Author + information
- Received March 31, 2015
- Revision received April 28, 2015
- Accepted May 7, 2015
- Published online August 24, 2015.
- Joo Myung Lee, MD, MPH∗,
- Joo-Yong Hahn, MD, PhD†,
- Jeehoon Kang, MD∗,
- Kyung Woo Park, MD, PhD∗,
- Woo Jung Chun, MD, PhD‡,
- Seung Woon Rha, MD, PhD§,
- Cheol Woong Yu, MD, PhD‖,
- Jin-Ok Jeong, MD, PhD¶,
- Myung-Ho Jeong, MD, PhD#,
- Jung Han Yoon, MD, PhD∗∗,
- Yangsoo Jang, MD, PhD††,
- Seung-Jea Tahk, MD, PhD‡‡,
- Hyeon-Cheol Gwon, MD, PhD†,
- Bon-Kwon Koo, MD, PhD∗ and
- Hyo-Soo Kim, MD, PhD∗∗ ( )()
- ∗Department of Internal Medicine and Cardiovascular Center, Seoul National University Hospital, Seoul, Republic of Korea
- †Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- ‡Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea
- §Korea University Guro Hospital, Seoul, Republic of Korea
- ‖Korea University Anam Hospital, Seoul, Republic of Korea
- ¶Chungnam National University Hospital, Daejeon, Republic of Korea
- #Chonnam National University Hospital, Gwangju, Republic of Korea
- ∗∗Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
- ††Yonsei University Severance Hospital, Seoul, Republic of Korea
- ‡‡Ajou University Hospital, Suwon, Republic of Korea
- ↵∗Reprint requests and correspondence:
Prof. Hyo-Soo Kim, Department of Internal Medicine, Cardiovascular Center, Seoul National University Hospital, 101 Daehakro, Jongro Gu, Seoul 110-744, Republic of Korea.
Objectives The purpose of this study was to investigate the differential clinical outcomes after percutaneous coronary intervention (PCI) for coronary bifurcation lesions with 1- or 2-stenting techniques using first- or second-generation drug-eluting stents (DES).
Background The 2-stenting technique has been regarded to have worse clinical outcomes than the 1-stenting technique after bifurcation PCI with first-generation DES. However, there has been a paucity of data comparing the 1- and 2-stenting techniques with the use of second-generation DES.
Methods Patient-level pooled analysis was performed with 3,162 patients undergoing PCI using first- or second-generation DES for bifurcation lesions from the “Korean Bifurcation Pooled Cohorts” (COBIS [Coronary Bifurcation Stenting] II, EXCELLENT [Registry to Evaluate Efficacy of Xience/Promus Versus Cypher in Reducing Late Loss After Stenting], and RESOLUTE-Korea [Registry to Evaluate the Efficacy of Zotarolimus-Eluting Stent]). The 3-year clinical outcomes were compared between 1- and 2-stenting techniques, stratified by the type of DES.
Results With first-generation DES, rates of target lesion failure (TLF) or patient-oriented composite outcome (POCO) (a composite of all death, any myocardial infarction, any repeat revascularization, and cerebrovascular accidents) at 3 years were significantly higher after the 2-stenting than the 1-stenting technique (TLF 8.6% vs. 17.5%; p < 0.001; POCO 18.1% vs. 28.5%, p < 0.001). With second-generation DES, however, there was no difference between 1- and 2-stenting techniques (TLF 5.4% vs. 5.8%; p = 0.768; POCO 11.2% vs. 12.9%; p = 0.995). The differential effects of 2-stenting technique on the prognosis according to the type of DES were also corroborated with similar results by the inverse probability weighted model. The 2-stenting technique was a significant independent predictor of TLF in first-generation DES (hazard ratio: 2.046; 95% confidence interval: 1.114 to 3.759; p < 0.001), but not in second-generation DES (hazard ratio: 0.667; 95% confidence interval: 0.247 to 1.802; p = 0.425).
Conclusions Patient-level pooled analysis of 3,162 patients in Korean Bifurcation Pooled Cohorts demonstrated that the 2-stenting technique showed comparable outcomes to 1-stenting technique with second-generation DES, which is different from the results of first-generation DES favoring the 1-stenting technique.
