Two-Year Outcomes and Predictors of Target Lesion Revascularization for Non-Left Main Coronary Bifurcation Lesions Following Two-Stent Strategy With 2nd-Generation Drug-Eluting Stents

Abstract

Background: Data on outcomes of non-left main coronary bifurcation lesions treated with the 2-stent strategy using 2nd-generation drug-eluting stents (DES) are insufficient.

Methods and Results: The 2-year outcomes and predictors of target lesion revascularization (TLR) in 356 patients with 364 non-left main coronary bifurcation lesions treated with the 2-stent strategy using 2nd-generation DES were retrospectively evaluated. The primary outcome measure was defined as TLR. The median follow-up duration was 3.6 years (interquartile range, 2.7–4.9 years). A 2-year clinical follow-up was achieved in 99.2%. The 2-year cumulative incidence of TLR was 9.2%. Multiple stents implanted in either the main branch (adjusted odds ratio [OR] 3.01; 95% confidence interval [CI]: 1.37–6.62; P=0.006) or the side branch (adjusted OR 4.55; 95% CI: 1.99–10.4; P<0.001) and the culprit in the left anterior descending artery and its diagonal branch (adjusted OR 0.33; 95% CI: 0.15–0.75: P=0.008) were independent predictors of TLR within 2 years.

Conclusions: The 2-year outcomes for the 2-stent strategy using 2nd-generation DES in non-left main coronary bifurcation lesions were acceptable. Coronary bifurcation location in the left anterior descending artery and its diagonal branch is protective against TLR, whereas multiple stents implanted in either the main branch or the side branch was associated with TLR.

Coronary bifurcation lesions have a significantly higher cumulative incidence of adverse events than non-bifurcation lesions.¹ Adverse events have occurred particularly in patients with bifurcation lesions treated with the 2-stent strategy,² and therefore the current guidelines recommend the provisional 1-stent strategy.³ However, there are certain situations in which the 2-stent strategy should be considered, such as true bifurcation lesions with a side branch dominating a large area of the myocardium. Data on outcomes and predictors of target lesion revascularization (TLR) in patients treated with the 2-stent strategy using 2nd-generation drug-eluting stents (DES) alone are insufficient. Also, long-term outcomes after non-left main bifurcation 2-stenting need clarification because the treatment strategy and its indication appear to be different between left main and non-left main coronary bifurcation lesions. Hence, we aimed to evaluate the 2-year outcomes and predictors of TLR in patients treated with the 2-stent strategy using 2nd-generation DES for non-left main coronary bifurcation lesions.

Methods

Study Sample and Protocol

The study sample retrospectively included 356 consecutive patients with 364 non-left main coronary bifurcation lesions treated with the 2-stent strategy using 2nd-generation DES between 2010 and 2014. Clinical follow-up was censored by death and loss to follow-up. A 2-year clinical follow-up was achieved in 353 patients (99.2%). Angiographic follow-up was scheduled 8 and 20 months after the procedure because the 2-stent strategy has been reported as an independent risk factor of both early- and late-term TLR.⁴ Early-term angiography was defined as angiography within 1 year after the procedure. Late-term angiography was defined as angiography between 1 and 2 years after the procedure. Early-term angiography was performed in 309 patients with 309 lesions (86.8%). Of the 286 patients with 286 lesions without TLR within 1 year, 239 patients with 239 lesions underwent late-term angiography (83.6%). Angiographic outcomes were assessed by early- and late-term angiograms, respectively (Figure 1). Bifurcation lesions were classified according to the Medina classification.⁵ Clinical outcomes were collected by either examining hospital charts or asking patients, their family members or referring physicians. All the patients were advised to continue dual-antiplatelet therapy with aspirin (100 mg/day) and thienopyridine (clopidogrel, 75 mg/day or prasugrel, 3.75 mg/day) for at least 8 months after the procedure. The study was conducted in accordance with the provisions of the Declaration of Helsinki and the guidelines for epidemiological studies issued by the Ministry of Health, Labor and Welfare of Japan. Informed consent was given for both the procedure and subsequent data collection and analysis for research purposes. The study was approved by the institutional ethics committee.

