INTRODUCTION — Coronary artery bypass graft surgery (CABG) is recommended for patients with obstructive coronary artery disease whose survival will be improved compared to medical therapy or percutaneous coronary intervention (PCI). In addition, other patients with angina refractory to medical therapy may receive a recommendation for CABG if PCI cannot be performed. The procedure involves the construction of one or more grafts between the arterial and coronary circulations.
This topic addresses issues related to late survival following CABG. The following issues are discussed separately:
●Operative mortality (see "Operative mortality after coronary artery bypass graft surgery")
●Early noncardiac complications (see "Early noncardiac complications of coronary artery bypass graft surgery")
●Medical therapy to prevent complications (see "Coronary artery bypass surgery: Perioperative medical management")
●Choice of graft (see "Coronary artery bypass graft surgery: Graft choices")
●Early cardiac complications (see "Early cardiac complications of coronary artery bypass graft surgery")
●Vein graft stenosis (see "Coronary artery bypass graft surgery: Prevention and management of vein graft stenosis")
●Late recurrent angina (see "Late recurrent angina pectoris after coronary artery bypass graft surgery")
SURVIVAL RATES — Many studies of late survival after coronary artery bypass graft surgery (CABG) were carried out before long-term interventions aimed at reducing overall cardiovascular risk, such as statin therapy, were routinely employed. Thus, past estimates of long-term survival after CABG are of uncertain applicability to current practice. In addition, survival rates vary with the population studied [1].
The best available data on long-term survival after CABG come from two 2012 reports:
●The ASCERT study linked data from the Society of Thoracic Surgeons Adult Cardiac Surgery Data base and the Centers for Medicare and Medicaid Services (United States) [2]. This study included nearly 350,000 isolated CABG patients aged ≥65 years who were discharged between January 1, 2002 and December 31, 2007. Kaplan-Meier estimated mortality was 3.2 percent at 30 days, 6.4 percent at 180 days, 8.1 percent at one year, 11.3 percent at two years, and 23.3 percent at three years of follow- up.
●In a report from the New York State Cardiac Surgery Reporting System database, the one-, three-, five-, and seven-year mortality rates of 8597 patients who underwent isolated CABG were 6.2, 11.2, 17.6, and 24.2 percent, respectively [3].
POSSIBLE PREDICTORS OF MORTALITY — Graft patency, advancement of disease in native vessels, and comorbid conditions are major predictors of long-term mortality, particularly in patients aged 65 years or older. The ASCERT study (see 'Survival rates' above) made the following observations [2]:
●Risk factors such as emergency status, shock, and reoperation are strong predictors of short-term outcome, but become nonsignificant within two years.
●Other risk factors such as dialysis-dependent renal failure, insulin-dependent diabetes mellitus, and smoking become more important with time.
●Age (increment of 10 years), chronic lung disease (≥moderate), and serum creatinine 1.5 to 2.5mg/dL predict poor outcomes both short- and long-term.
Preoperative factors
Preoperative hemoglobin level — Lower preoperative hemoglobin (as a continuous variable) and anemia (defined as <13 mg/dL for men and <12 mg/dL for women) were independent predictors of higher late mortality (after 30 days) in a study of over 10,000 patients undergoing isolated CABG [4].
Chronic kidney disease — Chronic kidney disease, even if mild, is associated with increased perioperative mortality after CABG. The mechanisms by which this occurs are not completely understood. (See "Chronic kidney disease and coronary heart disease" and "Early noncardiac complications of coronary artery bypass graft surgery", section on 'Acute kidney injury'.)
The baseline glomerular filtration rate (GFR) is also a predictor of long-term mortality after CABG. This was illustrated in a series of 2607 consecutive patients undergoing CABG in whom the baseline serum creatinine was used to estimate the GFR [5]. At 2.3 years, the estimated GFR was an independent predictor of mortality in models with other univariable predictors and in the EuroSCORE cardiac operative risk evaluation (hazard ratio [HR] 0.80 to 0.88 per 10 mL/min per 1.73 m2 increase in estimated GFR compared with an HR of 0.71 without adjustment).
One mechanism by which chronic kidney disease might lead to a lower survival is by causing a lower rate of bypass graft patency. This question was evaluated in the PREVENT IV trial, in which there was no significant difference between saphenous vein or internal thoracic artery graft failure rates in patients with or without preoperative renal dysfunction at two years [6]. (See "Coronary artery bypass graft surgery: Graft choices", section on 'Late occlusion'.)