- clinical outcome
- coronary bifurcation lesion
- drug-eluting stent
- percutaneous coronary intervention
Even with improvements in techniques and technologies, the coronary bifurcation lesion is still 1 of the most challenging lesion subsets in the field of percutaneous coronary intervention (PCI). Among the several procedural steps, the most important decision might be the choice between 1- and 2-stenting strategies. Previously, the consensus has been conflicting, but modestly favored the 1-stenting technique with provisional side branch intervention over the systemic 2-stenting technique for bifurcation lesions (1). Following these results, the current guidelines recommend a provisional strategy with a 1-stenting technique only as an initial approach for bifurcation lesions (Class I, Level of Evidence: A from the ACCF/AHA/SCAI 2011 guideline ; Class IIa, Level of Evidence: A from the ESC/EACTS 2014 guideline ). However, these previous results were all on the basis of studies using first-generation drug-eluting stents (DES). In real-world practice, second-generation biocompatible or biodegradable-polymer coated stents have replaced first-generation DES, and these DES have proven to have better efficacy and safety in nonbifurcation lesions (4). Thus, we can expect better results from second-generation DES than the first-generation DES also in the bifurcation subset, even using complicated strategies like the 2-stenting technique. Whether the 2-stenting technique with the use of second-generation DES will show comparable results to the 1-stenting technique is still an elusive issue in the field of bifurcation PCI. Although few previous studies (5,6) have tried to evaluate this issue, none have shown a clear answer to this question, mainly due to relatively small sample sizes.
Therefore, we sought to compare the 3-year clinical outcomes following 1- or 2-stenting techniques with the use of first- or second-generation DES with a patient-level pooled data from dedicated, large-scale, real-world registries.
Extended description of study methods are presented in the Online Appendix.
Pooled patient population
The analysis population of this study was the “Korean Bifurcation Pooled Cohorts,” which includes 3 different registries in Korea. First, the COBIS II (Coronary Bifurcation Stenting) registry (NCT01642992) is a dedicated bifurcation PCI registry with the use of first- or second-generation DES. From 2003 through 2009, 2,897 consecutive patients were enrolled from 18 major coronary intervention centers in Korea (7). The inclusion criteria were: 1) coronary bifurcation lesions treated with DES only; 2) main vessel (MV) diameter of ≥2.5 mm and side branch (SB) diameter of ≥2.3 mm confirmed by quantitative coronary angiography (QCA). Patients with cardiogenic shock, who received cardiopulmonary resuscitation, or who had protected left main (LM) disease were excluded.
The EXCELLENT (Registry to Evaluate Efficacy of Xience/Promus Versus Cypher in Reducing Late Loss After Stenting) (NCT00960648) and RESOLUTE-Korea (Registry to Evaluate the Efficacy of Zotarolimus-Eluting Stent) (NCT00960908) registries were dedicated second-generation DES registries for everolimus-eluting stents (Xience V [Abbott Vascular, Santa Clara, California]/Promus [Boston Scientific, Natick, Massachusetts]) or zotarolimus-eluting Resolute stents (Endeavor Resolute [Medtronic, Minneapolis, Minnesota]) that enrolled all-comers treated with ≥1 everolimus-eluting stent or zotarolimus-eluting Resolute stent (3,056 patients in 29 centers and 1,998 patients in 25 participating centers, respectively) without exclusions during the period of 2008 through 2010 (8). Among the total 5,054 patients from the EXCELLENT and RESOLUTE-Korea registries, 265 patients who met the inclusion criteria of the COBIS II registry were included in our analysis. These 265 patients met the same inclusion and exclusion criteria and were analyzed by the same bifurcation QCA system as the COBIS II registry.
Therefore, the final sample size of the Korean Bifurcation Pooled Cohorts was 3,162 patients. Among these patients, 2,475 were treated with first-generation DES and 687 were treated with second-generation DES (Figure 1). Every patient in the Korean Bifurcation Pooled Cohorts was followed for clinical outcomes up to 3 years (median follow-up duration 1,096.0 days, IQR: 778.8 to 1,497.0 days).
