Reliability of quantitative coronary angiography of the target lesion immediately and 1 day after coronary balloon and excimer laser angioplasty.

OBJECTIVES: This prospective trial was performed to evaluate the impact of the morphologic complications of angioplasty on the reliability and results of quantitative angiographic assessment of the residual stenosis. BACKGROUND: Postintervention quantitative coronary analysis is limited by a variety of such complications. METHODS: In 199 patients undergoing an early control angiographic study within 24 h after coronary balloon or excimer laser angioplasty (24-h study), detailed quantitative angiographic measurements were performed on the target lesion immediately after intervention and at the 24-h study. Reproducibility of quantitative arteriography was determined by repeat measurements on the same angiogram. RESULTS: Intraobserver/interobserver variability was significantly higher (p < 0.0001/p < 0.03) for the postintervention angiogram than for the 24-h angiogram. Patients were classified into three subgroups with respect to the occurrence of angiographic complications or chest pain after intervention. In patients with angiographic complications after balloon angioplasty alone/stand-alone laser angioplasty/laser angioplasty with adjunctive balloon dilation, a significant difference in mean minimal lumen diameter (p = 0.0001/p = 0.03/p = 0.035) was observed between the immediate postintervention and 24-h angiogram. In patients without angiographic complications or patients with recurrent chest pain undergoing balloon angioplasty, stand-alone or adjunctive laser angioplasty, mean minimal lumen diameter remained nearly unchanged (p = NS). CONCLUSIONS: Angiographic measurements of the target lesion immediately after angioplasty were significantly less reliable than measurements obtained at 24 h after angioplasty in patients with angiographic complications. The occurrence of postintervention vascular complications was associated with significant early lesion changes between the immediate postangioplasty and the 24-h angiogram.

Low molecular weight heparin (reviparin) in percutaneous transluminal coronary angioplasty. Results of a randomized, double-blind, unfractionated heparin and placebo-controlled, multicenter trial (REDUCE trial). Reduction of Restenosis After PTCA, Early Administration of Reviparin in a Double-Blind Unfractionated Heparin and Placebo-Controlled Evaluation.

OBJECTIVES: The specific objective of the REDUCE trial was to evaluate the effect of low molecular weight heparin on the incidence and occurrence of restenosis in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Unfractionated heparin and its low molecular weight fragments possess antiproliferative effects and have been shown to reduce neointimal smooth muscle cell migration and proliferation in response to vascular injury in experimental studies. METHODS: The REDUCE trial is an international prospective, randomized, double-blind, multicenter study. Twenty-six centers in Europe and Canada enrolled 625 patients with single-lesion coronary artery obstructions suitable for PTCA. Three hundred six patients received reviparin as a 7,000-U bolus before PTCA, followed by 10,500 U as an infusion over 24 h and then twice-daily 3,500-U subcutaneous application for 28 days. The 306 patients in the control group received a bolus of 10,000 U of unfractionated heparin followed by an infusion of 24,000 U over 24 h. These patients then underwent 28 days of subcutaneous placebo injections. The primary end points were efficacy (defined as a reduction in the incidence of major adverse events [i.e., death, myocardial infarction, need for reintervention or bypass surgery]), absolute loss of minimal lumen diameter and incidence of restenosis during the observation period of 30 weeks after PTCA. RESULTS: Using the intention to treat analysis for all patients, 102 (33.3%) in the reviparin group and 98 (32%) in the control group have reached a primary clinical end point (relative risk [RR] 1.04, 95% confidence interval [CI] 0.83 to 1.31, p = 0.707). Likewise, no difference in late loss of minimal lumen diameter was evident for both groups. Acute events within 24 h occurred in 12 patients (3.9%) in the reviparin group and 25 (8.2%) in the control group (RR 0.49, 95% CI 0.26 to 0.92, p = 0.027) during or immediately after the initial procedure. In the control group, eight major bleeding complications occurred, and in the reviparin group, seven were observed within 35 days after PTCA. CONCLUSIONS: Reviparin use during and after coronary angioplasty did not reduce the occurrence of major clinical events or the incidence of angiographic restenosis over 30 weeks.

