Pharmaceutical aspects of drug eluting stents.

This review focuses on the pharmaceutical aspects of the development of drug eluting stents. It discusses the different processes that can be used to obtain a controlled release of a drug from the stent as well as the coatings therefore applied. Results obtained for stents already available on the market or in a far stage of development are discussed. In a final part possible future research areas as well as expected new evolutions in the design of drug eluting stents are presented.

Methotrexate loaded SAE coated coronary stents reduce neointimal hyperplasia in a porcine coronary model.

OBJECTIVE: To evaluate the effect of stent based methotrexate delivery on neointimal hyperplasia. METHODS: Stainless steel coronary stents and biological polymer coated (SAE) stents were randomly implanted in coronary arteries of pigs with a stent to artery ratio of 1.1:1. The pigs were killed after five days (10 stents) or four weeks (20 stents). Second, stainless steel coronary stents were dip coated in a 10 mg/ml methotrexate-SAE polymer solution, resulting in a total load of 150 microg methotrexate/stent. SAE coated stents and methotrexate loaded stents were randomly implanted in porcine coronary arteries with a stent to artery ratio of 1.2:1 and followed up to four weeks. RESULTS: SAE coated stents and bare stents elicited a similar tissue response at five days. At four weeks, neointimal hyperplasia induced by the coated stents was less pronounced than with the bare stents (1.32 (0.66) v 1.73 (0.93) mm2, p > 0.05). In vitro drug release studies showed that 50% of the methotrexate was released in 24 hours, and all drug was released within four weeks. No impact on vascular smooth muscle cell proliferation or viability was observed in in vitro cell cultures. At four weeks the arteries with methotrexate loaded stents had decreased peristrut inflammation and neointimal hyperplasia (1.22 (0.34) v 2.25 (1.28) mm2, p < 0.01). CONCLUSIONS: SAE coating had an excellent biocompatibility with vascular tissue. Stent based delivery of methotrexate in the SAE coating effectively reduced neointimal hyperplasia in a porcine coronary stent model, potentially due to reduced peristrut inflammation.

Long term effects of nisoldipine on the progression of coronary atherosclerosis and the occurrence of clinical events: the NICOLE study.

BACKGROUND: Earlier angiographic studies have suggested that calcium antagonists may prevent the formation of new coronary lesions and the progression of minimal lesions. Conversely, a meta-analysis suggested that these drugs may increase cardiovascular mortality and morbidity in patients with coronary heart disease. OBJECTIVE: To investigate whether nisoldipine retards the progression of coronary atherosclerosis or reduces the occurrence of clinical events. DESIGN AND SETTING: The NICOLE study (NIsoldipine in COronary artery disease in LEuven) is a single centre, randomised, double blind, placebo controlled trial with coronary angiography at baseline, six months, and three years of follow up. PATIENTS: 826 patients who had undergone successful coronary angioplasty were randomised to nisoldipine 40 mg once daily or placebo. The intention to treat and per protocol population consisted of 819 and 578 patients, respectively. RESULTS: In the per protocol population, 625 of the nisoldipine treated and 655 of the placebo treated patients (NS) showed angiographic progression in at least one coronary arterial segment, defined as an increase in diameter stenosis of > or = 13%. The average minimum luminal diameter of the non-dilated lesions decreased by 0.163 mm and 0.167 mm in the nisoldipine and placebo groups, respectively (NS). The respective numbers of new lesions detected were 7 and 13 (NS). In the intention to treat population, the rates of death, stroke, and acute myocardial infarction were similar in both treatment groups. However, nisoldipine use was associated with fewer revascularisation procedures and thus the percentage of patients with any clinical event was lower (44.6% v 52.6%, p = 0.02). CONCLUSIONS: Nisoldipine has no demonstrable effect on the angiographic progression of coronary atherosclerosis or the risk of major cardiovascular events but its use is associated with fewer revascularisation procedures.

Assessment of myocardial viability in a porcine model of chronic coronary artery stenosis with dual dose dobutamine magnetic resonance imaging.