Follow-up, data collection, and analysis
Coronary angiograms were reviewed and analyzed quantitatively by an independent core laboratory at Samsung Medical Center (COBIS II registry) or Seoul National University Hospital (EXCELLENT and RESOLUTE-Korea registries). For the QCA, standardized definitions for each segment of bifurcation lesion (proximal MV, distal MV, and SB ostium) were used as previously described (7). For any clinical events, all relevant medical records were reviewed and adjudicated by an external clinical event committee. Using the Korean health system’s unique identification numbers, the vital status of 100% of patients was crosschecked. The study protocol was approved by the ethics committee at each participating center and was conducted according to the principles of the Declaration of Helsinki. All patients provided written informed consent.
Outcomes and definitions
The primary outcome was target lesion failure (TLF), a composite of cardiac death, myocardial infarction (MI) (not clearly attributed to a nontarget vessel), or a clinically indicated target lesion revascularization. The key secondary outcome, the patient-oriented composite outcome (POCO), included all-cause mortality, any MI (including nontarget vessel territory), any revascularization, and cerebrovascular accidents. All deaths were considered cardiac unless an undisputed noncardiac cause was present. Other secondary outcomes included individual components of TLF and POCO, and stent thrombosis (ST), defined as definite, probable, or possible according to the Academic Research Consortium (ARC) definitions.
The main comparison group was the 1-stenting versus 2-stenting technique, and this comparison was stratified according to the type of DES (first- or second-generation). The analysis was performed in 2 parts. First, analysis and comparison of primary and secondary clinical outcomes between the 1- and 2-stenting techniques were conducted in the original pooled patient population. Second, the comparison of clinical outcomes was repeated using an inverse probability weighted (IPW) Cox proportional hazard regression model as well as propensity score matching with a stratified Cox proportional hazard regression model to adjust for uneven distribution of baseline characteristics between the 1- and 2-stenting techniques. In addition, an IPW Cox proportional hazard model was used to identify independent predictors of the primary clinical outcome, TLF, in each stratum according to type of stent. C-statistics with 95% confidence intervals (CIs) were calculated to validate the discriminant function of the model. To assess the effect of unmeasured confounders, which could not be adjusted by IPW analysis or propensity score matched analysis, we performed Bayesian modeling with internal validation data as an additional sensitivity analysis. All probability values were 2-sided, and p < 0.05 was considered statistically significant.
Patient and lesion characteristics of the korean bifurcation pooled cohorts
The baseline characteristics of patients are shown in Table 1. Of the 3,162 patients in the Korean Bifurcation Pooled Cohorts, 2,475 patients (78.3%) were treated with first-generation DES, whereas the remaining 687 (21.7%) patients were treated with second-generation DES. Among the patients in the first-generation DES stratum, 1,802 (72.8%) and 673 (27.2%) patients were treated with the 1- and 2-stenting techniques, respectively. In the second-generation DES stratum, 409 (59.5%) and 278 (40.5%) patients were treated with the 1- and 2-stenting techniques, respectively. The proportion of true bifurcation (Medina 1,1,1; 1,0,1; or 0,1,1) were higher in the 2-stenting group in both strata of DES. Final kissing balloon inflation (FKI) in the 2-stenting group was performed in 84.7% of the first-generation DES stratum or 80.9% of the second-generation DES stratum (Table 2). Other procedural and angiographic characteristics are shown in Table 2. Regardless of the type of DES, SB lesions in QCA were significantly longer and more stenotic in the 2-stenting group (Table 3). In addition, post-interventional residual percent diameter stenosis in SB was significantly milder in the 2-stenting group (Table 3). When comparing patients enrolled in the COBIS II and EXCELLENT/RESOLUTE-Korea registries, the patients enrolled from the EXCELLENT and REOLUTE-Korea registries showed more severe risk factor profiles, higher SYNTAX scores, higher proportion of true bifurcation lesions, and more usage of 2-stenting techniques (Online Tables 1 and 2).