Cardiovascular risk factors — Other variables affecting long-term outcome have been described in several reports and consist mostly of the known coronary risk factors [7-10]. In the CASS registry, factors impacting negatively upon late survival, other than the use of saphenous vein grafts (SVGs) alone, were heavier weight, MI, diabetes, smoking, and left main and left anterior descending disease [7]. This issue was also addressed in a study of 3559 patients who underwent CABG at a single center and were followed for ≥25 years; the following predictors of survival were reported [8]:
●Age - Relative risk 1.54 for each decade
●Total cholesterol - Relative risk 1.11 for each 50 mg/dL (1.3 mmol/L) increase
●Diabetes mellitus - Relative risk 1.45
●Systemic hypertension - Relative risk 1.28
●Cigarette smoking - Relative risk 1.33
As described below, chronic kidney disease is now recognized as an important adverse predictor of survival after CABG.
In a retrospective review of 6428 patients who were followed for a median of eight years after CABG, over 90 percent of those who died had at least one of these risk factors [9]. The HR increased from 1.64 when one factor was present to 3.95 when all four risk factors were present. Women with this quartet had a poorer outcome than men (HR 13.4 versus 2.6).
The impact of therapies to lower cardiovascular risk is discussed below. (See 'Preventive therapies' below.)
Atrial fibrillation — The relationship between preoperative atrial fibrillation and mortality is discussed separately. (See "Atrial fibrillation and flutter after cardiac surgery", section on 'Adverse outcomes following atrial fibrillation'.)
Frailty — Prefrailty and frailty were prevalent among United States veterans undergoing CABG and were associated with five-year mortality. In a retrospective cohort study at 40 United States Veterans Association medical centers, 13,554 patients underwent CABG and were followed for mortality outcomes. Frailty was quantified by the Veterans Administration Frailty Index (VA-FI), which uses 30 pertinent diagnosis codes. Patients were classified as nonfrail (VA-FI ≤0.1), prefrail (VA-FI ≤0.2), or frail (VA-FI > 0.2). Frail patients were older and had higher comorbidity burdens than pre- and nonfrail patients. Compared with nonfrail patients, frail and prefrail patients had increased mortality at five years (13 versus 24.8 percent [HR 1.75; 95% CI 1.54-2.00] and 13 versus 16.8 percent [HR 1.2; 95% CI 1.08-1.34], respectively). Compared with nonfrail patients (mean 362 [SD 12]), prefrail (mean 361 [SD 14]) and frail patients (mean 358 [SD 18]) spent fewer days alive and out of the hospital in the first postoperative year.
Surgical factors
Use of the left internal thoracic artery — The higher long-term patency seen with arterial compared to SVGs (figure 1) translates into improved long-term survival (figure 2). This issue is discussed in detail separately. (See "Coronary artery bypass graft surgery: Graft choices", section on 'Arterial grafts'.)
Two arterial grafts — Placement of two (rather than one) arterial grafts should be attempted in most patients with a life expectancy of greater than 7 to 10 years. Although the use of two arterial grafts, compared with one, has not been clearly shown to improve survival, benefits include a lower rate of repeat revascularization and myocardial infarction, particularly when a radial artery is used as the second arterial graft. This issue is discussed separately. (See "Coronary artery bypass graft surgery: Graft choices", section on 'Arterial grafts'.)
Incomplete revascularization — While complete revascularization (CR) has been the usual goal for CABG, the evidence to support superiority of CR compared to incomplete revascularization (IR) is not consistent, with studies suggesting that incomplete revascularization (IR) may be equally safe and effective.
Multiple older studies (1992 to 2000) support CR [11-13]. For example, in a report from the CASS registry of patients who underwent CABG for three vessel disease, placing grafts to three or more vessels was independently associated with improved survival at five years (87 to 90 percent versus 78 percent with a graft to only one vessel) and event-free survival at six years (30 versus 23 percent with a graft to only one vessel) in patients with severe but not mild to moderate angina [11].
The applicability of these older studies to the current era is uncertain and the effect of other confounding high-risk factors is difficult to control.
The following studies do not support an advantage to CR:
●In a review from the BARI trial comparing CABG to PCI (bare metal stents), there was no independent survival advantage from CR compared to IR [14].
●In the ARTS I trial comparing CABG to PCI (bare metal stents) in patients with multivessel disease, there was no difference in mortality out to five years in the two groups [15], despite a higher rate of CR with CABG (84 versus 71 percent) [16]. However, stented patients with IR were more significantly more likely to require CABG at one year (10 versus 2 percent of stented patients with CR). (See "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention".)
