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Treatment of Bifurcation Lesions Using Dedicated Bifurcation Stents versus Classic Bare-Metal Stents
Randomized, Controlled Trial with 12-Month Angiographic Follow Up
ABSTRACT: Background. The aim of this study was to compare the use of classic bare- metal stents with dedicated bifurcation bare-metal stents in patients who were not eligible for drug-eluting stents (DES) implantation. Methods. Sixty patients with bifurcation stenosis were randomly assigned to received either a dedicated bifurcation or a bare-metal stent (n = 30) or classic bare-metal stent (n = 30) with stenting of the parent vessel and angioplasty/or provisional stenting of the side branch. Fifty-nine patients underwent 12-month clinical and angiographic follow up unless this was performed earlier due to symptoms. Dual antiplatelet treatment was administered for 1 month. Acute success as well as the long-term clinical and angiographic outcome have been assessed in both groups. Results. Baseline demographic, angiographic and procedure-related characteristics were well balanced in both groups. The use of dedicated stents was associated either with reduced procedure or fluoroscopy time (34 ± 9 minutes vs. 46 ± 20 minutes; p = 0.004 and 9 ± 6 minutes vs. 15 ± 9 minutes; p = 0.003, respectively) and lesser contrast volume (168 ± 86 milliliters vs. 199 ± 103 ml; p = 0.02). At the 12-month follow-up, no statistically significant difference was found between both groups regarding major adverse cardiovascular events (MACE) (13.7 vs. 13.3%; p = 0.9). Conclusions. In our study we failed to demonstrate the superiority of a dedicated stent versus classic a bare-metal stent for the treatment of bifurcation lesions regarding MACE in patients who were not eligible for DES implantation. However, the use of dedicated stents may be preferable due to reduced procedure and fluoroscopy time and lesser contrast volume.
J INVASIVE CARDIOL 2008;20:516–520
Treatment of bifurcation lesions remains challenging even in the drug-eluting stents (DES) era. It has previously been shown that among various different techniques, the stenting of the main vessel with provisional stenting of a side branch is probably the best approach for the treatment of bifurcation stenosis.1,2 However, the outcome of percutaneous interventions (PCI) with bare metal stents (BMS) is hindered by increased rates of restenosis and target lesion revascularization (TLR).1 Although the introduction of DES in preventing restenosis has been well established over the last years in randomized trials as well as registries in relatively simple lesions,3–9 recently, concerns have been raised about a possibly increased incidence of late stent thrombosis (LST).10–12 In the case of bifurcation stenosis, the incidence of LST is high and has been reported in some studies between 3.5–6.4%, especially when a complex treatment strategy employing two stents has been used with TLR and major cardiovascular events (MACE) varying between 10–23% and 13–26%, respectively.13–15 It has also been concluded that the restenosis at side branch still remains a major limitation of PCI regardless of technique or stents used.13,14 On the contrary, the largest study comparing two treatment strategies (stenting of the main branch and optional stenting of side branch versus routine implantation of stents in both vessels employing either Cullotte or crush technique) of de novo coronary artery bifurcation lesions with SES has been reported a low incidence of both, LST and TLR regardless of treatment strategy used. However, the simple strategy has been associated with significantly shorter procedure and fluoroscopy time and a lesser contrast volume. In this trial, dual antiplatelet treatment with aspirin and clopidogrel has been recommended for 6–12 months.15
Unfortunately, there is still a large cohort of patients who are not able or willing to use prolonged dual antiplatelet treatment for whatever reason and therefore the use of DES may even be harmful due to increase risk of LST. The use of dedicated stents for bifurcation lesions has been reported as promising tool simplifying the procedure by keeping the entry in side branch open within the entire procedure and reducing troubles with recrossing the stent struts. However, this device has largely not been tested in head-to-head comparison either with BMS or DES.16
We conducted a randomized, single center trial comparing acute and mid-term (12-month) efficacy of bare-metal dedicated bifurcation stent (Twin-Rail®; Invatec, Roncadelle, Italy) versus classic bare-metal stent (Liberté™, Boston Scientific, Natick, Massachusetts) in the treatment of bifurcation stenosis in the cohort of patients with de novo bifurcation stenosis who were not able or willing to use prolonged (12 months) dual antiplatelet treatment.