[Simplified production of multimedia based radiological learning objects using the flash format]. / Vereinfachte Herstellung multimedialer radiologischer Lernobjekte mit dem Flash-Format.

PURPOSE: Evaluation of the applicability of the Flash Format for the production of radiological learning objects used in an e-learning environment. MATERIAL AND METHODS: Five exemplary learning objects with different didactic purposes referring to radiological diagnostics are presented. They have been intended for the use within the multimedia, internet-based e-learning environment LaMedica. Interactive learning objects were composed using the Flash 5.0 software (Macromedia, San Francisco, USA) on the basis of digital CT and MR images, digitized conventional radiographs and different graphical elements prepared as TIFF files or in a vector graphics format. RESULTS: After a short phase of initial skill adaptation training, a radiologist author was soon able to create independently all learning objects. The import of different types of images and graphical elements was carried out without complications. Despite manifold design options, handling of the program is easy due to clear arrangement and structure, thus enabling the creation of simple as well as complex learning objects that provided a high degree of attractiveness and interaction. Data volume and bandwidth demand for online use was significantly reduced by the Flash Format compression without a substantial loss of visual quality. CONCLUSION: The universally compatible Flash Format offers an opportunity for the simple production of radiological learning objects that fulfill all relevant needs of modern internet based e-learning environments, such as interactivity, employment of multimedia and convertibility.

Low molecular weight heparin in prevention of restenosis after PTCA.

Late restenosis occurring after successful PTCA continues to represent a major problem limiting the clinical efficacy of the procedure. It has been shown that smooth muscle cell proliferation plays a major role in this accelerated atherosclerotic process. In vitro and in vivo experiments with the low molecular weight heparin reviparin showed a pronounced inhibitory effect by this compound on smooth muscle cell proliferation. To evaluate the safety of reviparin and the incidence of angiographic restenosis in humans, a study of increasing dosages was conducted in 41 patients. Repeat coronary angiography was performed 3 months after angioplasty. Restenosis occurred in 5 of 37 evaluable patients with initially successful PTCA. No major bleeding complication was documented for any patient in this first pilot trial. A randomized, double-blind, multicentre trial is being carried out to define the real impact of this compound in reducing restenosis in patients who undergo successful balloon angioplasty.

Experimental and early clinical experience with reviparin-sodium for prevention of restenosis after percutaneous transluminal coronary angioplasty.

Restenosis after successful percutaneous transluminal coronary angioplasty (PTCA) remains a major problem limiting the clinical efficacy of the procedure. It has been shown that smooth muscle cell proliferation plays a major role in this accelerated atherosclerotic process. In vitro and in vivo experiments with a low molecular weight heparin, reviparin-sodium suggest a pronounced inhibitory effect of this compound on smooth muscle cell proliferation. To evaluate the safety of reviparin-sodium and the incidence of angiographic restenosis in humans a study with increasing dosages was conducted in 41 patients. Repeat coronary angiography was performed 3 months after angioplasty. Restenosis occurred in five of 37 evaluative patients (14%) with initially successful PTCA. No major bleeding complications were documented for any patient in this trial. Thus, in this limited series, administration of reviparin-sodium resulted in a low incidence of restenosis following PTCA without causing major bleeding complications. A randomized, double-blind, multicentre trial is being carried out to define the real impact of this compound for reduction of restenosis in patients who underwent successful balloon angioplasty.

The CardioOP-Data Clas (CDC). Development and application of a thesaurus for content management and multi-user teleteaching in cardiac surgery.

