Optimizing medical therapy in the coronary artery bypass graft patient


Despite complete revascularization using multiple arterial conduits and optimal myocardial protection, coronary artery bypass graft (CABG) patients are still susceptible to recurrent MACE (major adverse cardiovascular events). Atherosclerotic changes can develop in saphenous vein grafts (SVGs) , and progression of atherosclerosis may occur in native coronary vessels distal to the site of the anastomosis, and in other arteries which had been previously free of disease . This progression of atherosclerotic disease is more likely to occur in patients who are obese, have diabetes, hyperlipidemia, hypertension, chronic kidney disease, are females, and who are smokers. Unless these risk factors are properly controlled, the long-term benefits of CABG will be jeopardized. Unfortunately, the use of postoperative guideline directed medical therapy (GDMT) is underutilized in the CABG patient . In a recent review of compliance with GDMT in contemporary coronary revascularization trials, the implementation of secondary medical prevention therapies was significantly lower in CABG patients versus patients who had undergone a percutaneous coronary intervention (PCI) over a 5-year period . As a result, the superior outcomes achieved with CABG versus PCI early after revascularization became less apparent as the compliance with GDMT decreased in CABG versus PCI patients.

This chapter will review the current status of the use of GDMT in CABG patients, identify those interventions which have been shown to prolong survival and reduce MACE, and provide mechanisms by which GDMT can be instituted to achieve maximal compliance in CABG patients.

Current status of guideline directed medical therapy for secondary prevention in the coronary artery bypass graft patient

Fonarow et al. first demonstrated that implementing therapies to decrease the progression of atherosclerotic disease following an acute coronary event was best instituted during that same hospitalization . Patients who prescribed medical therapy at the time of hospital discharge were more likely to achieve long-term compliance with GDMT . Based on these results, Denton et al. adopted a program by which nine goals should be targeted at the time of hospital discharge following an acute coronary syndrome (ACS) to decrease recurrent ischemic events and prolong survival . These goals include the institution of:

  • 1.

    aspirin (ASA)/antithrombotic/antiplatelet medications,

  • 2.


  • 3.

    angiotensin converting enzyme (ACE) inhibitors,

  • 4.

    lipid therapy to decrease low density lipid (LDL) <70 mg/dL,

  • 5.

    diabetes control to achieve a HbA1c <7%,

  • 6.

    antihypertensive medication to maintain systolic blood pressure <130 mmHg,

  • 7.

    programs for smoking cessation,

  • 8.

    exercise for 30 minutes; 3–4 times/week, and

  • 9.

    weight management to achieve a BMI between 18.5 and 24.9.

These metrics were incorporated into the Society of Thoracic Surgeons (STS) rating system for quality improvement in which a “star” was awarded for compliance of four quality domains; one of which was adherence to recommended secondary-prevention measures.

Unfortunately, the use of statins, beta-blockers, and ACE inhibitors remain low at discharge after CABG and continue to be underutilized in the years following surgery . Furthermore, CABG patients are less likely to fill secondary prevention medications on discharge compared to patients undergoing a PCI . Pinho-Gomes et al. found that GDMT fell to only 50% in CABG patients 5 years after surgery . Filion et al. found that in 2389 CABG patients only 23% received an ACE inhibitor on discharge, only 31% of patients with a history of hypertension received an ACE inhibitor, and only 64% received a statin . Looi et al. found that after 3 years, only 43% of CABG patients were on ACE inhibitors and only 72% received a statin . Belcher et al. reported that 1 year following CABG, only 70% of patients were on an ASA, 18% received no antiplatelet agents, 24% received an ACE inhibitor, 17% received a beta-blocker, and only 28% received a statin . There was no reduction in the incidence of active smokers, and there was a significant rise in systolic blood pressure (135±20 vs 148±25 mmHg; P <.001). The importance of adhering to GDMT was demonstrated by Goyal et al. who surveyed the use of antiplatelet agents, beta-blockers, ACE inhibitors, and statins at discharge and 1 year following CABG in 2970 patients . Patients taking 50% or less of these medications had a significantly higher incidence of death or a myocardial infarction (MI) 2 years following CABG; ( P =.013). As noted earlier by Pinho-Gomes et al., CABG patients who were noncompliant with GDMT were more likely to have decreased survival and decreased freedom from MACE .

