pproximately 40% to 60% of patients undergoing percutaneous revascularization have multivessel coronary artery disease (CAD), defined as >70% stenosis in >2 coronary arteries or involving the left main (1
). Although multivessel percutaneous coronary interventions (PCI) comprise less than 10% to 15% of PCIs performed (2
), as many as 30% to 40% of patients with multivessel disease and class I indications for coronary artery bypass grafting (CABG) undergo PCI (3
). The utilization of PCI in patients with multivessel disease may be partially explained by data supporting early invasive strategies in patients with acute coronary syndromes (4
) or patient comorbidities that preclude surgical candidacy (5
). Importantly, technical advancements in PCI and recent studies comparing PCI with CABG may justify multivessel interventions as a clinically viable option for some patients.
Improvements in stent design, guide catheters, coronary wires, and debulking technologies, along with emerging techniques and dedicated equipment for treating chronic total occlusions and bifurcation lesions, have improved the procedural success of PCI in patients with complex disease, making multivessel PCI more attractive from a technical standpoint. The availability of percutaneous ventricular support devices have allowed for longer and difficult procedures to be performed in high-risk patients (6
). Improved image quality and lower radiation from newer fluoroscopy equipment with digital image processing have also reduced the radiation exposure of patients undergoing multivessel PCI. Furthermore, the emergence of effective and safer anticoagulants, antiplatelet therapies, and lipid lowering agents has made a major contribution to improved outcomes in patients undergoing multivessel coronary interventions.
Concomitantly, however, the outcomes of medical therapy alone have also improved significantly, and there are scarce data supporting improved survival with revascularization, compared with optimal medical therapy (7
). Improved patient comfort and long- and short-term operative morbidity of CABG have also improved with shorter pump times, off-pump procedures, complete arterial revascularization, and minimally invasive approaches (8
). In the current era, the decision to perform multivessel coronary interventions has become less a matter of operator skill or technique than a thoughtful consideration of a myriad of clinical trial data, assessments of myocardial viability and ischemia, potential restenosis rates, and patient surgical risks that rarely present a choice that is simple or unambiguous.
CLINICAL TRIALS AND GUIDELINES: CABG VERSUS MULTIVESSEL PCI
A major challenge in interpreting clinical trials that evaluate the safety and benefit of multivessel PCI is the same difficulty that any study of long-term outcomes of a rapidly changing field must face—that the data will inevitably lag behind ever improving techniques and technology. The results of the studies comparing angioplasty with CABG were soon eclipsed by the ubiquitous use of coronary stents, while the studies performed in the stent era have tended to evaluate outmoded technologies as thinner, open cell, and drug eluting stents (DES) that have improved deliverability and reduced restenosis were introduced. Second generation drugeluting stents, polymer and stent design modifications appear to further reduce restenosis rates (9
In the Bypass Angioplasty Revascularization Investigation (BARI) study comparing CABG with percutaneous transluminal coronary angioplasty (PTCA) balloon angioplasty, 70% of patients randomized to PTCA underwent multivessel interventions. While there was no difference in the primary outcome of death or myocardial infarction (MI) at 5 years, the need for repeat revascularization was dramatically higher in the PTCA group. There was a significant survival advantage for diabetic patients undergoing CABG who received a left internal mammary artery (LIMA) graft, but none for the nondiabetic group or those with multivessel disease (10
). Among those with multivessel disease randomized to PTCA, patients who had successful complete percutaneous multilesion revascularization had the lowest death and MI rates, compared with those in whom multi-vessel PTCA was unsuccessful or not attempted (11
). A meta-analysis of trials comparing multivessel angioplasty with CABG reinforced these results, demonstrating similar outcomes between these two revascularization strategies in nondiabetics, but a survival benefit of CABG among diabetics (12
Multivessel PCI studies performed in the bare metal stent (BMS) era produced similar results, with only a modest reduction in repeat revascularization rates compared with CABG (Table 22-1
). The 5-year death and MI outcomes were equivalent to CABG in the major studies in which bare-metal stents were used in the PCI arm, with the exception of the Surgery or Stent (SOS) study, in which mortality was significantly higher at 2 years for patients undergoing PCI. Although there was an unequal distribution of diabetics in the PCI group, further adjustment in the SOS study did not change the higher observed mortality at 2 years and subsequent time points (13
). A recent meta-analysis of the ARTS, ERACI II, MASS II, and SOS studies, which compared bare-metal stenting to CABG, found no significant differences between the two strategies in death, MI, or stroke. There was no heterogeneity in treatment in any of the subgroups, including diabetics and patients with left-ventricular dysfunction (14
). Repeat revascularization was the primary driver behind differences in the composite outcome in all of these studies. Revascularization rates at 5 years following PCI was 20% to 30% in these studies, many times higher than the 3% to 8% rates for CABG, although an improvement from the 54% revascularization rate for PTCA in the BARI study.
