outcome is less dependent on the complexity and diffuseness of lesions than PCI, and when a graft is placed, the whole proximal 6–8 cm of the coronary artery is protected from MI induced by plaque rupture (Table 3.3). Keep in mind that plaque ruptures and acute coronary occlusions occur overwhelmingly in the proximal third of the coronary arteries, a segment protected by CABG (80-90% of acute LAD and LCX plaque ruptures are in the proximal 5 cm).78 Hence, CABG is consistently associated with a lower risk of MI and angina recurrence than PCI. Even when MI occurs after CABG, it is less likely to be fatal and more likely a small MI, as compared with patients receiving medical therapy or PCI (CASS registry, BARI trial, and SYNTAX trial).79
Table 3.3 Reasons for superiority of CABG vs. PCI.
| CABG success is much less affected by the anatomical complexity (e.g., CTO) and the diffuseness of CADWhile PCI treats focal disease, a graft improves flow to the whole coronary territory, including segments with moderate diffuse disease, and protects from MI resulting from occlusion of the proximal 6–8 cm coronary segment. Plaque ruptures and acute coronary occlusions occur overwhelmingly in the proximal 5 cm of coronary arteriesVery long longevity of LIMA graftMore complete revascularization with CABG (vessels with CTO are sometimes left untreated in a multivessel PCI strategy) |
BARI and ARTS trials – In the balloon angioplasty era, the BARI trial randomized very select patients with focal multivessel CAD to CABG vs. PCI. In comparison with PCI, CABG dramatically reduced mortality in diabetic patients by an absolute 16% at 5 years, and dramatically reduced repeat revascularizations in all patients.80 The benefit on repeat revascularizations was shown in the BMS era as well (ARTS trial).81 The superiority of CABG was seen despite the very careful selection of patients with non-extensive CAD amenable to PCI (<10% of screened patients were randomized to CABG vs. PCI).
Isolated proximal LAD disease – A meta-analysis of randomized trials of CABG vs. PCI for isolated proximal LAD disease suggests the lack of mortality difference, although repeat revascularizations were much lower with CABG (pre-DES era).82
SYNTAX trial – In the DES era, the SYNTAX trial randomized patients with three-vessel and/or left main disease to CABG vs. PCI with DES. This trial included patients with extensive, complex CAD, and graded the angiographic severity of CAD using the SYNTAX score. In the overall trial, at 5 years of follow-up, CABG was associated with a significant reduction in MI (~10% vs. 4%), a marked reduction in the need for repeat revascularizations (26% vs. 14%), but no mortality difference (13.9% vs. 11.4%). CABG significantly reduced mortality by an absolute 8% in the high SYNTAX scores (>32).83,84 Conversely, patients with a low SYNTAX score (≤22) had comparable death, MI and even repeat revascularization rates with CABG and PCI, whether they had three-vessel or left main disease. Regarding 5- and 10-year mortality, CABG and PCI were equipoise for the left main subset (=left main +1, 2 or 3-vessel CAD), but CABG reduced mortality in 3-vessel CAD without left main. Interestingly, CABG outcomes were not affected by SYNTAX score, i.e., CABG success and post-CABG survival were not affected by angiographic complexity, in contradistinction with PCI. The only pitfall of CABG was the higher early risk of stroke (2.2% vs. 0.6% at 1 year).
The SYNTAX score assigns a number for the location of each stenosis (e.g., left main 5, proximal LAD 3.5, proximal LCx 1.5, OM 1, RCA 1), and multiplies this number by 2 in case of a 50–99% stenosis, and 5 in case of a CTO. Additional points are added at every lesion for tri- or bifurcation, long disease, calcium, and CTO complexity. Overall, the score emphasizes proximal stenoses (especially LAD) and angiographic complexity, especially CTO.
FREEDOM trial – Diabetic patients with two- or three-vessel CAD involving the LAD were randomized to CABG vs. PCI with DES.85 At 5 years of follow-up, CABG significantly reduced mortality vs. PCI, almost as much as in the high SYNTAX group of SYNTAX trial (16.3% vs. 10.9%). It reduced MI (~14% vs. 6%) at the price of an increase in postoperative stroke and a higher early postoperative mortality. The benefit in these diabetic patients was consistent across all SYNTAX score groups, including the low SYNTAX group.
EXCEL and NOBLE trials of left main disease- Both EXCEL and NOBLE trials specifically randomized patients with left main disease and mainly low or intermediate SYNTAX score (≤32) to CABG vs. PCI; 81% of patients had distal left main disease, and 15-29% had diabetes. In both trials, CABG was slightly superior to PCI at 5 years of follow-up.86,87 In EXCEL, the 5-year composite death/MI/stroke was not different, but CABG slightly yet significantly reduced mortality (13 vs. 9.9%), nonprocedural MI (6.8 vs. 3.5%), and repeat revascularizations (target and non-target, 16.9 vs 10%). In the CABG group, the composite outcome was increased in the first 30 days but reduced beyond 30 days (survival curves crossed at 1 year). In NOBLE, CABG significantly reduced the primary outcome, which included repeat revascularizations (28.9% vs 19%), and reduced nonprocedural MI, but did not reduce mortality.
For three-vessel CAD- Both SYNTAX and FREEDOM trials support CABG. PCI is an option in patients with a low SYNTAX score ≤22 and no diabetes.
For left main disease- Both EXCEL and NOBLE trials support PCI as an alternative to CABG, including in complex distal left main. In fact, PCI seems a more viable option in left main disease than complex 3-vessel CAD, as per SYNTAX left main analysis. PCI is associated with lower early stroke and periprocedural MI, but higher late MI and revascularizations.
Note some of the features of the SYNTAX, FREEDOM, NOBLE and EXCEL trials:
LVEF was normal or >40% in almost all patients. Very few patients had HF (4% in SYNTAX trial).
Patients with acute MI, including large acute NSTEMI, were excluded. The superiority of CABG is extrapolated to those patients whose event rates are higher than stable CAD.
While the CABG benefit on repeat revascularization emerges early within the first year, the survival and MI benefit only starts to emerge beyond 2 years of follow-up, after an early perioperative hazard (in all trials). This benefit appeared sooner in the high SYNTAX score group in SYNTAX trial. Overall, this implies that CABG mainly applies to patients who are expected to have a long longevity (e.g., > 3–4 years).
Near consistent increase in the risk of stroke with CABG (by an absolute ~2%).
Patients with prior stroke were essentially excluded from these trials. In fact, very few patients had carotid disease. Yet, despite this, CABG led to a higher risk of stroke than PCI, which is expected to be even higher in patients with prior stroke or carotid disease.
Randomized patients were relatively young (median age ~65).
Thus, these trials do not necessarily prove the superiority of CABG in a sicker population: older patients, higher prevalence of stroke, lower expected longevity, severe LV dysfunction or HF. In SYNTAX trial, elderly patients (>70) had similar 5- and 10-year mortality with CABG and PCI, and even similar combined cardiovascular events, despite a high mean SYNTAX score of 30, while patients <70 had a reduction in mortality and events with CABG.88,89 Similarly when an older but also sicker population was randomized to CABG vs. PCI in the VA-AWESOME trial, the 6-month survival was better with PCI, and the 5-year survival was equivalent with both strategies.90 In the VA-AWESOME trial, patients had at least one of the following: age >70 (50%), MI <7 days (33%), EF ≤35% (20%), prior CABG (33%). Thus, PCI still has a role in ill patients with multivessel CAD and comorbidities who are deemed at a high surgical risk.
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