OBJECTIVES: Self-directed and customized medical education programs are gaining importance in health care instruction. We prototypically implemented a repository-driven online computer system (CardioOP) for teleteaching in Heart Surgery. It supports authoring and multiple re-use of multimedia data for different user groups in different instructional applications and therefore requires a process of content management. METHODS: We defined objectives for a terminological system to support semantic, cross-media type annotation and retrieval of learning objects: domain completeness, German (natural) language processing, multi-user concepts, extensibility and maintenance, content based annotation and technical implementation. Existing terminologies (ICD10, READ V3, Snomed III, UMLS 1997, MESH) have been analysed according to these objectives. RESULTS: We found that the analysed terminologies did not meet our criteria sufficiently. Therefore, we developed a domain-specific thesaurus, the CardioOP-DataClas (CDC). The application of the CDC within a database-driven authoring process using specifically developed tools is reported. CONCLUSIONS: Metadata play an important role in the effective discovery and search, access, integration and management of educational multimedia data in medicine but so far, there is no terminology to support content management for instructional multimedia. We prototypically designed and applied a thesaurus for the CardioOP educational system. Additional work is needed to evaluate the system in terms of user-friend-liness, concept coverage and information retrieval performance.

[LaMedica. The medical education academy on the internet]. / LaMedica. Die medizinische Lernakademie im Internet.

At present, "modern media" are still a novelty in medical education. The "LaMedica Project"--a program supported by the Federal Ministry for Education and Research--intends to provide an Internet-based education and training system for the entire field of medicine, using all available media resources. This online educational program will provide subjects for medical laypersons as well as medical experts. Various styles of learning and different learning requests will be promoted. The project presented mirrors the cutting edge of database technology, computer-based training and media didactics, critical content processing as well as supplying individual subjects. This report summarizes our 10 months of experience with this program at the Department for Urology and Pediatric Urology of the Johann Wolfgang Goethe University of Frankfurt Main.

CardioOp: an integrated approach to teleteaching in cardiac surgery.

INTRODUCTION/PURPOSE: The complexity of cardiac surgery requires continuous training, education and information addressing different individuals: physicians (cardiac surgeons, residents, anaesthesiologists, cardiologists), medical students, perfusionists and patients. Efficacy and efficiency of education and training will likely be improved by the use of multimedia information systems. Nevertheless, computer-based education is facing some serious disadvantages: 1) multimedia productions require tremendous financial and time resources; 2) the obtained multimedia data are only usable for one specific target user group in one specific instructional context; 3) computer based learning programs often show deficiencies in the support of individual learning styles and in providing individual information adjusted to the learner's individual needs. In this paper we describe a computer-system, providing multiple re-use of multimedia-data in different instructional sceneries and providing flexible composition of content to different target user groups. TOOLS AND METHODS: The ZYX document model has been developed, allowing the modelling and flexible on-the-fly composition of multimedia fragments. It has been implemented as a DataBlade module into the object-relational database system Informix Dynamic Server and allows for presentation-neutral storage of multimedia content from the application domain, delivery and presentation of multimedia material, content based retrieval, re-use and composition of multimedia material for different instructional settings. Multimedia data stored in the repository, that can be processed and authored in terms of our identified needs is created by using a next generation authoring environment called CardioOP-Wizard. High-quality intra-operative video is recorded using a video-robot. Difficult surgical procedures are visualized with generic and CT-based 3D-animations. RESULTS: An on-line architecture for multiple re-use and flexible composition of media data has been established. The system contains the following instructional applications (prototypically implemented): a multimedia textbook on operative techniques, an interactive module for problem based-training, a module for creation and presentation of lectures and a module for patient information. Principles of cognitive psychology and knowledge management have been employed in the program. These instructional applications provide information ranging from basic knowledge at the beginner's level, procedural knowledge for the advanced level to implicit knowledge for the professional level. For media-annotation with meta-data a metainformation system, the CardioOP-Clas has been developed. The prototype focuses on aortocoronary bypass grafting and heart transplantation. CONCLUSION: The demonstrated system reflects an integrated approach in terms of information technology and teaching by means of multiple re-use and composition of stored media-items to the individual user and the chosen educational setting on different instructional levels.

The paradigm of restenosis following percutaneous transluminal coronary angioplasty.