Current recommendations for optimal medical therapy in the coronary artery bypass graft patient

Antiplatelet therapy


Postoperative ASA therapy after CABG has been shown to improve SVG patency; especially during the first postoperative year . In addition to improving graft patency, ASA is also associated with improved long-term outcomes following CABG, including decreased mortality, MIs, strokes, and renal failure . The ideal time for initiation of ASA appears to be within 6 hours after CABG. Doses between 81 and 325 mg daily have been used, although the optimal dose is still undecided. In a metaanalysis of five randomized control trials (RCTs) comparing low dose ASA (50–100 mg QD) versus higher (300–325 mg QD) dosages, there was a trend toward improvement in graft patency with the higher dosages . These results are in agreement with previous studies which found that lower doses of ASA (100–200 mg QD) may be insufficient to effectively inhibit platelet function in the post-CABG patient . This may due to ASA resistance which has been shown to decrease SVG patency . The current guidelines for ASA use in CABG patients are as follows:

  • ASA should be administered preoperatively and within 6 hours after CABG in doses of 81–325 mg and should be continued indefinitely to reduce the incidence of graft occlusion and MACE (Class I; LOE A) .

  • Clopidogrel (75 mg QD) is a reasonable alternative following CABG for patients who are intolerant or allergic to ASA and should be continued indefinitely (Class IIA; LOE C) .

The European guidelines have recommended a reduced ASA dose, less than or equal to 161 mg QD to reduce the side effects of ASA therapy .

While the role of ASA in the post CABG patient has been shown to enhance SVG patency and reduce long-term MACE, the use of ASA prior to CABG remains controversial. Concerns have been raised that preoperative ASA may increase bleeding and does not reduce perioperative mortality or MIs. However, several recent studies have shown that preoperative ASA therapy in CABG patients is safe and may improve postoperative outcomes. Bybee et al. found that ASA usage within 5 days of CABG followed by 325 mg QD post-CABG resulted in significantly lower postoperative mortality (1.7% vs 4.4%; P =.007) without any increased incidence of reoperations for bleeding or blood product transfusions . The survival benefit was seen in patients with both acute ACS and stable disease. In a metaanalysis of 12 RCTs and 28 observational studies, Aboul-Hassan et al. found that preoperative ASA at any dose decreased perioperative mortality and acute kidney injury (AKI) . Although the administration of ASA at any dose increased postoperative bleeding, it did not increase the incidence of reexploration for bleeding or the incidence of red blood cell transfusions. While the current guidelines provide no recommendations for the use of preoperative ASA in CABG patients, existing data suggest that ASA therapy be continued until the time of CABG and resumed per the current guidelines within 6 hours following surgery .

Aspirin in the off-pump coronary artery bypass graft patient

Several studies have shown that off-pump CABG may result in a hypercoagulable state characterized by increased platelet adhesion and decreased sensitivity to ASA raising concerns that antiplatelet therapy with ASA alone may not be sufficient for off-pump CABG patients . In a single center, prospective RCT in off-pump CABG patients receiving 100 versus 100 mg ASA+75 mg QD clopidogrel for 1 year, adding clopidogrel to ASA resulted in a significant reduction in SVG occlusion (7.4% vs 13.1%; P =.04) . Similar results were reported by Deo et al. in which SVG occlusion was reduced by 55% in patients receiving ASA+clopidogrel following off-pump CABG . Therefore the current guidelines recommend:

  • Following off-pump CABG, dual antiplatelet therapy (DAPT) should be administered for 1 year with ASA (81 mg QD) and clopidogrel (75 mg QD) to reduce graft occlusion (Class I; LOE A) .

Aspirin therapy in patients undergoing total arterial grafting

ASA alone has not been shown to enhance arterial graft patency . However, it still may be beneficial in preventing or limiting atherosclerotic disease in distal native arteries, or ungrafted native arteries in diabetic patients . Therefore all CABG patients, irregardless of the types of conduits used, will benefit from ASA therapy.

Dual antiplatelet therapy

DAPT refers to that combination of antiplatelet therapy combining ASA with a P2T12 receptor inhibitor (clopidogrel, prasugrel, or ticagrelor). Prasugrel and ticagrelor have more potent and consistent platelet inhibition and faster onset of action compared to clopidogrel. Currently, DAPT therapy is recommended for CABG patients who have previously undergone PCI stent implantation, and in those CABG patients in whom DAPT has already been instituted for ACS. There is currently insufficient evidence to recommend DAPT in stable CABG patients who have not previously undergone a PCI with a stent. Furthermore, there are no existing guidelines for the duration of DAPT following a CABG. Previous studies suggest that DAPT decreases SVG occlusion, especially in off-pump patients, but has no effect on arterial grafts . In the recent ARTs trial involving single versus bilateral mammary revascularization, there was no difference in MACE at 1 year following CABG between ASA alone and DAPT . Chakos et al. in their metaanalysis of DAPT in 2133 CABG patients could not find any significant difference in graft patency between ASA alone versus DAPT . In all studies, DAPT was associated with an increased risk of surgical bleeding. The current recommendations for DAPT in the CABG patient are:

  • In patients treated with DAPT a daily ASA dose of 81 mg QD is recommended; Class I, LOE B .

  • In patients who have received DAPT for PCI stent implantation and then undergo CABG, DAPT should be resumed postop until the recommended duration for stent implantation is completed; Class I, LOE C .

