Treatment with fenofibrate did not sig- nificantly reduce the risk of the primary outcome of cardio- vascular death or nonfatal MI (HR, 0.89; 95% CI, 0.75 1.05; P=0.16), but it was associated with a reduction in the second- ary end point of total cardiovascular events (including nonfa- tal MI and coronary revascularization).160 Published more recently, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial was a double-factor, randomized, clinical trial that studied inten- sive glucose and blood pressure (BP) control and the addition of fenofibrate therapy to statin treatment. In the lipid arm of ACCORD, 5518 participants who were treated with open- label simvastatin to achieve LDL levels <80 mg/dL were ran- domized to receive either fenofibrate or placebo. Treatment with fenofibrate therapy led to significant decreases in triglyc- eride levels and increases in HDL levels, but no difference was seen between groups in the primary composite outcome of a major fatal or nonfatal cardiovascular event (HR, 0.92; 95% Subsequent subgroup analyses of the FIELD and ACCORD Lipid trials confirmed the safety of fenofibrate when used alone or in combination with a statin. Moreover, potential benefits with fenofibrate therapy were suggested in terms of decreasing cardiovascular risk among patients with the most pronounced dyslipidemia, including those with the highest levels of triglycerides and lowest levels After CABG, elevated triglyceride levels may increase the risk of postoperative adverse outcomes. In an observational study of >25000 patients who underwent primary isolated CABG between 1971 and 1998, investigators noted that a higher baseline triglyceride level at the time of surgery was significantly associated with a higher risk of repeat coronary revascularization (stent or reoperation) during long-term Similarly, Sprecher et al177 reported that higher triglyceride levels at the time of surgery were asso- ciated with significantly greater risk of mortality and worse event-free survival in a prospective study of 6602 CABG patients. Of interest, after CABG, women with high triglyc- eride levels have far worse long-term survival (HR, 1.5; 95% CI, 1.1 2.1) compared with men with high triglyceride levels (HR, 1.1; 95% CI, 0.9 1.3). Other studies also have demon- strated that elevated triglyceride values after surgery predict vein graft occlusion,178 recurrent angina and MI,179 181 and the need for redo CABG.182,183 In a secondary analysis of the Post- CABG Trial, the study investigators demonstrated that a high triglyceride level was a significant prognostic factor for vein graft atherosclerosis progression.165 Although the mechanism by which elevated triglyceride levels increase cardiovascu- lar risk is not entirely clear, triglyceride-rich lipoproteins in the vessel wall may lead to fatty streaks, which are noted in saphenous vein grafts as early as 18 months after CABG.184,185 High triglyceride levels have been shown to be a marker of worse outcomes after CABG. However, very few data are available to support the use of medical therapy to lower tri- glyceride levels after CABG. Before the advent of routine statin therapy, Barbir et al186 performed a small pilot trial of combination therapy with colestipol 10 mg and bezafibrate 400 mg/d for 2 months after CABG, noting a reduction in total cholesterol of 17%, in LDL cholesterol of 23%, and in triglyc- eride levels of 19%. In the previously described LOCAT study in which gemfibrozil reduced the development of new bypass graft lesions, gemfibrozil increased HDL levels and led to a 36% reduction in triglyceride levels (P<0.001).156 To date, no trial has investigated the use of fenofibrate ther- apy to reduce triglyceride levels and to potentially improve outcomes after CABG, highlighting the need for more research on the subject. For CABG patients with severely elevated tri- glyceride levels >500 mg/dL, fenofibrate therapy should be administered in addition to statin therapy to help prevent The use of combination fenofibrate-statin therapy may also be considered in diabetic patients recover- ing from CABG who have high triglyceride levels and low HDL cholesterol levels that persist despite statin therapy,141 as indicated by post hoc subgroup analyses from the FIELD and Lipid Management Recommendations 1. Unless contraindicated, all CABG patients should receive statin therapy, starting in the preoperative period and restarting early after surgery (Class I; Level of Evidence A). 2. High-intensity statin therapy (atorvastatin 40 80 mg, rosuvastatin 20 40 mg) should be administered after surgery to all CABG patients <75 years of age (Class I; Level of Evidence A). 3. Moderate-intensity statin therapy should be adminis- tered after CABG for those patients who are intoler- ant of high-intensity statin therapy and for those at greater risk for drug-drug interactions (ie, patients >75 years of age) (Class I; Level of Evidence A). 4. Discontinuation of statin therapy is not recommended before or after CABG unless patients have adverse reactions to therapy (Class III; Level of Evidence B). -Blocker Therapy Activation of the adrenergic nervous system to excessive lev- els contributes to the pathophysiology and symptoms of many cardiovascular diseases. -Blockers are competitive antago- nists at the -adrenergic receptors, thus modulating activities in this pathway. Although most of the pharmacological effects are attributed to this receptor blockade, some -blockers are relatively selective for the 1 -adrenergic receptor, others are nonselective, and still others have intrinsic sympathomimetic activity, -adrenergic receptor blockade, and direct vasodilat- Data to support the use of -blocker therapy in ischemic heart disease date back to the early 1980s, when randomized trial data were first generated evaluating the use of -blocker therapy in patients with acute MI.188 At that time, it was not uncommon for CABG operations to be postponed if patients were treated with -blocker therapy (ie, propranolol) because of the presumption of increased risk of surgical mortality. This sentiment undoubtedly contributed to the lower use of -blocker therapy at discharge among MI patients undergo- ing CABG compared with those treated with medical ther- Subsequently, Chen et al189 noted in a cohort study that -blocker therapy was just as effective in reducing 1-year mortality for patients undergoing revascularization as it was for patients not undergoing revascularization. In the Chen et al189 study, 33.1% of patients undergo- ing CABG in 1994 to 1995 were not prescribed -blocker therapy at discharge. Thereafter, in 2002, Ferguson and col- raised awareness of the importance of -blocker Kulik et al Secondary Prevention After CABG 937 therapy among CABG patients by documenting an association between preoperative -blocker therapy and improved 30-day mortality. Evaluating the outcomes of >600000 CABG patients in the Society of Thoracic Surgeons Database from 1996 to 1999, these authors noted that patients who received -blockers before surgery had significantly lower 30-day mor- tality rates compared with those who did not (adjusted OR, 0.94; 95% CI, 0.91 0.97). However, it remained for a number of quality-improvement projects that emerged in the early-to-mid-2000s to link sec- ondary prevention and -blockade therapy in CABG. These studies created the environment for attention to and adoption of -blocker therapy after CABG. Foody et al191 documented in a national database that only 61.5% of CABG patients received -blocker therapy after presenting with MI between 1998 and 1999, which was lower than the non-CABG patient population. This study laid the foundation for establishing baseline secondary prevention benchmarks for aspirin, angio- tensin-converting enzyme (ACE) inhibitors, and lipid-lower- ing medications. With this study as a call to action, a number of regional and national quality-improvement efforts using a variety of techniques established increases in postdischarge -blocker therapy. The Alabama CABG project demonstrated an increase in -blocker therapy at discharge from 65% to 78% Similarly, Williams et al193 reported a significant increase in adherence for