Restenosis after successful percutaneous transluminal coronary angioplasty remains a major clinical problem limiting the long-term efficacy of this treatment for coronary artery disease. All clinical attempts to reduce the incidence of restenosis have failed. Recent advances in the understanding of the cellular biology of restenosis indicate that intimal hyperplasia is the predominant cause for restenosis. The neo-intimal proliferative response to injury is due to an interaction of platelet-fibrin thrombus and smooth muscle cells, release of mitogens, followed by a secretion of extracellular matrix. Based on these concepts concerning the biology of restenosis, several proposals have been made as regards research into potential forms of therapy. Low molecular weight heparin (LMWH) has documented antiproliferative effects on smooth muscle cells in cell cultures. Animal studies with LMWH in rabbits have demonstrated considerable inhibition of smooth muscle cell proliferation during the first 7 days after balloon angioplasty, resulting in only a moderate increase of intimal wall thickness after 28 days. In a first pilot study, application of LMWH was adjusted according to the dosage that resulted in a significant reduction of smooth muscle cell proliferation in the experimental setting. A specific delivery protocol was used, according to the previous documented time course of smooth muscle cell proliferation after vascular injury. The results of this safety trial indicate a promising therapeutic option for prevention of restenosis following coronary angioplasty.

First clinical experience with low molecular weight heparin LU 47311 (reviparin) for prevention of restenosis after percutaneous transluminal coronary angioplasty.

Restenosis after successful percutaneous transluminal coronary angioplasty (PTCA) remains a major problem limiting the clinical efficacy of the procedure. It has been shown that SMC proliferation plays a predominant role in this accelerated atherosclerotic process. In vitro and in vivo experiments with the LMWH reviparin (LU 47311) suggest a pronounced inhibitory effect of this compound on SMC proliferation. To evaluate the safety of reviparin and the incidence of angiographic restenosis in humans a study with increasing dosages was conducted in 41 patients. Repeat coronary angiography was performed 3 months after angioplasty. Restenosis occurred in 5 of 37 evaluable patients (14%) with initially successful PTCA. No major bleeding complication was documented for any of the patients included in this trial. Thus, in this limited series, administration of LU 47311 (reviparin) resulted in a low incidence of restenosis following PTCA without causing major bleeding complications. A randomized trial in a larger population is warranted to define the real impact of this compound for reduction of restenosis in patients who underwent successful balloon angioplasty.

Acute vessel closure following excimer laser coronary angioplasty: can we predict it?

Of 124 consecutive patients undergoing elective excimer laser coronary angioplasty, 33 (26%) had periprocedural occlusion following excimer laser irradiation. Successful management (reopened vessel, no death, no myocardial infarction, no emergency bypass surgery) including repeat lasing, subsequent percutaneous transluminal coronary angioplasty, use of intracoronary nitroglycerin or streptokinase was achieved in 32 of the patients with acute occlusion following excimer laser coronary angioplasty. In one patient a nonfatal anterior myocardial infarction occurred. A late event occurred in two patients despite patency at the control angiography 24 h later. Multiple logistic regression modeling was used to examine the relationship between various characteristics and the risk of acute vessel closure. The preprocedural and procedural variables analyzed included progressive spasm prior to occlusion and lesion morphology after intervention (angiographic complications after percutaneous transluminal coronary angioplasty were prospectively divided into class 0, no complication, and classes 1-3, according to purely descriptive morphological characteristics). These showed a multivariate correlation with acute occlusion during excimer laser coronary angioplasty. These results suggest that acute vessel closure during stand-alone excimer laser coronary angioplasty is a benign but unpredictable event.

Case report: formation of vessel aneurysm after stand alone coronary excimer laser angioplasty.

Formation of aneurysms in coronary arteries can be observed following percutaneous transluminal balloon angioplasty but has not been reported previously after coronary excimer laser angioplasty in humans. Stand alone coronary excimer laser angioplasty was performed in a 49-year-old man with a 75% left anterior descending artery stenotic lesion and exertional angina, documenting a good angiographic result postintervention. Control angiography 6 months after the procedure revealed an aneurysm distal to a 90% restenosis in the area of ablation.