In a non-surgical porcine coronary stenosis model resulting in chronic left ventricle dysfunction, we aimed in this study to evaluate the potential of magnetic resonance imaging (MRI) to distinguish dysfunctional but viable from necrotic myocardium by using multiple levels of dobutamine inotropic stimulation during a cine MRI protocol (F.P. van Rugge et al. Circulation 1994; 90: 127-138). We compared our results with histopathology. We were able to demonstrate a biphasic effect at increasing doses of dobutamine in a subgroup of animals with a high-grade coronary stenosis, while in another subgroup the coronary stenosis produced a chronic myocardial infarction, in which no functional recovery could be obtained. In this experimental protocol, dual dose dobutamine MRI proved to be an accurate and reproducible technique to perform viability studies in chronic obstructive coronary artery disease. It permits distinguishing chronic ischemic, but viable myocardium from infarcted tissue. The detection of chronically underperfused but potentially salvageable myocardium is of significant clinical importance since it may aid in determining which patients are eligible for revascularization.

Optimal dosing of intravascular low-power red laser light as an adjunct to coronary stent implantation: insights from a porcine coronary stent model.

BACKGROUND: It is believed that restenosis following coronary interventions is the result of endothelial denudation that leads to thrombus formation, vascular remodeling, and smooth muscle cell proliferation. Low-power red laser light (LPRLL) irradiation enhances endothelial cell growth in vitro and in vivo, and reduces restenosis in animal models. The present study investigated the optimal dose of intravascular LPRLL therapy in the prevention of in-stent stenosis in a porcine coronary stent model. METHODS AND RESULTS: Selected right coronary artery segments were pretreated with a LPRLL balloon, delivering a dose of 0 mW during 1 min (group 1, n = 10), 50 mW during 1 min (group II, n = 10), or 100 mW during 1 min (group III, n = 10) before stenting. Quantitative coronary analysis of the stented vessel was performed before stenting, immediately after stenting, and at 6 weeks follow-up. The pigs were sacrificed, and histologic and morphometric analyses were conducted. At 6 weeks, minimal luminal stent diameter was significantly narrower in the control group compared to the 50-mW dose group (p < 0.05). These results were confirmed by morphometric analysis. Neointimal area was also significantly decreased in the 50-mW dose group. CONCLUSIONS: Intravascular LPRLL contributes to reduction of angiographic in-stent restenosis and neointimal hyperplasia in this animal model. The optimal dose using the LPRLL balloon system seems to be approximately 5 mW delivered during 1 min.

L-arginine administration reduces neointima formation after stent injury in rats by a nitric oxide-mediated mechanism.

The clinical outcome of vascular stenting is limited by in-stent stenosis. Increased nitric oxide (NO)/cGMP signaling by L-arginine (L-Arg) supplementation, the substrate for NO synthase (NOS), or NOS gene transfer may reduce in-stent neointima formation. After stenting, vascular cell proliferation in rat carotid arteries, as measured by 5'-bromodeoxyuridine (5'-BrdU) incorporation, indicated 15+/-8%, 28+/-5%, and 33+/-7% 5'-BrdU-positive vascular cells at 4, 7, and 14 days, respectively. Reporter beta-galactosidase gene transfer efficacy was evidenced by 30% beta-galactosidase-expressing medial smooth muscle cells at 14 days. The intima-to-media ratio (I/M) progressively increased to 2.32+/-0.24 at 14 days. To target in-stent neointima formation, animals were infected with adenoviral vectors (4x10(10) plaque-forming units per mL) expressing NOS2 (AdNOS2) or no transgene (AdRR5), or they received daily doses of L-Arg (500 mg. kg(-1). (d-1) IP). The neointima at 14 days was smaller in L-Arg-treated than in untreated rats (I/M 1.25+/-0.35 vs 2.32+/-0.24, P<0.05, n=7 each) or in AdRR5- and AdNOS2-infected rats (I/M 2.57+/-0.43, n=7 and 1.82+/-0.75, n=8, respectively; P<0.05 for both). The effect of L-Arg was abolished by simultaneous administration of N(G)-nitro L-arginine methyl ester, an NOS inhibitor (2.03+/-0.39, P<0.05, vs L-Arg). Inflammation was markedly less in L-Arg- and AdNOS2-treated than in AdRR5-infected rats. Supplemental L-Arg reduces neointima formation after stenting by way of an NOS-dependent mechanism and may be a valuable strategy to target in-stent stenosis.

Quantification of the spectrum of changes in regional myocardial function during acute ischemia in closed chest pigs: an ultrasonic strain rate and strain study.