Figure 1.

Study flow chart. TLR, target lesion revascularization.

Interventional Procedure

The interventional procedure was performed according to the current guidelines.⁶ The 2nd-generation DES included Xience^® (everolimus-eluting; Abbot Vascular, Santa Clara, CA, USA), Promus Element^TM (everolimus-eluting; Boston Scientific, Natick, MA, USA), Resolute^TM (zotarolimus-eluting; Medtronic, Santa Rosa, CA, USA), and Nobori^® (biolimus-eluting; Terumo, Tokyo, Japan) stents. The 2-stent strategy was defined as deployment of at least 1 stent in both the main and side branches of a bifurcation lesion. Multiple stents were defined as at least 2 stents deployed in either the main branch or the side branch.

Clinical Outcome Measures

The primary outcome measure was TLR, which was defined as any repeat percutaneous coronary intervention or coronary artery bypass surgery because of either (1) angiographic diameter stenosis ≥50% and symptoms or objective signs of ischemia or (2) angiographic diameter stenosis ≥70% without symptoms or objective signs of ischemia. Other clinical outcome measures included all-cause death, cardiac death, myocardial infarction (MI), and stent thrombosis (ST). Cardiac death included any death from mainly cardiac causes, unwitnessed death, death of unknown cause, and all deaths related to concomitant treatment. MI and ST were defined according to the Academic Research Consortium definitions.⁷ Spontaneous MI was defined as infarction related to ischemia caused by a primary coronary event together with elevated cardiac enzymes (troponin or creatine kinase-MB fraction) greater than the upper limit of normal. Periprocedural MI was defined as cardiac enzymes (troponin or creatine kinase-MB fraction) elevated 3-fold more than the upper limit of normal within 48 h after the procedure.

Angiographic Outcome Measures

Quantitative coronary angiography (QCA) analysis by QCA-CMS (Medis Medical Imaging Systems, Leiden, The Netherlands) was independently conducted by 2 experienced observers who were blinded to the clinical characteristics of the patients. The 2-part measurement of bifurcation lesions was performed as follows: the first was the main branch ranging from the proximal stem to the distal main branch with boundaries defined as 5 mm proximal and distal to the stent-implanted area; the second was the side branch ranging from the bifurcation carina to the distal side branch with boundaries defined by the carina and 5 mm distal to the stent-implanted area. Binary restenosis was defined as stenosis occupying ≥50% of the diameter. Late restenosis was defined as late-term diameter stenosis ≥50% in lesions with <50% diameter stenosis in the early term. Late lumen loss was defined as the minimal lumen diameter (MLD) immediately after the procedure minus the MLD at early angiographic follow-up. Delayed late lumen loss was defined as the MLD at early angiographic follow-up minus the MLD at late angiographic follow-up. Restenosis patterns were classified according to the Mehran classification,⁸ and restenosis sites were also identified. Restenosis at bifurcation sites was defined as restenosis within 5 mm from a stent-implanted bifurcation lesion in both the main and side branches.

Statistical Analysis

Data are presented as mean±standard deviation for continuous variables and compared using Student’s t-test or the Wilcoxon rank-sum test based on the distribution of the variables. Numbers and percentages are reported for categorical variables and were compared using the chi-square test. The cumulative incidences of clinical events were estimated by the Kaplan-Meier method and compared using the log-rank test. Predictors of TLR were analyzed on a per-lesion basis using a multivariable logistic regression model instead of a Cox proportional hazard model because the timing of TLR depends on the physician’s or patient’s decision. Variables with a P-value <0.05 in the univariate models were selected as candidates for the multivariate models. Stepwise multivariate logistic regression analysis was applied to obtain the final model to individuate the independent variables associated with TLR and expressed as odds ratio (OR) and 95% confidence interval (CI). We analyzed the data without adjusting correlations between patients with and without multiple bifurcation lesions because only 2% (8/356 patients) had multiple bifurcation lesions, but we used a generalized estimating equations model to assess the robustness of the final model as a sensitivity analysis taking the correlation into account. Data were analyzed using IBM SPSS Statistics 23 (Armonk, NY, USA) and SAS 9.4 (SAS Institute Inc., Cary, NC, USA). Two-tailed P-values <0.05 were considered statistically significant.