[The influence of coronary artery dissection on long-term outcome after percutaneous transluminal coronary angioplasty]. / Einfluss der Schwere der Gefässdissektion auf das Langzeitergebnis nach transluminaler perkutaner koronarer Angioplastie.

UNLABELLED: The influence of a coronary dissection on long-term outcome after PTCA has been controversely discussed in the past. Whereas diverse experimental studies have shown a positive relation between dissection and the incidence of restenosis, clinical trials could not document an influence of dissection on long-term outcome. However, most of the trials did not distinguish between the different morphologic configuration of the vascular dissection. Thus, the aim of the present study was to determine the influence of dissections on restenosis in regard to their amount and morphologic configuration. The prognostic importance of the National Heart, Lung, and Blood Institute classification on dissection as well as the importance of an additional classification of angiographic complications after PTCA were investigated to determine possible pathophysiologic mechanisms of the restenosis process. The study included 141 consecutive patients with 143 stable dissections after PTCA. A follow-up study was performed 13 months in mean after successful PTCA, which included clinical, symptomatic, and functional aspects of patients. In this patient population, type C dissections (Dorros et al.) showed a relevantly increased risk of a clinical adverse event (41.0%), whereas patients with a type A dissection had only a small risk of an adverse event (10.0%) over the investigation period. Type B dissections revealed an intermediate risk (18.0%), and type D dissections showed a risk of 33.3% of an adverse event, which was lower than that observed for type C dissections. The AC-classification of the postinterventional coronary morphology was a stronger predictor of an adverse outcome after PTCA (p = 0.0003) than was the Dorros-classification (p = 0.0056). CONCLUSION: The grade of a coronary dissection was highly, positively related to an ischemic event after PTCA using both the Dorros and the AC-classification (p = 0.0056/p = 0.0003). In regard to the special association of the AC-class with the amount of vascular injury, we conclude that the amount and configuration of coronary dissection correlates with the long-term outcome after PTCA.

Early luminal deterioration following successful percutaneous transluminal coronary angioplasty. Frequency, prediction and clinical implications.

In order to develop a predictive model for the risk of early lesion deterioration following successful coronary balloon angioplasty (PTCA) based on clinical, pre-angioplasty and procedural characteristics, 154 lesions in 146 consecutive patients undergoing successful PTCA for stable/unstable angina were examined by quantitative coronary analysis immediately after and within 24 h of angioplasty. An angiographic complication score was used prospectively, classifying the lesion morphology post-PTCA into class 0: no complication and classes 1 to 3, according to purely descriptive morphological characteristics. Significant deterioration, defined as a decrease in minimal luminal diameter of more than 2 standard deviations of duplicate measurements post-intervention (0.54 mm; 95% confidence limit for variability using quantitative angiography) was found in 28 lesions (18%), and a total reocclusion in seven lesions (5%). The angiographic complication score (P = 0.019), prior to myocardial infarction (P = 0.076), minimal luminal diameter immediately post-intervention (P = 0.021) and gain of PTCA (P = 0.042) were found to be independently predictive of early lesion deterioration by multiple logistic regression analysis. Identification of these factors and their associated risk should improve success, and understanding of the early vascular response following coronary angioplasty. Moreover, these results have implications for clinical restenosis studies, particularly those assessing the effect of pharmacological interventions on late restenosis rates.

-Diagnostic shunt oximetry of atrial septal defect in adulthood-. / Oxymetrische Shuntdiagnostik des Vorhofseptumdefektes im Erwachsenenalter.