  • In patients with ACS who are being treated with DAPT and who must now undergo a CABG, DAPT should be resumed after CABG to complete 12 months of DAPT therapy after ACS; Class I, LOE C .

Angiotensin converting enzyme inhibitors

ACE inhibitors benefit CABG patients not only by their antihypertensive effects but also from their vasculoprotective and antiatherogenic properties. They minimize thrombosis by reducing platelet aggregation and limit vascular inflammation and oxidative stress by enhancing nitric oxide production . Since increased levels of ACE have been found in the atherosclerotic plaques of native coronary arteries and in SVGs of CABG patients , ACE inhibition may also limit the progression of atherosclerosis in both bypass conduits and distal native coronary vessels. These vasculoprotective properties of ACE inhibitors were found to decrease infarct size, improve ventricular function, and prolong survival in patients with MIs and ACS, irrespective of whether or not they had hypertension . These favorable effects of ACE inhibition were also noted in porcine experimental studies involving periods of coronary occlusion followed by cardioplegic arrest and reperfusion on cardiopulmonary bypass simulating CABG surgery. Hearts treated with ACE inhibitors prior to and during coronary ischemia had significantly reduced infarct size, better recovery of regional wall motion, and better preservation of endothelial function .

Two major RCTs helped to establish the role of ACE inhibitor therapy in the CABG patient. In the QUOVADIS (effects of Quinapril on Vascular ACE and Determinants of Ischemia) trial, 149 CABG patients were prospectively randomized 4 weeks prior to CABG to receive quinapril (40 mg QD) or placebo for 1 year . Quinapril reduced the risk of any ischemic event (MI, recurrence of angina, transient ischemic attack) from 15% to 4% ( P =.02). The APRES (Angiotensin Converting Enzyme Inhibition Post Revascularization) study randomized 130 normotensive CABG patients with moderately reduced ejection fractions (30%–50%) to receive Ramipril (10 mg) 5–7 days following surgery . After 33 months, Ramipril reduced the risk of the composite endpoint of cardiac death, acute MI, or congestive heart failure (CHF) by 58% ( P =.03). In both trials, ACE inhibition therapy was well tolerated and resulted in no adverse events. Similar results were seen in the HOPE trial which enrolled 9297 high risk cardiovascular patients, 26% of whom had already undergone a CABG, randomized to receive Ramipril (10 mg QD) versus placebo for 5 years . Compared to placebo, Ramipril significantly decreased the rates of MIs, stroke, and death ( P <.001). These beneficial effects of ACE inhibitors were seen in multiple populations; men and women, all age groups, and in those with or without hypertension, diabetes, hyperlipidemia, and cerebrovascular disease. Furthermore, the mean reduction in systolic blood pressure in the Ramipril group was only 2–3 mmHg; suggesting that these beneficial effects were due to the vasculoprotective “pleiotrophic” effects of ACE inhibitors and not to its antihypertensive properties. Similar reductions in mortality and MACE in CABG patients receiving ACE inhibitors in the perioperative period have been reported by others . However, several other studies reported no benefits from ACE inhibitors and possible detrimental side effects. In the Ischemia Management with Accupril Post Bypass Graft via Inhibition of Angiotensin Converting Enzyme (IMAGINE) trial involving 2553 CABG patients, accupril (40 mg QD) started <7 days following surgery significantly increased the incidence of death and MACE in the first 3 postoperative months (3.2% vs 4.8%; P =.036) . However, there were no significant differences in outcomes after 3 months (10.0% vs 10.7%; P =.5). This study included only “low risk” patients already receiving statins, ASA, and beta-blockers. Only 13% of eligible patients were actually randomized. In addition, there was a significant incidence of postoperative hypotension in the ACE group (12% vs 5.5%; P <.001), that was not observed in the HOPE, QUOVADIS, or APRES trials. This raises concerns as to how ACE inhibitors were instituted and monitored in the early postoperative period. Miceli et al. also reported an increased risk of postoperative mortality (1.3% vs 0.7%; P <.03) in CABG patients receiving ACE inhibitors . However, ACE inhibitor patients had a significantly increased incidence of cardiovascular risk factors and the timing, dosages, and the specific ACE inhibitors that were used were not reported. Cheng et al performed a metaanalysis of patients receiving ACE inhibitors comprising 18 studies; 3 RCTs, and 15 observational trials involving 54,528 patients of which 46% of the patients underwent a CABG . They found no difference in the incidence of postop death, MI, or strokes between patients with and without ACE inhibitor therapy. However, ACE inhibitor patients had an increased incidence of hypotension and the need for inotropic support. Nevertheless, there was a significant decrease in all-cause mortality in diabetic patients ( P =.04). This is consistent with other studies in CABG patients which found that ACE inhibitors significantly reduce mortality and improve 3-year event free survival in diabetic patients .

