030410 care after coronary-artery bypass surgery

The new england journal of medicine Care after Coronary-Artery Bypass Surgery Mary E. Charlson, M.D., and O. Wayne Isom, M.D.
This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors’ clinical recommendations. A 71-year-old woman who had a myocardial infarction five years previously and un-
derwent coronary-artery bypass surgery six months ago visits a primary care physician.
She had no complications after surgery, but intraoperative transesophageal echocardi-
ography revealed a grade V atheroma in the descending aorta. She has no cardiac or
neurologic symptoms but notes that she feels depressed and has difficulty concentrat-
ing. She had not been depressed before. Her blood pressure is 110/80 mm Hg, and her
pulse is 76 and regular. The physical examination is notable only for a weight of 160 lb
(72 kg) at a height of 5 ft 4 in. (1.6 m). The fasting plasma glucose level is 109 mg per
deciliter (6.1 mmol per liter), the low-density lipoprotein cholesterol level is 128 mg
per deciliter (3.3 mmol per liter), the high-density lipoprotein cholesterol level is 40 mg
per deciliter (1.0 mmol per liter), and the triglyceride level is 200 mg per deciliter
(2.3 mmol per liter). What would you advise to improve her long-term outcome?

From the Division of General Internal Med- Despite the fact that an increasingly older population with a higher rate of coexisting icine (M.E.C.), the Center for Complemen- conditions is undergoing coronary-artery bypass grafting (CABG), outcomes have been tary and Integrative Medicine (M.E.C.), and improving steadily. Over the long term, patients with successful CABG may be at risk the Department of Cardiothoracic Surgery(O.W.I.), Weill Medical College, Cornell Uni- for angina, myocardial infarction, or stroke, as well as for cognitive deterioration and versity, New York. Address reprint requests depression. In this article we focus on CABG with cardiopulmonary bypass, since the to Dr. Charlson at Weill Medical College, long-term outcomes of “off-pump” surgery remain to be defined.
525 E. 68th St., Box 46, New York, NY 10021,or at [email protected].
After CABG, the majority of patients report a clinically significant improvement in physical function and energy level.1-3 Accordingly, 70 to 80 percent of patients who want to work are doing so by one year after surgery. By five years after CABG, anginal Copyright 2003 Massachusetts Medical Society. symptoms recur in 15 percent of patients, and 10 percent have ischemic events.4 Pa-tients who have had a postoperative myocardial infarction have a risk of angina and is-chemic events that is two to three times as high as that in patients who have not hadsuch an infarction.5 By 10 years after surgery, patients who have received internal-thoracic-artery grafts have a mortality rate that is 10 percent lower than that amongpatients who have had saphenous-vein grafts.6 Stroke is a less common long-term problem. The single most important cause of stroke is aortic atheromatous disease, which is detected with high reproducibility by in-traoperative transesophageal echocardiography or epiaortic scanning.7,8 Patients withlarge (>5 mm) or mobile aortic atheromas have an increase in the rate of perioperativestroke by a factor of 5 to 10 and are likely to have a significantly increased long-term riskof stroke.7-9 Up to 27 percent of patients report some forgetfulness after CABG, but most of these patients have no measurable impairment on neuropsychological testing.10 Comparinga given patient’s preoperative and postoperative scores on neuropsychological tests isthe only certain method of evaluating the cognitive effects of cardiac surgery,11 but such Downloaded from www.nejm.org by SCHLOMO ASCHKENASY on November 28, 2004 . Copyright 2003 Massachusetts Medical Society. All rights reserved. testing is rarely performed before surgery.11,12 The percent to 72 percent (although lipid levels werereported rates of cognitive deterioration six months unchanged).4 Nonetheless, many patients do notafter CABG vary widely, from 5 percent to over 33 adopt such changes in lifestyle after CABG, and thepercent.2,11,13 This large variation reflects differ- best strategies for motivating patients to initiate andences in study methods, including the specific maintain such changes have not been clearly iden-tests used, the criteria for deterioration on each tified.
test, and the ways of combining the results of dif-ferent tests to determine whether or not the pa- Smoking Cessationtients had cognitive deterioration.