●A single-center registry report of 514 patients undergoing CABG for multivessel coronary artery disease compared outcomes between those who received CR (67 percent) and those who received IR (33 percent) [17]. Multiple analyses using differing definitions of IR (applied to the diagnostic angiogram prior to revascularization) found no significant difference in the adjusted rates of five-year death or the composite of death, MI, or stroke between those with CR and those with IR.
We believe that the goal for surgical revascularization should remain CR (with arterial grafts), whenever possible and safe. However, the above findings suggest that not all patients who undergo CABG require CR. In the setting of a left internal thoracic artery (ITA) conduit to the LAD, IR may be appropriate for non-LAD vessels that are small or to vessels that supply only a small amount of viable myocardium. In addition, IR, as part of a strategy to simplify the surgical procedure in order to reduce operation-related complications, may be reasonable. This may be a situation in which a combined (staged) revascularization approach, with both CABG and PCI, may be reasonable.
Vein graft failure — The issue of whether vein graft patency affects long-term outcomes in patients who receive a left ITA graft was evaluated in the PREVENT IV trial of over 1800 patients who underwent CABG and had an angiogram performed up to 188 months after surgery. (See "Coronary artery bypass graft surgery: Graft choices", section on 'Late occlusion'.) Over 92 percent of patients received an ITA graft. The main outcome measure of death, MI, and repeat revascularization through four years occurred more often in patients who had any vein graft failure compared with those who had none (adjusted hazard ratio [HR], 1.68, 95% CI 1.21-2.06) [18]. This finding was due principally to a higher rate of repeat revascularization; there were no significant differences in the rates of death or MI.
Endoscopic vein-graft harvesting — Endoscopic vein-graft harvesting is preferred to an open technique due to a comparable rate of major adverse cardiovascular events (MACE) such as mortality or vein-graft failure but a lower incidence of wound (leg) complications, better cosmetic appearance, and less pain. (See "Early noncardiac complications of coronary artery bypass graft surgery", section on 'Leg wound complications'.)
Early observational studies of relatively small size came to differing conclusions regarding MACE [19-22].
The 2018 REGROUP trial randomly assigned 1150 patients undergoing CABG to open or endoscopic vein-graft harvesting [23]. All vein-graft harvesting was performed by operators with a high level of clinical experience. During a median follow-up of almost three years, there was no significant difference in the rate of a primary composite outcome that included all-cause death, nonfatal MI, and repeat revascularization (15.5 versus 13.9 percent; HR 1.12, 95% CI 0.83-1.51). The rates of the individual outcomes were similar. There was a trend toward more leg wound infections in the open harvest group. (See "Early noncardiac complications of coronary artery bypass graft surgery", section on 'Leg wound complications'.)
Perioperative outcomes
Perioperative myocardial infarction — Perioperative MI, defined as new Q waves and/or elevations in biomarkers, is associated with postoperative complications and increases in both short- and long-term mortality [24,25]. (See "Early cardiac complications of coronary artery bypass graft surgery", section on 'Perioperative MI'.)
Acute kidney injury — Acute kidney injury (AKI) is an independent predictor of both short- and long-term mortality after CABG [26-29]. (See "Overview of the management of acute kidney injury (AKI) in adults" and "Definition and staging criteria of acute kidney injury in adults" and "Early noncardiac complications of coronary artery bypass graft surgery" and "Early noncardiac complications of coronary artery bypass graft surgery", section on 'Acute kidney injury'.)
In a retrospective cohort analysis of nearly 30,000 individuals, the magnitude of creatinine increase after CABG was associated in a graded manner with a significant increase in mortality at three months and five years [29]. For example, the hazard ratios (HRs) for death at three months were 1.4, 1.9, 2.8, and 5.0 in patients with 1 to 24, 25 to 49, 50 to 99, and ≥100 percent rise in postoperative serum creatinine.
AKI is also associated with an increased risk of end-stage kidney disease (ESKD). In a study of over 29,000 patients who underwent primary isolated CABG, the HR for ESKD after multivariable adjustment was 2.92 (95% CI 1.87-4.55) for individuals with a rise in creatinine >0.3 mg/dL or a 50 to 100 percent increase and 3.81 (95% CI 2.14-6.79) for those with a >100 percent increase [30].
Postoperative factors
Depression — Depression is a common problem after CABG and is associated with an adverse effect on patient outcomes. (See "Psychosocial factors in coronary and cerebral vascular disease", section on 'Outcome after CABG'.)
Atrial fibrillation — The relationship between postoperative atrial fibrillation and mortality is discussed separately. (See "Atrial fibrillation and flutter after cardiac surgery", section on 'Adverse outcomes following atrial fibrillation'.)