Patients who receive ACE inhibitors prior to CABG surgery may develop hypotension due to decreased systemic vascular resistance, especially while on cardiopulmonary bypass . However, this is usually associated with normal or increased cardiac output and is usually reversed with short periods of low-dose vasopressor support. Nevertheless, the periods of hypotension may contribute to AKI and hyperkalemia. Several studies have reported no adverse effects with preop ACE inhibitors on renal function and some have actually reported a reduced incidence of AKIs . AKI after institution of ACE inhibitors in the postop CABG patient is usually related to the dosages used, the level of hydration and intravascular volume, and the presence of any underlying renovascular disease. In my own experience, and those of others, holding ACE inhibitors in elective CABG cases for 24–48 hours prior to surgery attenuates its vasodilatory effects and reduces the need for vasopressor agents . In the postoperative period, ACE inhibitors should only be initiated after beta-blockers have been instituted for 24–48 hours and systemic blood pressure is >100 mmHg. A low dose (2.5 mg) long-acting ACE inhibitor should be ordered and the dose gradually increased over several days to maintain a systolic blood pressure >100 mmHg. Serum creatinine and signs of increasing cough should be carefully monitored to avoid renal injury and sternal instability. If the systolic blood pressure cannot be maintained >100 mmHg, ACE inhibitors should not be initiated or discontinued, and referring physicians are asked to begin ACE inhibitors during follow-up outpatient visits. This regimen helps to avoid periods of hypotension, limits AKI, and prevents SVG occlusion. The current guidelines for the use of ACE inhibitors in the CABG patient are:

  • ACE inhibitors or angiotensin receptor blockers (ARBs) that were given prior to CABG should be instituted postoperatively once the patient is stable; unless contraindicated; Class I;LOE B .

  • ACE inhibitors or ARBs should be initiated postoperatively and continued indefinitely in CABG patients who were not receiving them preoperatively and who are stable, have an ejection fraction <40%, have hypertension, diabetes, or chronic kidney disease unless otherwise contraindicated; Class I, LOE A .

  • It is reasonable to initiate ACE inhibitors or ARBs postoperatively and to continue them indefinitely in all CABG patients who were not receiving them preoperatively and are considered to be at low risk (patients with a normal ejection fraction and in whom cardiovascular factors are well controlled), unless contraindicated; Class IIA, LOE B .

Hypertension management in the coronary artery bypass graft patient

Although hypertension is a major modifiable risk factor for limiting the development and progression of atherosclerosis and has been shown to increase long-term mortality in CABG patients , there have been no trials undertaken to determine the role of blood pressure control and outcomes in this group of high risk patients. Furthermore, the ideal target for blood pressure control has not been formally addressed in the CABG patient. There is a critical need for such a study since too stringent blood pressure control, that results in hypotension, may effect renal function and SVG patency. With this in mind, it is reasonable to target a blood pressure goal of <140 mmHg in CABG patients using antihypertensive agents (Class IIA; LOE B) . In view of their vasculoprotective and antihypertensive properties, ACE inhibitors should be included in all antihypertension-management therapies for the CABG patient.

Antilipid therapy


Statins have been shown to reduce both the incidence of SVG stenosis as well as the risk of MACE in the post-CABG patient . In addition to their lipid lowering effects, statins also have important “pleiotropic” properties, independent of their cholesterol lowering effects, which contribute to reducing post-CABG ischemic events. These include improved endothelial and vasomotor function, decreased oxidative stress and vascular inflammation, and the prevention of thrombosis due to increased platelet aggregation . In the Cholesterol and Recurrent Events (CARE) multicenter trial, patients receiving 40 mg QD of pravastatin for 5 years following either a CABG or PCI had a 33% reduction in cardiovascular deaths ( P =.034), a 43% reduction in the incidence of MIs ( P =.009), a 22% reduction in the need for repeat revascularization ( P =.05) and a 72% reduction in the incidence of strokes ( P =.006) . These beneficial effects on long-term outcomes following CABG were also seen in smaller, single center studies. Christenson et al. reported that angiograms obtained 1 year following CABG showed significantly less new lesions and a lower incidence of SVG occlusions ( P =.02) along with a significant decrease in MIs in patients receiving statins . Dotani et al. found that postoperative statin therapy resulted in a significant reduction in the composite endpoint of death, MIs, and unstable angina ( P =.006) 1 year after CABG . Similar results were found in other studies which showed that postoperative statin therapy resulted in significantly lower long-term mortality and MACE . Administering statins prior to CABG have also been shown to reduce the risk for postoperative mortality , atrial fibrillation , AKI , infections , and strokes . These beneficial effects have occurred even in patients without elevated lipid profiles prior to surgery.

