Prospective randomized comparison of early and late results of a carbonized stent versus a high-grade stainless steel stent of identical design: the PREVENT Trial [corrected].

BACKGROUND: Restenosis after coronary interventions with stent implantation is still the main obstacle of interventional cardiology. The aim of this study was to compare a carbonized and high-grade stainless steel stent of identical design with regard to early and late adverse events. METHODS: In this prospective randomized trial the carbonized MAC stent (amg GmbH, Raesfeld-Erle, Germany) was compared with the stainless steel MAC stent of identical design. Primary end point was diameter stenosis at follow-up; secondary end points were angiographic parameters, rate of restenosis, and major cardiac adverse events (MACE; myocardial infarction, reintervention, and death). RESULTS: Between August 1999 and June 2002, 396 patients were randomized in 2 centers of Germany. Diameter stenosis at follow-up (38.6% +/- 23.4% vs 39.1% +/- 22.2%, P = .49) as primary end point, relative late lumen loss (26.8% +/- 23.7% vs 27.7% +/- 22.3%, P = .26), absolute late lumen loss (0.92 +/- 0.71 vs 0.92 +/- 0.66 mm, P = .58), net gain (1.4 +/- 0.8 vs 1.4 +/- 0.8 mm, P = .96), as well as restenosis rates (18.0% vs 19.0%, P = .81) and MACE (13.5% vs 12.2%, P = .71) were not significantly different between the carbonized and the pure stainless steel study arm, respectively. CONCLUSION: The hypothesis of superiority of the carbonized stent over a stainless steel stent of identical design with regard to restenosis and MACE could not be proved. Inactive coating of stents seems to have no advantage over pure stainless steel stents, which was also demonstrated in other trials. The future probably lies in active coating of stents with drugs that reduce the neointimal proliferation process.

Percutaneous left atrial appendage closure: Technical aspects and prevention of periprocedural complications with the watchman device.

Transcatheter closure of the left atrial appendage has been developed as an alternative to chronic oral anticoagulation for stroke prevention in patients with atrial fibrillation, and as a primary therapy for patients with contraindications to chronic oral anticoagulation. The promise of this new intervention compared with warfarin has been supported by several, small studies and two pivotal randomized trial with the Watchman Device. The results regarding risk reduction for stroke have been favourable although acute complications were not infrequent. Procedural complications, which are mainly related to transseptal puncture and device implantation, include air embolism, pericardial effusions/tamponade and device embolization. Knowledge of nature, management and prevention of complications should minimize the risk of complications and allow transcatheter left atrial appendage closure to emerge as a therapeutic option for patients with atrial fibrillation at risk for cardioembolic stroke.

Prospective randomized comparison of early and late results of 4 different stent designs.

BACKGROUND: Late results of interventional procedures using coronary stents are largely determined by the rate of restenosis. So far, few data are available addressing the effect of stent design on this crucial variable and on early and late adverse events after stent implantation. METHODS: From 1996 through 1998, a total of 965 lesions in 925 patients with coronary artery disease were randomized to treatment with 1 of 4 different stent designs (Micro stent II [M] AVE, Düsseldorf, Germany; Sito [S] Sitomed, Rangendingen, Germany; Pura Vario [PV], Devon, Hamburg, Germany; Inflow [ID] Inflow Dynamics, München, Germany). The primary end point of the study was the degree of diameter stenosis measured by quantitative coronary angiography 6 months after stent implantation. RESULTS: Diameter stenosis at 6 months follow-up was not different in the 4 study arms (M 40.3 +/- 24.1, S 42.8 +/- 27.0, PV 42.6 +/- 26.9 and ID 42.3 +/- 26.8, P =.7). No significant differences could be detected in net lumen gain and late lumen loss, resulting in comparable restenosis rates (>or=50% diameter stenosis) at follow-up (M 26.0%, S 30.5%, PV 31.3%, and ID 28.7%, P =.7). Early adverse events like stent loss, stent thrombosis, periinterventional acute myocardial infarctions and emergency coronary artery bypass graft also showed no significant differences. Multivariate regression analyses revealed reference vessel diameter <3.0 mm, overall stented length, a history of bypass grafting, localization of the target lesion in the left anterior descending coronary artery, type C lesions, dissection before stent implantation, and diabetes mellitus to be independent predictors for restenosis. CONCLUSION: Stent design does not have significant influence on development of restenosis. Adverse event rates were similar with all stent types used in this trial.

Comparison of early and late results of a Carbofilm-coated stent versus a pure high-grade stainless steel stent (the Carbostent-Trial).