Given that repeat revascularization was the primary driver for differences between PCI and CABG in these studies, the introduction of DES would be expected to narrow the gap for multivessel PCI. The ERACI III (15
) and the ARTS II (16
) registries followed patients who underwent nonblinded multivessel PCI using first generation paclitaxel and sirolimus-eluting stents. The event rates
in the ARTS II registry more closely approximated the CABG outcomes of the original study (5-year major adverse cardiac events, including repeat revascularization 27.5% for PCI vs. 21.1% for CABG, p = 0.02, compared with 41.5% for BMS, p < 0.01), although the rates were statistically higher. A similar finding was reported among patients in the ERACI III registry, where patients with multivessel PCI with DES had a much lower repeat revascularization rate, similar to the CABG patients in ERACI II. An analysis of the New York cardiac surgery and PCI reporting system, however, found a persistently high level of repeat revascularization among patients with multivessel disease initially treated with PCI compared with CABG, even among patients receiving DES (17
TABLE 22-1 Studies Comparing Multivessel Percutaneous Coronary Intervention with Coronary Artery Bypass Grafting
Significant survival benefit of
Death or MI
CABG among diabetics
No difference among diabetics
No difference among diabetics
No difference among diabetics
Death, Stroke, MI
Trend for benefit of PCI among
Death or M
No difference among diabetics
No difference among diabetics
Death or MI
Death, stroke, MI
No difference for DES
Death, MI, stroke
Death, MI, stroke, revascularization
a The bypass angioplasty revascularization investigation (BARI) investigators. Comparison of coronary bypass surgery with angioplasty in patients with multivessel disease. N Engl J Med. 1996;335:217-225.
b Kurbaan AS, Bowker TJ, Ilsley CD, et al. Difference in the mortality of the cabri diabetic and nondiabetic populations and its relation to coronary artery disease and the revascularization mode. Am J Cardiol. 2001;87:947-950;A943.
c Rodriguez A, Mele E, Peyregne E, et al. Three-year follow-up of the argentine randomized trial of percutaneous transluminal coronary angioplasty versus coronary artery bypass surgery in multivessel disease (ERACI). J Am Coll Cardiol. 1996;27:1178-1184.
d Serruys PW, Ong AT, van Herwerden LA, et al. Five-year outcomes after coronary stenting versus bypass surgery for the treatment of multivessel disease: The final analysis of the arterial revascularization therapies study (ARTS) randomized trial. J Am Coll Cardiol. 2005;46:575-581.
e Rodriguez AE, Baldi J, Fernandez Pereira C, et al. Five-year follow-up of the argentine randomized trial of coronary angioplasty with stenting versus coronary bypass surgery in patients with multiple vessel disease (ERACI II). J Am Coll Cardiol. 2005;46:582-588.
f Hueb W, Lopes NH, Gersh BJ, et al. Five-year follow-up of the Medicine, Angioplasty, or Surgery Study (MASS II): A randomized controlled clinical trial of 3 therapeutic strategies for multivessel coronary artery disease. Circulation. 2007; 115:1082-1089.
g Booth J, Clayton T, Pepper J, et al. Randomized, controlled trial of coronary artery bypass surgery versus percutaneous coronary intervention in patients with multivessel coronary artery disease: six-year follow-up from the Stent Or Surgery trial (SOS). Circulation. 2008;118:381-388.
h Serruys PW, Morice MC, Kappetein AP, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med.2009;360:961-972.
i Kapur A, Hall RJ, Malik IS, et al. Randomized comparison of percutaneous coronary intervention with coronary artery bypass grafting in diabetic patients. 1-year results of the CARDia (Coronary Artery Revascularization in Diabetes) trial. J Am Coll Cardiol. 2010;55:432-440.
The Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) clinical trial is the largest study to date comparing stenting to surgery. The study randomized 1,800 patients with left main and/or three vessel coronary disease to CABG or PCI using paclitaxel drug-eluting stents, with the intent of achieving complete revascularization (18
). Operators were allowed to be aggressive in treating chronically occluded vessels, long lesions, bifurcations, and unprotected left main disease. Reflecting this aggressive approach, in the PCI group 63% had a bifurcation or trifurcation treated, 39.5% had left main disease, 33% of patients had more than 100 mm of stents placed, and on average 3.6 ±1.6 lesions were treated and 4.6 ± 2.3 stents were implanted per patient. A higher proportion of CABG patients had complete revascularization, 63.2% versus 56.7% (p < 0.01). While the study was designed as a non-inferiority trial, at 12 months, death from any cause, stroke, MI, or repeat revascularization was lower among CABG patients (12.4%) than the PCI group (17.8%, p < 0.01). This endpoint was almost entirely explained by revascularization since the rate of death, stroke, or MI was 7.7% for CABG versus 7.6% for PCI, p = 0.98. There were over 3 times as many strokes in the CABG group (2.2% vs. 0.6%, p < 0.01), while all-cause death and MI were not statistically different. At 3 years follow-up, the death, stroke, and MI rates remained similar between the two groups. The early difference in stroke was no longer present. The revascularization rates continued to be twice as high in the PCI group (Table 22-1
Almost all CABG patients in these studies received an internal mammary artery graft, and several patients had bilateral internal mammary grafts and full arterial revascularization, which helps to explain the lower need for repeat revascularization, as vein graft failure is as high as 40% in the first 18 months following CABG (20
). Therefore, despite improvements in the techniques and outcomes of PCI, CABG remains the standard of care for patients with multivessel and left main disease owing to its relatively lower revascularization rates. The 2011 American College of Cardiology Foundation/American Heart Association/Society for Cardiac Angiography and Interventions (ACCF/AHA/SCAI) Practice Guideline for Percutaneous Coronary Intervention recommends CABG (Class I) for patients with significant >70% stenosis in the three major coronary arteries, >50% stenosis in the left main coronary, or >70% stenosis of the proximal left anterior descending (LAD) and an additional major vessel (Table 22-2
). PCI may be acceptable, however, for such patients when the lesions are focal, the overall atherosclerotic burden is low, and the patient’s left ventricular (LV) function is normal (22
). Generally, either PCI or CABG can be chosen for treating symptomatic 2-vessel disease not involving the proximal LAD (Class IA); however, there are several patient, anatomic, and functional considerations that influence the choice of one procedure over the other. Yet these revascularization strategies are far from mutually exclusive—with the growth of minimally invasive bypass techniques, hybrid approaches may be beneficial for specific patient subgroups. A minimally invasive approach to place a left internal mammary to LAD graft with PCI of the remaining lesions may improve the recovery time and shorten the early morbidity of surgery, while taking advantage of the superior longevity of the mammary graft (Class 2A). Several single center and registry studies have shown improved recovery time with the hybrid approach and similar outcomes to those expected by routine surgery (23
), but randomized data to evaluate the long-term major clinical outcomes of hybrid approaches, compared with multivessel PCI or conventional surgery are lacking at this time.
Given the benefit of CABG for multivessel revascularization and the guideline recommendation that CABG be preferentially considered for disease involving the left main, 3-vessels, or 2-vessels with proximal LAD artery, one key consideration for deciding on treatment for such patients is a comprehensive assessment of surgical risk. Age, diabetes, renal dysfunction, liver disease, chronic obstructive pulmonary disease, prior stroke, burden of vascular disease, and reduced LV function are among the major clinical factors that must be weighed in considering whether a patient can undergo CABG surgery. The patients enrolled in the clinical trials described previously were required to be reasonable CABG candidates, and so were at comparatively low risk for major perioperative complications.