High versus low-intensity statin therapy

There is now evidence to show that high intensity statin therapy may provide increased protection from cardiovascular events in the CABG patient. In the post-CABG trial, patients were randomized to aggressive therapy with lovastatin (80 mg) to achieve an LDL<85 mg/dL or moderate treatment with 40 mg to target an LDL of 135 mg/dL . After 5 years, patients receiving aggressive therapy had less progression of atherosclerotic lesions in vein grafts (27% vs 39%; P <.001), fewer occluded SVGs (10% vs 21%; P <.0001), and a 29% reduction in the need for a re-revascularization procedure (6.5% vs 9.2%; P =.03). After 7.5 years, these beneficial effects persisted, with a 30% reduction in the need for a repeat revascularization procedure ( P =.001). In the Treating to New Target trial, CABG patients receiving 80 mg of atorvastatin had a significantly lower incidence of MACE ( P =.0004) and less need for a rerevascularization procedure ( P <.0001) compared to patients receiving 10 mg of atorvastatin . In the post hoc analysis of the CASCADE trial, 1 year graft patency was significantly higher for CABG patients on statins who reached an LDL level <100 mg/dL, compared to patients with an LDL>100 mg/dL; P =.03 . However, there was no further improvement in graft patency when the LDL was reduced to <70 mg/dL.

Statins are well tolerated in the postoperative CABG patient with little side effects . There is no evidence to support the use of one statin over another. Studies in cardiac surgery patients have shown a significantly higher risk of postoperative morbidity and mortality in patients in whom statins are discontinued after surgery . The current guidelines for statin therapy in CABG patients are:

  • All patients undergoing CABG should receive statin therapy, unless contraindicated, prior to surgery and restarted early after surgery when patients can tolerate oral medications and continued indefinitely; Class I, LOE A .

  • In CABG patients, high-dose statin therapy (40–80 mg) should be used to achieve at least a 30% lowering of LDL in patients <75 years; Class I, LOE A .

  • Moderate intensity statin therapy should be administered to CABG patients who are intolerant of high-intensity therapy and for patients at greater risk for drug interactions (age >75 years); Class I, LOE A .

  • Statin therapy should not be discontinued before or after CABG unless a patient is having an adverse reaction to therapy, Class III, LOE B .

High-density lipoprotein management

A low HDL level is a risk factor for increased cardiovascular events following CABG . In a prospective, observational study, fewer than one-third of males survived CABG surgery after 15 years if HDL levels were less than 35 mg/dL . While smoking cessation, weight loss, exercise, and limiting alcohol intake may increase HDL, statins appear to have little effect on HDL levels. The Lopid Coronary Angiography Trial (LOCAT), the only HDL trial involving CABG patients, was performed in the era prior to the use of statins in CABG patients . Patients were randomized to receive either slow-release gemfibrozil (1200 mg QD) or placebo. Gemfibrozil significantly increased HDL levels ( P <.001), decreased the progression of native vessel disease ( P =.009), and decreased the incidence of new lesions in SVGs on follow-up angiograms (27% vs 14%; P <.001). However, gemfibrozil therapy has been associated with an increased incidence of muscle pain and rhabdomyolysis, especially in patients already receiving statin therapy . Since statins are now the primary therapeutic agents for lipid lowering in CABG patients, HDL lowering agents are no longer recommended for CABG patients who are already receiving statins.

Triglyceride management

High triglyceride levels at the time of CABG have been associated with an increased risk of death, MACE, SVG occlusion, and the need for a repeat revascularization procedure . The first line therapy for these patients include diet modification with the restriction of carbohydrates, exercise, weight loss, and reduced alcohol intake. Statins may also have some beneficial effects in reducing triglycerides; but there have been no prospective RCTs to show their benefits in CABG patients with hypertriglyceridemia. However, in diabetic patients with severely elevated triglyceride levels (>500 mg/dL), the combination of fenofibrate and statin therapy has been shown to decrease MACE .


Beta-blocker therapy remains the treatment of choice for rate control and decreasing the incidence of atrial fibrillation in the post-CABG patient . Although the use of beta-blockers has been made a quality metric for cardiac surgery in the STS database , it ability to decrease postoperative morbidity and mortality and its use as a quality metric has been questioned . The combination of better operative and myocardial preservation techniques and the use of ACE inhibitors and statins may have diminished the individual benefits of beta-blockers to reduce perioperative morbidity and mortality. However, in a study of CABG patients <75 years of age, beta-blockers reduced the incidence of MACE or morbidity after 2 years . Several other studies have found that long-term beta-blocker therapy following CABG can reduce both mortality and MACE in patients who had an MI prior to surgery , those with CHF , elderly patients , and those with reduced ejection fractions (<40%) . The long-term beneficial effects of beta-blockers have also been seen in patients with and without a history of an MI or CHF . Chan et al found that in 2547 CABG patients, 1 year mortality was significantly lower in patients discharged on beta-blockers (2.2% vs 7.2%; P <.01) . This significant decrease in mortality was seen in all subgroups, including patients with and without MIs and CHF, and in patients discharged with and without statins and ASA. The current recommendations for beta-blockers in the CABG patient include the following:

  • All CABG patients, without contraindications, should have beta-blockers administered for at least 24 hours prior to CABG, to reduce the incidence of postoperative atrial fibrillation; Class I; LOE A .