Results

Patients’ Baseline Characteristics

Most of the patients were elderly, had diabetes mellitus and multivessel disease. The most common culprit vessel in bifurcation lesions was the left anterior descending artery (LAD) and its diagonal branch (61.2%). Nearly all the lesions (97.2%) were true bifurcation lesions. Culotte stenting was used in 81.0% and T-stenting in 19.0% (Table 1).

Table 1. Baseline Characteristics of Study Patients Undergoing 2-Stent Strategy With 2nd-Generation DES

Number of patients	356
Patients’ characteristics
Age (years)	70.7±10.4
≥80 years	75 (31)
Men	283 (80)
Hypertension	276 (78)
Diabetes mellitus	154 (43)
Insulin-treated diabetes	40 (11)
Dyslipidemia	239 (67)
Current smoking	56 (16)
eGFR <60 (mL/min/1.73 m2) and non-HD	159 (45)
HD	12 (3)
Previous PCI	134 (38)
Previous MI	120 (34)
Previous CABG	12 (3)
Peripheral vascular disease	19 (5)
ACS	109 (31)
Multivessel disease	206 (58)
Left main disease	49 (14)
No. of lesions	364
Lesion characteristics
Treated bifurcation
LAD/Dg	223 (61.3)
RCA/branch	63 (17.3)
LCX/OM	78 (21.4)
Medina classification
(1,1,1)	270 (74.2)
(1,0,1)	12 (3.3)
(1,1,0)	5 (1.4)
(0,1,1)	72 (19.8)
(1,0,0)	1 (0.3)
(0,1,0)	2 (0.5)
(0,0,1)	2 (0.5)
True bifurcation	354 (97)
Main branch
Severe calcification	53 (15)
In-stent restenosis lesion	10 (3)
Long lesion (≥30 mm)	102 (28)
Side branch
Severe calcification	37 (10)
In-stent restenosis lesion	2 (1)
Long lesion (≥30 mm)	29 (8)
Procedural characteristics
Stenting strategy
Culotte stenting	295 (81)
T-stenting	69 (19)
Rotablator atherectomy	20 (6)
IVUS use	211 (58)
Final kissing balloon inflation	364 (100)
Main branch
Multiple stents	110 (30)
Stent size ≤2.5 mm	158 (43)
Stent length ≥30 mm	147 (40)
Non-compliant balloon use	341 (94)
Side branch
Multiple stents	57 (16)
Stent size ≤2.5 mm	284 (78)
Stent length ≥30 mm	65 (18)
Non-compliant balloon use	273 (75)
Quantitative coronary angiographic analysis
Preprocedure
Main branch
Reference diameter, mm	2.90±0.43
Minimal lumen diameter, mm	0.68±0.56
Percent diameter stenosis, %	75.4±19.7
Lesion length, mm	25.6±12.2
Side branch
Reference diameter, mm	2.53±0.39
Minimal lumen diameter, mm	0.72±0.45
Percent diameter stenosis, %	69.8±18.5
Lesion length, mm	17.8±9.1
Postprocedure
Main branch
Minimal lumen diameter, mm	2.55±0.45
Percent diameter stenosis, %	16.3±9.2
Acute gain, mm	1.87±0.70
Side branch
Minimal lumen diameter, mm	2.12±0.37
Percent diameter stenosis, %	20.9±10.3
Acute gain, mm	1.41±0.52

Data are expressed as number (%) unless otherwise indicated. ACS, acute coronary syndrome; CABG, coronary artery bypass grafting; DES, drug-eluting stent; Dg, diagonal branch; eGFR, estimated glomerular filtration rate; HD, hemodialysis; IVUS, intravascular ultrasound; LAD, left anterior descending coronary artery; LCX, left circumflex coronary artery; MI, myocardial infarction; OM, obtuse marginal branch; PCI, percutaneous coronary intervention; RCA, right coronary artery.