Clinical outcomes between 1- versus 2-stenting techniques using first- or second-generation DES
In the first-generation DES stratum, the incidence of TLF was significantly higher in the 2-stenting technique group compared with the 1-stenting technique group (8.6% vs. 17.5%; hazard ratio [HR]: 2.08; 95% CI: 1.64 to 2.64; p < 0.001), mainly driven by higher incidences of MI and TLR. In the second-generation DES stratum, however, TLF was comparable between the 2 groups (5.4% vs. 5.8%; HR: 0.91; 95% CI: 0.47 to 1.74; p = 0.659), along with similar rates of MI and TLR. The POCO showed a similar trend to that of TLF; POCO was significantly higher in the 2-stenting technique group of the first-generation DES stratum, but was comparable between the 1- and 2-stenting technique groups in the second-generation DES stratum (Table 4, Figure 2). The individual components of TLF are presented in Figure 3.
The results of the IPW Cox proportional hazard model comparing clinical outcomes between the 1- and 2-stenting techniques in each DES stratum showed a similar trend with the unadjusted results; there was no difference in clinical outcomes after the 1- and 2-stenting technique in second-generation DES (Table 4, Figure 4).
The rates of ARC-defined definite or probable ST were significantly higher in the 2-stenting group using first-generation DES even after the adjustment of baseline differences (IPW adjusted HR: 3.77; 95% CI: 1.95 to 7.28; p < 0.001). With the use of second-generation DES, however, there was no difference of ST between the 1- and 2-stenting techniques (IPW adjusted HR: 1.60; 95% CI: 0.47 to 5.48; p = 0.451).
The comparison of clinical outcomes in the propensity score-matched population showed similar results to the IPW Cox proportional hazard model (Online Tables 3 and 4). The results from the Bayesian analysis to assess the impact of unmeasured confounders were consistent with the original unadjusted analysis, inverse probability weighted analysis, and propensity score matched analysis, suggesting a robustness of the results (Online Table 5).
In addition, there was no difference regarding the rates of TLF or POCO among various 2-stenting techniques (T-stenting, crush, culotte, kissing, or V-stenting), regardless of DES type (Online Table 6).
Restenosis pattern in left main bifurcation subgroup after 1- versus 2-stenting technique using first- or second-generation DES
Among the total population, 27.8% (n = 689) and 31.1% (n = 214) of patients were treated for LM bifurcation lesions in the first- and second-generation DES stratum, respectively (Table 2). Through the 3-year follow-up period, the incidence of TLR in LM bifurcation was 10.7% (first-generation DES stratum, 74 of 689 patients) and 5.6% (second-generation DES stratum, 12 of 214 patients). The incidence of TLR was significantly reduced with second-generation DES compared with first-generation DES (p = 0.025).
The patterns of TLR sites in MV and SB were markedly different between the first- and second-generation DES stratum, and the locations of TLR site in LM bifurcation are shown in Figure 5. In the first-generation DES stratum, the main restenosis site was the proximal MV after the 1-stenting technique compared with the SB after the 2-stenting technique. In the second-generation DES stratum, however, restenosis mainly occurred at SB after 1-stenting whereas it occurred evenly and rarely both at the MV and SB (Figure 5).
In addition, the rates of TLR were also different between the 1- and 2-stenting techniques according to the type of DES. In first-generation DES, the 2-stenting technique showed significantly higher rates of TLR than 1-stenting (5.5% vs. 17.8%; p < 0.001). However, there was no difference in TLR rates between the 1- and 2-stenting techniques in second-generation DES (6.7% vs. 3.8%; p = 0.361) (Figure 5).
Independent predictors for target lesion failure according to type of stents
Independent predictors for 3-year TLF are presented in Table 5. The 2-stenting technique was significantly associated with higher incidence of TLF in the first-generation DES stratum (HR: 2.046; 95% CI: 1.114 to 3.759; p = 0.021), but not in the second-generation DES stratum (HR: 0.667; 95% CI: 0.247 to 1.082; p = 0.425). Unlikely from the results of first-generation DES, LM bifurcation was still an independent predictor for TLF in the second-generation DES stratum. In terms of anatomical factors, MV reference diameter was a protective factor in first-generation DES, whereas SB minimum lumen diameter was a protective factor in second-generation DES. Both models showed an acceptable range of discriminant function (Table 5).
