Clinical results of stenting in patients chosen for PCI, either because of prohibitive surgical risk or as a bailout for angioplasty complications, depend mainly upon baseline clinical characteristics, such as left ventricular function and coexisting conditions. The ULTIMA registry enrolled 279 patients with unprotected LMCA stenosis who were treated with bare-metal stents (BMS); of these, 46% were inoperable or at high surgical risk. Among these high-risk patients, the in-hospital mortality was 13.7%, and the 1-year incidence of all-cause mortality was 24.2%; whereas among the 32% patients at low risk (age < 65 years, ejection fraction > 30%), there were no periproce-dural deaths and the 1-year mortality rate was only 3.4%.3 In a series of elective, low-risk patients, who were also not at increased risk for CABG, PCI with BMS for unprotected LMCA disease showed favorable short- or mid-term outcomes (in-hospital mortality, 0-4.3%; mortality at 6-12 months, 2.5-10.8%).4-8 However, considerable risks of restenosis (18-31%) and repeat revascularization (7.3-33.6%) have limited the durability of LMCA stenting with BMS, because the development of restenosis in such patients may lead to worst-case outcomes, such as sudden death or acute MI.

With advances in stenting techniques, the availability of DES, and adjuvant pharmacotherapy such as clopidogrel, statins and antiplatelet therapy, many experienced interventional cardiologists now perform PCI with stenting for patients with unprotected LMCA disease. Several observational studies, although limited by its non-randomized nature, small number of patients, and short follow-up periods, have shown promising PCI outcomes using DES compared with BMS.9-11 Most initial reports documented that DES afforded higher procedural success rates as well as lower rates of angiographic restenosis and TVR, with similar or lower rates of death and MI compared to BMS.

In a direct comparison, 103 patients with unprotected LMCA disease were randomly assigned to receive BMS (n = 50) or DES (n = 53) implantation and were followed for 6 months, at which time the DES group showed a statistically significant reduction in binary restenosis (6% vs. 22%) and target-lesion revascularization (TLR) (2% vs. 16%), as well as a significant reduction in the rate of major adverse cardiac events (death, MI, or TLR; 13% vs. 30%), all of which were entirely attributable to reduction in repeat revascularization rate.12

Recently, concerns have been raised regarding the long-term safety of DES, with particular regard to late stent thrombosis and late mortality.13-15 Increasing concern over stent thrombosis, which may have more catastrophic consequences in patients undergoing unprotected LMCA stenting, and a lack of long-term clinical data, have hampered the widespread use of PCI with DES as an alternative to CABG.

However, recent data alleviate concerns about the safety of PCI with DES in the treatment of unprotected LMCA disease.16-18 A recent multicenter registry evaluated the occurrence of late and very late stent thrombosis in 731 patients undergoing elective LMCA stenting with DES.16 At 30 months, four patients had definite stent thrombosis (two acute, one subacute, and one late) and three had probable thrombosis, for a combined incidence of definite or probable thrombosis of 0.95%. The cumulative rates of death, MI, and TVR were 6.2%, 1.5%, and 12.9%, respectively. Older age, lower ejection fraction, and EuroSCORE were identified as predictors of thrombotic events. A report from the DELFT registry, which included 358 patients undergoing LMCA stenting with a minimum of 3 years follow-up, noted that the incidence of definite, probable, and possible stent thrombosis were 0.6%, 1.1%, and 4.4%, respectively.17 Among the overall registry population, cardiac death occurred in 9.2% of patients, and MI, TLR, and TVR were noted in 8.6%, 5.8%, and 14.2% of patients, respectively. Compared to emergent PCI, elective PCI was associated with excellent 3-year rates of mortality (6.2% vs. 21.4%), reinfarction (8.3% vs. 10.0%), and TLR (2.8% vs. 6.6%). In a recent clinical study, the ISAR-LEFT MAIN trial, in which 607 patients were treated with DES, the 2-year rate of definite or probable stent thrombosis was about 0.5-1.0%. In a large real-world observation (the MAIN-COMPARE registry), the incidence of definite thrombosis at 3 years was 0.6%.18 These results indicated that DES implantation in patients with unprotected LMCA disease results in relatively lower, or, at worst, similar rates of stent thrombosis and long-term mortality than seen when DES is used in subsets of patients with other coronary lesion.19

To prevent stent thrombosis, dual antiplatelet therapy is emphasized, and clopidogrel (75 mg daily) is recommended for at least 1 year in patients treated with DES who are not at an increased risk of bleeding.20 The long-term benefits of clopidogrel use beyond 6 or 12 months are, however, unclear in such patients.21-23 Although the risk-benefit ratio of long-term clopidogrel therapy is not well-studied, many clinicians prolong dual antiplatelet therapy for up to several years or indefinitely after LMCA stenting with DES. Despite the various durations of applied clopidogrel treatment (at least 3 months, to life),16-18 the overall incidence of early and late stent thrombosis were very low, and similar among studies. Additional studies with large populations and longer-term follow-ups are warranted to evaluate the antithrombotic benefit vs. major bleeding risk of long-term clopidogrel use, and to determine the optimal duration of clopidogrel therapy after DES placement in patients with LMCA disease.