UNLABELLED: There are several circumstances in which data obtained at catheterization should alert the cardiologist to look for a shunt that had not been suspected previously. Aim of the study was to explore the most sensitive parameter which is easily practicable and which gives strong evidence for an atrial septal defect (ASD). Moreover, a simplified method for quantifying left-to-right shunts was analyzed. In 84 patients (58 with an atrial septal defect and 26 patients without shunt) a complete oxygen saturation status was determined. The oxymetrically determined relation between pulmonary bloodflow QP and systemic bloodflow QS was 1.31 to 5.60 in patients with ASD and 0.75 to 1.19 in patients without shunt. The analysis of sensitivity and specificity was determined to define the marginal value which gives suspicion of an ASD. The best values for sensitivity and specificity was found for PA O2-SVC O2 = 7.4% (sens. = 98.3%, spec.= 96.2%), PA O2 -IVC O2 = 2.0% (sens./spec.= 100%), PA O2 - MV O2 = 5.0% (sens./spec.= 100%) and PA O2 = 78.4% (sens./spec. = 97.5%). The correlation between the modified ratio QP/QS and various differences in O2-saturation with the shunt size was examined. A high correlation was found for the modified QP/QS with SVC O2 instead of MV O2 (r = 0.98), PA O2-SVC O2 (r = 0.77) and PA O2 - MV O2 (r = 0.74) with QP/QS, respectively. CONCLUSION: The results demonstrate that an O2-saturation >78% in the pulmonary artery is highly suspicious for the diagnosis of an ASD. With the modified ratio QP/QS = (ART O2-SVC O2)/(PV O2-PA O2) a high sensitive and specific modus of quantifying shunts can be reached. Determination of oxygen saturation from the V. cava interior is therefore not useful.

Incidence, outcome and prediction of early clinical events following percutaneous transluminal coronary angioplasty. A comparison between treatment with reviparin and unfractionated heparin/placebo (results of a substudy of the REDUCE trial).

BACKGROUND: Unfractionated heparin and its low molecular weight fragments possess antithrombotic properties, properties that are routinely exploited in coronary angioplasty (PTCA). OBJECTIVES: In the setting of the REDUCE trial, a randomized, double-blind, multicentre trial, the occurrence of acute or early clinical events was compared in patients treated with either unfractionated heparin/placebo or low molecular weight heparin (reviparin). METHODS AND RESULTS: Six hundred and twelve patients with native coronary artery obstructions randomized between unfractionated heparin/placebo and reviparin, were analysed. Baseline characteristics were similar in both groups. Using the intention-to-treat analysis, major acute or early events (myocardial infarction, re-PTCA, bypass surgery, death) occurred in 42 patients (7%), 29 in the control group and 13 in the treatment group (P=0.027). In order to develop a predictive model for the risk of early events following coronary balloon angioplasty, clinical as well as pre-PTCA and procedural characteristics were analysed. Thrombi at the treated lesion site (P=0.02), dissection (P<0.001), lesion type B2 and C according to the NHLBI classification (P<0.001), diameter stenosis >50% post-PTCA (P<0.001), and length of stenosis >20mm (P=0.005) were significantly associated with the occurrence of acute events. By multiple logistic regression analysis, in which these variables and the treatment regimen were entered, dissection (P=0.042), diameter stenosis >50% (P<0.028) and lesion type B2 and C (P=0.017) were found to be independently predictive of early adverse events. Bleeding complications were similar in the two treatment groups. CONCLUSIONS: Reviparin, given in a very early stage of vascular injury, compares favourably with unfractionated heparin/placebo, by reducing abrupt closure and acute-phase adverse outcome following PTCA. With respect to the evaluated risk factors for acute events, the positive effect of reviparin on early adverse outcome after PTCA may be due to improved antithrombotic properties as compared to unfractionated heparin.

Acute closure during coronary excimer laser angioplasty and conventional balloon dilatation: a comparison of management outcome and prediction.

Of 523 consecutive patients undergoing elective percutaneous transluminal coronary angioplasty (PTCA) and 83 patients treated with coronary excimer laser angioplasty (ELCA), 17 (3.3%) had in-laboratory occlusion following PTCA and 25 (30%) following ELCA; they were enrolled into a prospective study. Successful management (reopened vessel, patency at repeat angiography within 24 h, no death, no myocardial infarction (MI), no emergency bypass surgery) including repeat lasing, subsequent PTCA, use of intracoronary nitroglycerin or streptokinase was achieved in 24 (96%) of the 25 patients with acute occlusion during ELCA. An anterior MI occurred in one patient of the laser group. Repeat balloon dilatation was successfully performed in seven of the 17 patients (41%) with acute closure during PTCA. Among the 10 patients with persistent occlusion after PTCA, five developed a limited myocardial infarction (35%). One patient required emergency CABG, and died peri-operatively. Severe spasm prior to occlusion defined by a new coronary flow depression without evidence of dissection or thrombus showed a significant positive association with acute occlusion during ELCA (P = 0.0008). Thus, in contrast to occlusion during PTCA, subsequent balloon dilatation was successfully performed in the majority of patients with acute occlusion during ELCA, implying that different underlying mechanisms are responsible for this complication. In this limited patient group, occlusion after excimer laser angioplasty was much more frequent than closure during PTCA, but was infrequently associated with major events such as myocardial infarction or death.