all secondary preven- tion medications, including -blocker therapy, in a national quality-improvement program. Single centers during the same time frame were able to achieve even more impressive results, with the University of Kentucky improving its -blocker use after CABG from 95% to 100% by implementing an intensive Finally, in a study exploring the Get With The Guidelines database, investigators noted that 90.8% of patients were discharged on -blocker therapy after Interestingly, this was less than comparable patients discharged after percutaneous coronary intervention. All of these studies were limited by their observational nature, and only 1 randomized trial of -blocker therapy after CABG has been performed. In 1995, Sjoland et al196 conducted a double-blind, placebo-controlled, randomized, controlled trial of 967 patients undergoing CABG. In this study, patients were randomized 4 to 21 days after CABG to 50 mg meto- prolol twice a day for 2 weeks and 100 mg metoprolol twice a day thereafter versus placebo for 2 years. The authors found no difference between the 2 arms of the trial with respect to the risk of death or the development of cardiac events, and there was no improvement in exercise capacity among the 618 patients who received an exercise test at follow-up. However, patients treated with placebo were found to have a higher (worse) chest pain score compared with patients treated with Contraindications to -blocker therapy can be particu- larly relevant in the post-CABG population because of the prevalence of reactive airway and pulmonary disease in these patients. However, the management of this comorbid condi- tion in the perioperative setting has improved substantially, and the specificity of 1 - and 2 -blockers has minimized the cross-reactivity between the cardiac and pulmonary effects of -blockade. Even more recently, the pharmacogenetics of -adrenergic receptor antagonists have become clear, with certain genes being identified that influence the pharmacody- namic and pharmacokinetic effects of -blocker compounds.187 To clearly establish the benefit of -blocker therapy and secondary prevention after CABG, a link to improved mortal- ity is needed. An important study by Goyal et al198 assessed both the use and clinical impact of secondary preven- tion medications after CABG. The use of aspirin, -blockers, ACE inhibitors or angiotensin receptor blockers (ARBs), and lipid therapy was measured in patients enrolled in the Project of Ex-Vivo Vein Graft Engineering via Transfection (PREVENT IV) trial of 3014 patients. In ideal candidates for these therapies, -blocker rates at discharge (88.8%) and 1 year (76.9%) were suboptimal, but in this trial context, the rates of use were substantially higher than in contemporane- ous observational studies. The authors noted a stepwise asso- ciation between medication use at discharge and a lower risk of adverse patient outcomes (death or MI).198 Most recently, a study by Bangalore et al199 evaluated the use of -blocker therapy in stable patients with risk factors for CAD or a history of CAD or MI. This longitudinal, obser- vational registry study demonstrated that the use of -blocker therapy was not associated with a lower risk of cardiovascular events, including cardiovascular death, nonfatal MI, or non- fatal stroke, whether patients had risk factors only, a known prior MI, or known CAD without MI.199 Many patients under- going CABG would likely fall into one of these categories. However, it is not yet clear how this information should be directly applied to the postoperative patient because many CABG patients have additional clinical conditions that war- rant -blocker therapy after surgery, including hypertension and AF. Because AF continues to occur at a high rate after -blocker therapy remains the mainstay of both AF prevention and rate control through its 1 -adrenergic A meta-analysis of contemporary clinical trials illustrated a 50% reduction in the risk of postoperative AF with prophylactic -blocker therapy.202 Moreover, many patients on preoperative -blocker therapy have rebound tachycardia if -blocker therapy is not resumed early in the postoperative period. The role of -blocker therapy in the perioperative period remains controversial. A substantial percentage of patients undergoing CABG receive preoperative -blocker therapy because it has been demonstrated to convey a mortality ben- Consequently, preoperative -blocker therapy was determined to be a quality metric for cardiac surgery by the National Quality Forum and was included in the Society of Thoracic Surgeons Composite Score for CABG Quality pro- However, other more recent studies have questioned whether preoperative -blocker therapy actually affects mor- It is possible that the outcomes from surgical revas- cularization have improved to the point where a benefit from preoperative -blocker therapy can no longer meet the thresh- old of statistical significance.204 Nevertheless, continuation of preoperative -blockade therapy into the postoperative period remains an important consideration. The use of -blocker therapy for the treatment of hyperten- sion remains a controversial subject. In a critical review of the literature, Bangalore et al205 documented that -blockade was not as effective long-term compared to other antihypertensive thera- pies (eg, diuretic therapy). In addition, -blockers are often asso- ciated with side effects such as weight gain, fatigue, and sexual dysfunction, reducing rates of adherence. Thus, for long-term secondary prevention therapy, the use of -blockers for hyperten- sion is influenced by the presence or absence of other cardiovas- cular conditions (such as previous MI and heart failure). The most compelling data on -blocker therapy exist after an acute MI, and this circumstance pertains to most post- CABG patients. Several studies from the 1980s and 1990s demonstrated the benefits associated with -blockade dur- ing and after MI.188,206 In a meta-analysis of >54000 patients, Freemantle et al207 reported a 23% reduction in the odds of death with -blocker therapy for long-term secondary preven- tion after MI. These studies and others laid the foundation for routine -blocker therapy after MI. The use of -blockade in chronic heart failure has also evolved over the years, from a relative contraindication in the past to a mainstay of therapy now, leading to a consistent 30% reduction in mortality, improved well-being, and an improvement in symptoms.205 -Blockers likely protect the heart from the chronic upregulation of adrenergic receptors on the myocardium from epinephrine and norepinephrine, thus reducing remodeling and fibrosis in congestive heart failure. Three -blockers have been shown to be effective in reducing the risk of death in patients with chronic heart and sustained-released metoprolol both of which selectively block 1 -receptors, which blocks 1 -, and 2 -receptors. Many CABG patients with left ventricular (LV) dysfunction have significant heart failure both before and after surgical revascularization, and -blocker therapy can be adminis- tered safely and effectively to the majority. As a rule, LV dysfunction alone is not a contraindication to -blocker therapy after CABG. In summary, -blocker therapy is a mainstay of secondary prevention strategies after surgical revascularization for isch- emic heart disease. -Blocker Therapy Recommendations 1. All CABG patients should be prescribed periopera- tive -blocker therapy to prevent postoperative AF, ideally starting before surgery, unless contraindi- cated (ie, bradycardia, severe reactive airway dis- ease) (Class I; Level of Evidence A). 2. CABG patients with a history of MI should be pre- scribed -blocker therapy unless contraindicated (Class I; Level of Evidence A). 3. CABG patients with LV dysfunction should be pre- scribed -blocker therapy (bisoprolol, sustained- release metoprolol succinate, or carvedilol), unless contraindicated (Class I; Level of Evidence B). 