Although drug-eluting stents (DES) show very good results in terms of early restenosis rates in patients with coronary artery disease as compared to bare-metal stents (BMS), there is little information available on the safety and efficacy of stent implantation for management of acute myocardial infarction (AMI).1–4
The primary goal of the present outcome quality control registry was to investigate the safety of the Camouflage® stent (Eucatech AG, Rheinfelden, Germany) with regard to serious cardiovascular events during the hospital stay and up to 6 months after the percutaneous coronary intervention (PCI) in patients with AMI. The secondary objective of the registry was to investigate the efficacy of the stent as reflected by the angiographic results and restenosis rates.
The outcome quality control study was carried out in order to obtain initial clinical experience with a passive-coated stent in patients with AMI, and thus provide the basis for the generation of hypotheses for a future clinical study.
Materials and Methods
Patients with AMI who underwent stent implantation were included in a prospective registry. The definition of AMI corresponded to the guidelines of the European Society for Cardiology and of the American College of Cardiology5: typical increase and decrease in troponin levels and/or rapid increase and decrease of CK-MB in combination with at least one of the following findings and/or intervention:
• symptoms of ischemia;
• development of pathological Q-waves on electrocardiography (ECG);
• typical changes in the ECG indicative of ischemia (STelevation or ST-depression on the ECG);
• coronary intervention. The following criteria were considered to confirm infarction:
• development of new pathological Q-waves on the ECG;
• pathological evidence of a healing or healed infarction; Patients meeting the following criteria were excluded:
• in-stent restenosis;
• bypass graft stenosis;
• ejection fraction < 26%;
• target vessel diameter < 2.5 mm;
• target vessel diameter > 4.0 mm.
Patients visiting the center who met the inclusion and exclusion criteria were consecutively registered. The benefits and risks of coronary intervention were explained to all patients. Written informed consent was obtained from all patients prior to inclusion in the registry. The patients also agreed that their anonymous data could be entered into a register and scientifically evaluated.
The duration of the follow-up period was 6 months. Death, revascularization, infarction in the area supplied by the stented artery or a pathological exercise ECG within up to 6 months after stent implantation were considered major adverse cardiovascular events (MACE). The secondary parameter could be followed up only in patients who underwent re-angiography after 6 months and/or had restenosis confirmed on angiography within 6 months. In these cases, the re-angiography was analyzed quantitatively. Coronary arterialstenoses were imaged in multiple projections, minimizing overlapping of side branches and foreshortening of relevant coronary arterial stenoses. Coronary angiograms were evaluated offline by an independent observer using quantitative coronary angiographic (QCA) software (Quansad, Arri, Munich, Germany) and used as the gold standard for stenoses detection.
The platelet-inhibiting therapy consisted of acetylsalicylic acid (300 mg in the first 4 weeks, 100 mg thereafter) and clopidogrel (for up to 4 weeks after the intervention).
All patients were interviewed over the phone 1 week, 1 month and 3 months after stent implantation and asked if a serious event had occurred. All patients were asked to present themselves for an ergometry test at 6 months.
The Camouflage stent is manufactured from 316 L stainless steel by means of a laser beam procedure and subsequent electrolytic polishing. The stent is coated with hemoparin. Hemoparin is an N- and O-desulfated, N-reacetylated and therefore polymer-analogouslymodified heparin6 that no longer possesses an active anticoagulation effect due to the removal of the sulfate groups.7 The high negative charge of the heparin molecule is also removed in the process such that the passive nature of the surface is evident from the lack of plasma protein binding. Hemoparin is permanently bound to the stent surface by multiple covalent bonding. Hemoparin is a polysaccharide, and as a precursor in the biosynthesis of heparin and heparin sulfate, it is present in all human cells. A systemic effect of the hemoparin coating can be excluded since the total mass of the coating is low (on the order of 10 picomols).
Data are reported as mean value ± standard deviation for continuous variables, or as percentages for categorical variables. Survival according to Kaplan-Meier was calculated and grouped for STEMI and N-STEMI patients. Differences in survival were assessed by the use of a log rank (Mantel Cox) test. A p-value < 0.05 was considered significant.
Study population. A total of 68 patients were enrolled in the registry: 38 patients (55.9%) with acute ST-elevation myocardial infarction (STEMI) and 29 patients with non-STEMI (41.2%). One patient was classified as a non-participant after completion of the diagnostic workup (unstable angina pectoris; Braunwald IIIb). One patient could not be contacted at 6 months (dropout), such that the prospective data of 66 patients were included in the analysis.
Anterior wall infarction was evident in 41 patients (60.3%), and inferior wall infarction in 25 patients (36.8%). Table 1 provides demographic data on the patients. Table 2 shows the patients’ cardiovascular risk factor profile.
The total cholesterol concentration was 191.7 ± 37 mg/dl, the total LDL-cholesterol concentration was 133.9 ± 34.5 mg/dl, the HDL-cholesterol concentration was 50.4 ± 14.5 mg/dl, and the Lp(a) concentration was 35.4 ± 38.5 mg/dl. Concomitant vascular diseases are shown in Table 3, and patient enzyme levels are shown in Table 4.
Description of the invasive procedure. Table 5 shows parameters of the procedure. Table 6 summarizes all parameters related to the “target lesion”.
No calcified stenoses were observed in any of the cases. Primary stenting was performed in 24 patients (12 STEMI, 12 NSTEMI), whereas the stenosis was predilated in the other patients. The vessel angulation was > 45 degrees in all cases. Two patients had main trunk stenosis. The implantation pressure was 11.2 ± 1.6 bar (STEMI: 11.0 ± 1.4; N-STEMI: 11.6 ± 1.8 bar).
