Clinical and Angiographic Safety and Efficacy Trial with a New
Coronary Stent: The RESTOR Study of the R Stent

Over the last decade, coronary stent implantation has gradually become the choice treatment of choice in percutaneous coronary intervention (PCI).1,2 The enhanced safety of coronary interventions, the lower complication rate, the better immediate angiographic and functional results and especially the lower restenosis rate compared to balloon angioplasty have won the battle with other interventional treatment modalities in all but a few types of lesions.3–9 Today, a huge number of different models and makes of coronary stents are available. In the early years of the 21st century all attention is focused on the new development of drug eluting stents, promising the ultimate solution of the restenosis problem.10,11 An argument could exist that the mechanical properties of drug-eluting stents become increasingly important as indications shift towards more complex and multivessel PCIs. A new stent design therefore has to offer optimal radial strength, vessel conformability, side branch access, and a high flexibility and low profile for ease of delivery. Moreover, new stents still have to be evaluated with proven clinical and angiographic scientific study methods before they can safely be further developed into drug carrying and eluting platforms. The RESTOR trial (R Stent Efficacy and Safety Trial by Orbus) was undertaken to evaluate the safety and efficacy of a novel stent design, the R stent, by measuring Major Adverse Cardiac Events (MACE) at 210 days post implantation and by assessing quantitative coronary angiography (QCA) results at 6 months follow-up. Methods Patients. Between May and December 2000 a total number of 121 patients (mean age 58.8 years, range 32–79 years, 75% male and 25% female) were included in 2 Dutch centers: the Amphia Hospital Breda and the Thoraxcenter Rotterdam. Their baseline demographic and angiographic characteristics are shown in Table 1. Patients with symptomatic stable or unstable angina pectoris or documented silent ischemia and a significant single, de novo coronary lesion of a length up to 25 mm and a reference diameter between 2.75 and 4.0 mm could be included in this trial. Patients with a total occlusion, unprotected left main stem disease, large intracoronary thrombus, acute myocardial infarction, an ejection fraction below 30%, and known allergies to aspirin, clopidogrel, heparin or stainless steel were excluded. The study protocol was approved by the local ethics committees and written, informed consent was obtained in all cases. Stent design. The R Stent (Orbus Medical Technologies, Ft. Lauderdale, Florida) is a balloon expandable device fashioned from 316LVM stainless steel tubing. The patented dual helix design of the R Stent is unique. It provides more flexibility than regular slotted tube configurations yet maintains high radial strength which is a weakness of coil wire designs. The strut thickness of the R Stent results in moderate radiopacity without obscuring the lesion area. The cell geometry allows for easy side branch access and dilatation of side branch orifices up to 4.5 mm without distortion of the opposite stent wall. The R Stent is pre-mounted on a low-profile rapid exchange PTCA catheter. Stent implantation. All PCI procedures were carried out through femoral artery access and 6 French guiding catheters. The R stents were implanted after predilatation with adequately sized balloon catheters. Additional stents were implanted in cases of suboptimal results or edge dissections in adjacent segments. All patients received an oral loading dose of 300 mg clopidogrel and 5000–10000 units of intravenous heparin before the procedure, and were subsequently treated with ASA 80–300 mg. and clopidogrel 75 mg daily. Glycoprotein IIb/IIIa inhibitors were administered if considered necessary by the operator. Quantitative coronary angiography. Coronary angiography was performed before and after PCI and at 6 months follow-up in multiple views after intracoronary administration of nitrates. Quantitative analysis with standardized edge detection techniques using the CAAS II system (Pie Medical, Maastricht, the Netherlands) was performed at the independent core laboratory (Cardialysis, Rotterdam, the Netherlands). Restenosis was defined as a stenosis of 50% or more at the follow-up angiogram. Late luminal loss was defined as the difference between the minimal luminal diameter (MLD) after the procedure and at 6 months. Endpoints and definitions. The primary endpoint of the study was the incidence of major adverse cardiac events (MACE) at 210 days post-procedure. MACE were defined as cardiac death, MI (Q-wave and non-Q wave, CK levels > 2 times normal), CABG and TLR. The secondary endpoints were MACE at 30 days post-procedure, major bleeding and vascular complications, and angiographic parameters (percentage diameter stenosis, minimal luminal diameter and restenosis rate) by means of central core laboratory analysis. Angiographic success was defined as a diameter stenosis post-procedure of Statistical methods. The statistical and safety analysis were performed according to the intention-to-treat principle. Statistical significance testing was not performed because this was an observational, non-randomized study. Descriptive statistics were performed for all relevant variables. For categorized variables the data were collected as counts and incidence rates, for continuous variables as mean, standard deviation, median, minimum and maximum. The occurrences of major clinical events and target lesion revascularization were analyzed using the actuarial life table method. Results Acute results. The diameters and lengths of the R Stents used in this study are shown in Table 2. A single study stent was implanted in 102/121 patients (84.3%), 2 study stents in 16/121 patients (13.2%), and 3 study stents in 1 patient (0.8%). In one patient (0.8%) a non-study stent was implanted as well as a study stent because of non-availability of the appropriate size of the study stent at that moment. There was 1 case of emergency CABG because of guidewire-induced spiral dissection in a severely diseased RCA before stent implantation could be attempted. Thus, the angiographic success rate of R Stent implantation, defined as 50% diameter stenosis at angiographic follow-up was 20.8% (21/101 patients). Figure 4 shows the cumulative distribution of diameter stenosis pre- and post-PCI and at follow-up angiography. With numerous new coronary stents becoming available on the market the attention of investigators in this field is shifting towards coating these stents with antiproliferative and other drugs. It is in our opinion however still mandatory to investigate the safety and efficacy of a new design on its mechanical, clinical and angiographic merits using a well established prospective study method and core lab. This is especially true if such a stent will be further developed as a carrier of such drugs in the near future. The RESTOR trial demonstrates that the R Stent as a bare, non-coated stent, is a safe and effective device. It is associated with a high primary success rate and a MACE rate comparable to other modern stainless steel coronary stents.7,12–16 The binary restenosis rate of 20.8% found in this trial is in the expected range for a study with an average stented length of treated segments of 15.7 mm per patient, using more than 1 stent in 19/121 patients (15.7%) (Table 2).17,18 The R Stent has special mechanical properties because of its unique dual helix design. The resulting flexibility can be seen from Figure 4: A single R Stent was implanted easily in a study patient with an extremely tortuous RCA. Other potential advantages such as the suitability of the R Stent for direct stenting and sidebranch/bifurcation treatment will be addressed in future, more specific studies. Conclusions The R Stent is a new coronary stent with a dual helix design, which offers the flexibility, conformability and sidebranch access of a coil stent in combination with the radial strength and scaffolding properties of a tubular stent. The RESTOR study has established its safety and efficacy in an open, prospective clinical endpoint and quantitative angiography trial. Its angiographic restenosis rate lies within the expected range for a bare, non-coated stent. The R Stent is well suited as a platform for the further development of drug-eluting stents. Acknowledgement. The authors wish to acknowledge the helpful support of Cardialysis, Rotterdam, the Netherlands, for their data and manuscript review.

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