The objectives of this study were to define the spectrum of regional myocardial function changes during acute ischemia in closed chest animals by using newly developed ultrasonic strain rate and strain indexes derived from regional color Doppler myocardial imaging (CDMI) velocity data. Myocardial ischemia was induced in 18 pigs either with acute total 20-second occlusions (group 1, n = 12) or graded hypoperfusion (40 to 0 mL/min, group 2, n = 6) of the circumflex coronary artery. In addition, a dobutamine challenge (5 to 10 microg/kg per minute) was performed during sustained subtotal ischemia (10 mL/min) in group 2. CDMI acquisitions with parasternal views monitored the myocardial posterior wall function. Regional radial strain rate and strain (epsilon(r)) were measured for systole, isovolumic relaxation, early diastole, and atrial filling, respectively. During total and graded ischemia, epsilon(r) profiles were consistently modified, showing a delayed onset and a decrease in regional systolic thickening as well as increased postsystolic thickening. Radial strain rate and epsilon(r) indexes decreased consistently during systole and early diastole and increased during isovolumic relaxation. End-systolic epsilon(r) could differentiate total ischemia from severe hypoperfusion (10 mL/min), decreasing from 32% +/- 8% to 16% +/- 5% (versus 60% +/- 10% at baseline). During dobutamine infusion (10 microg/kg per minute), end-systolic epsilon(r) tended to decrease from 27% +/- 5% to 18% +/- 11%, whereas postsystolic thickening increased by 2-fold (P <.05). The combined analysis of regional deformation characteristics and global cardiac event timing derived from CDMI data can identify and quantify regional function changes induced by experimental acute ischemia in closed chest pigs. This would appear to be a potentially promising new noninvasive approach to the clinical evaluation of ischemia-induced changes in segmental myocardial function.

The influence of stent length on clinical and angiographic outcome in patients undergoing elective stenting for native coronary artery lesions; final results of the Magic 5L Study.

AIMS: To prospectively evaluate the influence of stent length on 6 month clinical and angiographic outcome, in patients with native coronary lesions up to 45 mm in length, undergoing elective Magic Wallstent implantation. METHODS AND RESULTS: On the basis of pre-procedural angiography, 276 patients (aged 61.3+/-10.2 years; 78.6% male; 41.7% unstable angina) with a total of 302 lesions were prospectively assigned to one of five different length categories of Magic Wallstent. Angiography in multiple matched projections before and after implantation and at 6 months follow-up was analysed at the core laboratory. Primary end-points for the efficacy analysis were cumulative incidence of major adverse cardiac events and quantitative coronary angiography analysis 6 months after stent implantation. Magic Wallstent implantation was successful in 301 of 302 lesions and in 98.6% a residual stenosis <20% by online quantitative coronary angiography was achieved. At 30 days, 6.2% (1.8% subacute occlusion) of patients had experienced major adverse cardiac events, 27.5% at 6 months and 30.4% at 9 months. Angiographic restenosis occurred in 37%. Restenosis rates for the mini, extra-short, short, medium and long Wallstent groups were 25.9%, 25%, 22.6%, 36.2% and 67.5%, respectively. Multivariate analysis revealed stent length to be independently associated with greater angiographic restenosis and major adverse cardiac events. CONCLUSIONS: While shorter Magic Wallstents provided late outcomes comparable with short balloon-expandable stents, excessive restenosis with longer Wallstents should obviate their use in elective percutaneous intervention. Long coronary lesions provide a challenging substrate for emerging antirestenosis therapies, such as stent coatings and brachytherapy.

Noninvasive quantification of the contractile reserve of stunned myocardium by ultrasonic strain rate and strain.

BACKGROUND: We sought to investigate ultrasonic strain rate and strain as new indices to quantify the contractile reserve of stunned myocardium during dobutamine infusion. METHODS AND RESULTS: Stunning of the left ventricular posterior wall was induced in 9 closed-chest pigs after 30 minutes of severe hypoperfusion followed by 60 minutes of reperfusion of the left circumflex coronary artery territory. A second group of 7 animals had no coronary occlusion and served as normal controls. An incremental dobutamine infusion protocol was used in both groups. Changes in regional radial function were monitored by use of ultrasound-derived maximal systolic radial strain rate (SR) and systolic strain (epsilon). In the control group, dobutamine induced an increase in both SR and maximal dP/dt, which correlated linearly (r=0.85). Conversely, epsilon values increased at low doses of dobutamine (2.5 to 5 microg. kg(-1). min(-1)) but decreased during higher infusion rates (10 to 20 microg. kg(-1). min(-1)). During circumflex hypoperfusion, SR and epsilon of the posterior wall decreased from 5.0+/-0.3 s(-1) and 63+/-6% to 2.9+/-0.3 s(-1) and 27+/-4%, respectively (P<0.01). After 60 minutes of reperfusion, SR and epsilon failed to fully resume because of stunning, averaging 3.6+/-0.2 s(-1) and 35+/-3%, respectively (P=0.12 versus ischemia, P<0.05 versus baseline). During dobutamine infusion, SR increased at 5 microg. kg(-1). min(-1) and exceeded baseline values at 20 microg. kg(-1). min(-1) (P<0.05), whereas epsilon increased only at high doses and remained below baseline levels (P<0.05). CONCLUSIONS: The changes in regional function of stunned myocardium during inotropic stimulation could be characterized by use of ultrasonic deformation parameters. During dobutamine infusion, strain-rate values quantified the contractile reserve better than strain values.

