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(Circulation. 2002;105:1883.)
© 2002 American Heart Association, Inc.
Brief Rapid Communications |
From Catheterization Laboratories, Ospedale San Raffaele, and Emo Centro Cuore Columbus, Milan, Italy.
Correspondence to Antonio Colombo, MD, EMO Centro Cuore Columbus Hospital, Via M. Buonarroti 48, 20145, Milan, Italy. E-mail columbus{at}micronet.it
| Abstract |
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Methods and Results Fifteen consecutive patients with elective indication to percutaneous coronary intervention for in-stent restenosis were treated with the QuaDS-QP2 stent implantation. The QuaDS-QP2 stent was successfully implanted in all but 2 target lesions. In one lesion, the restenotic segment could not be completely covered by the stent, and in another lesion, a bare metal stent was implanted distally to the QuaDS-QP2 stent. One patient suffered from postprocedural nonQ-wave myocardial infarction (NQWMI). No other adverse events were observed during hospital stay. Six- and 12-month angiographic and clinical follow-up was scheduled for all patients. At 6 months, 3 patients had target lesion revascularization (20%). Two patients had restenosis (13.3%); one experienced restenosis in a gap between 2 drug-eluting stents, and the other had stent occlusion leading to NQWMI. Minimal intimal hyperplasia was observed in all the segments covered by drug-eluting stents (late loss=0.47±1.01 mm with a loss index=0.17±0.39). At 12 months, 1 patient suffered from NQWMI, and 8 of 13 patients (61.5%) had angiographic restenosis (late loss=1.36±0.94 mm with a loss index=0.62±0.44).
Conclusion This first experience with QuaDS-QP2 stent implantation for in-stent restenosis revealed minimal intimal hyperplasia at the 6-month follow-up. However, the antiproliferative effect was not maintained at the 12-month follow-up, resulting in delayed occurrence of angiographic restenosis.
Key Words: restenosis stents angiography
| Introduction |
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| Methods |
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Pharmacological Treatment
Combined antiplatelet therapy with aspirin (at least 100 mg/d) and ticlopidine 500 mg/d (or clopidogrel 75 mg/d) was started at least 48 hours before procedure and continued for at least 6 months.
Stent
The stent used was a 316L stainless steel slotted tube with 50% of its surface area covered by multiple polymer sleeves that released QP2. The drug was loaded into the polyacrylate sleeve at 800 µg of QP2 per 2.4 mm of sleeve. The number of sleeves varied with the size of the stent, with a maximum number of 4 sleeves on the 17-mm stent. In this registry, either 13- or 17-mm stents were used. Kinetic studies in animals have shown drug release up to 180 days into subjacent tissues (personal communication from Dr E. Grube, Heart Center, Siegburg, Germany, March 2001).
Procedure
A bolus of unfractionated heparin was administered at dose of 70 IU/kg. Balloon predilation was performed in all target lesions with at least a 2.5x20-mm balloon aimed to provide sufficient coronary lumen to limit friction between the lesion and the stents drug-eluting membrane.
Angiographic Analysis
Coronary angiograms were analyzed by a semiautomated edge contour detection computer analysis system (MEDIS QCA CMS, version 4). ISR was classified according to the angiographic patterns reported by Mehran et al.2 Reference diameter (RD), minimal lumen diameter (MLD), percentage diameter stenosis (DS), and lesion lengths were measured before and at the end of the procedure, as well as at follow-up. Acute gain, late loss, and loss index were calculated.
Follow-Up
Clinical and angiographic follow-up was planned for all patients 6 and 12 months from the index procedure. Major adverse cardiac events (MACE) were defined as death from any cause, myocardial infarction (MI), coronary artery bypass grafting (CABG,) or repeated percutaneous coronary angioplasty (Re-PTCA), either in the hospital or during follow-up. MI was defined as Q-wave MI (development of new regional pathological Q waves) or nonQ-wave MI (total creatine kinase >2 times upper normal limit with elevated myocardial brain (MB) fraction).
| Results |
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In-Hospital, 6-Month, and 12-Month Clinical Outcome
Cumulative in-hospital, 6-month, and 12-month follow-up MACE were obtained in all patients and are reported in Tables 4 and 5. One patient had postprocedural nonQ-MI with a creatine kinase (CK) peak value of 657 U/L and a CK-MB value of 63 U/L, which were due to the occlusion of a small side branch. No other events occurred during hospital stay.