4. Chronic -blocker therapy for hypertension treat- ment after CABG (in the absence of prior MI or LV dysfunction) may be considered, but other antihy- pertensive therapies may be more effective and more easily tolerated (Class IIb; Level of Evidence B). Hypertension Management Hypertension is a common antecedent condition before CABG, occurring in as many as 80% of patients.212 The preop- erative antihypertensive regimens used in patients undergoing CABG can be quite varied but generally include a -blocker or an ACE inhibitor, in part because of their cardioprotective Despite the routine use of these drug classes, however, pre-CABG and post-CABG BP control remains Previous AHA guidelines recommended a BP goal of <130/80 mmHg for patients with CAD.216 More recent guideline statements have proposed less aggressive BP target mmHg) for patients with CAD risk factors such as diabetes mellitus and chronic kid- ney disease. This is a controversial subject. Inconsistent ben- efits have been noted in clinical trials comparing intensive BP reduction (systolic <130 mmHg) and standard BP treatment goals (systolic <140 mmHg) for patients with previous coro- nary events and a history of hypertension and diabetes mel- litus, therefore justifying the currently recommended systolic target value of <140 mmHg.220 225 With regard to diastolic BP goals, targeting a value of <85 mmHg appears to be safe and has been shown in 3 randomized trials to improve the clinical outcomes of patients with a history of hypertension, diabe- tes mellitus, or multiple cardiovascular risk factors compared with higher diastolic values.226 228 Admittedly, no clinical trials to date have specifically assessed BP targets after CABG with respect to clinical outcomes. However, given the high inci- dence of diabetes mellitus and other cardiovascular risk fac- tors in the CABG population, a BP goal of <140/85 mmHg217 appears reasonable and broadly applicable to all patients who have undergone CABG. Achieving the BP goal for secondary prevention in the patient having undergone CABG requires an understanding of the effectiveness of pre-CABG antihypertensive therapies and the temporary reduction in BP that occurs during recovery from postoperative surgical circumstances such as anemia and reduced myocardial function. With an emphasis on BP con- trol in the broad context of secondary prevention measures, antihypertensive medication regimens and BP goals should be adapted to the individualized circumstances of each patient.198 BP patterns and the response to treatment can be best assessed with the use of home BP monitoring.229 Lifestyle measures such as exercise, reducing weight, and limiting sodium intake are useful adjunct measures in the post-CABG patient with hypertension. In addition, identifying comorbid risk factors for hypertension such as the BP change seen with post-CABG cognitive disorders, anxiety, depression, and sleep abnormalities and providing the indicated therapies can improve the overall effectiveness of the chosen antihyperten- sive therapies. No studies have prospectively evaluated the rapidity with which BP should be reduced in the post-CABG patient with hypertension. In addition, it is not known whether the J-curve relationship for morbidity and mortality occurs at a higher BP level in the post-CABG patient than in the patient without CAD. In the post-CABG patient with hypertension, the choice of antihypertensive agents and the order of their introduc- tion have not been methodically studied. Two major therapy groups, -blockers and ACE inhibitors, are routinely given Kulik et al Secondary Prevention After CABG 939 for their established cardioprotective features, as much as they are used for BP reduction.213,214 -Blockers should be administered as soon as possible after CABG in those patients without contraindications to reduce the risk of AF201,202 and to improve outcomes in those patients with congestive heart failure and LV dysfunction.205 However, their effect on BP has not been systematically explored. In the only randomized trial to date, Sjoland et al196 found no clinical benefit asso- ciated with a 2-year treatment with metoprolol after CABG. Compared with placebo, metoprolol did not reduce the inci- dence of repeat revascularization, unstable angina, nonfatal MI, or death.197 ACE inhibitors should also be considered for CABG patients after surgery, particularly for those with recent MI, LV dysfunction, diabetes mellitus, and chronic kidney dis- ease. The BP-lowering effect of ACE inhibitors is dependent on a patient s volume state, thus the basis for their frequent administration together with a diuretic.230 ACE inhibitor use can be associated with a syndrome of functional renal insuf- ficiency or hyperkalemia. This form of acute kidney injury develops shortly after the initiation of ACE inhibitor therapy but can be observed after months or years of therapy, even in the absence of prior ill effects. It may relate to the drug dose or level of hydration, as well as to the degree of small and large renal artery obstructive disease.231 An ARB may be considered as an alternative in an ACE inhibitor intolerant patient. Two randomized, controlled trials have studied the use of ACE inhibitors after CABG. In a 149-patient trial evaluating the use of quinapril after surgery, investigators noted a reduc- tion in the composite outcome of angina, death, MI, repeat revascularization, stroke, or transient ischemic attacks in patients who received quinapril for 1 year compared with pla- cebo (3.5% versus 15%, quinapril versus placebo; P=0.02).232 However, these findings were not confirmed in the larger, mul- ticenter Ischemia Management With Accupril Post-Bypass Graft via Inhibition of the Converting Enzyme (IMAGINE) trial of 2253 stable CABG patients. In this study, patients were excluded from randomization if they already had indications for ACE inhibitor therapy such as LV dysfunction, insulin- dependent diabetes mellitus, or renal dysfunction. Quinapril (40 mg daily) had no benefit compared with placebo when initiated within 7 days after surgery, with a 13.7% incidence of the primary composite end point (cardiovascular death, car- diac arrest, nonfatal MI, unstable angina or heart failure requir- ing hospitalization, and stroke) among quinapril patients and 12.2% in the placebo group (HR, 1.15; 95% CI, 0.92 1.42; P=0.21) over a median follow-up of 2.95 years. The incidence of the primary composite end point increased significantly in the first 3 months after CABG in the quinapril group (P=0.04), and adverse events (such as hypotension) were also increased in the quinapril group, particularly during the first 3 postop- Thus, in this select trial population, routine ACE inhibitor therapy led to more harm than benefit when initiated early after CABG. In those patients who remain above the BP goal despite a suitably titrated regimen including a -blocker and, if appro- priate, an ACE inhibitor, then a calcium channel blocker or a diuretic can be considered as a next therapy choice.A long-act- ing dihydropyridine calcium channel blocker can effectively reduce BP and prevent graft spasm (radial artery conduit) and may offer an antianginal effect. Nondihydropyridine calcium channel blockers such as verapamil and diltiazem are effec- tive antihypertensive agents, but they are generally reserved for rate control in patients with coexisting chronic obstructive pulmonary disease and normal LV function. Diuretic therapy can be used in the CABG patient with hypertension either for volume removal if the patient is edematous or for further BP reduction when given together with an ACE inhibitor or a Selection of a diuretic class depends on the level of renal function, with thiazide-type drugs generally reserved for patients with a glomerular filtration rate >30 mL/min and loop diuretics used for patients with lower glomerular filtra- tion rates and the need for a diuretic of greater potency.234 Resistant hypertension is no more common in the post- CABG patient than in the general hypertensive population, and the approach to treatment is fairly similar. In patients already treated with an ACE inhibitor, -blocker, diuretic, and calcium channel blocker who remain above goal BP, other treatment options include compounds that reduce adrenergic activity such as clonidine or doxazosin. In addition, a min- eralocorticoid receptor antagonist such as spironolactone or eplerenone can be effective in lowering BP in the patient with resistant hypertension, particularly in the setting of LV dys- function, while affording cardiovascular benefits, including reduced myocardial fibrosis, prevention or reversal of cardiac remodeling, or a reduction in arrhythmogenesis.235 Hypertension Management Recommendations 1. -Blockers should be administered as soon as possi- ble after CABG, in the absence of contraindications, to reduce the risk of postoperative AF and to facili- tate BP control early after surgery (Class I; Level of Evidence A). 