  • CABG patients with a history of an MI, with and without reduced ejection fraction, should receive a beta-blocker, unless contraindicated; Class I, LOE A .

  • CABG patients with LV dysfunction should receive beta-blocker therapy unless contraindicated; Class I, LOE B .

  • Beta-blockers should be prescribed to all CABG patients without contraindications postoperatively, and at the time of discharge; Class I, LOE C .

Diabetes mellitus

Hyperglycemia (serum blood sugar >180 mg/dL) which persists prior, during, and following cardiac surgery is an independent predictor of operative mortality and morbidity including infections, strokes, MIs, and the low cardiac output syndrome . Previous studies have shown that continuous glucose infusions designed to maintain serum glucose <180 mg/dL in the immediate preop, intraop, and postop periods decrease perioperative mortality, the need for inotropic support, the incidence of infections, atrial fibrillation, and ICU and hospital length of stay . Furthermore, Lazar et al. found that maintaining serum glucose between 120 and 180 mg/dL in the perioperative period following CABG improved 5-year survival ( P =.04), decreased the incidence of recurrent angina ( P =.03) and other ischemic events ( P =.01) . More intensive glycemic control (90–120 mg/dL) has not been shown to improve clinical outcomes that can be obtained with more moderate control (120–180 mg/dL) and results in a higher incidence of hypoglycemia . Unfortunately, for many patients coming for CABG, the diagnosis of diabetes mellitus is unknown prior to surgery. Therefore the current guidelines recommend:

  • All patients undergoing CABG should have a fasting glucose and a HbA1c prior to surgery; Class I, LOE C .

This greatly facilitates the management of diabetes mellitus in the perioperative period. Those patients without a history of diabetes mellitus, with a preop HbA1c<6.5%, and who maintain intraoperative and postoperative serum glucose levels <180 mg/dL will not benefit from continuous insulin infusions .

Initiating and maintaining glycemic control in the coronary artery bypass graft patient

In the CABG patient, glycemic control is best instituted in the perioperative period by an in-hospital glucose monitoring team consisting of intensivists, endocrinologists, pharmacists, and dieticians in conjunction with the nursing and cardiac surgical service. The following are the current guidelines for instituting and maintaining glycemic control in the CABG patient:

  • A continuous intravenous insulin infusion is the method of choice to achieve and maintain glycemic control (120–180 mg/dL) in the perioperative period; Class I, LOE A .

  • All oral diabetic medication should be withheld 24 hours prior to surgery; especially sulfonylureas and glinides which are more apt to result in hypoglycemia in the absence of food. Outpatients on insulin should take their basal insulin dose on the morning of surgery but hold their nutritional insulin (IE lispro). NPH insulin should be reduced by 1/2–1/3 prior to surgery; Class I, LOE B .

  • For inpatients with persistently elevated glucose values >180 mg/dL, an insulin drip should be initiated at least 12 hours prior to surgery, Class I, LOE C . In the operating room, serum glucose levels should be monitored every 30 minutes and more frequently during systemic cooling, rewarming, and when large amounts of glucose containing cardioplegia is being infused. It is important to recheck serum glucose levels prior to leaving the operating room when the effects of temperature and cardioplegia are no longer present to avoid hypoglycemia. All patients who require intraoperative insulin infusions should be seen by an endocrinologist in the postoperative period so that the appropriate diabetic medications can be instituted.

  • In the ICU, patients with persistently elevated serum glucose levels >180 mg/dL should receive a continuous insulin infusion to keep serum glucose between 120 and 180 mg/dL, Class I, LOE A .

  • Patients who require >3 days of ICU care due to ventilatory, inotropic, or mechanical support, renal replacement therapy, or the need for antiarrhythmic agents should have serum glucose levels <150 mg/dL, Class I, LOE B .

  • Following discharge from the ICU, patients receiving IV insulin infusions should be transitioned to a subcutaneous insulin-dosing schedule. The target glucose goal should be <110 mg/dL premeal and <180 mg/dL postprandial; Class I, LOE A . This is best achieved with a daily subcutaneous basal and a bolus, short-acting insulin agent such as lispro.

  • Patients with type 2 diabetes may be started on their oral medications once they have reached their targeted glucose goals and are tolerating a regular diet. Metformin should not be restarted until stable renal function has been achieved, Class I, LOE C .