To date, a large body of data supports the feasibility, efficacy, and safety of stenting as compared with CABG for treatment of unprotected LMCA disease. We also expect that longer-term (5-year and 10-year) data will soon be forthcoming.

Although several studies have reported on the mid-term safety and feasibility of stenting in LMCA disease, long-term benefits of PCI compared with bypass surgery are less clear, in part because they have been evaluated less extensively. Several, small observational studies have compared PCI with stenting of unprotected LMCA to CABG.25-28 The early clinical events of left main stenting are similar or superior to those of bypass surgery because of a significant increase in periprocedural MI25 or cerebrovascular events26 in the CABG patients. Longer-term mortality up to approximately 1 year was similar in the PCI and the CABG groups. However, the risk of TVR was consistently higher with PCI than with CABG.

The MAIN-COMPARE registry is the first long-term study comparing PCI with stenting with bypass surgery for LMCA disease.18 This study evaluated 2,240 patients with unprotected LMCA disease who underwent stenting (BMS, 318 and DES, 784) or CABG (1,138) at 12 major cardiac centers in Korea, where left-main stenting is far more common than in Western countries. Outcome measures were compared during the first 3 years after treatment and included death; a composite outcome of death, Q-wave MI, or stroke; and TVR using propensity-score matching. The risks of death and the composite of death, Q-wave MI, or stroke were similar in the PCI and CABG groups and these results were consistent when either BMS or DES was compared with concurrent CABG. However, the rate of TVR was significantly lower in the CABG group than in the PCI group with hazard ratios varying by the type of stent. DES recipients were almost 6-fold more likely, and BMS recipients almost 10-fold more likely, to require revascularization, compared to those who underwent surgery.

The LeMANS trial was the first randomized comparison of PCI with stenting (52 patients) and CABG (53 patients) for the treatment of unprotected LMCA stenosis, with or without multivessel CAD.29 DES were placed in 35% of PCI patients and left internal mammary artery grafts were used in 72% of CABG patients. At 1 year, the primary endpoint of absolute change in left ventricular ejection fraction was significantly greater in the PCI than in the CABG group (3.3 ± 6.7% vs. 0.5 ± 0.8%; p = 0.047), whereas the secondary endpoints, survival and MACCE, were comparable in the two groups. Although this was a prospective, randomized initial trial comparing outcomes of stenting versus CABG for LMCA disease, the results were limited by the small number of patients and the non-specific and inconclusive primary endpoint chosen to evaluate treatment effects.

As shown in the left main subsets (348 patients treated with CABG and 357 treated with PES) from the SYNTAX (SYNergy Between PCI With TAXUS and Cardiac Surgery) trial,30 PCI demonstrated 1-year clinical outcomes equivalent to those seen after standard bypass surgery. In particular, PCI-treated patients showed a trend towards lower MACCE rates in cases with anatomically simple LMCA disease (LMCA only and LMCA plus single-vessel disease), compared with CABG-treated patients. The rate of revascularization was significantly higher in PCI-treated patients, whereas the stroke risk was significantly greater in CABG-treated patients. However, due to the exploratory, hypothesis-generating nature of subgroup analysis, results from more specific LMCA-targeted trials are needed. The ongoing PRECOMBAT (PREmiere of COMparison of Bypass Surgery and Angioplasty Using Sirolimus-Eluting Stents in Patients With Unprotected Left Main Coronary Artery Disease) trial, which is a prospective, multicenter, randomized study to compare the safety and efficacy of SES and CABG for treatment of unprotected LMCA disease with a primary study end-point of 1-year MACCE (death, MI, stroke, and TVR), is expected to provide a more definitive evaluation of the two primary interventions.

A recent meta-analysis, which considered results of 16 observational studies on 1,278 patients undergoing PCI with DES for unprotected LMCA disease, showed a low in-hospital mortality rate of 2.3% and a low mid-term mortality rate of 5.5% at a median of 10 months follow-up, as well as adjusted odds ratios for MACCE (death, MI, TVR, or stroke) of 0.46 (0.24-0.90), favoring PCI with DES over CABG.31 In contrast, another systemic review suggested that early (in-hospital, to 30 days) and longer-term (1-2 year) mortality rates were better after CABG (early, 2-4%, average 3%; late, 5-6%, average 5%) than PCI with BMS (early, 0-14%, average 6%; late, 3-31%, average 17%) or DES (early, 0-10%, average 2%; late, 0-14%, average 7%).32 However, these results should be interpreted with caution and regarded as only exploratory findings, given the limited number of patients, selection or publication bias in the literature reviewed, and caveats on internal validity of the included clinical studies.