bypass graft to a territory natively perfused by a vessel with at least a 50% proximal stenosis. Under

most circumstances, the revascularization is incomplete because target vessels were unsuitable for

bypassing because they were small, inaccessible, or too heavily diseased. The differences observed are

typically not apparent in 30-day survival but manifest as a reduced long-term prognosis. Although the

angiographic appearance of potential coronary targets may suggest unsuitability, interpretation of

vessel quality is extremely subjective and very difficult to quantify, which is why it has not been

incorporated into the two large risk creation models. Nonetheless, the quality of the bypass targets

should be considered when weighing the options for treatment of advanced coronary artery disease.

The purpose of coronary bypass surgery is to create unimpeded blood flow to ischemic myocardial

territories. While short- and long-term mortality may reflect the adequacy of revascularization, bypass

graft patency is a more precise assessment of the technical success of the operation. Patency rates are

typically reported based on clinical trials in which routine angiography is performed at regular

intervals, excluding biases from studies in which angiography is only performed in symptomatic

patients. Saphenous vein grafts are hampered by a higher early graft loss, as much as 20% in the first

year. Mechanisms include technical anastomotic problems, graft kinking, inadequate epicardial run-off,

vein graft endothelial dysfunction from injury or chronic stasis, competitive flow from relatively

unobstructed native coronary flow, and early development of neointimal hyperplasia. Late vein graft

occlusion develops at a rate of approximately 5% per year from progressive native vessel disease and

the development of accelerated vein graft atherosclerosis. Patency at 10 years is generally 40% to 50%.

It remains to be seen if these outcomes improve with advances in statin and antiplatelet agents. As

described previously, the internal mammary artery is generally spared of both atherosclerotic disease

and early development of neointimal hyperplasia. Not surprisingly, its patency is vastly superior,59

although these outcomes may be biased by the fact that the left internal mammary artery is typically

placed on the LAD. The higher outflow of this target results in greater flow rates, reducing the risk of

stagnation from limited run-off. In addition, its anterior location make it less likely to kink. Patency at 1

year is approximately 95%, and there is very little attrition over time, with 85% to 90% patency at 10

years. In fact, the use of the internal mammary artery is an independent predictor of long-term survival,

presumably because of better graft outcomes.60 The radial artery is generally intermediate to saphenous

vein grafts and the internal mammary artery. Patency rates have been described as 90% at 1 year and

80% to 90% at 5 years. The radial artery is particularly prone to spasm from competitive flow, resulting

in a patent but dysfunctional graft, referred to as a string sign. The radial artery should be avoided

when stenotic lesions are less than 70%.

COMPARATIVE TRIALS

9 With the advent of coronary bypass surgery in the late 1960s, questions arose as to which patients are

appropriate to offer this highly invasive and costly treatment. Three landmark randomized trials were

constructed comparing CABG with medical treatment for a variety of patient populations. The Veterans

Administration Cooperative Study,61 the European Coronary Surgery Study,62 and the Coronary Artery

Surgery Study63 all demonstrated that CABG improves survival as compared to medically treated

patients, and the benefits of CABG are enhanced by more severe disease, as well as left ventricular

dysfunction. Although these trials are now more than 30 years old and medical and surgical treatments

have evolved considerably, the principles continue to apply and are repeatedly described in more

contemporary series.

Although these clinical trials definitively demonstrated the superiority of CABG over medical therapy

for patients with advanced coronary artery disease, the advent and widespread adoption of

intracoronary balloon angioplasty raised the possibility that a less invasive approach to

revascularization may be as beneficial as the surgical approach. Several multicenter clinical trials were

conducted comparing CABG with angioplasty for a variety of patient populations. The most notable of

these studies was the Bypass Angioplasty Revascularization Investigation, or BARI trial.64 A total of

1,829 patients were deemed eligible and were randomized to angioplasty or CABG in 18 centers across

the United States and Canada. While there were no differences for in-hospital death or 5-year survival,

the rate of repeat revascularization was significantly higher in the percutaneously treated patients. Only

8% of patients in the CABG group required repeat revascularization within the first 5 years, as

compared to 54% in the angioplasty group. Although survival analysis was intention to treat, 31% of

patients in the angioplasty group underwent subsequent CABG. Importantly, subgroup analysis

demonstrated a survival advantage at 5 years for diabetic patients treated with CABG as opposed to

2412

angioplasty (80.6% vs. 65.5%; p = 0.003). The BARI study demonstrated that surgical revascularization

was more durable and resulted in improved survival for diabetic patients with advanced coronary artery

disease.