A patient-level pooled analysis of 3,162 patients in the Korean Bifurcation Pooled Cohorts, which explored 3-year clinical outcomes following 1- or 2-stenting techniques using first- or second-generation DES, has demonstrated: 1) the 2-stenting technique showed significantly worse TLF or POCO than the 1-stenting technique using first-generation DES; 2) however, the 2-stenting technique using second-generation DES showed comparable results up to 3-year follow-up with the 1-stenting technique; 3) the rate of ARC-defined definite or probable ST was significantly higher after the 2-stenting technique with first-generation DES, but there was no difference between the 1- and 2-stenting techniques using second-generation DES; 4) the 2-stenting technique was an independent predictor of TLF only in the first-generation DES group; and 5) in the real-world practice of bifurcation PCI with second-generation DES, all independent predictors were patient-related comorbidities, without any procedure-related factors such as 1- or 2-stenting technique.
An old paradigm regarding the 2-stenting strategy in the first-generation DES era
Although there have been some conflicting results, previous studies comparing a 1- and 2-stenting strategy showed worse clinical outcomes after the 2-stenting strategy using first-generation DES. There have been 6 randomized controlled trials (RCTs) (9–14), and these studies showed a tendency toward worse clinical outcomes in the 2-stenting group compared with the 1-stenting group, mainly driven by MI (15). A patient-level pooled analysis of the NORDIC and BBC-ONE (British Bifurcation Coronary Study: Old, New, and Evolving strategies) trials reported that at 9 months, the incidence of the composite endpoint of all-cause mortality, MI, and target vessel revascularization (TVR) was significantly higher in the complex PCI group with a 2-stenting technique than the simple PCI group (10.1% vs. 17.3% in simple vs. complex group; HR: 1.84; 95% CI: 1.28 to 2.66; p = 0.001) (16). In addition, the meta-analysis of Zhang et al. (17) also reported worse outcomes for the complex group due to a significantly higher incidence of periprocedural MI and MI occurring at follow-up. On the basis of these results, the current guidelines recommend a provisional strategy of 1-stenting technique in MV only as an initial approach for bifurcation lesions.
However, these previous results do not reflect the current real-world practice, because first-generation DES are no longer used. Although second-generation DES are shown to have superior efficacy and safety to first-generation DES (4), most RCTs or meta-analyses comparing first- and second-generation DES could not represent the patients with bifurcation lesions, because the proportion of bifurcation lesions was generally <20% of the enrolled patients, even in the all-comers RCT: 17% in COMPARE (Comparison of the everolimus eluting XIENCE-V stent with the paclitaxel eluting TAXUS LIBERTE stent in all-comers: a randomized open label trial), 12.5% in SORT OUT IV (Scandinavian Organization for Randomized Trials With Clinical Outcome IV), and 10.8% in the EXCELLENT (Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting) trial (18–20). Therefore, we need more evidence regarding the performance of second-generation DES in the treatment of bifurcation lesions, especially the results of the 2-stenting technique.