2. ACE inhibitor therapy should be administered after CABG for patients with recent MI, LV dysfunction, diabetes mellitus, and chronic kidney disease, with careful consideration of renal function in determin- ing the timing of initiation and dose selection after surgery (Class I; Level of Evidence B). 3. With the use of antihypertensive medications, it is reasonable to target a BP goal of <140/85 mmHg after CABG; however the ideal BP target has not been formally evaluated in the CABG population (Class IIa; Level of Evidence B). 4. It is reasonable to add a calcium channel blocker or a diuretic agent as an additional therapeutic choice if the BP goal has not yet been achieved in the peri- operative period after CABG despite -blocker ther- apy and ACE inhibitor therapy as appropriate (Class IIa; Level of Evidence B). 5. In the absence of prior MI or LV dysfunction, anti- hypertensive therapies other than -blockers should be considered for chronic hypertension manage- ment long term after CABG (Class IIb; Level of Evidence B). 6. Routine ACE inhibitor therapy is not recommended early after CABG among patients who do not have a history of recent MI, LV dysfunction, diabetes mellitus, or chronic kidney disease because it may lead to more harm than benefit and an unpredictable BP response (Class III; Level of Evidence B). Previous MI and LV Dysfunction Surgical revascularization is commonly performed for patients with reduced ejection fraction (EF) <40%.236 The most com- mon cause of reduced EF is previous MI, although other abnormalities such as valvular heart disease and hypertension are also recognized causes. Some patients have post-MI stun- ning or myocardial hibernation attributable to chronic isch- emia from severe CAD. Although many have improvement or recovery in their cardiac function after surgical revasculariza- tion, others have persistent heart failure and LV dysfunction The current discussion focuses on the appli- cation of secondary prevention therapies, including medical and device therapy after CABG, for patients with persistently reduced EF despite revascularization. -Blocker Therapy Elevated plasma catecholamine levels and direct sympathetic activity have deleterious effects on the heart by causing tachy- cardia, vasoconstriction, increased contractility, and ventricu- -Blockers blunt these effects and impede the maladaptive ventricular remodeling from chronic sympa- thetic activation. As described above, in addition to preventing heart failure, -blockers prevent recurrent ischemia and AF, a common postoperative condition. Most patients with persistently reduced EF after CABG are likely to have had a prior MI, and in this patient popula- tion, evidence supports the use of -blockers on top of back- ground therapy with ACE inhibitors, even in the absence of heart failure. Three specific -blockers (carvedilol, bisoprolol, and sustained-release metoprolol succinate) have documented benefits for morbidity and mortality and are highly recom- mended for patients with active or past symptoms of heart In addition, these medications reduce heart fail- ure symptoms, enhance patients overall sense of well-being, and reduce hospitalization, even among patients already tak- ing ACE inhibitors.197,208,238,239 Contraindications to -blocker use include bradycardia, hypotension, severe bronchospastic airway disease, low-output state, or severe, actively decom- pensated heart failure. ACE Inhibitor and ARB Therapy ACE inhibitors exert their effects by suppressing the effects of angiotensin II, a potent vasoconstrictor that reduces renal perfusion, stimulates LV hypertrophy and cardiac remodel- ing, and enhances the release of arginine, vasopressin, proin- flammatory cytokines, and aldosterone.237 Inhibition of ACE results in decreased levels of angiotensin II and inhibits the breakdown of bradykinin, a peptide with favorable properties, including antihypertensive, antiremodeling, and natriuretic effects. ARBs directly inhibit the action of angiotensin II by blocking the type 1 receptor, but their effects on bradykinin Oral ACE inhibitors have been shown to reduce symptom- atic heart failure and mortality among patients with previous MI and reduced EF.241 243 Among patients with reduced EF and active or prior heart failure symptoms, ACE inhibitors reduce mortality and heart failure hospitalization, improve New York Heart Association (NYHA) classification, reduce heart size, and prevent the need for escalating medical therapy.244 246 The routine initiation of an ACE inhibitor early after CABG is not recommended for patients with an EF >40%.233 However, it is unlikely that surgical revascularization mitigates the benefits of an ACE inhibitor in the post-CABG patient with a persis- tently reduced EF. Among patients with reduced EF who are intolerant of ACE inhibitors, an ARB can be used as an alternative therapy for those with a prior MI or symptoms of heart failure unless con- Angiotensin II can be generated by alterna- tive pathways, and its production is only partially inhibited by Therefore, concomitant treatment with both an ARB and ACE inhibitor (on a background of -blocker therapy) among patients with reduced EF may be selectively considered in patients with persistent heart failure symptoms and has been shown in clinical trials to reduce cardiovascu- lar death and heart failure hospitalization.252 Nevertheless, the combination of an ACE inhibitor and an ARB should not be used routinely, and this regimen is contraindicated if an aldosterone antagonist is also being used because of increased side effects. These side effects include excessive hypotension, hyperkalemia, and worsening renal function necessitating dis- continuation of therapy.248,249,252 Aldosterone Antagonists Spironolactone is a nonselective aldosterone antagonist that has demonstrated benefits for patients with severe heart fail- ure. In the RandomizedAldactone Evaluation Study (RALES), spironolactone was associated with a 30% RR reduction in overall mortality and a reduction in heart failure hospitaliza- tion and symptoms among patients with NYHA class III to IV symptoms and an EF <35%.253 Subsequently, the Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF) extended the benefits of aldoste- rone antagonists to patients with mild heart failure (includ- ing NYHA class II symptoms) and an EF <35% with the use It is important to note that an aldosterone receptor antagonist is indicated as an add-on therapy for patients who have persistent heart failure symptoms despite treatment with both classes of neurohormonal inhibitors ( -blockers and ACE inhibitor/ARBs). In accordance with both aforementioned studies253,254 and previous guidelines,236 aldosterone antagonists appear most applicable to post-CABG patients with persistent LV dysfunction (EF <35%) and mild or more severe heart failure symptoms. Careful monitoring of potassium, renal function, and diuretic dosing should be per- formed at initiation and serially thereafter in these patients. Aldosterone antagonists should be avoided in patients with estimated glomerular filtration rate <30 mL min 1 or potassium levels >5.0 mEq/L. Devices A substantial body of evidence supports the use of implantable cardioverter-defibrillators (ICDs) to prevent sudden cardiac Kulik et al Secondary Prevention After CABG 941 death among patients with reduced EF.255 257 However, ICD therapy at the time of surgical revascularization has failed to improve patient outcomes. In the CABG Patch Trial,258 routine ICD insertion did not improve survival among patients with an EF <35% if an ICD was