Percutaneous Coronary Intervention for Unprotected Left Main Coronary Disease

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The percutaneous interventional approach for the implantation of coronary stents has been shown to be feasible for patients with unprotected left main coronary artery (LMCA) stenosis.1 In addition, drug-eluting stents (DES), together with advances in peri-procedural and post-procedural adjunctive pharmacotherapies, have improved the outcome of percutaneous coronary interventions (PCIs) for these complex coronary lesions.2–9 However, there is growing concern about the long-term safety of DES. In particular, the incidence of late stent thrombosis has been reported to be higher with DES compared with bare-metal stent (BMS) implantation.10–13 Indeed, the US Food and Drug Administration (FDA) has warned that the risk of stent thrombosis may outweigh the benefits of DES in off-label use, such as for unprotected LMCA stenosis.14 Although mid-term pilot studies have shown that, compared with BMS, DES are safe and effective for unprotected LMCA stenosis, these results were obtained in small study populations and in single centres, and after relatively short-term clinical observation.

Safety and Efficacy of Drug-eluting Stents

In a series of LMCA DES studies, the incidence of stent thrombosis at one year ranged from 0 to 4% and it was not statistically different from that with BMS.2–4 Recent pooled data comprising randomised clinical trials for native coronary lesions showed a modest increase in stent thrombosis after DES implantation than with BMS of between one and four years. However, overall incidence was not statistically different.11,12 Therefore, although it is hard to evaluate the true incidence of stent thrombosis in this particular subgroup, further studies with larger populations and longer follow-up are warranted. Until such clinical trials are complete, rigorous use of the antiplatelet combination with aspirin and thienopyridine at least for one year and meticulous follow-up of clinical features are recommended after DES placement. In particular, for patients receiving multiple complex stenting at the bifurcation or who have antiplatelet resistance, a high loading dose and lifelong administration of clopidogrel with aspirin should be considered. Indeed, bifurcation DES placement has been an independent predictor of stent thrombosis in multivariate analysis.10,13

Predictably, peri-procedural and long-term mortality depend strongly on the patient’s clinical presentation. In the ULTIMA registry, which included 279 patients treated with BMS, 46% of whom were inoperable or at high surgical risk, in-hospital mortality was 13.7% and one-year incidence of all-cause mortality was 24.2%.15 On the other hand, in the 32% of patients at low surgical risk (age <65 years, ejection fraction >30%), there were no peri-procedural deaths and a one-year mortality of 3.4%.

Similarly, with DES implantation, high surgical risk represented by high EuroSCORE or Parsonnet score was the independent predictor of death or myocardial infarction (MI).16,17 Therefore, a lot of attention should continue to be paid to the procedure for patients at high surgical risk. The PCI procedures may be best performed by experienced interventionalists with the aid of intravascular ultrasound, mechanical haemodynamic support and optimal adjunctive pharmacotherapies after judicious selection of patients.

Compared with BMS, DES reduced the incidence of angiographic restenosis and subsequently the need for repeat revascularisation in unprotected LMCA stenosis.2–4 In the early pilot studies, the one-year incidence of repeat revascularisation in DES implantation was 2–19%, compared with 12–31% with BMS. In the long-term study to two years, the incidence of repeat revascularisation remained steady and without significant observation of the ‘late catch-up’ phenomenon of late restenosis noted after coronary brachytherapy.18

The risk of restenosis was significantly influenced by lesion location. DES treatment in the ostial and shaft LMCA lesions had a very low incidence of angiographic or clinical restenosis.19 In a study including 144 patients with ostial or shaft stenosis in three cardiac centres, angiographic restenosis and target vessel revascularisation at one year occurred in one (1%) and two (1%) patients, respectively. Although the lack of availability of DES sizes bigger than 3.5mm imposed an overdilation strategy to match LMCA reference diameter, there was no incident of cardiac death, MI or stent thrombosis in the study.