An evolving paradigm regarding systemic 2-stenting strategy with second-generation DES
There have been 5 reports comparing 1- with 2-stenting techniques using second-generation DES, which showed vast discrepancies across studies (5,6,15,21–23). In the subgroup analysis from the RESOLUTE ALL COMERS trial, 382 patients received bifurcation PCI (310 treated with the provisional approach and 82 treated by systemic 2-stenting) (6). At 2-year follow-up, TLF rates were numerically but not statistically higher in those receiving the 2-stenting technique, mainly due to significantly higher rates of target-vessel MI, which were mostly periprocedural. The bifurcation substudy of the SPIRIT V (A Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Patients With de Novo Coronary Artery Lesions) registry showed that those who underwent stent implantation (n = 90) into the SB (and who thus ultimately had received the 2-stenting technique) showed a higher incidence of TLR (6.9% vs. 0.6%; log rank p = 0.0028), compared with those receiving simple balloon inflation (24,25). These 2 studies suggest that, similar to the data from first-generation DES, 2-stenting results are worse than the 1-stenting technique even with second-generation DES. In contrast, some studies reported at least a trend toward favorable outcomes of the 2-stenting technique (5,23). The DKCRUSH-II (Double Kissing Crush versus Provisional Stenting Technique for Treatment of Coronary Bifurcation Lesions) trial, exclusively using the everolimus-eluting bioabsorbable stent (EXCEL stent, JW Medical System, Weihai, China), randomly assigned 370 patients with true bifurcation lesions (Medina 1,1,1 or 0,1,1) to either the double kissing double crush technique or provisional 1-stenting technique (21). The rates of TLR (4.3% vs. 13.0%; p = 0.005) or TVR (6.5% vs. 14.6%; p = 0.017) were significantly lower in the 2-stenting groups at 12-month follow-up, whereas the incidence of major adverse cardiovascular events, MI, and definite or probable ST were comparable between the 2 groups. The Nordic-Baltic Bifurcation Study IV, which randomly assigned 450 patients to the 2- or 1-stenting group, also showed similar trends with numerically lower but statistically insignificant rates of major adverse cardiovascular events (cardiac death, nonprocedural MI, TLR, or definite ST), TLR, or TVR at 6 months in the 2-stenting technique groups (5).
Although there may be several reasons for the discrepancies across different studies, a relatively small number of patients and substantial proportion of non–true bifurcation lesion without any disease in the SB might be potential confounders that diluted the true differences between 2 different stenting strategies. In this regard, we demonstrated longer-term clinical outcomes from the Korean Bifurcation Pooled Cohort, the largest sample size of an unrestricted population that reflects real-world practice of bifurcation PCI.
It should be noted that even bifurcation lesions with the same Medina classification can significantly differ with regard to ostial SB lesion severity, SB lesion length, angulation between MV and SB, SB size, and the corresponding myocardial territory (22). This fact implies that the treatment strategy should be individualized in every patient with bifurcation lesions, and that universal application of provisional 1-stenting approach should be reconsidered. The comparable outcomes of the 2- and 1-stenting technique with second-generation DES may support the complete coverage of the lesion, especially in case of the subtended myocardial territory of the SB is sufficiently large, rather than the effort to minimize metallic burden due to fear of delayed endothelialization and subsequent detrimental events, which were mainly observed in first-generation DES.
Some important factors that may have contributed to improved clinical outcomes with the 2-stenting technique should be considered. There has been mounting evidence that contemporary techniques improved clinical outcomes in bifurcation PCI. Main technical advances include the use of proximal optimization technique (POT), noncompliant (NC) balloon for FKI, intravascular ultrasound-guided PCI, or mandatory FKI in the 2-stenting technique (23,26). In the current study, we observed a substantial increase of adjunctive NC ballooning after the 2-stenting technique using second-generation DES (28.4% in the first-generation DES group vs. 66.9% in the second-generation DES group). Although the exact proportion of POT among cases with adjunctive NC ballooning in the main vessel could not be assessed due to the missing data of POT performance in each registry, the increased proportion of adjunctive NC ballooning in the main vessel suggests the increased use of POT as well. These technical advances might be another important factor in the improvement of clinical outcomes after the 2-stenting technique, besides the use of second-generation DES.
In addition, most of the independent predictors for TLF in second-generation DES were patient or lesion-related factors, such as peripheral artery disease, chronic renal failure, or LM bifurcation lesion, but not device or procedural techniques. This result emphasizes the importance of general medical treatment for comorbidities and optimal patient or lesion selection for the success of bifurcation PCI.