Intravascular low-power laser irradiation after coronary stenting: long-term follow-up.

BACKGROUND AND OBJECTIVE: A high restenosis rate remains a limiting factor for percutaneous transluminal coronary angioplasty and stenting. The objective of this study was to evaluate the effect of intravascular red laser therapy (IRLT) on restenosis after stenting procedures in de novo lesions. STUDY DESIGN/MATERIALS AND METHODS: A total of 68 consecutive patients were treated with IRLT in conjunction with coronary stenting procedures. Mean lesion length was 16.5 +/- 2.4 mm. Reference vessel diameter (RVD) and pre-minimal lumen diameter (MLD) were 2.90 +/- 0.15 mm and 1.12 +/- 0.26 mm, respectively. RESULTS: After treatment, MLD was 2.76 +/- 0.32 mm with no procedural complications or in-hospital adverse events. Angiographic follow-up (n = 61) revealed restenosis in nine patients (14.7%) with rate by artery size of > 3 mm (n = 21) 0%; 2.5--3.0 mm (n = 28) 14.2%; and < 2.5 mm (n = 12) 41.6%. CONCLUSION: Intravascular red light therapy is safe, feasible, and reduces expected restenosis rate after coronary stenting.

Usefulness of Nisoldipine for prevention of restenosis after percutaneous transluminal coronary angioplasty (results of the NICOLE study). NIsoldipine in COronary artery disease in LEuven.

The NIsoldipine in COronary artery disease in LEuven (NICOLE) study investigates (1) whether nisoldipine, a dihydropyridine calcium antagonist, reduces the progression of minor coronary arterial lesions in the long term, and (2) whether it reduces the restenosis rate after successful percutaneous transluminal coronary angioplasty (PTCA). The NICOLE study is a single-center, randomized, double-blind trial in 826 patients, who underwent a successful PTCA. Nisoldipine 40 mg coat-core or placebo was started the morning after the procedure and continued for 3 years. All coronary arterial segments were measured on preprocedural angiogram and on the second follow-up angiogram at 3 years. On the first follow-up angiogram at 6 months only the dilated segments were measured. Although the study is still ongoing until the primary end point is reached, we report in this study the angiographic restenosis data as well as the clinical events observed at 6-month follow-up. The per-protocol population consisted of 646 patients. Restenosis, defined as a > or =50% loss of the initial gain (National Heart, Lung, and Blood Institute criterion IV) occurred in 49% and 55% of the 308 nisoldipine-treated and the 338 placebo-treated patients, respectively (p = NS). At follow-up, the rates of death and myocardial infarction were low and similar in both groups, but in the nisoldipine group, less patients required early coronary angiography (18% vs 26%, p = 0.006) and subsequent revascularization procedures (32% vs 41%, p = 0.057). Thus, nisoldipine did not significantly reduce the angiographic restenosis rate after PTCA, but reduced the number of repeat revascularization procedures, which may be due to its antianginal action.

A novel platinum-iridium, potentially gamma radioactive stent: evaluation in a porcine model.