An important limitation of DES implantation for unprotected LMCA stenosis has been the involvement of distal bifurcation. In the previous studies the majority of repeat revascularisations were performed in patients with bifurcation stenosis.2–4 A recent study assessing the outcomes of LMCA DES showed that the risk of target vessel revascularisation was six-fold (95% confidence interval [CI] 1.2–29) in bifurcation stenosis compared with non-bifurcation stenosis (13 versus 3%).16 The risk of bifurcation stenosis was highlighted in a recent study by Price et al. in which the target lesion revascularisation rate after sirolimus-eluting stent implantation was 44%.5 In the study, 94% of patients (44 of 50) had lesions at the bifurcation and 98% underwent serial angiographic follow-up at three and/or nine months. This discouraging result questioned the efficacy of DES and brought about the need for meticulous surveillance of angiographic follow-up in PCI for LMCA bifurcation stenosis.

However, the study was limited by the exclusive use of complex stenting strategy (two stents in both branches) in 84% of patients, which may increase the need for repeat revascularisation. Although there has been debate about it,20 a recent report proposed a probability that the complex stenting technique might be associated with high occurrence of restenosis compared with the simple stenting technique.21 Taken together, before the novel treatment strategy is settled, the simple stenting approach (LMCA to left anterior descending artery with optional treatment in the circumflex artery) is primarily recommended in patients with relatively patent or diminutive circumflex arteries. In addition, we hope that future stent platforms specifically designed for bifurcation lesions will provide better scaffolding and more uniform drug delivery to the bifurcation LMCA stenosis.

Comparison with Bypass Surgery

It is surprising to note that current guidelines for unprotected LMCA treatment, in which elective PCI for patients who are treatable with bypass surgery is a contraindication,22 are based mostly on the 20-year-old clinical trials.23,24 These studies demonstrated a definite benefit of survival of coronary artery bypass grafts (CABGs) in LMCA stenosis compared with medical treatment. However, application of these results to the current practice may not be appropriate because the surgical technique, as well as medical treatment, in these studies was outdated by today’s standards, and no randomisation studies between PCI and CABGs have been conducted. The lack of data on the current CABG procedure used in unprotected LMCA stenosis further precludes a theoretical comparison of the two revascularisation strategies.

Currently, several non-randomised studies comparing the safety and efficacy of DES treatment for unprotected LMCA stenosis with CABGs have been published.6,7,25 In the early series of studies comprising small study populations, the outcomes of PCI with DES showed comparable incidences of death or MI but a higher risk of repeat revascularisation compared with CABGs. A recent large registry study supported the early studies with a novel statistical adjustment using propensity-score matching.26 In the MAIN-COMPARE (revascularization for unprotected left MAIN coronary artery stenosis: COMparison of Percutaneous coronary Angioplasty versus surgical REvascularization) study, overall 2,240 patients who underwent PCI or CABG in Korea were recruited.

In 542 pairs of patients matched with propensity score, the risk of death (hazard ratio 1.18, 95% CI 0.77–1.80) and the risk of the composite outcome (hazard ratio 1.10, 95% CI 0.75–1.62) were not significantly different for patients undergoing PCI versus CABG. The rates of target-vessel revascularisation were significantly higher in the PCI group (hazard ratio 4.76, 95% CI 2.80–8.11). Similar results were obtained in comparisons of BMS with concurrent CABGs and of DES with concurrent CABGs.


The current registry studies, although limited by the non-randomised study design, have demonstrated promisingly the procedural and mid-term safety and effectiveness of DES compared with BMS or CABG. With these attempts, in our opinion, the use of PCI with DES will progressively increase and can be recommended as a reliable alternative to bypass surgery for patients with unprotected LMCA stenosis, especially as the first-line therapy for ostial or shaft stenosis. Although bifurcation stenosis remains challenging for the percutaneous approach, we are still optimistic because further research on the novel procedural technique, a new dedicated stent platform and optimal pharmacotherapies may improve the outcomes. In addition, we hope that with the upcoming randomised clinical trials comparing PCI with CABGs for unprotected LMCA stenosis, more confidence in the long-term safety, durability and efficacy of PCI will be achieved in the near future.


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