Clinical Outcomes

The median follow-up duration was 3.6 years (interquartile range, 2.7–4.9 years). The 2-year cumulative incidence of TLR was 9.2%, and those of other clinical outcome measures were as follows: all-cause death, 8.2%; cardiac death, 3.7%; MI, 6.8%; and definite or probable ST, 1.1% (Figure 2). Definite ST occurred in 4 cases, all of which had an early onset. No intravascular-imaging device was used when the 2-stent strategy was performed, although dual-antiplatelet therapy was continued in all 4 cases (Table S1). No cases of definite or probable very late ST occurred in the entire cohort (Table 2).

Figure 2.

Cumulative incidence of target lesion revascularization (TLR).

Table 2. Cumulative Incidence (1- and 2-Year) of Clinical Events

	1-year, n (%)	2-year, n (%)
TLR	23 (6.7)	31 (9.2)
All-cause death	17 (4.8)	29 (8.2)
Cardiac death	10 (2.8)	13 (3.7)
Any MI	24 (6.8)	24 (6.8)
Periprocedural MI	18 (5.2)	18 (5.2)
Spontaneous MI	6 (1.7)	6 (1.7)
Any ST	5 (1.4)	6 (1.7)
Definite ST	4 (1.1)	4 (1.1)
Probable ST	0 (0)	0 (0)
Possible ST	1 (0.3)	2 (0.7)

MI, myocardial infarction; ST, stent thrombosis; TLR, target lesion revascularization.

Predictors of TLR

Predictors of TLR within 2 years after the procedure were assessed by univariate and multivariate analyses. Univariate analysis showed 3 patient-associated, 4 lesion-associated, and 3 procedure-associated factors with P<0.05 (Table 3). A difference in the 2-year cumulative incidence of TLR was not detected among stent types (Figure S1). Multivariate analysis showed that multiple stents implanted in either the main branch (adjusted OR 3.01; 95% CI: 1.37–6.62; P=0.006) or the side branch (adjusted OR 4.55; 95% CI: 1.99–10.4; P<0.001) and the culprit in the LAD and its diagonal branch (adjusted OR 0.33; 95% CI: 0.15–0.75; P=0.008) were independent predictors of TLR within 2 years (Table 3, Figure 3).