Between January 2006 and July 2007, 1509 PCI have been performed in our department. Among these, 60 patients (4% of all PCI procedures and 28% of PCI for bifurcation stenosis) have been randomly assigned (sealed envelope) to receive either dedicated bare-metal bifurcation stent (n = 30) (Twin-Rail) or classic bare-metal stent (n = 30) (Liberté) with the stenting of parent vessel and angioplasty/or provisional stenting of the side branch.
Inclusion criteria were as follows: symptoms or signs of angina (including acute coronary syndromes), all types but one (0,1,0) of bifurcation stenosis according to the Medina classification,17 lesion’s length shorter than 15 mm, main vessel diameter between 2.7–4.0 mm and sidebranch diameter > 2.2 mm. The severity of coronary artery disease was assessed at least at two orthogonal views, employing Quantcore software (Pie Medical, The Netherlands). All patients were scheduled for 12-month angiographic follow up. Dual antiplatelet treatment has been administered for 1 month, and then aspirin has been continued for long life. The protocol of the study has been approved by local ethic committee and all participating patients signed informed consent.
The Twin-Rail dedicated bifurcation stent (Figure 1) is laser cut from a 316L stentless steel tube with closed cell design. The stent is available in a length of 15 mm with the diameter of the main-vessel balloon either 3.0 or 3.5 mm, and the diameter of the side branch-balloon 1.5 mm. The device is compatible with 6 Fr guiding catheter. The implantation technique has been described previously. In general, extra support types of guidewires are recommended for side branch with wiring as deep as possible. To decrease the chance of wire-twisting, several small rotations (< 180°) in clock- and counter-clockwise directions are recommended while wiring the main vessel. Predilatation of the lesion is helpful, especially in the case of true bifurcation lesions. However, stent implantation without predilatation is also feasible. To assure optimal positioning and coverage of the side-branch ostium, stent deployment is recommended while exerting a slight pushing force against the carina.
Procedure. One interventional cardiologist performed all procedures (first author). The procedure was performed employing a transfemoral approach with a 6 Fr guiding catheter. Two wires were inserted in the distal bed of the two branches. ACS Hi-Torque Traverse® 0.014 inch guidewires (Guidant Europe, Diegem, Belgium) were used exclusively in this trial. Afterward, predilatation with small, semicompliant balloons (usually 2.5 mm) shorter than 15 mm at a pressure < 10 atm was performed at the operator’s discretion. Either sequential or kissing predilatation was approved by the operator.
The Twin-Rail was delivered with meticulous attention to avoid twisting of the wire. The stent was implanted with a slight force against the carina at 15 atm. Then “kissing” postdilatation was carried out using a shorter compliant balloon with an appropriate diameter for the vessel diameter distal to the lesion and inflated at high pressure (≥ 15 atm) in both branches. The Liberté stent was implanted in the main vessel while “jailing” a wire in the side branch. Only 16 mm-long stents were implanted in this group. The stent was deployed at low pressure (< 10 atm). Then, the wire was removed from the main vessel and was used to recross the struts of the stent and into the side branch using the wire in the side branch as a marker. Afterward, the wire from the side branch was removed and reinserted in the main vessel. Then, a final kissing simultaneous inflation (> 15 atm) was carried out in both branches using a balloon diameter appropriate for the size of both segments beyond the bifurcation. In both groups, the goal was to achieve TIMI 3 flow in both vessels and a residual stenosis < 10% in the main vessel, and < 50% in the side branch. The only reason for implantation of a second stent in a daughter vessel was dissection with limiting flow in the side branch. After wire withdrawal, final angiography was performed in at least three projections.
Antithrombotic regimen. The antithrombotic regimen consisted of aspirin (100 mg) and clopidogrel (300 mg or 600 mg) before the procedure, heparin 100 international units per 1 kilogram with additional bolus if the activated clotting time was < 300 seconds. The use of glycoprotein (GP) IIb/IIIa inhibitors has been left to the discretion of interventional cardiologist. After the procedure, patients used a clopidogrel 75 mg for 4 weeks and aspirin 100 mg indefinitely.