All patients received heparin (between 2,500 and 5,000 IU), intravenous acetylsalicylic acid (250 mg), clopidogrel (1 loading dose of 600 mg; in patients already receiving clopidogrel, the 75 mg dose was continued), and a glycoprotein (GP) IIb/IIIa inhibitor (except for 6 patients) at the start of the procedure. Table 7 shows some parameters of the target lesion after stent implantation.
Dissection occurred in 5 patients, 4 of whom were patients with STEMI. No emergency bypass operations were required in any of the patients. The mean time of hospitalization was 5 ± 3.9 days.
Follow up to 6 months. 30-day follow-up. The mortality rate — recorded up to day 30 after the operation — was 1.5% (1 patient died on day 9 after the operation due to reinfarction). Moreover, there were 3 patients (4.5%) with subacute occlusion of the target vessel with a need for reintervention (1 patient on day 1, and 2 more patients on day 5). Therefore, the overall event rate up to day 30 was 6.1%. 180-day follow up. A total of 16 endpoints (24.2%) occurred among the 66 patients by day 180. Three patients died within these 6 months (cardiogenic shock, sudden cardiac death, acute myocardial infarction), which corresponds to a mortality rate of 4.6%.
Revascularization was required in 12 cases (1 coronary bypass operation, 12 revascularizations by means of stent implantation), and 1 patient had a pathological exercise ECG after 6 months. Thus, 75.8% of the patients did not experience a cardiovascular event and showed good physical performance at the end of the 6-month follow-up period (Figure 1).
There were 7 events (among 27 patients, 25.9%) in the N-STEMI group as compared to 9 events (among 38 patients, 23.7%) in the STEMI group (log rank [Mantel-Cox] test: p = 0.8220). The sequence of these events is shown in Figure 2.
In theory, the advantage of the passive-coated stent investigated in the present study could be that the implanted stent exposes no “bare” stainless steel surface — known to be thrombogenic8 — to the blood circulation and thus to the particularly reactive blood cells (platelets) during the period of time required for reendothelialization (approximately 4 to 6 weeks),9,10 but rather exposes a hemocompatible surface.6,7 Therefore, one might expect an advantage of the coated stent to become evident particularly during the time interval of 4 to 6 weeks after the intervention, since, after reendothelialization, the entire surface of the stent is located in the vascular wall under the layer of endothelium such that it is no longer in contact with the blood cells.11
Indeed, the incidence of serious cardiovascular events was low (7.8%) in the time interval of up to 6 weeks after the intervention. This included 1 case of fatal infarction (1.5%) and 4 target vessel revascularizations with stent implantation (6.1%). Unfortunately, there are only a few studies investigating stent implantation in patients with acute myocardial infarction.4 In the United Kingdom, the 30-day mortality rate after myocardial infarction decreased from 13% to 4% between 1995 and 1999, which is still significantly higher than the result attained in the present study.12
A U.S. study also used a population of consecutive patients with AMI and reported the periprocedural mortality rate to be 5.3% after the implantation of BMS.13 In another study, MACE rates of 4.6% (in a low-risk group with a successful procedure) and 7% (high-risk group, also with a successful procedure) were presented, whereas patients with an unsuccessful procedure had MACE rates of 22% and 21%, respectively.14
Analyses of the Rotterdam registry showed patients with AMI to have MACE rates of 7.5% and 10.4% 30 days after the implantation of a sirolimus-eluting and bare-metal stents, respectively.15 The 30-day results obtained in the present study using a passive-coated stent are therefore within the range of the drug-releasing stents. The mortality rate 6 months after stent implantation was 4.6%, which is consistent with the results obtained in largescale stent studies. For example, a meta-analysis of 11 clinical studies showed a mortality rate of approximately 5% after 6 months,16 while in the TYPHOON study — primary PCI in patients with ST-segment elevation — a death rate of only 2.2% after 1 year for the BMS group occurred.19
The incidence of MACE after 6 months was 24.2% and was thus quite consistent with the results of the Canadian STAT study on patients with acute STEMI which also reported a MACE rate of 24.2% after primary stent implantation.17 Similar results were obtained in a recently published comparative study from Germany.18 In this study, the MACE rate for the BMS group was 22% (death: 4%, reinfarction: 2%, restenosis rate: 18%). However, there was a trend towards a possible advantage of the sirolimus-eluting stent, since the corresponding MACE rate was significantly lower (6%), although there was no difference in total mortality.
In the very recent TYPHOON study19 the use of sirolimus-eluting stents significantly reduced the rate of target vessel revascularization at 1 year compared to a BMS. The primary endpoint (target vessel failure, recurrent myocardial infarction, or target vessel revascularization) at 8 months was 7.3% versus 14.3% in the BMS group (p = 0.004).
In general, when comparing different studies, it is important to take into consideration that the patient populations may be very different. In this context, Yip and colleagues showed that patients with AMI and elevated C-reactive protein (CRP) (Group 1: hsCRP > 2.37 mg/L) had significantly higher MACE rates (23.5%) than the comparator group (4.1%) with lower CRP (hsCRP 2.37 mg/ L).19 Similarly, concomitant diabetes can increase the MACE rate after coronary intervention in the presence of AMI by a factor of 2.7. The same effect was observed for decreased left ventricular ejection fraction or the presence of cardiogenic shock.21
The PREMIER registry demonstrated that stopping thienopyridine therapy by 30 days after DES application was strongly associated with subsequent mortality.22 In our registry, clopidogrel was stopped 30 days after the placement of the passive-coated stent. Whether this influenced our results will be analyzed in future studies.
In conclusion, the results obtained in the present pilot study show that passive-coated stents can produce good results. The data presented herein provides the foundation for the generation of a robust hypothesis and facilitates the estimation of the number of cases needed for clinical comparative studies with other coronary stents, particularly DES, for this indication on the basis of actual data.
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