Angioplasty alone carries a restenosis rate of 30% to 40% from at least two mechanisms. One is

entirely mechanical, related to elastic recoil, and is seen within weeks of intervention. The other

mechanism is related to progressive neointimal hyperplasia, likely occurring as a result of local trauma.

Intracoronary stents have reduced the restenosis rate and improved outcomes of percutaneous

intervention. In the setting of these advances, several multicenter, prospective, randomized trials were

performed, again with the hypothesis that percutaneous intervention would be superior or equivalent to

surgical revascularization for patients with advanced coronary artery disease. Among the most

prominent of these studies was the SoS, or Surgery or Stent, trial.65 A total of 988 patients from 53

medical centers in 11 countries were enrolled based on eligibility criteria, including the presence of

multivessel coronary artery disease. Patients were randomly assigned to receive either coronary bypass

surgery or percutaneous intervention using intracoronary stents. At a median follow-up of 2 years,

20.7% of patients in the stent arm required repeat revascularization, as compared to only 6% in the

CABG arm (p < 0.001). Surprisingly, there was also a survival advantage seen with surgery (mortality

4.5% vs. 1.6%, stent vs. surgery, respectively; p = 0.01). These mortality advantages persisted with a

median follow-up of 6 years (10.9% vs. 6.8%; p = 0.02).66 Consistent with previous clinical trials, the

survival advantage was even more pronounced for diabetics (17.6% vs. 5.4%). The SoS trial was similar

to other randomized trials comparing coronary stents with CABG with respect to superior rates of repeat

revascularization. However, SoS was unique in describing a mortality benefit. Some have argued that

enrollment criteria were much less stringent in SoS, enrolling sicker patients with more complex

anatomic lesions. SoS may therefore better reflect “real-world” practice.

Among the biggest limitations of bare metal intracoronary stents is the development of obstructing

neointimal hyperplasia resulting in in-stent restenosis, which occurs at a rate of 15% to 30%. Recently,

antiproliferative drugs have been incorporated into the platform of stents to inhibit this occlusive

process. These drug-eluting stents have been demonstrated in prospective randomized fashion to reduce

the rate of repeat revascularization, when compared to bare metal stents. Because of improved

outcomes using this new technology, a prospective, multicenter, randomized trial was conducted

comparing coronary bypass grafting with a strategy using drug-eluting stents for patients with left main

or three-vessel coronary stenosis.67 Eighty-five centers in the United States and Europe enrolled patients

who met these criteria and whose anatomic disease was determined by both the surgeon and

interventional cardiologist to be amenable to either strategy. A total of 3,075 patients were enrolled,

but only 1,800 patients were randomized, 897 to CABG and 903 to PCI with the Taxus drug-eluting

stent (Boston Scientific). The remaining patients were not felt to be good candidates for both

procedures, and 1,077 underwent CABG and 198 underwent PCI. Outcomes of these excluded patients

were collected into a separate registry. Of the randomized patients, more patients in the PCI arm had

major cardiac or cerebrovascular events at 12 months (12.4% vs. 17.8%, CABG vs. PCI, respectively; p

= 0.002). The majority of these differences were seen in the rate of repeat revascularization (5.9% vs.

13.5%; p < 0.001). The authors also created a numerical system to comparatively describe the

complexity of the coronary anatomy. This “syntax” score was higher for chronic total occlusions,

bifurcation lesions, heavily calcified vessels, and lesions greater than 20 mm in length. The differences

in major cardiac or cerebrovascular events between CABG and PCI were even more pronounced in the

subgroup of patients with a high “syntax” score (10.9% vs. 23.4%). This study once again demonstrated

that despite improved outcomes of percutaneous treatment of coronary artery disease with drug-eluting

stents, CABG remains the best therapy for patients with significant left main and three-vessel coronary

artery disease. The benefits of CABG are accentuated for patients with more severe and complex

disease.

These important randomized trials have consistently demonstrated that surgical coronary artery

revascularization is the ideal technique to reduce symptoms, myocardial infarctions, cardiac-related

future hospitalizations, and death in patients with advanced coronary artery atherosclerosis.