Definitions. Death was reported as cardiac or noncardiac. Q-wave MI was defined as the development of new, pathologic Q-waves in 2 or more ECG leads, with postprocedural creatine kinase (CK) levels of three times the upper limit of normal (< 2.9 µkatal/l) and CK-MB > 10% CK levels. Non-Q-wave MI was defined as an elevation of postprocedural CK levels of three times the upper limit of normal, with a CK-MB above normal and non-Q-waves. Device success was defined as a residual stenosis < 10% in the main vessel and < 50% in the side branch by quantitative coronary angiography (QCA).
Procedural success was defined as device success without in-hospital major adverse cardiac events (MACE), including death, MI, emergency coronary artery bypass graft surgery or repeat angioplasty. Target vessel revascularization (TVR) was defined as revascularization within the treated vessel, and target lesion revascularization (TLR) as revascularization within 5 mm of the stent edges (in-segment) on follow-up angiography. All TLR/TVRs required significant stenosis and objective evidence of ischemia related to the restenotic artery before treatment.
Follow up. Twelve months after the procedure, exercise stress tests and coronary angiography were performed (unless it had been performed earlier due to symptoms). During the follow-up period, the incidence of MACE included death, MI, (Q-wave and non-Q-wave), TVR and TLR. We also analyzed the rate of angiographic restenosis and late lumen loss.
QCA analysis. Coronary angiograms were digitally recorded at baseline, post procedure and at follow up and assessed offline by experienced personnel unaware of the type of stent implanted. Digital angiograms were analyzed with an automated edge-detection system (Quantcore; Pie Medical, Netherland). The projection that best showed the stenosis was used at all times. A nontapered catheter tip was used for calibration. Quantitative data included the reference vessel diameter, MLD, lesion length, percentage diameter stenosis (%DS), and late lumen loss (the difference between the minimal luminal diameter after the procedure and the minimal luminal diameter at follow up). Binary restenosis was defined at least 50% DS in the target lesion at angiographic follow up. Quantitative analysis was used to evaluate the stented area (“in-stent”) as well as the 5 mm margins proximal and distal to the stent (“in-segment”).
Statistical analysis. Statistical analysis was performed using NCSS 2004 statistical software. Continuous variables are expressed as the mean ± standard deviation (SD). Categorical variables are expressed as percentages. Continuous variables were compared with the Student t-test. Categorical variables were compared by means of the chi-square test. A two-tailed p-value < 0.05 was considered statistically significant.
Results
Both groups had similar baseline demographic, clinical and angiographic characteristics (Table 1). The procedural characteristics and immediate outcomes are presented in Table 2. There was one technical failure in the dedicated bifurcation stent group (the stent had not crossed tortuous proximal segment of the vessel); otherwise the procedures themselves, as well as further hospitalization, were uneventful. In the classic bare-metal stent group, re-wiring was not possible in 1 case, resulting in a small non-Q-wave MI due to partial side branch occlusion. The fluoroscopy and procedure times were significantly shorter in the dedicated stent group (15 ± 7 vs. 10.5 ± 5; p = 0.05 and 46 ± 20 vs. 34 ± 9 minutes; p = 0.04, respectively). Furthermore, there was also less contrast used (168 ± 86 ml vs. 199 ± 103 ml; p = 0.02) in the dedicated stent group. On the contrary, a wire twisting requiring re-wiring of the main vessel occurred significantly more often in the bifurcation stent group (7% versus 60%; p = 0.000001). However, the re-wiring was done in all cases without difficulties. Final kissing postdilatation was carried out in all patients with implanted dedicated bifurcation stents and in all but 1 patient with bare-metal stents (p = 0.3). All patients received a stent only in the parent vessel in this study. The clinical outcomes and angiographic characteristics at 12-month follow up are summarized in Table 3. At 12-month follow up, no statistically significant difference was found between the dedicated stent and classic bare-metal stent groups in terms of MACE, rate of restenosis, TLR and TVR (13.7 vs. 13.3%; p = 0.9, 13.7 vs. 13.3%; p = 0.9, and 0% vs. 0%; p = 1, respectively). Furthermore, there was no statistically significant difference in late lumen loss in the main vessel (0.64 ± 0.46 mm vs. 0.61 ± 0.58 mm; p = NS) or in the side branch (0.39 ± 0.31 vs. 0.41 ± 0.36; p = NS).