In this regard, it should be noted that LM bifurcation lesions are still a significant predictor for TLF even with the use of second-generation DES. The distal LM bifurcation lesion has shown worse clinical outcomes than ostial or shaft lesions (27). There are some possible explanations for the significant prognostic effect of LM bifurcation lesions even in second-generation DES. First, this is a result of the clinical importance and relatively lower threshold of repeat revascularization of SB in LM bifurcation lesions. Another factor is the unique anatomic feature of LM bifurcation lesions. It is difficult to accurately assess the segment and conduct optimal revascularization of the LM lesion due to several factors, such as its short length, the presence of overlapping daughter branches, the concealment of diffuse atherosclerosis due to arterial remodeling, the distinct lack of a reference segment, and reverse tapering pattern of the LM lesion (26). In addition, LM bifurcation lesions usually showed a wider bifurcation angle, which has been shown to be an independent predictor of major adverse cardiac events, especially in the crush or culotte stenting, whereas no such association was observed in the 1-stenting technique group (28). Indeed, the bifurcation angle was significantly wider in LM bifurcation lesions compared with non-LM bifurcation lesions, regardless of 1- or 2-stenting technique or first- or second-generation DES group in the current study (83.1 ± 27.4° vs. 56.5 ± 18.9°; p < 0.001). This geometric uniqueness of LM bifurcation lesions might be 1 potential explanation of why the LM lesion is an independent predictor of TLF in second-generation DES. Whether the second- or third-generation DES will improve the outcome after distal LM bifurcation PCI compared with CABG is still unknown. Currently, 2 large ongoing trials (EXCEL [Evaluation of Xience Prime versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization] [NCT01205776] and NOBLE [Nordic-Baltic-British Left Main Revascularization] [NCT01496651]) would clarify this issue.
First, the inherent limitations of nonrandomized comparisons such as allocation bias and uneven distribution of risk factors should be considered. Although an inverse probability weighted Cox regression model was used to adjust the baseline differences, and the results from the Bayesian analysis were consistent with the original analysis, unmeasured variables such as improvements in bifurcation PCI technique (i.e., POT, general medical treatment) and other potential confounders could not be completely controlled. Second, the incidences of clinical events, especially MI, were relatively lower than in previous studies on bifurcation PCI. Although the possibility of under-reporting of the events cannot be ignored, it has been consistently reported that the incidence of MI is substantially lower in Asian populations than in Western populations (14,20,29). Third, it should be noted that the proportion of FKI was relatively lower in the 2-stenting technique using first-generation DES (84.7%) or 2-stenting with second-generation DES (80.9%) than in previous trials such as BBK (Bifurcations Bad Krozingen) (100%), CACTUS (Coronary Bifurcations: Application of the Crushing Technique Using Sirolimus-Eluting Stents) (92%), or DKCRUSH-II (100%), which compared 1- and 2-stenting strategies. Optimal FKI is mandatory, especially in the 2-stenting strategy (25). However, because there was no statistical difference regarding the proportion of FKI in the 2-stenting technique group between first- and second-generation DES, the confounding effect should be minimal. Fourth, we mainly focused on the comparison of clinical outcomes after bifurcation PCI with the 1- or 2-stenting technique. Although the operator decided the provisional 1-stenting strategy for the bifurcation PCI, additional implantation of a stent in SB is sometimes required. Among the total 3,162 patients, 8.2% (n = 260) were treated with the 2-stenting technique in spite of an initial decision of provisional 1-stenting strategy. We incorporated these patients into the 2-stenting group to clarify the differences of clinical outcomes between 1- and 2-stenting techniques. The incorporation of these patients to the 1-stenting technique group as initially assigned did not alter the overall results presented in the paper. Last, we could not evaluate the procedural time, radiation dose, and amount of contrast agents used. Although 2-stenting with second-generation DES showed comparable outcomes to the 1-stenting technique, the operator should consider the risk-benefit ratio related to a successful procedure and complete lesion coverage versus increased radiation and contrast dose when using the 2-stenting procedure.
Our patient-level pooled analysis of 3-year clinical results from 3,162 patients in the Korean Bifurcation Pooled Cohorts demonstrated that the 2-stenting technique showed comparable outcomes to a 1-stenting technique with second-generation DES, which is different from the results of first-generation DES that favored the 1-stenting technique. Such an improved performance of second-generation DES, even after a complex technique for bifurcation lesions, may provide room for a more aggressive approach for the selected bifurcation lesions with appropriate anatomy and sufficiently large subtended myocardium supplied by SB, rather than universal application of the 1-stenting strategy.
