Author + information
- Received November 24, 2004
- Revision received January 18, 2005
- Accepted January 25, 2005
- Published online May 17, 2005.
- Eleftheria Tsagalou, MD⁎,
- Alaide Chieffo, MD⁎,
- Ioannis Iakovou, MD†,
- Lei Ge, MD†,
- Giuseppe M. Sangiorgi, MD†,
- Nicola Corvaja, MD†,
- Flavio Airoldi, MD⁎,
- Matteo Montorfano, MD⁎,
- Iassen Michev, MD⁎ and
- Antonio Colombo, MD, FACC⁎,†,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Antonio Colombo, EMO Centro Cuore Columbus, Via M. Buonarrotti 48, 20145 Milan, Italy
Objectives We sought to determine the safety and efficacy of using multiple overlapping drug-eluting stents (DES) in patients with diffuse left anterior descending coronary artery (LAD) disease.
Background Diffuse LAD disease represents a therapeutic challenge. Results after coronary artery bypass surgery are suboptimal, whereas the use of bare metal stents is limited by high rates of restenosis. The introduction of DES prompted treatment of long diffuse disease with multiple overlapping stents.
Methods All consecutive patients with de novo diffuse LAD disease treated with more than 60-mm long DES from April 2002 to March 2004 were analyzed.
Results The study population consisted of 66 patients. Thirty-nine patients were treated with sirolimus-eluting stents (SES), average length 84 ± 22 mm, and 27 patients with paclitaxel-eluting stents (PES), average length 74 ± 14 mm. The number of stents implanted per patient was 2.8 ± 0.7, whereas the mean total stent length for the LAD treatment was 80 ± 20 mm. Angiographic as well as procedural success was achieved in 95% of cases. Eleven (16.6%) patients had in-hospital non-Q-wave myocardial infarction (five SES and six PES), and one patient developed intraprocedural stent thrombosis. All patients had clinical follow-up, and 52 patients (79%) had an angiographic follow-up at six months. Hierarchical major adverse cardiac event rate was 15% (7.5% for SES and 7.5% for PES). No patients died, one patient had non-Q-wave myocardial infarction (non-index vessel), and 10 patients (15%) underwent target vessel revascularization.
Conclusions The implantation of multiple overlapping DES in patients with a diffusely diseased LAD is relatively safe and associated with good midterm clinical outcomes.
Diffuse coronary artery disease poses a significant therapeutic challenge. In 25% of these patients, coronary artery bypass grafting (CABG) cannot be safely performed, and the condition often is deemed inoperable (1). Furthermore, in many of these cases, complete revascularization and adequate myocardial perfusion cannot be achieved with CABG. Alternative revascularization procedures (2–4) often are undertaken, with suboptimal results.
The percutaneous implantation of bare-metal stents (BMS) is associated with high rates of restenosis (5–7). The use of drug-eluting stents (DES) has greatly attenuated the relationship between stent length and restenosis (8–10). The aim of the present study was to evaluate the safety and efficacy of using multiple overlapping DES to treat patients with diffuse left anterior descending coronary artery (LAD) disease.
Patient population and procedures
Patients with diffuse de novo LAD disease undergoing implantation of minimum of 60-mm long sirolimus-eluting stents (SES) (Cypher, Cordis/Johnson & Johnson, Warren, New Jersey) or paclitaxel-eluting stents (PES) (Taxus, Boston Scientific, Natick, Massachusetts) between April 2002 and May 2004 composed the study population. Each patient signed an informed consent form. The implantation of DES was performed following the practice of fully covering the diseased segment. All patients had a combination of at least two overlapping stents (overlapping segment approximately 2 to 4 mm) in the LAD, with total stent length ≥60 mm. The reported stented length is based on the cumulative length of the adjacent stents. Heparin was administered at the beginning of the procedure at the dose of 100 IU/kg to achieve an activated clotting time >250 s. Glycoprotein (GP) IIb/IIIa inhibitors were administered at the discretion of the operator.
All patients received aspirin (at least 100 mg once daily) and clopidogrel 75 mg once daily or ticlopidine 250 mg twice daily at least three days before the procedure, with a loading dose of 300 mg of clopidogrel to patients not pretreated. Thienopyridines were continued for at least three months after the procedure.
Cineangiograms were analyzed using a validated edge system (CMS, version 5.2, MEDIS, Leiden, the Netherlands). Angiographic success was defined as Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 and <30% residual diameter stenosis by visual assessment. Restenosis was defined as >50% diameter stenosis by qualitative coronary angiography within a previously stented segment. Angiography was scheduled at six months or earlier if clinically indicated.
Clinical follow-up was performed by either telephone contact or office visit. All patients were evaluated for the occurrence of major cardiac events (MACE), a composite end point comprising death, myocardial infarction (MI), and target vessel revascularization. A diagnosis of non-Q-wave MI was made when there was an increase of creatine kinase two times the upper limit of normal accompanied by increased values of creatine kinase-myocardial band. Diagnosis of Q-wave MI was made when development of new abnormal Q waves, not present in baseline electrocardiogram, also occurred. Intraprocedural stent thrombosis was defined as an angiographically confirmed intraluminal filling defect within the stent resulting in TIMI anterograde flow grade 0 or 1 that occurred during the procedure. Postprocedural stent thrombosis was defined as any of the following between the end of the procedure and the end of follow-up: angiographic documentation of stent occlusion, unexplained sudden death when the stent was not known to be patent, or MI or urgent target lesion revascularization occurring in the territory of the LAD. Target vessel revascularization was defined as revascularization driven by significant luminal narrowing (>50%) within the stent or within the 5-mm borders proximal and distal to the stent.