For the individual patient, a physician must also weigh the risks of future repeat revascularization associated with PCI against the immediate risks of CABG, which may not fit within the scope of patients treated in clinical trials. Hence, a collaborative approach to decision making between interventional cardiologists, cardiac surgeons, and the patient’s general cardiologist is recommended. For patients with left main disease, 3-vessel disease, or 2-vessel disease involving the LAD in whom optimal revascularization strategy is not straightforward, a multidisciplinary “Heart Team” should evaluate the technical feasibility, risks and benefits of PCI and CABG, followed by discussion with the patient about treatment options. Patients with diagnostic angiograms demonstrating complex multivessel disease should be taken off the table to allow for a thorough discussion of surgical, percutaneous options, and medical options among the heart team (27
The Society of Thoracic Surgeons (STS) risk model for perioperative morbidity and mortality and the European System for Cardiac Operative Risk Evaluation (euroSCORE) can help risk stratify the patient, and provide a starting point for discussions among the cardiologists, surgeons, patient, and family (27
). These models provide some estimation of risk for CABG, valvular, and other thoracic surgeries by taking into account comorbidities such as age, diabetes, renal function, LV dysfunction, chronic obstructive pulmonary disease, and prior open-heart procedures, These models are by no means perfect and tend to underestimate risk due to significant conditions such as prior chest radiation, hepatic dysfunction, or pulmonary hypertension.
Beyond being a risk factor for CAD and comorbidities in general, advanced age is an important predictor of outcome following PCI, and more so following coronary artery bypass graft surgery (CABG). In the National Heart Lung and Blood Institute (NHLBI) dynamic registry, patients of advanced age (>80 years old) were twice as
likely to have 3-vessel CAD compared with younger (<65 years) patients (38% vs. 20%), and were more likely to have calcified arteries (40% vs. 20%) and undergo multivessel PCI (40% vs. 30%) (29
). Many clinical trials have excluded patients >75 years old, so trial data should only be cautiously extrapolated to the elderly population. Although coronary surgery can be safely performed in selected octogenarians, such patients are at particularly high risk for in-hospital mortality and postoperative complications (30
). In both the STS and the euroSCORE models, age is strongly weighted in calculating risk, particularly in patients >80 (31
). Thus, percutaneous revascularization may be a preferable approach even for the elderly with multivessel disease and other comorbidities.
TABLE 22-2 ACCF/AHA/SCAI Guidelines for PCI and CABG in Patients with Left Main or Multivessel Coronary Artery Disease
Unprotected Left Main Stenosis ≥ 50%
No surgical contraindication
High-risk surgical patients (STS ≥ 5%), with ostial or trunk lesion, and SYNTAX score < 22
Unstable angina/NSTEMI in nonsurgical candidates where left main is the culprit lesion
ST-elevation MI where left main is the culprit lesion
High-risk surgical patients (STS > 2%) and SYNTAX score < 33
Multivessel Disease (≥ 70% Stenosis in ≥ 2 Major Coronary Arteries)
Symptomatic 2-vessel disease despite medical therapy (not involving proximal LAD)
CABG or PCI
3-vessel disease or proximal LAD plus 1 other major artery
2-3 vessel or proximal LAD disease and LV dysfunction (EF 35%-50%) or > 20% perfusion defect
Diabetics with multivessel coronary artery disease, especially if a left internal mammary graft will be anastomosed to the LAD
2-3 vessel disease and prior CABG
Hybrid coronary revascularization (LIMA to LAD, and PCI of non-LAD vessels) if 1 of the following apply:
CABG + PCI
1. Surgical limitations
2. Lack of graft conduits
3. LAD unfavorable for PC
Non-infarct-related artery revascularization in patients with STEMI without hemodynamic compromise
Small side branch
Large side branch with disease
(Adapted from: Levine GN, et al. Circulation. 2011; 124:2574-2609, with permission.)
Nevertheless, elderly patients have more procedural complications and poor long-term outcomes after PCI compared with younger patients. Several contemporary retrospective studies of PCI in patients >80 years old, with approximately one-third undergoing multivessel interventions, found a significant graded association of age with increased in-hospital mortality, contrastinduced nephropathy, transfusion requirements, stroke, and vascular complications (32
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