Patients who quit smoking after CABG have a sur- Patients who are depressed after CABG surgery vival benefit of 3 to 5 percent at 5 years and a benefit may not have obvious affective features; they tend of 15 percent at 10 to 20 years, as compared withto have more cognitive and functional impairment those who continue to smoke.20-22 Patients whothan other surgical patients and are more likely to quit smoking are also less likely to require repeatedperceive themselves as having had cognitive deteri- CABG20,21 and have half the rate of subsequent my-oration after surgery.10,14,15 Thus, patients who re- ocardial infarction.22 The risk associated with nico-port having impaired memory or cognition should tine-replacement therapy is no greater than that as-be evaluated for depression. Between 25 and 50 per- sociated with smoking, and such an approach tocent of patients who undergo CABG have symptoms helping patients quit smoking should be consid-of depression before surgery; such patients typically ered.23 Bupropion should be used with caution inhave greater emotional stress and less social support patients who have recently had a myocardial in-than other patients before surgery.16 About half of farction.
those who are depressed before surgery have reso-lution of depressive symptoms by six months after Cardiac RehabilitationCABG.16 Patients who have had rapid progression Cardiac rehabilitation programs, which focus onof cardiac symptoms before surgery are at particular monitored aerobic exercise as well as the reductionrisk of worsening depressive symptoms after sur- of risk factors (smoking cessation, control of hyper-gery.16 About 18 percent of patients who are not de- tension and hyperlipidemia, and psychosocial inter-pressed before surgery have a significant increase in ventions),24 are important for improving the qualitydepressive symptoms after surgery. These newly of life after CABG.25 Only one small study withdepressed patients are at higher risk than nonde- matched controls has suggested that rehabilitationpressed patients for long-term cardiovascular events reduces the risk of cardiac events in patients whoand death from cardiovascular causes.17 These find- have undergone CABG.26 However, exercise train-ings are consistent with data showing that patients ing improves exercise tolerance, reduces the severitywith coronary heart disease who have more symp- of anginal symptoms, and improves both physicaltoms of depression also have an increased risk of and psychological functioning.27cardiovascular events.18,19 Progressive atheroscle-rosis may be responsible for both depression and Psychosocial Managementsubsequent cardiovascular events.14 Overall emotional functioning or mental health gen-erally improves 6 to 12 months after CABG.2,3,28Many patients have dramatic improvements in their s t r a t e g i e s a n d e v i d e n c e ability to perform daily activities after CABG. By one c h a n g e s i n l i f e s t y l e
year, 80 percent of patients have no limitations on Changes in lifestyle to reduce cardiovascular risk are their social life, sex life, or hobbies, as comparedespecially important after CABG. In patients en- with 60 percent before surgery.3 Patients who per-rolled in the Bypass Angioplasty Revascularization ceive themselves as having more social support re-Investigation (BARI), health behavior was signifi- port fewer depressive symptoms and less function-cantly improved one year after CABG. The propor- al impairment at six months.29tion of patients who smoked decreased from 24 per- Patients who adopt approaches to stress man- cent to 12 percent; the proportion participating in agement have significantly reduced rates of cardiacregular exercise increased from 16 percent to 47 per- events and improved quality of life.30 These ap-cent; and the percentage of patients who reported proaches may include relaxation, meditation, indi-that they followed a low-fat diet increased from 34 vidual counseling, and obtaining social support.
Downloaded from www.nejm.org by SCHLOMO ASCHKENASY on November 28, 2004 . Copyright 2003 Massachusetts Medical Society. All rights reserved. The new england journal of medicine p h a r m a c o l o g i c i n t e r v e n t i o n s
Angiotensin-converting–enzyme (ACE) inhib- itors decrease rates of myocardial infarction, stroke, Therapy with antiplatelet agents such as aspirin, and death in patients with coronary disease, al-started within 24 hours after CABG, reduces the risk though there are limited data to support their useof early occlusion of a saphenous-vein graft and re- specifically in patients who have undergone CABG.
mains effective in reducing the risk of occlusion for In the Heart Outcomes Prevention Evaluationone year. Antiplatelet agents do not afford addition- (HOPE) trial, use of the ACE inhibitor ramipril de-al protection against occlusion of a vein graft be- creased the rates of myocardial infarction, stroke,tween one and three years after surgery.31 However, and death among patients with diabetes or knownalmost half the patients who undergo CABG have vascular disease but without left ventricular dysfunc-had a previous infarction,32-34 and the benefit of as- tion38; about 25 percent of the participants had pre-pirin in secondary prevention after a myocardial in- viously undergone CABG.38 The ACE inhibitorfarction has been well established. In one study, as- quinapril has been shown in a blinded, randomized,pirin therapy begun after a myocardial infarction led controlled trial to reduce the risk of ischemic eventsto a 12 percent reduction in the rate of death, a 31 among patients who have undergone CABG butpercent reduction in the rate of reinfarction, and a who do not have heart failure, valvular disease, or42 percent reduction in the rate of stroke.35 There- atrial fibrillation.39 In this single small trial, the ratefore, aspirin is a standard intervention for patients of the combined outcome of death, myocardial in-who have undergone CABG.
