Evaluation of the Coroflex‚Ñ¢ Theca-Stent for Reduction of Restenosis (ECORI)

Martin Unverdorben, MD, PhD, Ralf Degenhardt, PhD, Peter Sick, MD, Adnan Kastrati, MD, Walter Desmet, MD, Antonio Colombo, MD, Eulegio Garcia, MD, Werner Klein, MD, Eberhard Wagner, MD, Henning Köhler, MD, Manfred Scholz, MD, Heiner K. Berthold, MD, PhD, Christian Vallbracht, MD
Martin Unverdorben, MD, PhD, Ralf Degenhardt, PhD, Peter Sick, MD, Adnan Kastrati, MD, Walter Desmet, MD, Antonio Colombo, MD, Eulegio Garcia, MD, Werner Klein, MD, Eberhard Wagner, MD, Henning Köhler, MD, Manfred Scholz, MD, Heiner K. Berthold, MD, PhD, Christian Vallbracht, MD
The outcome of coronary stenting has proved to be superior compared to balloon angioplasty for most indications. Improvements in device design and deployment technique were key components in reducing the restenosis rates of bare stents from 30%1 initially, to 26.6%,2 24.4%,3 or 15.7%.4 Additional approaches included active and passive coatings. The enthusiasm about devices with active coatings with respect to restenosis rates below 10%2,5 has recently been challenged by late thrombotic coronary occlusions associated with these stents.6 Aside from this uncertainty, reasons such as cost-savings justify investigating the use of stents covered with passive compounds.7–9 According to a recent market survey, drug-eluting coronary stents accounted for less than 10% of all devices deployed in 2003 and are estimated to remain 10 The short- and mid-term outcomes of the Polyzene®-F coated Coroflex™ Theca-Stent (B. Braun, Melsungen, Germany) were therefore investigated in this pilot study. Methods Design. This multi-center, prospective, non-randomized pilot study was conducted in accordance with Good Clinical Practice guidelines. The protocol was approved by the independent ethics committee of each participating center. The primary endpoint was the 6-month binary restenosis rate. Secondary endpoints encompassed acute success, target site revascularization, acute ischemic, vascular, and hemorrhagic complications, follow-up minimal lumen diameter, percent diameter stenosis, late loss, and late loss index. Clinical endpoints comprised combined major cardiac events (death, target lesion-related myocardial infarction, premature revascularization). Quantitative coronary analysis was performed by an independent core laboratory (Clinical Research Institute, Rotenburg/Fulda, Germany). The stents were provided by the manufacturer free of charge (B.Braun, Melsungen, Germany). Stent description and study rationale. The stent characteristics are given in Table 1 and Figure 1 (A and B). Only in its highly purified form, poly[bis(trifluoroethoxy) phosphazene] effectively reduces GPIIb/IIIa receptor density on thrombocytes, diminishes activation of the clotting and complement systems, reduces adhesion, activation and accumulation of platelets, decreases the infiltration of inflammatory cells, and reduces foreign body reactions.11,12 The decline in the amount of thrombocyte deposition on the arterial wall is associated with diminished neointimal formation in humans.13 Therefore, poly[bis(trifluoroethoxy)phosphazene] (Polyzene® -F) coated stents may be effective in reducing restenosis rates. Study population. One-hundred and three consecutive patients (Table 2) presenting with myocardial ischemia secondary to a de novo lesion in a native coronary artery (reference diameter: >= 2.75, = 70%, 2 mm), myocardial infarction within 72 hours preceding the intervention, planned multiple lesion PCI within the same vessel, left ventricular ejection fraction Operator technique. Stent deployment followed the medical practice guidelines of each institution. Heparin 100–200 IU/kg of body weight was administered after introduction of the sheath, and was supplemented as needed. Following intracoronary injection of nitroglycerin (100–200 µg), baseline angiography of the culprit vessel was performed in at least two near-orthogonal views, showing the target lesion to be free of foreshortening or vessel overlap. This was done by using 6–8 Fr guiding catheters. The procedure was considered successful when the remaining stenosis was Concomitant medical therapy. All patients received aspirin 100 mg/day pre-procedure and throughout the follow-up period. Clopidogrel (300 mg loading dose; 75 mg/day for 4 weeks) was also administered. Quantitative coronary analysis. The angiograms were reviewed by two blinded observers using qualitative morphologic and quantitative angiographic methods (CAAS II, Pie-Medical, Maastricht, The Netherlands) at the Angiographic Core Lab. In instances where differences between the two operators exceeded 3%, a third operator made the final decision based on his blinded evaluation. The contrast-filled catheters served as the calibration standard, while the reference and minimal lumen diameters were determined using an automated edge-detection algorithm. Reference contours were calculated by a linear regression algorithm. The diameters were taken from the view exhibiting the most severe degree of stenosis and its close orthogonal projection