In-stent restenosis (ISR) is a major problem within stented arteries. Surface treatment of stents with platinum and gold were found to have the maximum charge with least neointima formation (NF). This study was designed to evaluate platinum (maximum electrical charge) as a material to make stents to reduce NF. Iridium was added to make an alloy suitable for stent manufacture, with the potential to make the stent radioactive. We implanted the novel platinum-iridium (PI) stent in 10 porcine coronaries and compared to the Palmaz-Schatz (PS) stent implanted in 8 coronary arteries. Six weeks after implantation, angiography of the stented vessel was performed before sacrifice. The coronaries were perfusion-fixed and stained, and vessel parameters were analyzed by computer-aided histomorphometry. The thrombus formation and the inflammatory response was less in the PI stent (0.04 +/- 0.1 vs. 0.24 +/- 0.2, P = 0.005; and 1.1 +/- 0.5 vs. 2.4 +/- 0.3, P < 0.001). The NF from PI-stented arteries was smaller in size than the PS controls (1.9 +/- 0.6 mm(2) vs. 2.4 +/- 0.4 mm(2), P = 0.06). However, PI stents presented with higher recoil than the PS stent (16% vs. 5%, P < 0.001). Platinum-iridium is a highly biocompatible material with high performance, low inflammatory response with small NF. This stent does not lead to thrombus formation and has the potential (due to the presence of iridium) to be irradiated to form a gamma radioactive stent. Cathet. Cardiovasc. Intervent. 51:364-368, 2000.

Long-term follow-up after coronary stenting and intravascular red laser therapy.

A high restenosis rate remains a limiting factor for coronary angioplasty and stenting. Recently, use of intravascular red light therapy (IRLT) has been shown to be effective in different animal models and in humans in reducing the restenosis rate. Sixty-eight patients were treated with IRLT in conjunction with coronary stenting procedures. Mean age was 64 +/- 9 years. Treated lesions were type A (11), type B (42), and type C (18) with a mean lesion length of 16.5 +/- 2.4 mm. Reference vessel diameter and minimal lumen diameter (MLD) before therapy were 2.90 +/- 0.15 and 1.12 +/- 0.36 mm, respectively. After stenting and laser irradiation, MLD was 2.76 +/- 0.39 mm. No procedural complications or in-hospital adverse events occurred. All patients were followed up as depicted in the protocol. Sixty-one patients underwent angiographic restudy, which revealed restenosis in 9 patients (14.7%). Observed restenosis rate by artery size was > 3 mm (n = 21, 0%), 2.5 to 3.0 mm (n = 28, 14.2%), and <2.5 mm (n = 12, 41.6%). We conclude that IRLT is safe and feasible and reduces the expected restenosis rate in patients after coronary stenting in arteries of >2.5 mm.

Evaluation of the biocompatibility of two new diamond-like stent coatings (Dylyn) in a porcine coronary stent model.

UNLABELLED: Hydrogenated diamond-like carbon films (DLC, a-C:H), deposited using plasma-assisted or ion beam-assisted techniques, offer great potential as self-lubricating coatings in many tribological applications. Additionally, studies on biocompatibility have shown that DLC is an inert, impervious hydrocarbon with properties suitable for use in the biomedical field. One particular class of modified DLC coatings are diamond-like nanocomposite coatings (DLN or Dylyn , Bekaert, Kortrijk, Belgium), which offer promising solutions for many industrial applications. In this study, the biocompatibility of two diamond-like stent coatings are evaluated in a porcine coronary stent model. METHODS: Either coated or non-coated stents were randomly implanted in two coronary arteries of 20 pigs so that each group contained 13 stented arteries. Pigs underwent a control angiogram at 6 weeks and were then sacrificed. Quantitative coronary analysis before, immediately after stent implantation, and at 6 weeks was performed using the semi-automated Polytron 1000 system (Siemens, Erlangen, Germany). Morphometry was performed using a computerized morphometric program. Angiographic analysis showed similar baseline selected arteries and post-stenting diameters. At 6-week follow-up, there was no significant difference in minimal stent diameter. Histopathology revealed a similar injury score in the 3 groups. Inflammation was significantly increased in the DLN-DLC coating group. Thrombus formation was significantly decreased in both coated stent groups. Neointimal hyperplasia was decreased in both coated stent groups; however, the difference with the non-coated stents was not statistically significant. Area stenosis was lower in the DLN-coated stent group than in the control group (41 +/- 17% vs. 54 +/- 15%; p = 0.06). CONCLUSION: The results indicate that the diamond-like nanocomposite stent coatings are compatible, resulting in decreased thrombogenicity and decreased neointimal hyperplasia. Covering this coating with another diamond-like carbon film (DLC) resulted in an increased inflammatory reaction and no additional advantage compared to the single-layer diamond-like nanocomposite coating.

Coronary radiation therapy with liquid rhenium-186: a first clinical experience.