Prior to discharge following a CABG, the inpatient glycemic control team should review all glycemic control agents with the patient—especially when changes or new drugs have been instituted. Referring physicians should also be informed of any changes that have been made. Those patients started on insulin for the first time should receive specialized instructions on its use, and all new diabetic patients receiving either insulin or noninsulin oral agents should receive education on glucose monitoring, nutrition, and lifestyle changes as well as follow-up visits with an endocrinologist.

Glycemic control improves survival and decreases the incidence of MACE in all patients with cardiovascular disease. Therefore:

  • All attempts to achieve a HbA1c<7% is a reasonable goal for patients following CABG to reduce both microvascular and macrovascular complications, Class IIA, LOE B .

Managing coronary artery bypass graft patients with the metabolic syndrome

The metabolic syndrome consists of three or more of the following conditions: central obesity, hyperglycemia, elevated systolic blood pressure, hypertriglyceridemia, and decreased HDL levels . The prevalence of the metabolic syndrome in CABG patients may be as high as 50% and is associated with a significant increase in perioperative mortality, decreased long-term survival, an increased incidence of renal failure, arrhythmias, and decreased patency of SVGs . Treatment of the metabolic syndrome is multifactorial. Although pharmacotherapy with statins, ACE inhibitors, beta-blockers, and glycemic control will help to treat lipid disorders, hypertension and hyperglycemia, visceral and central adiposity (waist circumference >102 cm in men and >88 cm in women) is not totally reversed by these medications. This requires aggressive changes in lifestyle involving exercise, diet, and behavioral changes including smoking cessation, which are discussed further in the following sections.

Smoking cessation

Cigarette smoking results in cardiovascular vasoconstriction, endothelial dysfunction, hypertension, and hyperlipidemia which contributes to a prothrombotic state and leads to atherosclerotic changes in SVGs and ultimately occlusion . Patients who continue to smoke following CABG surgery have a 68% greater risk for all-cause mortality and a 75% greater risk of cardiac death . The prothrombotic state and associated endothelial dysfunction are quickly reversible after smoking cessation . Patients who stop smoking following CABG have a 41% reduction in the need for a repeat revascularization procedure . Smoking cessation is one of the most important risk-modified goals for the CABG patient.

  • Counseling should be offered to all patients who smoke during and after hospitalization for CABG to improve both short- and long-term outcomes after surgery; Class I, LOE A .

The postoperative period is the most effective time to institute smoking cessation strategies in the CABG patient. Patients are more likely to give up smoking immediately following surgery and the ensuing 6-month postoperative period . Strategies to decrease or eliminate smoking include behavioral counseling, nicotine replacement therapy, and medication with bupropion and varenicline. Nicotine-replacement therapy is safe for patients with stable coronary artery disease. However, in a retrospective study which included CABG patients, nicotine replacement therapy was associated with increased mortality in patients with ACS . In contrast, Bupropion has been shown to be safe and effective for smoking cessation and in patients following an MI . Varenicline has also been shown to be effective for smoking cessation but was found to result in a nonsignificant increase in the incidence of nonfatal MIs, peripheral vascular disease, and the need for coronary revascularization . As a result, the FDA has issued an advisory warning that varenicline may increase the risk of MACE and should be used with caution in the post-CABG patient. Current guidelines for nicotine replacement in the CABG patient state:

  • It is reasonable to offer nicotine replacement therapy with bupropion and varenicline as adjuncts to smoking cessation counseling for stable CABG patients after hospital discharge; Class IIA, LOE B .

To further assist clinicians with smoking cessation, the American College of Cardiology has recently released an “Expert Consensus Decision Pathway on Tobacco Cessation Treatment” which includes prescriptions for pharmacological smoking cessation aids and evidence-based behavioral support groups.

Cardiac rehabilitation and exercise programs

Cardiac rehabilitation (CR) programs initiated following CABG surgery have been shown to improve exercise tolerance and result in a faster return to work . They play an important role in educating patients about secondary prevention and help to facilitate lifestyle and behavior modification to minimize future MACE.

  • All CABG patients should be referred to a CR program during their postoperative hospital stay; Class I, LOE A .

Unfortunately, only 31% of Medicare patients receive at least 1 session of CR because of the lack of physician involvement in initiating the referral process . Physician advocacy has been found to be a key factor in determining whether patients will enroll in a CR program . Participation in an outpatient program that is hospital based allows for easier adherence to secondary prevention therapies that were initiated during the post CABG hospital stay.

Exercise is an important part of any CR program following CABG and may consist of large muscle dynamic exercises, short periods of moderate intensity, or resistance training . All exercise programs should be performed in a medically supervised program only after all wounds are fully healed and should be tailored to the patients’ needs and capabilities.

Mental health, emotional, and psychosocial therapy

Depression may occur in up to 33% of CABG patients in the first year following surgery . It has been associated with an increased incidence of postoperative mortality, recurrent angina, MIs, rehospitalization for CHF, and the need for repeat revascularization procedures .