implanted prophylactically at the time of elective CABG. Notably, 71% of deaths in this trial were not arrhythmogenic, hence the lack of mortality benefit,258 and empirical ICD therapy was even associated with diminished quality of life 6 months after CABG.259 As per previous AHA/ ACCF guidelines, patients with reduced EF should be treated with optimal neurohormonal therapies after surgical revascu- If the EF remains severely reduced (<35%) in a noninvasive assessment of LV function 3 months after surgery, then consideration should be given to implantation of an ICD for primary prevention at that time.260 In patients with reduced LV function who undergo CABG after resuscitation from cardiac arrest, the decision for ICD therapy early after CABG should be individualized.260 Among these patients, CABG can suppress malignant arrhythmias and reduce subsequent episodes of cardiac arrest,261,262 espe- cially if the arrhythmias are related to ischemia.263 On the other hand, CABG may not mitigate all the conditions pre- disposing to ventricular arrhythmias, as in the case of patients with sustained monomorphic ventricular tachycardia and prior MI, and concomitant ICD insertion after CABG may be war- ranted in such patients. Progression of LV dysfunction to clinical heart failure is frequently accompanied by impaired electromechanical coupling, which may further diminish effective ventricular contractility. Modification of ventricular electromechanical delay with cardiac resynchronization therapy (biventricular pacing) can improve ventricular systolic function, amelio- rate functional mitral regurgitation, and in some patients, reduce cardiac chamber dimensions.260 Cardiac resynchroni- zation therapy is generally indicated among patients with an EF <35% in the presence of left bundle-branch block, QRS interval >150 milliseconds, and NYHA class II to IIII heart failure symptoms, and it may be a reasonable therapeutic strategy if the QRS interval is in the 120- to 149-millisecond After 3 months of goal-directed postoperative medical therapy, patients recovering from CABG with these indications should receive an ICD in addition to cardiac resyn- chronization therapy, as detailed elsewhere.260 Previous MI and LV Dysfunction Recommendations 1. In the absence of contraindications, -blockers (biso- prolol, carvedilol, and sustained-release metopro- lol succinate) are recommended after CABG to all patients with reduced EF (<40%), especially among patients with heart failure or those with prior MI (Class I; Level of Evidence A). 2. In the absence of contraindications, ACE inhibitor or ARB therapy (if the patient is ACE inhibitor intoler- ant) is recommended after CABG to all patients with LV dysfunction (EF <40%) or previous MI (Class I; Level of Evidence B). 3. In the absence of contraindications, it is reasonable to add an aldosterone antagonist (on top of -blocker and ACE inhibitor therapy) after CABG for patients with LV dysfunction (EF <35%) who have class NYHA class II to IV heart failure symptoms (Class IIa; Level of Evidence B). 4. Among patients with LV dysfunction (EF <35%), ICD therapy is not recommended for the prevention of sudden cardiac death after CABG until 3 months of postoperative goal-directed medical therapy has been provided and persistent LV dysfunction has been confirmed (Class III; Level of Evidence A). Diabetes Mellitus The effects of diabetes mellitus and the metabolic syndrome on the development and progression of cardiovascular disease are well established. Indeed, diabetes mellitus is associated with increased mortality and morbidity after cardiac surgery in general and CABG specifically.268 Diabetes mellitus is classified as type 1 if it results from -cell destruction or as type 2 if it results from a progressive insulin secretory defect and insulin resistance, but other causes of diabetes mellitus exist, including genetic defects in insulin secretion, drug- induced diabetes mellitus, and gestational diabetes mellitus.269 Traditionally, the diagnosis of diabetes mellitus has been based on a fasting plasma glucose >126 mg/dL, a 2-hour plasma glu- cose >200 mg/dL after oral administration of 75 g glucose, or a random plasma glucose of >200 mg/dL in a patient with the classic symptoms of diabetes mellitus.270 In 2009, however, an International Expert Committee recommended the use of the ) test be added, with a threshold >6.5% as a diagnostic criterion for diabetes mellitus.271 Because it is not always known whether a patient has dia- betes mellitus or glucose intolerance before surgery, it is reasonable for all patients undergoing CABG to have pre- operative fasting plasma glucose and HbA1c measurements. This may facilitate optimal diabetes mellitus management in the perioperative and postoperative periods. As detailed else- the perioperative control of serum glucose (glucose goal, 125 200 mg/dL) has been shown to improve both short- outcomes after CABG in most stud- ies. However, an overly aggressive lowering of serum glucose during and after CABG surgery (glucose goal, 90 120 mg/ dL) may fail to improve clinical outcomes, mainly because of the adverse effects of hypoglycemic episodes, compared with more moderate glycemic control (glucose goal, 120 180 In a large observational study involving >4500 CABG patients, Bhamidipati et al277 noted that mortality and complication rates were lowest among diabetic patients who received moderate glycemic control with glucose levels of 127 to 179 mg/dL compared with those who were treated with tight ( 126 mg/dL) or liberal ( 180 mg/dL) insulin protocols. Patients with diabetes mellitus have less favorable long-term outcomes after CABG compared with nondiabetic patients.278 However, it is not well understood whether the diminished long-term survival and freedom from adverse cardiovascular events are attributable to a general progression of cardiovascu- lar disease seen in diabetic patients or if CABG patients with poorly controlled diabetes mellitus have specific characteris- tics that make them prone to diminished long-term survival. These factors may include decreased early graft patency, a more rapid progression of native vessel atherosclerosis, and a reduction in myocardial function. Vein graft patency has been reported in some studies to be diminished in patients with diabetes mellitus and the metabolic syndrome.279 This may relate to the association between type 2 diabetes mellitus and impaired endothelial function and intimal degeneration of saphenous vein grafts, changes that inversely correlate with the metabolic control of the diabetes mellitus.280 Interestingly, diabetes mellitus has much less effect on the properties of the internal mammary artery. In a long-term patency evaluation of 501 CABG patients, Lytle et al281 noted that insulin-dependent diabetes mel- litus was associated with late vein graft failure (P<0.004). Nevertheless, the adverse effects of diabetes mellitus on graft patency have not been seen in all studies. For example, in a 10-year follow-up of the VA Cooperative Study involving 1074 CABG patients, Goldman et al282 did not find diabetes mellitus to be an independent predictor of vein graft failure. Most recently, in a long-term observational study evaluating risk factors for adverse outcomes after CABG, Sabik et al164 reported that diabetes mellitus was a strong risk factor for cor- onary reintervention (either percutaneous coronary interven- tion or redo CABG) in the years after CABG. Patients treated with insulin or oral medications had a similarly elevated risk of undergoing reintervention (P<0.0001), whereas patients with diet-controlled diabetes mellitus also had an increased risk of reintervention, but lower than the risk in those treated pharma- cologically (P=0.005). Whether the degree of glucose control independently predicts vein graft patency remains unclear.283 This uncertainty likely relates to the difficulty in separating the effects of glucose control from the progression of cardio- vascular disease in general but may also be complicated by the challenges and inaccuracy of graft patency assessment, small study sample sizes, and separation of the effects of associated conditions