BACKGROUND: Coronary radiation therapy (CRT) is a new, attractive approach for the treatment and prevention of restenosis after percutaneous coronary interventions (PCI). The RadioCath device consists of a standard balloon dilatation catheter that can be charged with a solution of sodium 186Re perrhenate, a predominant beta emitter. The safety and performance of this new device was evaluated in a pilot trial. METHODS AND RESULTS: Thirty-three patients with a de novo lesion in a native coronary artery were treated with the RadioCath device after successful angioplasty. The average dwell time to deliver a dose of 20 Gy at 0.5 mm into the vessel wall was 418+/-64 seconds. The treatment was well tolerated by most of the patients. In 79%, only one inflation cycle was required to deliver the prescribed dose. There were two procedural device-related complications (5.9%) and three minor procedural related in-hospital complications (9%). CONCLUSIONS: CRT using a balloon catheter device, charged with a sodium 186Re perrhenate solution, seems feasible and safe. Clinical and angiographic 6-month follow-up data are pending.

M cells and transmural heterogeneity of action potential configuration in myocytes from the left ventricular wall of the pig heart.

OBJECTIVE: Heterogeneity of action potential configuration in the left ventricle (LV), and the contribution of M cells to it, has been observed in the human heart and is important for arrhythmogenesis. Whether the pig heart has similar properties remains a controversial but important issue as the pig heart is currently under study for use in xenotransplantation. METHODS: Single myocytes were enzymatically isolated from the epicardium (EPI, ncells = 29), midmyocardium (MID, ncells = 38), and endocardium (ENDO, ncells = 13) of the free LV wall (npigs = 26, 14-22 weeks old, 55-80 kg), and studied at different stimulation rates during whole-cell recording (normal Tyrode's solution, K(+)-aspartate-based pipette solution, 50 microM K5fluo-3 as [Ca2+]i indicator, 37 degrees C). Standard six-lead ECGs were recorded from anesthetized pigs. RESULTS: The action potential duration (APD) was not significantly different at 0.25 Hz vs. 2 Hz for the majority of cells in all three layers. However, a subpopulation of cells behaved like M cells and had a very steep frequency response (APD90 at 0.25 Hz 538 +/- 30 ms, vs. 337 +/- 9 ms at 2 Hz, P < 0.05, n = 22). These cells were found predominantly in the MID layer (34% of cells), but also (24%) in EPI. M cells had a more pronounced spike-and-dome configuration, with a significantly larger phase 1 magnitude and plateau voltage. The frequency response of these parameters was different from the other cell types. [Ca2+]i transients tended to be larger in M cells. For the in vivo ECG of anesthetized pigs, the QT time was close to the APD90 of M cells, and J waves were seen in 7/12 recordings. CONCLUSIONS: In young adult pigs, M cells can be identified by a steep frequency response of the APD and by a spike-and-dome configuration. These cells are mostly, but not exclusively, found in the midmyocardium, and could contribute to the ECG characteristics. Their properties may however be different from those of other species, including humans.

Evaluation of fluorinated polymers as coronary stent coating.

In this report, some fluorinated polyphosphazenes and polymethacrylates were selected for evaluation as coronary stent coating. After applying the polymer film by dipcoating, the stents were implanted in porcine coronary arteries. No acute thrombotic occlusions were observed. The neointimal proliferation was studied by a 6 week follow-up of the minimal lumen stented diameter, using quantitative coronary analysis. All polymers demonstrated a slight hyperplasia, resulting in a 10-20% lumen narrowing at follow-up. Only for one fluorinated polymethacrylate, PFM-P75, a minimal neointimal response (3% lumen narrowing) was found.

Intravascular low-power red laser light as an adjunct to coronary stent implantation: initial clinical experience.

Low-power red laser light (LPRLL) irradiation enhances endothelial cell growth in vitro and in vivo and reduces restenosis in animal models. The present study reports the preliminary clinical experience in our center. Eighty-one patients were treated with LPRLL, 30 mW/1 min, for in-stent restenosis (n = 27), elective stenting for recurrent restenosis (n = 16), and stenting for treatment of a suboptimal PTCA result (n = 38). All interventions were successful and no major adverse events due to LPRLL therapy were observed. At follow-up, 12 patients (14.8%) underwent an early control coronarogram due to target vessel restenosis. At 6 months, another 20 patients showed a significant restenosis of the target vessel. Preliminary clinical evaluation demonstrates that LPRLL is feasible and safe. The preliminary results suggest that LPRLL results in a decrease of in-stent restenosis when used during primary stenting.