whom to screen and how to screen preoperative patients beyond a history taking, physical examination, and preoperative electrocardiography is far from settled. The data reported by McFalls et al. are about therapy for patients with stable, well-defined coronary disease, not screening. There is clearly a tendency to view effective beta-blockade as sufficient to preclude noninvasive screening in most patients being considered for noncardiac surgery, especially in those with known stable coronary disease who are facing lower-risk operations. The DECREASE trial showed a nearly 85 percent reduction in the combined incidence of nonfatal myocardial infarction and death from cardiac causes after elective vascular surgery, owing to effective preoperative, intraoperative, and postoperative beta-blockade. However, there was a small group of patients with multiple clinical markers of risk and widespread ischemia on preoperative stress echocardiography who were not adequately protected by beta-blockers.9
Cost-effective identification of this minority of patients, who have extremely high preoperative risk, is the subject of the American College of Cardiology American Heart Association guidelines for perioperative cardiovascular evaluation for noncardiac surgery.2,10 The trial by McFalls and colleagues adds to our foundation of knowledge, answering a critical question about therapy. Now we need a series of additional randomized studies to settle remaining questions about screening and about the value of medical therapies beyond beta-blockade with statins, angiotensin-converting enzyme inhibitors, antiplatelet agents, and other myocardial protective or vascular stabilizing drugs that are in development.
Source Information
From the Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan Cardiovascular Center, Ann Arbor.
References
Dawood MM, Gupta DK, Southern J, Walia A, Atkinson JB, Eagle KA. Pathology of fatal perioperative myocardial infarction: implications regarding pathophysiology and prevention. Int J Cardiol 1996;57:37-44.
Eagle KA, Brundage BH, Chaitman BR, et al. Guidelines for perioperative cardiovascular evaluation for noncardiac surgery: report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 1996;93:1278-1317.
Lee TH, Marcantonio ER, Mangione CM, et al. Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation 1999;100:1043-1049.
Eagle KA, Coley CM, Newell JB, et al. Combining clinical and thallium data optimizes preoperative assessment of cardiac risk before major vascular surgery. Ann Intern Med 1989;110:859-866.
Mangano DT, Layug EL, Wallace A, Tateo I. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. N Engl J Med 1996;335:1713-1720.
Poldermans D, Boersma E, Bax JJ, et al. The effect of bisoprolol on perioperative mortality and myocardial infarction in high-risk patients undergoing vascular surgery. N Engl J Med 1999;341:1789-1794.
Poldermans D, Bax JJ, Kertai MD, et al. Statins are associated with a reduced incidence of perioperative mortality in patients undergoing major noncardiac vascular surgery. Circulation 2003;107:1848-1851.
McFalls EO, Ward HB, Moritz TE, et al. Coronary-artery revascularization before elective major vascular surgery. N Engl J Med 2004;351:2795-2804.
Boersma E, Poldermans D, Bax JJ, et al. Predictors of cardiac events after major vascular surgery: role of clinical characteristics, dobutamine echocardiography, and beta-blocker therapy. JAMA 2001;285:1865-1873.
Eagle KA, Berger PB, Calkins H, et al. ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery -- executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). Circulation 2002;105:1257-1267.
订阅登记：
请您在下面输入常用的Email地址、职业以便我们定期通过邮箱发送给您最新的相关医学信息，感谢您浏览首席医学网！