farction, recurrent angina, stroke, transient ische- There are no conclusive data indicating that pa- mic attack, or the need for reoperation decreased tients who are allergic to aspirin would benefit from from 15 percent to 4 percent at one year of follow-clopidogrel therapy. However, some patients may up, with most of the decrease attributable to a lowerbenefit from the use of this agent after CABG. In rate of recurrent angina.39 At present, ACE inhibi-particular, patients with a grade V aortic atheroma, tors should be used as indicated for patients withamong whom the risk of subsequent stroke is high, coronary disease.
generally start to receive clopidogrel or warfarinpostoperatively, although definitive evidence of ben- Lipid-Lowering Agentsefit is lacking. Clopidogrel should probably not be There are abundant data to support the use of lip-used preoperatively, especially in combination with id-lowering agents in patients with ischemic dis-aspirin, since patients who received clopidogrel be- ease,32,35,40 including several studies of patientsfore CABG had more perioperative bleeding and re- who have undergone CABG. In a study involvingquired more reoperations for bleeding.36 1351 patients who had undergone CABG with sa-phenous-vein grafts, aggressive lipid-lowering ther- Beta-Blockers and Angiotensin-Converting–Enzyme apy with lovastatin, with a target low-density lipo- protein (LDL) cholesterol level of 60 to 85 mg per In a large cohort of patients who underwent CABG deciliter (1.6 to 2.2 mmol per liter), was comparedafter myocardial infarction, beta-blockers reduced with a moderate lipid-lowering strategy, with a tar-one-year mortality from 12 percent to 4 percent.33 get LDL cholesterol level of 120 to 140 mg per decili-On the other hand, in a trial involving patients ran- ter (3.1 to 3.6 mmol per liter).34 Although there weredomly assigned to receive metoprolol after CABG, no differences in mortality from cardiovascularonly half of whom had had a previous myocardial causes or the rate of myocardial infarction, there wasinfarction, there was no decrease in the rates of a a lower rate of revascularization in the aggressive-composite end point including death, cardiovascu- treatment group.34 The aggressive strategy delayedlar events, or the need for revascularization; how- the progression of atherosclerosis regardless of age,ever, 40 percent of patients were withdrawn from sex, the presence or absence of hypertension, andthe trial because they required a beta-blocker.37 the presence or absence of diabetes.41Many patients who have undergone CABG but havenot had a myocardial infarction are given cardiose- Control of Blood Pressure and Diabetes lective beta-blockers such as metoprolol or ateno- Blood-pressure control reduces the extent of pro-lol postoperatively, primarily because of the strong gression of atherosclerosis in patients who have un-evidence of the efficacy of beta-blockers after myo- dergone CABG with saphenous-vein grafts and, ascardial infarction.
is well recognized,42 reduces the risk of stroke and Downloaded from www.nejm.org by SCHLOMO ASCHKENASY on November 28, 2004 . Copyright 2003 Massachusetts Medical Society. All rights reserved. recurrent myocardial infarction in the general pop- mains unknown whether there is benefit to takingulation.40 Although the BARI trial established that folic acid or vitamin B after CABG.
among patients with diabetes, CABG leads to a greater improvement in survival than does angio- receive anticoagulant therapy also remains uncer-plasty,43 whether control of the blood glucose level tain. The Post-CABG trial showed a reduced rate ofafter CABG reduces the long-term risk of cardiovas- progression of atherosclerosis with lipid-loweringcular events has not been evaluated. It is clear that therapy, but warfarin therapy had no effect on thispatients with diabetes who undergo CABG are at risk.42 The case for long-term anticoagulation ishigh risk for subsequent cardiovascular events, and more compelling with regard to patients with aaggressive lipid-lowering therapy may be especially grade IV or V aortic atheroma.52important in this group.44 There have been no randomized trials of exercise testing in asymptomatic patients who have under- gone CABG. However, since exercise testing with- Several strategies, including the use of selective se- out imaging studies has been shown to have limitedrotonin-reuptake inhibitors and cognitive–behav- prognostic value in patients who have undergoneioral therapy, have been useful in treating depres- CABG,53 stress testing in symptomatic patientssion in the general population.45 However, there are should include imaging studies.