LONG-TERM RISK PREDICTION MODELS — The New York State Cardiac Surgery Reporting System database was linked to United States National Data Index to evaluate long-term mortality in nearly 8600 patients who underwent isolated coronary artery bypass graft surgery (CABG) between July and December of 2000 [3]. The significant predictors of death were similar to the individual factors presented above and included age, body mass index, ejection fraction, unstable hemodynamic state or shock, left main coronary artery disease, cerebrovascular or peripheral artery disease, heart failure, malignant ventricular arrhythmia, chronic obstructive pulmonary disease, diabetes, renal failure, and history of open heart surgery. Using these risk factors, a risk model to predict death at one, three, five, and seven years was developed and the statistical performance of the model was robust (C-statistic between 0.768 and 0.783). The survival rates are discussed above.
PREVENTIVE THERAPIES — Aggressive risk factor reduction is recommended in all patients with coronary heart disease. This includes low-dose aspirin, reaching treatment goals for hypertension and serum lipids, avoidance of smoking, and, in patients with diabetes, controlling the serum glucose. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk".)
The impact of underutilization of preventive medical therapies after coronary artery bypass graft surgery (CABG) was evaluated in a follow-up study of 2970 patients enrolled in the PREVENT IV trial [31]. Patients were assessed for the use of aspirin, beta blockers, angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers, and lipid lowering agents after hospital discharge and at one year, and then categorized based upon their percentage use of indicated medications. Patients taking 50 percent or less compared with those taking all indicated medications after CABG had a significantly higher two-year rate of death or myocardial infarction (MI) (8 versus 4.2 percent, adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.12-2.55).
Antiplatelet agents — Antiplatelet agents, such as aspirin and clopidogrel, are given within 48 hours of CABG to improve both short- and long-term cardiovascular outcomes, including the reduction in the incidence of early and late graft occlusion [32]. There are no well-performed studies that have compared dual with single antiplatelet therapy in this setting.
We agree with the recommendations from the 2012 American College of Chest Physicians (ACCP) guideline on the primary and secondary prevention of cardiovascular disease that patients who undergo CABG should be started on aspirin and it should be continued indefinitely [33]. We recommend 75 to 162 mg/day.
Our recommendations for the use of clopidogrel after CABG in patients with acute MI are presented elsewhere. (See "Coronary artery bypass surgery: Perioperative medical management", section on 'Platelet P2Y12 receptor blocker therapy'.)
Lipid lowering — Clinical trials have shown that statin therapy is beneficial in almost all patients with atherosclerotic cardiovascular disease, including those who have undergone CABG [34-39]. (See "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease".)
In addition, aggressive lipid lowering therapy with a statin is associated with better outcomes than less aggressive therapy when started after CABG [35,36]. In the Post Coronary Artery Bypass Graft trial, 1351 patients with serum low density lipoprotein (LDL) cholesterol concentrations between 130 and 175 mg/dL (3.4 to 4.5 mmol/L) were randomly assigned to receive either aggressive therapy with lovastatin and, if needed, cholestyramine, to reduce LDL-cholesterol to less than 100 mg/dL (2.6 mmol/L) or to moderate therapy, which resulted in LDL-cholesterol concentrations of approximately 134 mg/dL (3.5 mmol/L) [37]. Compared to moderate therapy, aggressive therapy was associated with a delay in the progression of graft disease at angiography after an average of 4.3 years (figure 3) [37,38]. In addition, a 30 percent reduction in revascularization procedures and a 24 percent reduction in the composite end point of cardiovascular death, MI, stroke, CABG, or angioplasty (figure 4) was seen after clinical follow-up of 7.5 years [39].
Additional evidence supporting aggressive lipid lowering with a statin comes from a post hoc analysis from the TNT trial of patients with stable coronary artery disease [36]. In the 4654 (out of 10,000) patients with previous CABG, high-dose atorvastatin (80 mg daily) was significantly more effective than low dose (10 mg daily) at lowering the rate of a combined cardiovascular end point at a median follow-up of 4.9 years (9.7 versus 13.0 percent; HR 0.73, 95% CI 0.62-0.87). Repeat revascularization with either CABG or PCI was also significantly less frequent in patients with the higher dose (11.3 versus 15.9 percent). (See "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease".)
Beta blockers — The majority of patients who present for nonemergent CABG have been receiving beta blocker therapy for management of their angina, rate control in atrial fibrillation, or secondary prevention after acute MI. In addition, beta blockers reduce the likelihood of the development of atrial arrhythmias during and immediately after cardiac surgery. (See "Coronary artery bypass surgery: Perioperative medical management", section on 'Beta blockers' and "Atrial fibrillation and flutter after cardiac surgery", section on 'Beta blockers'.)