WHAT IS KNOWN? The 2-stenting technique has shown worse clinical outcomes than the 1-stenting technique after bifurcation PCI with first-generation DES. In real-world practice, second-generation biocompatible or biodegradable polymer-coated stents have replaced first-generation DES; however, there has been a paucity of data comparing 1- and 2-stenting techniques with the use of second-generation DES. A patient-level pooled analysis of 3,162 patients in the Korean Bifurcation Pooled Cohorts demonstrated the differential prognostic effect of a 2-stenting strategy between first- and second-generation DES.
WHAT IS NEW? The 2-stenting technique using second-generation DES showed comparable clinical outcomes, including stent thrombosis, target lesion revascularization, myocardial infarction, and mortality, up to 3-year follow-up compared with the 1-stenting technique.
WHAT IS NEXT? Such an improved performance of second-generation DES, even after a complex technique for bifurcation lesions, may provide room for a more aggressive approach for the selected bifurcation lesions with appropriate anatomy and sufficiently large subtended myocardium supplied by SB, rather than universal application of the 1-stenting strategy.
For a supplemental Methods section and supplemental tables, please see the online version of this article.
This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A102065) and a grant from the Innovative Research Institute for Cell Therapy, Seoul National University Hospital (A062260), sponsored by the Ministry of Health, Welfare & Family, Republic of Korea. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- confidence interval
- drug-eluting stent(s)
- percutaneous coronary intervention
- patient-oriented composite outcome
- target lesion failure
- Received March 31, 2015.
- Revision received April 28, 2015.
- Accepted May 7, 2015.
- American College of Cardiology Foundation
- Latib A.,
- Colombo A.
- Levine G.N.,
- Bates E.R.,
- Blankenship J.C.,
- et al.
- Windecker S.,
- Kolh P.,
- Alfonso F.,
- et al.
- Palmerini T.,
- Biondi-Zoccai G.,
- Della Riva D.,
- et al.
- ↵Kumsars I, Niemelä M, Erglis A, et al. Randomized comparison of provisional side branch stenting versus a two-stent strategy for treatment of true coronary bifurcation lesions involving a large side branch. Paper presented at: Transcatheter Cardiovascular Therapeutics; October 27 to November 1, 2013; San Francisco, CA.
- Diletti R.,
- Garcia-Garcia H.M.,
- Bourantas C.V.,
- et al.
- Hahn J.Y.,
- Chun W.J.,
- Kim J.H.,
- et al.
- Lee J.M.,
- Park K.W.,
- Han J.K.,
- et al.
- Colombo A.,
- Moses J.W.,
- Morice M.C.,
- et al.
- Ferenc M.,
- Gick M.,
- Kienzle R.P.,
- et al.
- Colombo A.,
- Bramucci E.,
- Sacca S.,
- et al.
- Hildick-Smith D.,
- de Belder A.J.,
- Cooter N.,
- et al.
- Maeng M.,
- Holm N.R.,
- Erglis A.,
- et al.
- Behan M.W.,
- Holm N.R.,
- Curzen N.P.,
- et al.
- Zhang F.,
- Dong L.,
- Ge J.
- Smits P.C.,
- Kedhi E.,
- Royaards K.J.,
- et al.
- Jensen L.O.,
- Thayssen P.,
- Christiansen E.H.,
- et al.
- Park K.W.,
- Chae I.H.,
- Lim D.S.,
- et al.
- Chen S.L.,
- Santoso T.,
- Zhang J.J.,
- et al.
- Dzavik V.,
- Kaul U.,
- Guagliumi G.,
- et al.
- Teirstein P.S.,
- Price M.J.
- Song Y.B.,
- Hahn J.Y.,
- Yang J.H.,
- et al.
- Park K.W.,
- Kang S.H.,
- Kang H.J.,
- et al.