pre-procedure, after stent deployment, and at follow-up. The mean of both values determined the severity of the stenosis. In cases where there was obvious false assessment of the vessel by CAAS, operator adjustment was permitted. Follow-up. Follow-up procedures included ECG, white blood cell count, hematocrit, hemoglobin, creatinine, creatine kinase, CK-MB, and catheterization at 6 months unless clinically indicated earlier. Definitions. A thrombus is a non-calcified filling defect within the vascular lumen, visible in several views and which may migrate into the peripheral artery. A rise in creatine kinase to twice the upper limit of normal, with significant CK-MB defined myocardial infarction. In non-Q-wave-infarctions, pathologic Q-waves were absent, while new pathologic Q-waves occurred in Q-wave infarctions . Acute complications occurred within 24 hours post-stenting, early complications Statistical analysis. All analyses were performed and reported in compliance with the August 1998 FDA device reporting guidelines for coronary stents. All endpoints were analyzed on an intention-to-treat basis. Those patients who met eligibility requirements for primary endpoint ascertainment included all patients who were enrolled. Statistical tests. The Kolmogoroff-Smirnoff-test was used to prove Gaussian distribution, allowing for calculation of the mean and standard deviation. Non-Gaussian samples were described by median, maximal and minimal value. Categorical variables were evaluated with the two-sided Fisher’s exact test. For all tests, the significance level a was 0.05. Results Deployment of the Coroflex Theca-Stent was successful in all 103 lesions attempted, and in 57/103 (55.3%) without pre-dilatation. No subject required administration of a glycoprotein IIb/IIIa antagonist. The lesion characteristics pre-procedure are given in Table 3, and the deployment data in Table 4. The clinical follow-up was completed by 100/103 (97.1%) of the patients after 7.1 ± 2.3 months and the angiographic follow-up by 77/103 (74.8%) after 6.4 ± 1.3 months. The percent stenosis decreased from 87.3 ± 5.7% to 14.2 ± 8.3% post-stent implantation and increased to 32.8 ± 22.7% at follow-up (Figure 2). The restenosis rate after 6.4 ± 1.3 months was 15.6% (12/77) with target lesion revascularization in 14.3% (11/77). The late loss and the late loss index were 0.6 ± 0.7 mm and 0.2 ± 0.4 mm, resulting in a recurrence rate of 12/77 (15.6%), and a clinically-driven reintervention rate in 11/77 (14.3%) of the patients. Major adverse cardiac events were low during the entire follow-up period (Figure 3). Discussion The new Polyzene-F coated Coroflex Theca-Stent showed a 100% procedural and device success rate, with 55/103 (55.3%) of the patients not receiving pre-dilatation. After 7.1 ± 2.3 months of clinical follow-up in the intention-to-treat analysis, the MACE rate was as low as 4%. This number is comparable to other stents coated with passive layers for which MACE rates have been reported in the order of 7.9% to 10.2%8,9,14 in similar settings, while in a “real world” scenario, the MACE rate rose to 13%.15 The restenosis rate of 15.6% in the present study was lower compared to the range of 21% to 49.7%14,16 reported for stents with other passive coatings. The late loss of 0.7 mm was also in the range of bare stents, for which values from 0.6 mm to 1.1 mm have been reported,1782,3,18,19 or for devices coated with passive compounds (0.8 mm).20 Stents with the active coating sirolimus and paclitaxel exhibit lower restenosis and recurrence rates after 6 to 12 months in lesions comparable to the ones included in the present pilot study. Diameter stenosis at follow-up was in the range of 14–23%,21–23 the restenosis rates ranged from 3–12%,21,23 or reached 0%;22 while MACE rates occurred from 3%22,23 to 5%.21 Paclitaxel-coated devices exhibited a late loss of 0.36 ± 0.48 mm and a late loss index of 22 ± 29%,22 while for the sirolimus coating, the numbers ranged from -0.06 ± 0.35 to 0.01 ± 0.25 mm and 0%,24 respectively. Since the approval of the sirolimus stent, 290 cases of subacute thrombosis and 50 cases of hypersensitivity reactions have prompted the FDA to request additional data to address the question about whether these adverse reactions are within the range of bare stents.6 Despite the apparent benefits of drug-eluting stents, however, the market share of non-drug-eluting stents is still in the order of 90% and is projected to remain in the range of 80% until 2009.10 The present study is limited by its small sample size and lack of control group. As in previous studies reporting on the initial usage of a stent platform, we only assessed the Theca-Stent system in patients with representative low-risk lesions. Given these limitations, we believe that our data show that the Theca-Stent system can be safely placed with reasonable short-term MACE results for a non-drug-eluting stent. Further investigation is warranted to adequately compare the Theca-Stent to other passively coated stents as alternatives to drug-eluting stents.
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