This was a single-center prospective, randomized trial approved by the ethnics committee at institution, with all patients giving their written informed consent. The study was conducted between August 2001 and June 2003.

155 coronary artery disease patients were scheduled to undergo elective PCI for single, short (<15 mm in length), de novo lesions in native coronary arteries with diameters between 2.5 and 4.0 mm. The patients with left main diseases, bifurcation lesions, graft stenosis and left ventricular dysfunction were excluded. ReoPro^®-coated and control stents were implanted in 77 and 78 patients, respectively.

A plasma polymerization reaction was performed to attach amine radicals to the stent surface. A stent was fixed in a tubular reactor made of a Pyrex glass tube, and then the pressure dropped to less than 5 mtorr using a vacuum pump. For attachment of the amine radicals to the stent surface, diaminocyclohexane (DACH) monomer was drifted into the tubular reactor at a constant dose rate (0.96 SCCM) and a plasma generated using a radiofrequency power generator. The power for polymerization of the plasma was 100 W for 5 minutes and then 60 W for 15 minutes.

ReoPro^® (Centocor BV, Leiden, Netherlands) is a human-murine chimeric antibody Fab fragment (c7E3 Fab), which directly blocks glycoprotein IIb/IIIa receptors. A glass tube, 7 cm in length, with a 1 cm in diameter, was boiled in water for 5 minutes, removed and allowed to dry in an incubator. 2 mL of ReoPro^® solution was also delivered to this glass tube, and the stent immersed in the solution. The carboxy radical of ReoPro^® was introduced to the amine radicals attached to the stent to achieve covalent bonds and improved the attachment power between the stent and ReoPro^®. This reaction was performed for 1 hour, after which the stent was removed and allowed to dry for more than 24 hours. The ReoPro^®-coating on the surface of the stent was confirmed by scanning electron microscopy (Figure 1, 2). For the release kinetics of the ReoPro^® from the stent, the stent was placed in a glass vial and immersed in 100 ml of phosphate-buffered saline. The amount of ReoPro^® released into the buffer solution was measured using the UV absorbance at 278 nm (Figure 3).

In an animal study using a porcine coronary stent restenosis model, ReoPro^®-coated stents were found to decreased the neointima area, percent diameter of stenosis and proliferating cell nuclear antigen positive rate more than the control stents¹⁷⁾.

Patients were randomly assigned to the groups in a 1:1 ratio. Lesions were treated with the use of standard interventional procedures. Each patient received one 17 mm or 18 mm stent. All lesions were pre-dilated. After successful predilation, the stents were mounted onto the delivery system and inflated to 10 to 16 atm.

All patients received aspirin (300 mg at least 12 hours prior to stent implantation and 100–200 mg daily, indefinitely) and clopidogrel (300 mg at least 6 h prior to stent implantation and 75 mg daily for 30 days). A bolus dose of 5,000 units of Heparin was given intravenously just before the PCI to maintain the activated clotting time to between 300 and 350 seconds over the duration of the procedure. When dalteparin, a low molecular weight heparin, was used, an initial bolus of 2,500 units was administered as a vascular sheath and advanced to an additional dose of 5,000 to 7,000 units during PCI. Successful PCI was defined as a residual stenosis of <30% with TIMI (Thrombolysis in Myocardial Infarction) flow ≥III, with no complications, such as Q wave acute myocardial infarction (AMI), emergent revascularization or cardiac death. Each angiogram or IVUS sequence was preceded by 200 to 300 μg of intracoronary nitroglycerin. The angiograms were analyzed with a validated QCA system (Phillips H5000 or Allular DCI program). Quantitative analyses of all angiographic data were performed by an independent skillful doctor. In-stent restenosis was defined as stenosis of ≥50% of the luminal diameter. Late lumen loss was defined as the difference between the minimal lumen diameters immediately after the stenting compared to that on the six month follow-up angiogram.

Bleeding events were classified as major, minor or insignificant according to the criteria of the TIMI Study group. Major bleeding events were defined as intracranial bleeding or a bleeding event that caused a decrease in hemoglobin of ≥4 g/dL or required a transfusion of ≥3 units of blood. Minor bleeding was defined as that resulting in a hemoglobin decrease of <4 g/dL or which required a transfusion of <3 units of blood. Thrombocytopenia was defined as a platelet count of 100×10⁹/L.

The primary end points were in-stent late lumen loss by quantitative angiography and a composite of major cardiac events, including cardiac death, any myocardial infarction and TVR at 12 months after the procedure. The secondary end points were percentage of the lumen diameter stenosis and the rate of restenosis.

Statistical analyses were performed with the aid of the commercially available software (SPSS Version 11). The data are presented as rates or mean values±SD. Probability values are two-sided with the Student t- and Fisher’s exact tests for continuous and categorical variables, respectively. A value of p < 0.05 was considered significant.

In terms of gender and age, the ReoPro^® stent group consisted of 64 males (83.1%), with a mean age of 56±10 years, and control stent group consisted of 53 males (67.9%), with a mean age of 57±11 years. There were no differences in the clinical diagnoses of the two groups, unstable angina pectoris was the most common: 39 patients (50.6%) and 39 patients (50.0%) in the ReoPro^® and stent groups, respectively. The number of patients that had previously undergone PCI were 4 (5.2%) and 5 (5.4%) in the ReoPro^® and control stent groups, respectively. There were no significant differences in risk factors for coronary artery disease, clinical diagnosis and left ventricular ejection fraction (Table 1).

Stenting was successfully performed in all patients, without the need for additional stenting and with no complications. The target artery, lesion classification by the ACC/AHA classification, TIMI flow and mean reference diameter and lesion length were similar between the two groups. The stent sizes and lengths were 3.32±0.35 and 17.1±1.1 mm, and 3.28±0.43 and 17.5±4.4 mm in the ReoPro^® and control stent groups, respectively, which were not significant (Table 2).

The PCI success rates were 100% in both groups. During hospitalization, an emergent percutaneous revascularization for myocardial infarction due to acute stent thrombosis occurred in 1 patient of the control stent group (Table 3). No events of major and minor bleeding occurred in either group. The incidences of bleeding complications were not significantly different (Table 4).

A 6-month follow-up coronary angiography was performed in 48 (62.3%) and 51 (65.4%) of the ReoPro^® and control stent groups, respectively. At the six-month follow-up angiogram, the minimal luminal diameter of the stent segment was significantly greater in the ReoPro^® stent group. The late losses were 0.33±0.28 and 0.88±0.41 mm in ReoPro^® and control stent groups (p=0.002), and the in-stent restenosis (ISR) developed in 7 (14.6%) and 15 (29.4%) patients in the ReoPro^® and 15 control stent groups, respectively (p=0.062) (Table 5, Figure 4).

A total of 97% patients were followed up for a period of 14.1±6.9 months. During the follow-up period, two patients in the control stent group suffered a myocardial infarction, but there were no cardiac deaths in either group. TVR was performed in 11 (14.7%) and 7 (9.2%) patients of the control and ReoPro^® stent groups, respectively (Table 6).