Improvements in nonsurgical therapy, both medical and percutaneous, have prompted recurring

investigations into the comparative efficacy of coronary bypass surgery. Surgical treatment continues to

successfully compete, largely because of simultaneous advances in surgical technique, intraoperative

patient care, and postoperative management. Despite concerns raised every year that CABG will no

longer be performed in the future, outcomes remain superior and as a result, volumes continue to rise.

It is likely that surgical revascularization of the ischemic heart will continue to be the dominant strategy

2413

for many years to come.

References

1. Davies JE, Burkhart HM, Dearani JA, et al. Surgical management of anomalous aortic origin of a

coronary artery. Ann Thorac Surg 2009;88:844–847.

2. Messer JV, Wagman RJ, Levine HJ, et al. Patterns of human myocardial oxygen extraction during

rest and exercise. J Clin Invest 1962;41:725–742.

3. Berne RM. The role of adenosine in the regulation of coronary blood flow. Circ Res 1980;47:807–

813.

4. Malek AM, Alper SL, Izumo S. Hemodynamic shear stress and its role in atherosclerosis. JAMA

1999;282:2035–2042.

5. Samnegard A, Hulthe J, Silveira A, et al. Gender specific associations between matrix

metalloproteinases and inflammatory markers in post myocardial infarction patients. Atherosclerosis

2009;202:550–556.

6. Singh SK, Suresh MV, Voleti B, et al. The connection between C-reactive protein and

atherosclerosis. Ann Med 2008;40:110–120.

7. Psaty BM, Lumley T, Furberg CD, et al. Health outcomes associated with various antihypertensive

therapies used as first-line agents: a network meta-analysis. JAMA 2003;289:2534–2544.

8. Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans

with type 2 diabetes. New Engl J Med 2009;360:129–139.

9. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.

Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP)

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult

Treatment Panel III). JAMA 2001;285:2486–2497.

10. The Lipid Research Clinics Coronary Primary Prevention Trial. Results II. The relationship of

reduction in incidence of coronary heart disease to cholesterol lowering. JAMA 1984;251:365–374.

11. Wilson K, Gibson N, Willan A, et al. Effect of smoking cessation on mortality after myocardial

infarction: meta-analysis of cohort studies. Arch Intern Med 2000;160:939–944.

12. Hasdai D, Topol EJ, Califf RM, et al. Cardiogenic shock complicating acute coronary syndromes.

Lancet 2000;356:749–756.

13. Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization in acute myocardial infarction

complicated by cardiogenic shock. SHOCK Investigators. Should we emergently revascularize

occluded coronaries for cardiogenic shock. N Engl J Med 1999;341:625–634.

14. Bakhtiary F, Keller H, Dogan S, et al. Venoarterial extracorporeal membrane oxygenation for

treatment of cardiogenic shock: clinical experiences in 45 adult patients. J Thorac Cardiovasc Surg

2008;135:382–388.

15. Haft JW, Pagani FD, Romano MA, et al. Short- and long-term survival of patients transferred to a

tertiary care center on temporary extracorporeal circulatory support. Ann Thorac Surg 2009;88:711–

717.

16. Jeppsson A, Liden H, Johnsson P, et al. Surgical repair of post infarction ventricular septal defects:

a national experience. Eur J Cardiothorac Surg 2005;27:216–221.

17. Russo A, Suri RM, Grigioni F, et al. Clinical outcome after surgical correction of mitral

regurgitation due to papillary muscle rupture. Circulation 2008;118:1528–1534.

18. Vohra HA, Chaudhry S, Satur CM, et al. Sutureless off-pump repair of post-infarction left

ventricular free wall rupture. J Cardiothorac Surg 2006;1:11.

19. Ohman EM, Armstrong PW, Christenson RH, et al., GUSTO IIA Investigators. Cardiac troponin T

levels for risk stratification in acute myocardial ischemia. N Engl J Med 1996;335:1333–1341.

20. Tonino PA, De Bruyne B, Pijls NH, et al. Fractional flow reserve versus angiography for guiding

percutaneous coronary intervention. N Engl J Med 2009;360:213–224.

21. Bruining N, de Winter S, Serruys PW. Intravascular ultrasound registration/ integration with

coronary angiography. Cardiol Clin 2009;27:531–540.