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Six-Month Follow-Up
Acute MI occurred in 1 patient in whom the QuaDS-QP2 stent occluded 2 months after the procedure. That stent was originally implanted without complete coverage of the target lesion. Target lesion revascularization (TLR) occurred in 3 patients. One patient had restenosis in a gap between 2 QuaDS-QP2 stents, and another patient had re-PTCA in a metallic stent (DS= 40%) overlapping with the distal edge of a QuaDS-QP2 stent. This patient had no proliferation inside the QuaDS-QP2 stent. The third patient underwent CABG for the presence of a new lesion in the proximal segment of the left anterior descending artery; however, the QuaDS-QP2 stent implanted in the mid-segment showed no restenosis.
Twelve-Month Follow-Up
Between 6 and 12 months, 1 patient suffered from a nonQ-wave MI, and 8 patients underwent TLR (2 had already repeated the procedure at the 6-month follow-up). All patients were taking combined antiplatelet therapy with aspirin and ticlopidine. Total incidence of TLR at 12 months was therefore 60%.
Six-Month and 12-Month Angiographic Follow-Up Results
Six-Month Follow-Up
Angiographic restenosis occurred in 2 lesions (13.3%), with stent occlusion in one. At the time of the index procedure, the QuaDS-QP2 stent could not be advanced to fully cover the lesion. The other patient had restenosis at a gap site between 2 QuaDS-QP2 stents. Taking into account the patient who developed total occlusion, late loss was 0.47±1.01 mm and late loss index was 0.17±0.39.
Twelve-Month Follow-Up
Twelve-month follow-up was performed in 13 of the 15 patients. One patient had stent occlusion that was not re-treated, and another who underwent CABG repeat angiography was not followed up. Angiographic restenosis occurred in 8 lesions (61.5%), with a late loss of 1.36±0.94 mm and late loss index of 0.62±0.44.
| Discussion |
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In our present study, the encouraging positive results in terms of low MACE rate at 6 months obtained using the QuaDS-QP2 stent are almost eliminated at 12 months. Six-month angiographic results in our patients revealed a low loss index (0.17±0.39), resembling those reported using the same drug-eluting stent for the treatment of de novo lesions.5 It is important to note that the only 2 instances of angiographic restenosis at 6 months occurred in 2 lesions not completely covered by the drug-eluting stent during the index procedure. However, at the 12-month follow-up, an angiographic restenosis rate of 61.5% was found, with a loss index of 0.62±0.44, showing clear disease progression from 6 to 12 months and suggesting that QuaDS-QP2 drug-eluting stents actually delayed rather than prevented neointimal growth. Several factors may be operative in this loss of effect. The high dose of drug loaded in the stents and the presence of plastic sleeves are important features of the drug-eluting stent used in this study, and both might contribute to the development of late cell proliferation. Prior studies with paclitaxel-eluting stents showed not only dose-dependent reduction in neointimal hyperplasia but also histological signs of delayed healing and local toxicity after high-dose paclitaxel exposure.13 In addition, the presence of plastic sleeves could result in a foreign-body reaction that triggers inflammation and cell proliferation.
We cannot draw conclusions with regard to the thrombogenicity of this stent because of the small number of patients enrolled in this study and the continuation of combined antiplatelet therapy for at least 6 months. It is reasonable to assume that the patient who had late stent occlusion developed restenosis distal to the stent at the site of the uncovered target lesion.
| Conclusion |
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| Acknowledgments |
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Received January 10, 2002; revision received March 1, 2002; accepted March 6, 2002.
| References |
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