  • Following CABG, all patients should be screened for depression; Class IIA, LOE B .

Interventions to treat post-CABG depression should be initiated immediately in the hospital. These interventions include antidepressant medication and psychotherapy and have been associated with decreased mortality, less use of analgesics, and reduced hospital length of stay . They improve quality of life, and as a result, patients are more likely to continue their daily activities independently and are more compliant with secondary prevention therapies . These therapies should be part of any in-house or outpatient rehab program.

Preoperative depression and anxiety also contributes to poor postoperative outcomes and has been associated with increased mortality, ICU and hospital length of stay, and hospital readmissions . Every effort should be made to identify and treat these patients prior to CABG and even delay surgery if they are stable. This has resulted in decreased morbidity and mortality and less need for analgesic medication . Patients tend to be more alert and can better participate in postoperative care programs to ensure faster discharge to home rather than an in-house rehabilitation program. These patients also require postdischarge, long-term antidepressant, and psychotherapy since they are prone to poor compliance with secondary prevention medication, resulting in increased hospital readmissions and decreased long-term survival. Symptoms of anxiety and postoperative depression may also be indicative of the presence of dementia and should not simply be dismissed as postoperative anxiety.

Methods to improve compliance with guideline-directed medical therapy in the coronary artery bypass graft patient

The data presented in this chapter has clearly shown that GDMT in CABG patients results in a significant reduction in long-term MACE and mortality. It has been estimated that using an ACE inhibitor, ASA, beta-blockers, and statins simultaneously in patients with cardiovascular disease can decrease ischemic events by at least 14% . In view of the overwhelming evidence showing that noncompliance with GDMT significantly negates the beneficial effects of CABG, why then is compliance with GDMT as low as 50% 5 years after CABG surgery? . There are several explanations for this observation:

  • Patients are frequently led to believe that CABG is the most definitive therapy for their coronary artery disease and, therefore, long-term treatment with medications may not be necessary.

  • Patients may find that medications for secondary prevention are too costly and are not always covered by third-party payers.

  • CABG patients may not always be followed by a cardiologist long-term. Unfortunately, primary care physicians and nurse practioners are not always aware of the latest guidelines for secondary prevention following CABG and are more likely to decrease or discontinue ASA, statins, beta-blockers, and ACE inhibitors once target goals have been reached.

  • There is a misconception amongst cardiologists that performing CABG with total arterial revascularization will eliminate the need for further GDMT.

What can be done to enhance compliance with GDMT in the CABG patient? Since patients who are prescribed medical therapy at the time of hospital discharge are more likely to achieve long-term compliance with GDMT , every effort should be made to institute “Get with the Guidelines” programs to target goals that can be maintained in outpatient programs and at home . One mechanism to improve compliance with discharge medical therapy is to use “quality indicators” such as the use of prescriptions for ASA, beta-blockers, statins, and ACE inhibitors to assess adherence with discharge medications, similar to the 3-star rating system adopted by the STS. In a study of STS participating hospitals, CABG patients were randomized into a control or intervention group . The intervention group received “feedback reports” on the compliance with discharge prescriptions for ASA, beta-blockers, statins, and ACE inhibitors every 6 months in addition to patient education materials that stressed the importance of secondary prevention medications and lifestyle modifications. Compliance with these four medications was significantly increased over a 24-month period following CABG in the intervention group. Enrollment in either inpatient or outpatient rehab programs is another method by which compliance with GDMT can be improved .

While these in-patient and early discharge programs can achieve initial success, maintaining adherence to long-term GDMT still remains a problem; especially for patients who are no longer followed by a cardiologist or an internist with an interest in cardiovascular diseases. Another option is to institute a “cardiac revascularization clinic” at the hospital where the CABG or PCI was performed which provides follow-up for both procedures, similar to a Heart Valve Clinic for both sAVR and TAVR patients. Such a clinic would ensure that all patients are seen by cardiovascular specialists who are well acquainted with the most recent guidelines. Patients would have their blood pressure, lipid levels, and HgbA1c checked on a regular basis. Not only would adherence to GDMT be assessed, but the necessary changes in medication and dosages could be made to ensure that the appropriate targeted values are achieved.


Maintaining GDMT following CABG is an important intervention to minimize MACE, prolong survival, and improve quality of life. These interventions are summarized in Table 24.1 and should be instituted by all surgeons in the postoperative period while patients are still hospitalized to ensure maximal patient compliance. Proper follow-up following discharge by physicians familiar with the latest guidelines is necessary to ensure that CABG patients continue to receive GDMT so that the superior benefits derived from surgical revascularization continue years after their CABG procedure.

Apr 6, 2024 | Posted by in CARDIOLOGY | Comments Off on Optimizing medical therapy in the coronary artery bypass graft patient

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