Long-term beta blocker use has not clearly been shown to improve survival after successful revascularization with CABG. For patients without other clear indications for beta blocker use, such as those with heart failure, we suggest that they not be routinely used long-term based on the following evidence:
●Older randomized trials performed before the routine use of other preventive strategies did not find evidence of benefit [40,41].
●A 2015 observational study evaluated long-term outcomes in 5926 patients who underwent CABG between 2004 and 2008 [42]. The primary outcome was all-cause death and the analysis evaluated patients with and without MI and by beta blocker use. After a median duration of 3.0 years, 5.3 percent died (54 percent from a cardiac cause) and this rate was similar between those with and without prior MI. In a matched cohort analysis of 1096 users and never users, the rate of death was significantly higher in the never user group (HR 1.50, 95% CI 1.01-2.24). This benefit was present for individuals with and without prior MI. However, as patients who consistently take medications generally have better outcomes compared to those who do not, our confidence is low that the findings in this study represent an effect resulting from beta blocker use.
While we do not recommend the routine use of beta blockers in patients who have undergone complete and successful revascularization, their use is appropriate in some patients, such as those with heart failure or those with rapid ventricular rates in atrial fibrillation. (See "Primary pharmacologic therapy for heart failure with reduced ejection fraction", section on 'Beta blocker' and "Control of ventricular rate in patients with atrial fibrillation who do not have heart failure: Pharmacologic therapy".)
The role of long-term beta blocker use after CABG in patients with prior MI has not been well studied. Our experts have varying approaches, with some continuing them indefinitely, some stopping at one or three years, and a few stopping after successful revascularization. (See "Acute myocardial infarction: Role of beta blocker therapy", section on 'Long-term therapy'.)
ACE inhibitors — We do not recommend the routine use of ACE inhibitors in patients who have undergone CABG.
Data from both the APRES and QUO VADIS trials suggested a benefit from ACE inhibition in patients who undergo CABG [43,44]. However, these trials cannot be used to support a specific benefit from ACE inhibitors or angiotensin II receptor blockers (ARBs) since the blood pressure was also significantly lower in the ACE inhibitor group (eg, 128/75 versus 136/81 mmHg with placebo at one year in the APRES trial). In a number of other trials that have evaluated ACE inhibitors or ARBs compared to placebo or other antihypertensive in high-risk groups, the intervention that was associated with the lower blood pressure consistently produced the better outcome.
In addition, individuals at low risk of cardiovascular events after CABG may not derive specific benefit from angiotensin inhibition. This issue was addressed in the IMAGINE trial in which 2553 low-risk patients following CABG were randomly assigned to either quinapril (target dose 40 mg daily) or placebo [45]. Low-risk was defined as stable patients with left ventricular ejection fraction ≥40 percent and no other clear indication such as uncontrolled hypertension, diabetes with microalbuminuria, or insulin dependency. After a median follow-up of almost three years, there was no significant difference between the two groups in the combined primary end point (cardiovascular death, resuscitated cardiac arrest, nonfatal MI, coronary revascularization, unstable angina or heart failure requiring hospitalization, documented angina, or stroke).
These findings do not preclude the use of ACE inhibitors or ARBs nor do they minimize the utility of these drugs as first-line therapy in all CABG patients who have specific indications for their use, such as left ventricular systolic dysfunction or proteinuric chronic kidney disease.
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)
●Basics topics (see "Patient education: Recovery after coronary artery bypass graft surgery (The Basics)" and "Patient education: Coronary artery bypass graft surgery (The Basics)")
●Beyond the Basics topic (see "Patient education: Coronary artery bypass graft surgery (Beyond the Basics)" and "Patient education: Recovery after coronary artery bypass graft surgery (CABG) (Beyond the Basics)")
SUMMARY
●Predictors of mortality – Graft patency, advancement of disease in native vessels, and comorbid conditions are major predictors of long-term mortality, particularly in patients aged 65 years or older. (See 'Possible predictors of mortality' above.)
●Types of conduit vessel – Internal thoracic artery grafts, compared with saphenous vein grafts, are associated with improved patient survival. The extent of arterial revascularization improves cardiovascular outcomes. (See 'Use of the left internal thoracic artery' above and 'Two arterial grafts' above.)
●Preventive therapies – Aggressive risk factor reduction and the use of antiplatelet therapy are recommended in all patients with coronary heart disease, including those who have undergone coronary artery bypass graft surgery. (See 'Preventive therapies' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff thank Julian M. Aroesty, MD, for his past contributions as an author to prior versions of this topic review.
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