such as hyperlipidemia and hypertension. Patients having undergone surgical revascularization are at increased risk for further progression of CAD. Because there is no reason to surmise that CABG patients have any inher- ent protection from the effects of poorly controlled diabetes mellitus and because well-controlled blood sugar markedly improves survival in patients with cardiovascular disease,269 long-term glucose control should ideally be optimized for all CABG patients. Tight control of blood glucose is in a patient s best interest because cardiovascular disease is the most prevalent cause of morbidity and mortality in the dia- betic population. In terms of glucose management, CABG patients with dia- betes mellitus should receive coordinated medical care from a diabetes mellitus monitoring team. Such teams may include internists and endocrinologists, dieticians, pharmacists, and in certain cases, mental health professionals. Plasma glucose and levels should be followed up regularly, with appropri- ate adjustments made in insulin and oral hypoglycemic thera- pies. Lowering the HbA1c to 7% is a reasonable goal for most patients because this has been shown to reduce microvascular diabetic complications and, if initiated early, may also be asso- ciated with a reduction in macrovascular disease.269 A strin- goal such as 6.5% may be beneficial if treatment is not associated with hypoglycemic episodes, but it may be more reasonable to consider a less stringent goal of 8% for elderly patients and others who are prone to hypoglycemia.269 Unlike microvascular disease such as retinopathy, the progression of macrovascular disease such as CAD does not always correlate with the intensity of glucose control. However, in the Diabetes Control and Complications Trial, intensive glucose control (target HbA1c , 6%) in type 1 diabetic patients was associated with a lower risk of cardiovascular disease. Patients who were randomized to intensive glucose control after 9 years of follow-up had a 57% reduction in the risk of nonfatal MI, stroke, or cardiovascular death compared with patients in the standard arm.284 For patients with type 2 diabetes mellitus, evidence also exists that a more intensive control of plasma glucose may reduce macrovascular cardio- vascular disease. In the UK Prospective Diabetes Study, a 16% reduction in fatal and nonfatal MI and sudden death was noted with intensive glucose control (target fasting plasma glucose <6 mmol/L), although this failed to reach statistical signifi- Nevertheless, consistent benefits have not always been observed for patients with type 2 diabetes mellitus, with several other trials finding no added benefit of intensive glucose control over standard control on the risk of adverse cardiovascular events, even among patients with base- line cardiovascular disease at the time of trial recruitment.287 It must be recognized that none of the aforementioned stud- ies specifically enrolled diabetic patients who had undergone CABG. Regardless, although these study findings are extrap- olated from non-CABG patients to the CABG population, a moderate control of plasma glucose with a goal HbA1c of 7% would seem appropriate for most diabetic patients after CABG. In addition to optimal plasma glucose management, it cannot be overstated that all patients recovering from CABG, and especially those with diabetes mellitus, should be coun- seled to optimize their weight and diet, to quit smoking, and to institute behaviors associated with improved cardiovascular health. Diabetes Mellitus Recommendations 1. Striving to achieve an HbA1c of 7% is a reasonable goal for most patients after CABG to reduce microvascular diabetic complications and macrovascular cardiovas- cular disease (Class IIa; Level of Evidence B). Smoking Cessation According to the World Health Organization, 100 million deaths resulted from tobacco use in the 20th century, and it has been estimated that 1 billion more deaths may occur in the Compared with those who have never smoked tobacco, smokers lose on average 1 decade of life expec- This mortality risk can be lowered through smoking cessation, and if smoking cessation occurs before the age of 40, the reduction in risk associated with smoking is 90%.289 The risk of cardiovascular disease associated with cigarette smoke exposure increases in a dose-response fashion, with the greatest increase in risk occurring in individuals who have no cigarette exposure compared with those who have low levels of exposure, including secondhand smoke.1 At the time of the Kulik et al Secondary Prevention After CABG 943 first report of the Surgeon General s Advisory Committee in 1964, smoking rates in the United States approached 45%. Although significant progress has been made since then, tobacco use remains a leading modifiable cause of death in the United States, with 21.3% of adult men and 16.7% of adult women still engaging in cigarette smoking.1 In patients who have had CABG, smoking can adversely affect both short- and long-term clinical outcomes. Early after surgery, smokers have an increased rate of atelectasis and pneumonia and an increased requirement for mechanical ventilation and intensive care support.290,291 In addition to an increased risk of pulmonary complications, smoking is associ- ated with an increased risk of deep sternal wound infections in adults who undergo cardiac surgery.292 Smokers have a higher prevalence of myocardial ischemia293 and require repeat coronary revascularization procedures more frequently.294,295 Specifically, smoking is associated with a higher rate of saphenous vein graft disease.165,296 Interestingly, despite the higher rates of morbidity in smok- ers, early mortality rates are not significantly different in smokers compared with nonsmokers. On the other hand, sig- nificant differences have been observed in long-term mortality On the basis of 30-year follow-up data, self- reported smoking cessation after CABG was associated with a life expectancy gain of 3 years, and smoking cessation had a greater effect on reducing the risk of mortality than any other intervention or treatment.295 Although smoking cessation should be addressed in all the postoperative period after CABG may be a particularly effective time to use smoking cessation strategies. Smokers undergoing CABG are hospitalized and therefore subject to the smoke-free policies of medical institu- tions, and they are also free of the usual cues to smoke. The conditions precipitating the need for CABG and the surgery itself may also reinforce the smoker s perceived vulnerability to the harms of tobacco use, motivating the patient to engage in an attempt at smoking cessation.299 In a Scandinavian cohort of patients undergoing cardiac surgery, approximately one half of current smokers gave up smoking after surgery. These changes in smoking behavior were most likely to occur during the first 6 postoperative months.300 As a result, CABG can serve as a teachable moment during which smoking ces- sation strategies may be highly effective. Smoking cessation strategies should begin with a full assessment of tobacco use and exposure. For instance, a cli- nician should determine the duration of smoking, the num- ber of cigarettes smoked daily, and the amount of time that passes between the patient waking up and having his or her first morning cigarette. Every smoker should be asked if he or she is interested in quitting smoking. If motivated to quit, smokers should have access to appropriate resources to assist in smoking cessation. For smokers who are not ready to quit, the clinician should assess the patient s perspective of the impact of smoking on his or her health. Education should then be provided to ensure that the patient has a full understand- ing of the adverse effects of continued smoking (including the effects of secondhand smoke on others) and the expected benefits associated with quitting. In addition, the clinician can use interviewing techniques to facilitate and engage intrinsic motivation within the patient to facilitate smoking cessation. Patients who are interested in quitting smoking should be offered behavioral approaches to tobacco cessation.301 Behavioral