22. Budoff MJ, Achenbach S, Blumenthal RS, et al. Assessment of coronary artery disease by cardiac

2414

computed tomography: a scientific statement from the American Heart Association Committee on

Cardiovascular Imaging and Intervention, Council on Cardiovascular Radiology and Intervention,

and Committee on Cardiac Imaging, Council on Clinical Cardiology. Circulation 2006;114:1761–

1791.

23. Ross SD, Allen IE, Connelly JE, et al. Clinical outcomes in statin treatment trials: a meta-analysis.

Arch Intern Med 1999;159:1793–1802.

24. Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting enzyme inhibitor, ramipril,

on cardiovascular events in high risk patients. N Engl J Med 2000;342:145–153.

25. Antiplatelet Trialists’ Collaboration. Collaborative overview of randomised trials of antiplatelet

therapy—I: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet

therapy in various categories of patients. BMJ 1994;308:81–106.

26. Ryden L. Efficacy of epanolol versus metoprolol in angina pectoris: report from a Swedish

multicentre study of exercise tolerance. J Intern Med 1992; 231:7–11.

27. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on

Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA

2003;289:2560–2572.

28. Chaitman BR, Skettino SL, Parker JO, et al. Anti-ischemic effects and long-term survival during

ranolazine monotherapy in patients with chronic severe angina. J Am Coll Cardiol 2004;43:1375–

1382.

29. Yusuf S, Collins R, MacMahon S, et al. Effect of intravenous nitrates on mortality in acute

myocardial infarction: an overview of the randomised trials. Lancet 1988;1:1088–1092.

30. Rutherford JD, Pfeffer MA, Moye LA, et al., SAVE Investigators. Effects of captopril on ischemic

events after myocardial infarction: results of the Survival and Ventricular Enlargement trial.

Circulation 1994;90:1731–1738.

31. Beckwith C, Munger MA. Effect of angiotensin-converting enzyme inhibitors on ventricular

remodeling and survival following myocardial infarction. Ann Pharmacother 1993;27:755–766.

32. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute

coronary syndromes without ST-segment elevation. N Engl J Med 2001;345:494–502.

33. Mehta RH, Roe MT, Mulgund J, et al. Acute clopidogrel use and outcomes in patients with non-STsegment elevation acute coronary syndromes undergoing coronary artery bypass surgery. J Am Coll

Cardiol 2006;48:281–286.

34. Ferguson JJ, Califf RM, Antman EM, et al. Enoxaparin vs unfractionated heparin in high-risk

patients with non-ST-segment elevation acute coronary syndromes managed with an intended early

invasive strategy: primary results of the SYNERGY randomized trial. JAMA 2004;292:45–54.

35. Yusuf S, Mehta SR, Chrolavicius S, et al. Comparison of fondaparinux and enoxaparin in acute

coronary syndromes. N Engl J Med 2006;354:1464–1476.

36. Fibrinolytic Therapy Trialists’ (FTT) Collaborative Group. Indications for fibrinolytic therapy in

suspected acute myocardial infarction: collaborative overview of early mortality and major

morbidity results from all randomised trials of more than 1000 patients. Lancet 1994;343:311–322.

37. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for

acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 2003;361:13–20.

38. Bradley EH, Nallamothu BK, Herrin J, et al. National efforts to improve door-to-balloon time:

results from the door-to-balloon alliance. J Am Coll Cardiol 2009;54:2423–2429.

39. Di Lorenzo E, Sauro R, Varricchio A, et al. Long-term outcome of drug-eluting stents compared with

bare metal stents in ST-segment elevation myocardial infarction: results of the paclitaxel- or

sirolimus-eluting stent versus bare metal stent in primary angioplasty (PASEO) randomized trial.

Circulation 2009;120:964–972.

40. van Werkum JW, Heestermans AA, Zomer AC, et al. Predictors of coronary stent thrombosis: the

Dutch Stent Thrombosis Registry. J Am Coll Cardiol 2009;53:1399–1409.

41. Patel MR, Dehmer GJ, Hirshfeld JW, et al. ACCF/SCAI/STS/AATS/AHA/ ASNC 2009

appropriateness criteria for coronary revascularization. Circulation 2009;119:1330–1352.

42. Lopes RD, Hafley GE, Allen KB, et al. Endoscopic versus open vein-graft harvesting in coronaryartery bypass surgery. N Engl J Med 2009;361:235–244.

43. Savage EB, Grab JD, O’Brien SM, et al. Use of both internal thoracic arteries in diabetic patients

2415