Discrete variables are presented as percentages and continuous variables as mean values ± SD. The Student paired ttest was used to identify changes over time in the same patients, whereas the Kaplan-Meier method was used to analyze the occurrence of the composite end point of MACE during follow-up.
Baseline clinical and procedural characteristics are presented in Table 1.Diabetes mellitus was present in 19 patients (29%), and 19 (29%) had unstable angina. Ten patients had an ejection fraction ≤40%, and coronary bypass surgery had been performed previously in eight (12%). Chronic total occlusions were present in 13 (20%) patients. The lesion length per vessel was 64 ± 18 mm and reference vessel diameter was 2.53 ± 0.6 mm.
Thirty-nine patients were treated with SES (average length, 84 ± 22 mm) and 27 patients with PES (average length, 74 ± 14 mm). Angiographic success was achieved in 95% of the patients treated. Three patients had TIMI flow grade 2 at the end of the procedure. Directional atherectomy was performed in five patients, rotational atherectomy in one patient, and cutting balloon in seven patients. The number of stents implanted per lesion was 2.8 ± 0.7 (range, 2 to 4 stents), and the diameter of the stents was 2.8 ± 0.7 mm. Thirty-five patients (53%) received bifurcation treatment of diagonal branches: balloon angioplasty of the side branch was performed in 13 patients, and DES implantation was performed in the remaining patients (SES in 15 patients and PES in 7 patients). Glycoprotein IIb/IIIa inhibitors were administered electively in 31 patients (47%). Intraprocedural thrombosis occurred in one patient. Eleven patients (16.6%) developed periprocedural non-Q-wave MI (five with SES and six with PES). No patient developed Q-wave MI or died during hospitalization.
Follow-up coronary angiography was performed in 52 patients (79%; Table 2).Binary restenosis in the LAD occurred in 10 (19.6%) patients (5 SES, 5 PES). Most (70%) restenotic lesions were focal (<10 mm in length), single in five patients, and multifocal in two patients (Fig. 1).In one of the patients (PES), the restenosis was diffuse and occurred in the vessel segment proximal to the stent. A second patient, originally treated for chronic total LAD occlusion with SES implantation, developed occlusive restenosis.
Among the patients who had concomitant treatment of diagonal branches, five patients developed restenosis at the ostium of the branch. All patients who did not undergo follow-up coronary angiography were asymptomatic and underwent exercise testing, which was negative for ischemia.
Clinical follow-up was available for all patients, and all follow-up extended at least six months. At an average period of 13.6 ± 6.5 months, there were no deaths, no stent thrombosis, and no Q-wave MI (Table 3).One patient experienced non-Q-wave MI one month after the procedure and underwent emergency percutaneous revascularization of the obtuse marginal branch. Ten patients (15%) underwent target vessel revascularization. The Kaplan-Meier estimated probability of cumulative MACE-free survival was 71.21% (Fig. 2).Thienopyridine therapy was discontinued in 28 patients (42.4%) after an average period of 9 ± 4.6 months (range, 3 to 18 months).
This study is the first to report that percutaneous treatment of diffuse LAD disease with multiple overlapping DES (total length ≥60 mm) is feasible, apparently safe, and associated with acceptable rates of MACE in the midterm follow-up. The implantation of multiple overlapping BMS is associated with high restenosis rates (5–7). The use of short stents (spot stenting) with intravascular ultrasound guidance (11) was proposed as an alternative strategy, but this technique is laborious.
Percutaneous treatment of LAD lesions with SES has been reported to result in revascularization rates comparable with historic single-vessel CABG revascularization rates (9). Data concerning the implantation of multiple overlapping DES in patients with diffusely diseased LAD are lacking. In our study, the mean stent length was 80 mm (range, 61 to 120 mm), that is, at least 20 mm longer than in previously reported series with DES (10) and 30 mm longer than the reported series with BMS .
Concerns exist about the increased probability of stent thrombosis (12) using very long stents; however, in our study only one patient developed intraprocedural stent thrombosis (with immediate resolution of the thrombus after GP IIb/IIIa inhibitor administration). No late thrombosis occurred.
The risk of compromising the flow in the numerous diagonal and septal branches originating from the LAD represents a valid concern. This fact may explain the high incidence of non-Q-wave MI compared with other studies (10). A more liberal administration of GP IIb/IIIa inhibitors (given to 47% of the patients and in 5 of 11 patients who sustained MI) could have reduced the incidence of myocardial infarction, but other factors may be implied.
A 19.6% incidence of restenosis is an area in which improvement is needed. A positive aspect, consistent with previous reports evaluating the mode of failure of DES (13), is that the angiographic pattern of restenosis in most of the restenotic lesions was focal. With the exception of one patient, who underwent CABG in another hospital, repeat percutaneous intervention was the mode of treatment for the rest of the patient population that developed restenosis.
The main limitation of this study is the lack of a control group treated with CABG or with medical therapy. The relative small number of patients included and the short follow-up time are other important shortcomings. A longer follow-up time is needed to evaluate any possible risk of late thrombosis, and uncertainties are present regarding the optimal duration of double antiplatelet therapy.
Implantation of multiple long overlapping DES in patients with diffuse LAD disease is relatively safe and is associated with good midterm clinical outcomes.
- Abbreviations and acronyms
- bare-metal stent
- coronary artery bypass grafting
- drug-eluting stents
- left anterior descending coronary artery
- major adverse cardiac events
- myocardial infarction
- paclitaxel-eluting stents
- sirolimus-eluting stents
- Thrombolysis In Myocardial Infarction
- Received November 24, 2004.
- Revision received January 18, 2005.
- Accepted January 25, 2005.
- American College of Cardiology Foundation
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