limited data about the effectiveness of interventionstargeted at patients with depression after CABG. Pa- tients with cardiac disease who are depressed mayhave relief of depressive symptoms and improved The American College of Cardiology, with thequality of life with cardiac rehabilitation.25 In the American Heart Association, has published rec-Enhancing Recovery in Coronary Heart Disease ommendations for the care of patients undergo-(ENRICHD) trial, which enrolled patients who had ing CABG and for the management of risk factorshad a myocardial infarction and were depressed or after revascularization (http://www.acc.org/clinical/lacked social support, cognitive–behavioral and so- guidelines/bypass/dirIndex.htm).54-56 The majorcial-support interventions did not reduce the risk of recommendations are listed in Table 1; blood-pres-reinfarction or death, but the interventions reduced sure and diabetes control are also stressed. Thedepressive symptoms and increased social ties.46 In Agency for Healthcare Research and Quality hasthe Sertraline Antidepressant Heart Attack Ran- also published recommendations for cardiac reha-domized Trial (SADHART),47 the treatment of ma- bilitation that include exercise training, education,jor depression in patients who had acute myocar- counseling, and behavioral interventions for all pa-dial infarction or unstable angina with sertraline, a tients who undergo CABG.57selective serotonin-reuptake inhibitor, was associ-ated with slight but not significant reductions in the After CABG, all patients should begin taking aspi- rin, and patients with a history of myocardial in- Although cognitive changes were previously be- farction (such as the patient described in the vi-lieved to be relatively specific sequelae of cardiac gnette) should also be given a beta-blocker, unlesssurgery, recent studies suggest that cognitive decline it is contraindicated. ACE inhibitors should be usedmay also occur after noncardiac surgery.48,49 In the in high-risk patients, as described in Table 1. All pa-BARI trial, the level of cognitive function after five tients should be encouraged to change their dietyears was identical in patients who had undergone and pursue a rehabilitation program involving ex-CABG and those who had undergone angioplasty ercise and stress management. Cessation of smok-(although no preoperative evaluations were per- ing is especially important. Weight reduction mayformed).4,28 also be helpful. Statins should be used to achieve There is a strong association between homocys- targets for LDL cholesterol (preferably a level of teine levels and cardiovascular risk,50 and homocys- 60 to 85 mg per deciliter, but certainly less thanteine levels are inversely related to the levels of folic 100 mg per deciliter).
acid, vitamin B , and vitamin B .51 However, it re- In addition, patients should be screened for Downloaded from www.nejm.org by SCHLOMO ASCHKENASY on November 28, 2004 . Copyright 2003 Massachusetts Medical Society. All rights reserved. The new england journal of medicine Interactions
Benefits or Goals
Dose or Recommended

Patients with
Recommendations for Pharmacologic and Lifestyle Interventions in Patients Who Have Undergone CABG.*
Downloaded from www.nejm.org by SCHLOMO ASCHKENASY on November 28, 2004 . Copyright 2003 Massachusetts Medical Society. All rights reserved. Interactions
oA hydroxymethylglutaryl coenzyme A, LDL Monitoring
disease, and MI myocardial infarction.
Benefits or Goals
Dose or Recommended

T alanine aminotransferase, AST aspartate aminotransferase, CK creatine kinase, CAD coronary artery Patients with

CABG denotes coronary-artery bypass grafting, ACE angiotensin-converting enzyme, NSAIDs nonsteroidal antiinflammatory drugs, H A dose of 325 mg daily should be given for the first year to prevent graft occlusion.
Only agents specifically evaluated in patients who have undergone CABG are listed.
Quinapril is the only ACE inhibitor that has been specifically evaluated in patients who have undergone CABG.
About 25 percent of patients in the Heart Outcomes Prevention Evaluation trial had undergone CABG.
Downloaded from www.nejm.org by SCHLOMO ASCHKENASY on November 28, 2004 . Copyright 2003 Massachusetts Medical Society. All rights reserved. The new england journal of medicine depression, since it is common and treatable. De- a grade V atheroma and an associated high risk ofpressed patients should be informed that treatment stroke, therapy with warfarin should be stronglyof depression is likely to improve their ability to considered in addition to aspirin, although the riskconcentrate. Aerobic exercise, as part of a rehabili- of bleeding may be increased. The patient willtation program, may also help to alleviate depres- need to be followed closely, and therapy will havesive symptoms.
to be adjusted periodically. Follow-up strategies Because the patient described in the vignette has are shown in Table 1.
r e f e r e n c e s
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