Table 3. Predictors of TLR Within 2 Years of Stenting

	Incidence of TLR		Univariate analysis		Multivariate analysis
	(+) (n=31)	(−) (n=333)	OR	P value	OR	95% CI	P value
Patients’ characteristics
Age ≥80 (years)	16.1%	21.0%	0.72	0.52
Men	90.3%	77.8%	2.67	0.10
Hypertension	77.4%	76.9%	1.03	0.95
Diabetes mellitus	45.2%	42.6%	1.11	0.79
Insulin-treated diabetes	19.4%	10.2%	2.11	0.12
Dyslipidemia	61.3%	68.2%	0.74	0.43
Current smoking	16.1%	15.9%	1.02	0.98
eGFR <60 (mL/min/1.73 m2) and non-HD	54.8%	42.9%	1.61	0.20
HD	3.2%	3.3%	0.98	0.98
Previous PCI	51.6%	36.3%	1.87	0.09
Previous MI	32.3%	33.9%	0.93	0.85
Previous CABG	9.7%	3.6%	3.46	0.06
Cerebral infarction	6.5%	7.8%	0.81	0.79
Peripheral vascular disease*	12.9%	4.5%	3.14	0.04
ACS*	12.9%	32.4%	0.31	0.02	0.39	0.13–1.18	0.10
Multivessel disease	51.6%	58.6%	0.76	0.45
Left main disease*	25.8%	12.6%	2.41	0.04
Lesion characteristics
Culprit in LAD/Dg*	35.5%	63.7%	0.31	0.002	0.33	0.15–0.75	0.008
True bifurcation	96.8%	97.3%	0.83	0.87
Main branch
Angulated lesion	9.7%	16.8%	0.53	0.30
Severe calcification	12.9%	14.7%	0.86	0.78
In-stent restenosis lesion*	9.7%	2.1%	4.99	0.01
Long lesion (≥30 mm)	35.5%	27.3%	1.46	0.33
CTO lesion	22.6%	12.3%	2.08	0.11
Side branch
Angulated lesion	22.6%	23.7%	0.94	0.89
Severe calcification	6.5%	10.5%	0.59	0.47
In-stent restenosis lesion*	3.2%	0.3%	11.1	0.04
Long lesion (≥30 mm)*	38.7%	15.9%	4.12	0.002
CTO lesion	9.7%	7.8%	1.27	0.71
Procedural characteristics
Femoral approach	51.6%	58.9%	0.75	0.43
Culotte stenting	83.9%	80.8%	1.24	0.68
Rotablator atherectomy	6.5%	5.4%	1.21	0.81
IVUS use	41.9%	59.5%	0.49	0.06
Main branch
Multiple stents*	54.8%	27.9%	3.13	0.002	3.01	1.37–6.62	0.006
Stent size ≤2.5 mm	48.4%	42.9%	1.25	0.56
Stent length ≥30 mm	54.8%	39.0%	1.90	0.09
Non-compliant balloon use	93.5%	93.7%	0.98	0.98
Side branch
Multiple stents*	41.9%	13.2%	4.74	<0.001	4.55	1.99–10.4	<0.001
Stent size ≤2.5 mm	71.0%	78.7%	0.66	0.32
Stent length ≥30 mm*	38.7%	15.9%	3.34	0.002
Non-compliant balloon use	75.7%	67.7%	0.68	0.33

*Potential independent risk-adjusting variables selected for stepwise multivariate logistic regression analysis. CTO, chronic total occlusion. Other abbreviations as in Tables 1,2.

Figure 3.

Independent predictors of target lesion revascularization (TLR) within 2 years. ACS, acute coronary syndrome; CI, confidence interval; Dg, diagonal branch; LAD, left anterior descending artery; MB, main branch; OR, odds ratio; SB, side branch; TLR, target lesion revascularization.

Angiographic Outcomes

The median intervals of serial QCA studies were as follows: early term, 8.2 (interquartile range, 8.2–8.5) months and late term, 20.5 (interquartile range, 20.3–20.7) months. The overall rates of binary restenosis in the early and late terms were 22.0% (68/309 lesions) and 9.2% (22/239 lesions), respectively. The focal restenosis pattern was dominant in both the early and late terms (70.6% and 72.7%, respectively). Bifurcation restenosis in the side branch accounted for more than half of the restenosis lesions in both the early and late terms (Figure 4). Late luminal loss was 0.33±0.68 mm in the main branch and 0.34±0.52 mm in the side branch. Delayed late luminal loss was 0.12±0.39 mm in the main branch and 0.09±0.40 mm in the side branch.

Figure 4.

Restenosis location in bifurcation lesions in the early and late terms. MB, main branch; SB, side branch. When a double location of restenosis was detected, both were counted as restenosis. In the early term, restenosis in both the MB and SB occurred in 9 bifurcation lesions. In the late term, restenosis in both the MB and SB occurred in 2 bifurcation lesions.

LAD vs. Non-LAD Stratum

The 2-year cumulative Kaplan-Meier curves showed a significantly lower rate of TLR in LAD bifurcation lesions than in non-LAD bifurcation lesions (5.3% vs. 15.1%, respectively; log-rank P<0.001) (Figure 5A). The binary restenosis rate of the main branch in the early term was significantly lower in LAD bifurcation lesions than in non-LAD bifurcation lesions (4.8% vs. 13.3%, respectively; P=0.007), whereas that in the late term showed no significant difference; that of the side branch showed no significant difference in either the early or late term (Figure 5B).

