Study Overview
Objective. To compare the effectiveness and safety profiles of various second-generation drug-eluting stents (DES) for left main coronary intervention.
Design. Retrospective study using 3 multicenter prospective registries (IRIS-DES, IRIS-MAIN, PRECOMBAT).
Setting and participants. Among the 4470 patients enrolled in the 3 registries treated between July 2007 and July 2015, the authors identified 2692 patients with significant left main coronary artery disease who received second-generation DES for inclusion in the study. The centers for IRIS-DES and PRECOMBAT are academic and community hospitals in South Korea, with IRIS-MAIN involving academic and community hospitals in South Korea, China, India, Indonesia, Japan, Malaysia, Taiwan, and Thailand. Of the patients in these registries, 1254 received cobalt-chromium everolimus-eluting stents (CoCr-EES), 232 biodegradable polymer biolimus-eluting stents (BP-BES), 616 platinum-chromium EES (PtCr-EES) and 590 Resolute zotarolimus-eluting stents (Re-ZES).
Main outcome measure. Target-vessel failure.
Main results. At 3 years, rates of target-vessel failure were not significantly different for the different types of stents (16.7% for the CoCr-EES, 13.2% for the BP-BES, 18.7% for the PtCr-EES, and 14.7% for the Re-ZES; P = 0.15). The adjusted hazard ratios (HRs) for target-vessel failure were similar in between-group comparisons of the different stents, except for the PtCr-EES versus the BP-BES (HR 1.60, 95% confidence interval 1.01 to 2.54; P = 0.046). There were no significant differences in risk of composite of all-cause death, any myocardial infarction, or any revascularization and its individual components according to the different types of stents.
Conclusion. There was no significant between-group differences in 3-year risk of target-vessel failure, except for a higher risk of primary outcome with PtCr-EES compared to BP-BES.
Commentary
Left main coronary artery disease is identified in 5% to 7% of the population and is one of the more perplexing lesions to treat given the poorer outcome compared to non–left main lesion and the importance of the vessels the left main supplies [1]. Historically, coronary artery bypass grafting (CABG) has been the standard of care on the basis of the survival benefit observed in early trials compared with medical therapy. Left main percutaneous coronary intervention (PCI) has evolved as an alternative to CABG over the past few decades. Early studies using balloon angioplasty or bare metal stents were limited primarily due to high restenosis rate [1]. In the DES era, results have been overall comparable to CABG. Unprotected left main PCI using first-generation DES was non-inferior compared to CABG in the pre-specified sub-study of SYNTAX trial and in PRECOMBAT trial using paclitaxel-eluting stents and sirolimus-eluting stents, respectively [2,3]. Largely based on these trials, the 2014 ACC/AHA guidelines give class IIa recommendation for patients with low-risk anatomy (Syntax score 0–22) and class IIb recommendation for patients with intermediate-risk anatomy (Syntax score 23–32) for left main PCI [4]. Moreover, European guidelines give class Ib recommendation for patients with low-risk anatomy, and class IIa recommendation for intermediate-risk anatomy for left main PCI [5]. However, the SYNTAX trial and PRECOMBAT trial were limited by not meeting non-inferiority (SYNTAX) and wide non-inferiority (PRECOMBAT) and selection bias due to large exclusion criteria. In addition, first-generation DES were used in these trials (tacrolimis-eluting stent for SYNTAX and sirolimus-eluting stent for PRECOMBAT). The standard of care has now shifted to wide use of second-generation DES [1].
Subsequently, 2 larger-scale clinical trials using second-generation DES were designed and results have been reported recently [6,7]. The EXCEL trial enrolled 1905 patients with significant left main coronary disease and compared CoCr-EES to CABG. At 3 years, the primary endpoint of a composite of death from any cause, stroke, or myocardial infarction occurred in 15.4% of the PCI patients and in 14.7% of the CABG patients (P = 0.02 for non-inferiority; P = 0.98 for superiority). Similarly, the NOBLE trial enrolled 1201 patients with significant left main coronary disease and compared PCI to CABG. In this trial, the biolimus-eluting second-generation stent became their preferred stent during the study period. At 5 years, the primary endpoint of a composite of all-cause mortality, non-procedural myocardial infarction, any repeat coronary intervention, and stroke was higher in PCI compared to CABG patients (28% vs 18%, HR 1.51, 95% CI 1.13–2.00), exceeding the limit of non-inferiority, and CABG was significantly better compared to PCI (P = 0.004). The difference in the results is likely due to trial design. The primary endpoint was different in the 2 studies—EXCEL did not include repeat coronary intervention in the composite endpoint. The NOBLE study had a longer enrollment period and earlier-generation stents (sirolimus-eluting) were used in the earlier stages of the trial. In addition, the NOBLE study did not assess for peri-procedural myocardial infarction as an endpoint, which is known to be associated with adverse outcome. In both trials, cardiovascular mortality and all-cause mortality were similar at the end of follow-up.
In this context, the Lee et al study compared 4 types of currently available second-generation stents by pooling data from 3 large registries in Asia [8]. The main finding from this study was that target-vessel failure, defined as the composite of cardiac death, target-vessel myocardial infarction, or target-vessel revascularization at 3 years follow-up was not different among the types of second-generation drug eluting stents (P = 0.15).
Another important finding from this study was that the stent thrombosis rate at follow-up was very low (< 1%). This is consistent with the EXCEL study, which reported a definite stent thrombosis rate of 0.7% and was lower than in the NOBLE study, which reported a rate of 3%. One of the possible explanations for this difference could be stent selection. In contrast to the EXCEL study, which exclusively used Co-Cr EES by study protocol, NOBLE
study included first-generation sirolimus-drug eluting stent (11%) and BP-BES (89%). However, there are multiple factors that contribute to stent thrombosis other than stent selection, such as lesion characteristics, adequate stent expansion, and use of dual antiplatelet therapy [9].
The observed finding of small increase in target-vessel failure in PtCr-EES versus the BP-BES needs to be interpreted with caution. First, this was an observational study, and the treatment strategy or choice of stent was determined by a local interventional cardiologist, which could lead to selection bias. Although the authors performed propensity analysis, residual cofounding is likely. Second, since there was no difference in the primary analysis, the subgroup analysis becomes less important. In addition, authors did not perform statistical correction for multiple comparisons.
Despite the above limitations, this large-scale observational study gives us important insights to the performance of each second-generation DES. All currently available second-generation DES appear to be an option for use for left main coronary intervention.
Applications for Clinical Practice
In patients presenting with significant left main disease, left main PCI using a contemporary second-generation stent is safe and effective and likely has equivalent outcomes to CABG. However, PCI may be associated with higher rate of repeat revascularization. The rate of target-vessel failure was similar between different types of second-generation DES.
—Taishi Hirai, MD, and John E.A. Blair, MD, University of Chicago Medical Center, Chicago, IL