Ultrafast imaging of tissue ablation by a XeCl excimer laser in saline.

To determine the temporal evolution of laser induced tissue ablation, arterial wall specimens with either hard calcified or fatty plaques and normal tissue were irradiated in a 0.9% saline solution using a XeCl excimer laser (wavelength 308 nm, energy fluence 7 J/cm2, pulse width 30 ns) through a 600 microns fused silica fiber pointing perpendicular either at a 0.5 mm distance or in direct contact to the vascular surface. Radiation of a pulsed dye laser (wavelength 580 nm) was used to illuminate the tissue surface. The ablation process and the arising bubble above the tissue surface were recorded with a CCD camera attached to a computer based image-processing system. Spherical cavitation bubbles and small tissue particles emerging from the irradiated area have been recorded. The volume of this bubble increased faster for calcified plaques than for normal tissue.

[Low molecular weight heparin, reviparin, after PTCA: results of a randomized double-blind, standard heparin and placebo controlled multicenter study (REDUCE Study]. / Niedermolekulares Heparin, Reviparin, nach PTCA: Ergebnisse einer randomisierten, doppelblinden, Standard-Heparin- und Plazebo-kontrollierten multizentrischen Studie (REDUCE-Studie).

BACKGROUND: Unfractionated heparin and its low molecular fragments possess antiproliferative effects and have been shown to reduce neointimal smooth muscle cell migration and proliferation in response to vascular injury in experimental studies. OBJECTIVES: The specific objective of the REDUCE trial was to evaluate the effect of a low molecular weight heparin on the incidence and occurrence of restenosis in patients undergoing percutaneous transluminal coronary angioplasty. METHODS: The REDUCE trial is an international prospective, randomized, double-blind, multicenter study. Twenty-six centers in Europe and Canada enrolled 625 patients with single lesion coronary artery obstructions suitable for PTCA. Three hundred and six patients received reviparin as a 7000 U bolus before PTCA followed by 10,500 U as an infusion over 24 hours and then twice a day 3500 U s.c. application for 28 days. The 306 patients in the control group received a bolus of 10,000 U unfractionated heparin followed by an infusion of 24,000 U over 24 hours. These patients then received 28 days of s.c. placebo injections. The primary endpoints were efficacy (defined as a reduction in the incidence of major adverse events, i.e., death, myocardial infarction, need for reintervention or bypass surgery), absolute loss of minimal luminal diameter, and incidence of restenosis during the observation period of 30 weeks after PTCA. RESULTS: Using the intention-to-treat analysis for all patients, 102 patients (33.3%) of the reviparin group and 98 patients (32%) of the control group have reached a primary clinical endpoint (relative risk = 0.98; 95% confidence limit, 0.88-1.09; p = 0.707). Likewise, no difference in late loss of minimal luminal diameter was evident for either group. Acute events within 24 hrs occurred in 3.9% of the reviparin group and in 8.2% of the control group (relative risk = 0.49; 95% confidence limit, 0.26-0.92; p = 0.027) during or immediately after the initial procedure. In the control group, 8 major bleedings occurred, and in the reviparin group, 7 major bleeding complications were observed within 35 days after PTCA. CONCLUSIONS: Reviparin use during and after coronary angioplasty did not reduce the occurrence of major clinical events or the incidence of angiographic restenosis over 30 weeks.