Discussion
In the present randomized, single-center trial, we failed to prove the superiority of bare-metal dedicated bifurcation stenting versus classic bare-metal stenting for the treatment of bifurcation stenosis in terms of MACE (cardiac death, MI and TLR) or restenosis 12 months. However, the use of dedicated stents was not as technically demanding and time-consuming as the use of classic bare-metal stents, even when re-wiring of the main vessel was needed in the majority of cases in the bifurcation stent group. Furthermore, a significantly lower volume of contrast was used in the dedicated stent group. The rates of MACE and restenosis after 12 months were remarkably low in both groups. These encouraging results might be because of the simple strategy of stent implantation only in the parent vessel and the systematic use of high-pressure kissing postdilatation. However, the relatively small number of patients enrolled in the trial must also be taken into account.
Although the DES reduced restenosis and TLR to a single-digit number even in these complex lesions,15 the higher incidence of late stent thrombosis must be considered, especially when a complex treatment strategy employing 2 stents is used. Furthermore, prolonged dual antiplatelet therapy is recommended for at least 12 months. Unfortunately, this therapy is not feasible in all patients for vareious reasons (increased risk of bleeding, planned surgery, economic status). In our cohort of patients treated for a bifurcation stenosis within the period from January 2006 through July 2007 (n = 214; 14% of all PCI procedures), almost one-third of patients (28%) were not able or willing to use dual antiplatelet therapy after PCI. The main reasons that patients did not receive DES were low socioeconomic status in 30 patients (50%), advanced age > 75 years in 10 patients (17%), large vessel diameter (> 3.5 mm) in 8 patients (13%), and ST-segment elevation MI in 6 patients (10%). Five patients (8%) were considered to be at high risk for bleeding, and 1 patient had a surgery scheduled within 3 months after the procedure.
The use of dedicated bare-metal stents for bifurcation lesions has not been widely tested in clinical practice. These innovative stents have some advantages over classic stents. They allow the operator to completely cover the entire bifurcation site and to keep the access to the side branch open throughout the entire procedure. In our earlier work16 we described the use of various types of bifurcation stents. Initially, the implantation technique was technically demanding and time-consuming and required a learning curve. However, substantial technical progress has been made with these devices since that time, making their use safe and comfortable. The main disadvantages of these stents are their limited sizes and lengths and, even with meticulous care, wire-twisting that required re-wiring occured in a majority of cases.
To our knowledge, this is the first, randomized trial making a head-to-head comparison of the use of specifically designed stents and classic bare metal stents for the treatment of bifurcation lesions, with stenting only in the parent vessel. This simple strategy produced acceptable 12-month clinical and angiographic outcomes in both groups. However, the use of classic bare-metal stents for the treatment of bifurcation stenosis was associated with an longer procedure and fluoroscopy times and an increase in the volume of contrast media used.
Study limitations. The major limitation of our study is relatively small number of patients and the lack of a prespecified primary endpoint and power calculation. Furthermore, our study’s single-center and, particularly, its single-operator design should also be taken into account before generalizing the findings to routine practice.
Conclusions
In conclusion, acceptable 12-month clinical and angiographic outcomes were achieved with PCI employing either dedicated bare-metal or classic bare-metal stents for the treatment of bifurcation lesions with stenting of the main vessel in patients who were not eligible for DES implantation with prolonged dual antiplatelet therapy for various reasons. Our results show that for a considerable cohort of patients, the use of either dedicated or classic bare-metal stents for the treatment of bifurcation stenosis is still a viable solution that provides acceptable mid-term clinical outcomes. The use of dedicated stents may be preferable due to the resulting reduction in procedure and fluoroscopy times and contrast volume use.