Figure 5.

(A) Cumulative incidence of TLR in LAD and non-LAD bifurcation lesions. (B) Angiographic binary restenosis in the main and side branches compared between LAD and non-LAD bifurcation lesions. (C) Cumulative incidence of TLR in lesions with and without multiple stents. (D) Angiographic binary restenosis in the main and side branches compared between lesions with and without multiple stents. LAD, left anterior descending artery; MB, main branch; SB, side branch; TLR, target lesion revascularization. When restenosis occurred in both the MB and SB, both were counted as binary restenosis in each branch. In the early term, restenosis in both the MB and SB occurred in 2 bifurcation lesions in the LAD and 7 bifurcation lesions in the non-LAD. In the late term, it occurred in 1 lesion in the LAD and 1 lesion in the non-LAD. In the early term, restenosis in both the MB and SB occurred in 7 lesions treated with multiple stents and lesion not treated with multiple stents. In the late term, it occurred in 1 lesion treated with multiple stents and 1 lesion without multiple stents.

Multiple vs. Non-Multiple Stents Stratum

The 2-year cumulative Kaplan-Meier curves showed a significantly lower rate of TLR in lesions not treated with multiple stents than in those treated with multiple stents (2.5% vs. 18.6%, respectively; log-rank P<0.001) (Figure 5C). The overall rate of binary restenosis was significantly different in the early term (17.6% vs. 28.9%, respectively; P=0.02), but was not significantly different in the late term (6.6% vs. 13.8%, respectively; P=0.06). A significant difference existed in the restenosis rate of the main branch in the early term (Figure 5D). The difference in restenosis location was also seen in terms of bifurcation restenosis in the early term, in addition to distal or edge restenosis in the early and late terms (Table S2, Figure S2). In patients treated with multiple stents, distal restenosis at overlapping sites occurred in 25.0% (3/12 lesions) in the early term and in 14.3% (1/7 lesions) in the late term.

Discussion

The main findings of this study were: (1) 2-year clinical and angiographic outcomes of non-left main coronary bifurcation lesions treated with the 2-stent strategy using 2nd-generation DES were acceptable; (2) multiple stents implanted in either the main branch or the side branch and the culprit lesion in the LAD and its diagonal branch were independent predictors of TLR within 2 years; and (3) significant differences in angiographic outcomes, especially in restenosis of the main branch in the early term, existed between lesions treated with multiple stents and those not treated with multiple stents, and also between LAD and non-LAD bifurcation lesions.

Recent randomized controlled trials demonstrated that clinical outcomes of bifurcation lesions treated with the 2-stent strategy were favorable irrespective of the type of strategy, showing cumulative incidences of TLR between 2% and 6% per year.^9,10 In the present study, the cumulative incidence of TLR was consistent with that reported by those trials. It was also remarkable that there were no cases of definite or probable very late ST during the follow-up period of our study. In a meta-analysis, the 2-stent strategy was associated with increased risk of ST compared with the 1-stent strategy; however, 1st-generation DES were mainly used in the studies analyzed.¹¹ Palmerini et al reported that 2nd-generation DES implantation was associated with a lower risk of definite ST compared with 1st-generation DES implantation.¹² The use of 2nd-generation DES might reduce the risk of ST even when using the 2-stent strategy.

In the SIRTAX (Sirolimus-Eluting Versus Paclitaxel-Eluting Stents for Coronary Revascularization) study, overlapping 1st-generation DES were associated with adverse clinical and angiographic outcomes.¹³ In a recent pooled analysis, clinical and angiographic outcomes of overlapping 2nd-generation DES were comparable to those of non-overlapping DES,¹⁴ but relatively simple lesions were treated. In bifurcation lesions treated with the 2-stent strategy, multiple stents implanted in each branch appeared to aggravate the lesions by placing a high load and causing a greater vascular response.