approaches to smoking cessation can be provided in a variety of formats, including direct patient-clinician encounters, telephone calls, computer programs, text messag- ing, or group-based sessions. A meta-analysis of 25 random- ized trials found that intensive counseling, which consisted of at least 1 contact during the hospital stay with continued sup- port for at least 1 month after discharge, increased the likeli- hood of smoking cessation.302 A point of emphasis in behavioral approaches to smoking cessation is having the patient set a quit day. A follow-up encounter, either in person or on the telephone scheduled soon after the patient s quit day, can strengthen the significance of the quit day and provide greater motivation for the patient to quit. In a systematic review of 10 randomized trials, no dif- ference was observed in abstinence rates between those who reduced smoking before the quit date and those who quit Thus, patients should be given the choice to reduce smoking before a quit date or to stop smoking abruptly on the quit date. In combination with counseling, nicotine replacement ther- apy can be an important adjunctive strategy to help achieve smoking cessation. In a randomized trial of 5887 smokers, long-term rates of smoking and mortality were reduced with the application of a 10-week smoking cessation program that included a strong physician message, nicotine gum, and 12 group sessions using behavior modification.304 On the basis of a systematic review of the literature in 2008, the US Public Health Service advocated the use of 5 nicotine replacement medications (gum, patch, nasal spray, inhaler, and lozenge) and reported that the combination of a long-term nicotine patch and ad lib nicotine spray or gum produced significantly higher long-term abstinence rates than did the nicotine patch Compared with nicotine replacement medications, electronic cigarettes (e-cigarettes) have not been demonstrated to improve smoking cessation rates, and important concern has been raised about their potential for adverse health effects.306 Nicotine replacement therapy has been shown to be safe for patients with stable CAD. In a randomized, double-blind, pla- cebo-controlled trial, a 10-week outpatient course of transder- mal nicotine did not increase the rate of cardiovascular events among patients with at least 1 diagnosis of cardiovascular dis- In hospitalized patients, nicotine replacement therapy is commonly used as an effective strategy to manage nicotine but less is known about the routine use of nicotine replacement therapy during an acute cardio- vascular event. In a retrospective analysis of smokers admitted with acute coronary syndromes, transdermal nicotine therapy was not associated with an increased risk of mortality.308 On the other hand, in a retrospective analysis of smokers hospital- ized during CABG, nicotine replacement therapy was asso- ciated with an increased mortality rate after adjustment for Both of these studies were limited by their observational design and specifically by the biases associated with the use of nicotine replacement therapy such as the degree of prior smoking. As a result, prospective studies are needed to determine the safety of using nicotine replace- ment therapy in patients with acute cardiovascular disease. At this time, judicious use and dosing of nicotine replacement therapy are recommended for patients admitted to hospital with an acute cardiovascular event. In addition to nicotine replacement medications, bupropion and varenicline can be effective adjuncts to smoking cessa- tion strategies, and their use has been supported by the US Public Health Service.305 Bupropion is generally well toler- ated and has been shown to be safe to use in the immediate period after MI.310,311 Among 629 patients with cardiovas- cular disease, a 7-week treatment with bupropion resulted in twice as many smokers quitting at 1 year compared with Varenicline has also been shown to be effective in reducing rates of smoking.313,314 In a randomized, placebo- controlled trial of 714 smokers with stable cardiovascular disease, varenicline was effective at reducing rates of smok- Based on data from this trial, however, the US Food and Drug Administration issued an advisory that varenicline may increase the risk of adverse cardiovascular events on the basis of statistically nonsignificant increases in the rates of nonfatal MI, coronary revascularization, and new peripheral vascular disease in this trial population.315 Although the car- diovascular risk profile of varenicline remains unsettled, the long-term benefits of smoking cessation far outweigh any potential adverse effects with varenicline. Therefore, it should still be carefully considered as a possible medication to assist in smoking cessation for patients with cardiovascular disease. During the process of smoking cessation, patients may face many potential obstacles to achieving their goal. They may struggle with high dependence on nicotine, severe withdrawal problems, low self-confidence, poor social support, weight gain, comorbid psychiatric illnesses, and suboptimal use of Addressing each of these issues as they arise is critical to achieving smoking cessation. In addition, criti- cal evaluation of the helpful and unhelpful aspects of prior attempts at smoking cessation can guide the development of revised and more effective treatment plans. Even among those smokers who have initial success, it is important to remain focused on these issues because most smokers try quitting several times before they finally achieve durable success.316 Ultimately, successful smoking cessation strategies require a long-term disease management approach to achieve perma- nent abstinence. Smoking Cessation Recommendations 1. Smoking cessation is critical, and counseling should be offered to all patients who smoke, during and after hospitalization for CABG, to help improve both short- and long-term clinical outcomes after surgery (Class I; Level of Evidence A). 2. It is reasonable to offer nicotine replacement therapy, bupropion, and varenicline as adjuncts to smoking cessation counseling for stable CABG patients after hospital discharge (Class IIa; Level of Evidence B). 3. Nicotine replacement therapy, bupropion, and var- enicline may be considered as adjuncts to smoking cessation counseling during CABG hospitalization, but their use should be carefully considered on an individualized basis (Class IIb; Level of Evidence B). Cardiac Rehabilitation Outpatient CR is a medically supervised, exercise-based pro- gram that is designed for patients with recent cardiovascular events to optimize overall health status and to minimize the risks for future adverse outcomes.317 325 In a meta-analysis of 48 trials involving CAD patients, CR was associated with a 26% risk reduction in the rate of cardiovascular mortality and a 20% risk reduction in overall mortality.321 Moreover, a strong, inverse dose-response relationship has been observed between the number of CR sessions attended and long-terms rates of MI and death.326 On the basis of this compelling evi- dence, CR has been strongly recommended for patients with several different cardiovascular diseases,327 including those recovering from recent CABG.3,317 The benefits of CR such as improved survival have been reported for all types of CAD patients, including younger and older patients, as well as men and women, independently of the nature of CAD diagnosis, the form of CR, and the dose of exercise intervention.317 325 The very first CR programs were launched in the 1960s, at a time when patients with cardiovascular disease were warned These initial CR programs, imple- mented for post-MI patients recovering in hospital, consisted of graded exercise programs. After a demonstration of their safety and success, these programs were later expanded into the outpatient setting.328 Over the years, CR programs have continued to adapt and to address the broad range of factors affecting cardiovascular outcomes, which has allowed them to evolve from purely supervised exercise programs to compre- hensive secondary prevention programs. The core components of contemporary CR programs include baseline patient assessments, nutritional counseling, risk factor management (lipids, BP, weight, diabetes mellitus, and smoking), psychosocial interventions, and physical activ- ity with counseling and exercise training.329 As a result of the broad effects of exercise training and the multiple components of these programs, CR has been shown to improve a wide range of health factors. Significant improvements have been demonstrated in CAD risk factors, functional capacity, vas- cular conditioning, and psychosocial well-being, all of which likely contribute to the robust effects of CR on overall clinical Among Medicare beneficiaries who have undergone CABG, patients are covered for up to 36 sessions of CR over the course of 1 year after the incident surgical hospitalization; other medical payers offer similar coverage plans. Despite the wealth of evidence and the presence of insurance coverage, CR use patterns remain poor nationwide.329 333 In an analysis of Medicare claims data, only 31% of CABG patients received at least 1 session of CR, and there was considerable geo- graphic heterogeneity in CR use patterns.333 One of the key barriers to CR use is the process of refer- ral to CR.327 Even among hospitals using the AHA Get With The Guidelines program, only 56% of eligible patients were referred to CR.332 Clearly, improving referral patterns to CR programs is a key area in need of greater focus.331 Recognizing Kulik et al Secondary Prevention After CABG 945 the importance of CR and the poor referral patterns to CR, the AHA and ACC, in collaboration with the American Association of Cardiac and Pulmonary Rehabilitation, have released performance measures for CR referral.327 Although CR referral rates are currently low, newly devel- oped referral strategies hold great promise to overcome this In a randomized trial of 2635 patients with CAD admitted to 11 different hospitals, a referral process that con- sisted of a combination of CR liaisons and an automated refer- ral system resulted in 85.8% of patients being referred to CR and 73.5% being enrolled in CR compared with 32.2% and 29.0%, respectively, in the control group.337 In addition, strat- egies such as educational interventions335 and early appoint- ments and start dates338 340 have been shown to improve CR referral and use patterns. However, as new referral strategies become adopted into clinical practice, it will be important for clinicians to remain active in the referral process because physician advocacy remains a strong factor in determining whether patients will enroll in CR programs.341 Beyond the challenges in the referral process, many patient and health system factors negatively affect CR use patterns. Referral to CR is particularly low among specific populations such as patients of low socioeconomic status, women, older adults, and ethnic minorities.323 In addition, CR program loca- tions and hours of operation prohibit the use of this service by some patients, and CR programs may not even be available in some rural or medically underserved areas. Finally, the finan- cial costs, related to copays, transportation, and time off from work, over the course of an entire CR program dissuade some patients from using this service. To address all these barriers to CR use, multiple strategies will need to be undertaken. First, greater attention will need to be paid in the referral process to identify and address an indi- vidual s unique barriers to CR use. This will require greater communication with patients and better coordination between the referring center (hospitals or office-based practices) and CR programs. Second, healthcare reform efforts will need to provide further incentives to patients and healthcare sys- tems to use CR programs. Third, new paradigms for deliv- ering comprehensive CR programs such as home-based CR programs will need to be further developed. Although these challenges are daunting, they are of central importance to improving clinical outcomes after CABG. CR Recommendations 1. CR is recommended for all patients after CABG, with the referral ideally performed early postopera- tively during the surgical hospital stay (Class I; Level of Evidence A). Self-Management of Cardiovascular Disease After CABG, CR programs help patients develop self-man- agement skills to facilitate lifestyle and behavior modifi- cation. Self-management is the process by which patients assume control of their health-related behaviors.342 Ultimately, patients decide what they will eat, if they will exercise, and what medication they will take. As healthcare experiences a paradigm shift from physician-centered to patient-centered care, CR programs play an integral role in education and transitioning patients to adopt health-related behaviors.342 CR personnel can act as health coaches, providing self-manage- ment support, collaborating with patients to establish goals, and developing problem-solving skills to foster risk factor modification. Successful CR programs stimulate patients to acquire the knowledge, skills, and confidence necessary to alter health-related behavior.342 346 The Reduction of Atherothrombosis for Continued Health (REACH) international registry reported that among patients who have undergone CABG, when secondary prevention goals are not met at 1 year, the incidence of adverse cardio- vascular events increases, regardless of the number of risk factors present at baseline. This highlights the importance of CR programs to help patients achieve their goals and to improve long-term outcomes.212 Multiple barriers exist to the adoption of preventive therapies, including knowledge defi- cit, ambivalence, comorbidities, preconceived beliefs, lack of support, employment, and readiness for change.347 349 For example, older patients with comorbidities who live alone are more likely after 1 year to remain sedentary and to have poor medication and diet compliance.350 Interventions for self-management of risk factors should be individualized to meet specific sex concerns. Women in par- ticular have difficulty with self-management of heart disease because of fatigue, anxiety, and depression, as well as feel- ings of guilt that home and family responsibilities are being Adherence to physical activity remains a challenging issue; 35% of women are no longer exercising 3 months after discharge from CR.353 In contrast, men experi- ence different barriers to secondary prevention compared with women. Some of the obstacles to compliance among men include comprehension of disease, dietary barriers (depen- dence on others for meals), and activity barriers (such as employment superseding CR).354 Participation in a hospital-based outpatient CR program compared with a home-based program helps improve exer- cise adherence for both men and women, increases knowledge about the condition for men, and improves stress control for Continuation of the secondary prevention education after discharge from CR can improve adherence to long-term self-management. Secondary prevention programs should be individualized, considering the patient s knowledge deficit. Self-efficacy and self-management skills can be developed by incorporating education and counseling techniques in either individualized or group sessions and focusing on motivational Applying technology through the use of the Internet and mobile phones can help provide education and trained peer support for CABG patients after surgery, even for those who are unable to access CR programs because of Finally, individual diaries have been shown to increase patient accountability for self-management of exercise activity after CR.360 Self-efficacy, along with an individualized plan for behavior change, is imperative to help optimize adherence to secondary prevention after CABG. Mental Health and Cognitive Impairment The negative impact of mental illness and cognitive impair- ment after CABG is well recognized, leading to greater risk of morbidity and mortality in the perioperative period and poor adherence to secondary preventative therapies in the long term. Screening for and preventing these neuropsychological conditions from developing may therefore improve outcomes after CABG. 