Although retrospective cohort studies have revealed that the 2-stent strategy for left main coronary bifurcation lesions increases the risk of TLR compared with the 1-stent strategy,^15,16 clinical outcomes of non-left main coronary bifurcation lesions were similar in 1- and 2-stent strategies.¹⁷ These findings indicate that coronary bifurcation locations have a clinical effect on the outcomes following the 2-stent strategy. A subanalysis has demonstrated that bifurcation angles are associated with clinically adverse events following left main bifurcation 2-stenting.¹⁸ In an observation from the j-Cypher registry, the side branch angulation of the LAD and its diagonal branch was sharper than that of left main bifurcation lesions,¹⁹ which may also have affected the clinical outcomes in our study. In addition, coronary artery motion and the degree of coronary hinge motion during the cardiac cycle have been reported to be larger in the right coronary and left circumflex arteries than in the LAD.^20,21 The mechanical stimulation might have acceralated neointimal hyperplasia, especially at bifurcation sites of non-LAD bifurcation lesions. The 2-stent strategy creates a serious problem for subsequent treatment of recurrent restenosis because multiple layers of stents exist in the coronary artery. In a previous study, the 1-stent strategy after the use of a paclitaxel-coated balloon in patients with bifurcation lesions had favorable outcomes up to 4 months.²² The use of a paclitaxel-coated balloon in the side branch may have a more favorable outcome, especially in non-LAD bifurcation lesions in which multiple stenting can be avoided.

Two angiographic studies have revealed that the major restenosis location treated with the 2-stent strategy was the side branch ostium.^16,17 In our angiographic findings, the restenosis rate in the ostial side branch remained high, even with the use of 2nd-generation DES. A more suitable type of DES that can mimic bifurcation geometry and prevent carina displacement is awaited. Contrastingly, the rates of late restenosis and late adverse events beyond 1 year have reduced. When using the 2-stent strategy, 2nd-generation DES have been reported as the most negative predictor of target vessel failure.²³ In the 2-stent strategy subset of patients, using 2nd-generation DES may produce better late-term clinical and angiographic outcomes than 1st-generation DES.

Study Limitations

First, this was a retrospective observational study. Second, possible selection bias existed because of each operator’s preference for the type of stent or procedure. Third, the optimal 2-stent strategy is not proposed because most of the lesions were treated by culotte stenting. Fourth, the sample size was too small to evaluate such low-frequency events as ST and MI. Fifth, follow-up coronary angiography might have increased the cumulative incidence of TLR. The Kaplan-Meier curve of TLR actually showed a steep increase at 8 months. Finally, we used single-vessel QCA software instead of dedicated bifurcation QCA software.²⁴ Moreover, the QCA studies were not performed in an independent core laboratory. Instead, a well-validated in-hospital system was used.

In conclusion, 2-year outcomes of patients treated with the 2-stent strategy using 2nd-generation DES for non-left main coronary bifurcation lesions were acceptable. Coronary bifurcation location in the LAD and its diagonal branch was protective against TLR, whereas multiple stents implanted in either the main branch or the side branch were associated with TLR.

Acknowledgments

The authors appreciate the staff members of the cardiac catheterization laboratory, and Miho Kobayashi, Makiko Kanaike, and Yoshimi Sano for their assistance with the manuscript.

Disclosures

None of the authors report any conflicts.

Name of Grant

None.

Supplementary Files

Supplementary File 1

Figure S1. Cumulative incidence of target lesion revascularization according to stent type.

Figure S2. Restenosis location in (Upper) the early and (Lower) late terms compared between lesions with and without multiple stents.

Table S1. Cases of definite stent thrombosis

Table S2. Angiographic outcomes for multiple vs. non-multiple stents

Please find supplementary file(s);

http://dx.doi.org/10.1253/circj.CJ-17-1092

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