The long-term success of coronary interventions with stents is largely determined by the development of restenosis. The aim of this study was to compare a Carbofilm-coated and a pure stainless steel stent with regard to early and late adverse events. In this prospective, randomized trial, the Carbofilm-coated Carbostent and Sirius stent (same stent design, newly developed delivery system) were compared with the stainless steel stents S660, S670, and S7 (newly developed delivery system, same principal stent design with a few changes). The primary end point was relative late luminal loss, and secondary end points were diameter stenosis at 6 months, rate of restenosis, and major adverse cardiac events (MACEs) (myocardial infarction, reintervention, and death). From March 2000 to June 2002 at 18 centers in Canada and Europe, 420 patients were randomized. Relative late luminal loss (Carbofilm 28.9 +/- 23.0% vs stainless steel 26.7 +/- 20.2%, p = 0.95) as the primary end point, absolute late luminal loss (1.00 +/- 0.72 vs 0.93 +/- 0.62 mm, p = 0.95), net gain (1.32 +/- 0.82 vs 1.40 +/- 0.74 mm, p = 0.75), and the degree of stenosis (40.7 +/- 22.9% vs 38.0 +/- 20.1%, p = 0.92), as well as restenosis rates (23.5% vs 15.9%, p = 0.09) and MACEs (20.1% vs 13.7%, p = 0.11) were not significantly different. Thus, the Carbofilm coating of stents does not lead to an improvement in angiographic results or a reduction of restenosis rate and MACEs. These results agree with other trials using inactive coatings on stents, which also could not demonstrate any advantage over pure stainless steel stents.

Left Atrial Appendage Occlusion for Stroke Prevention in Patients with Nonrheumatic Atrial Fibrillation.

Introduction: Atrial fibrillation is a common rhythm disorder, which is related to a higher risk of thrombembolism resulting in a high rate of cerebral stroke or transient ischemic attacks. According to the CHADS2- or CHA2DS2Vasc-Score there is an indication for oral anticoagulation to prevent patients from mostly disabling strokes. However, more than 50% of patients are not adequately treated with oral anticoagulation due to different reasons, especially contraindications. More than 90% of thrombi develop in the left atrial appendage (LAA), which lead to the idea of developing devices to exclude the LAA from the systemic circulation to prevent patients from embolisations. Another approach is surgical ligation or removal of the LAA during operation procedures. Content: Different devices and their clinical data are discussed in this review. Available literature for most of the devices is evaluated and last but not least some surgical results are discussed at the end. Existing data of randomized and non-randomized studies show that the concept of LAA-occlusion instead of anticoagulation therapy works. However, complication rates during intervention have to be kept in mind, but with adequate training also new and inexperienced operators can do the procedure safely. Most data and the only randomized studies are available for the Watchman Device. Despite some few complications like pericardial effusions, bleeding complications and thrombus formation on the devices, the data showed a non inferiority of device-implantation in comparison with anticoagulation therapy in the first few years. In long term follow up more than 4 years after implantation, there is even a superiority of the device compared with anticoagulation therapy, safety issues are no longer significantly different despite some periprocedural complications. This has to be reflected with the background, that operators could treat 3 patients with a totally new method, thereafter all patients had to be randomized into the study. So experience was limited in the first phase of this trial. Surgical data vary much due to different techniques of LAA-occlusion. With newer devices results are also promising. Conclusion: LAA-occlusion is a developing field of interventional and surgical techniques. The concept of LAA-occlusion could be proved in one randomized trial. At least for patients contraindicated for anticoagulation therapy, LAA-occlusion is a real alternative to only aspirin therapy or doing nothing. With emerging techniques and lower complication rates, LAA-occlusion might develop to a real alternative to anticoagulation therapy, at least for vitamin-K-antagonists. There are no data available so far in comparison with new oral anticoagulants. Further studies are needed to compare device therapy with new oral anticoagulants.

Percutaneous Left Atrial Appendage Exclusion Therapy: Who, Why and How?

Purpose: Patients with atrial fibrillation are at an increased risk of having a cardio embolic stroke. Stroke is a leading cause of death and disability worldwide. Current guidelines recommend an antithrombotic regimen to prevent thromboembolism in medium and high risk patients with AF. However, a substantial number of patients are not eligible for this therapy. The exclusion of the left atrial appendage (LAA) from circulation seems to be an alternative strategy for stroke prevention in AF. This review focuses on the different strategies for LAA exclusion with special focus on the WATCHMAN Device. Two devices are currently in use for percutaneous transcatheter occlusion of the LAA: the WATCHMAN® - device and the AMPLATZER® -septal occluder. For both devices safety and feasibility data are available. Additionally about 200 patients received a PLAATO® -device- which is currently no more available due to economic reasons. Patients treated with the PLAATO device were at high risk for thromboembolic stroke and had contraindications for oral anticoagulation therapy. The Watchman® -device was implanted in 800 patients that were eligible for long-term anticoagulation therapy with a moderate risk for thromboembolic stroke due to non-valvular AF. Summary: For both devices, a reduction in the risk of stroke was documented and device implantation was shown to be safe and feasible. Provided the ongoing trials show noninferiority to oral anticoagulation, another therapeutic option will become available to prevent ischemic strokes.

Interventional treatments for stroke prevention in atrial fibrillation with emphasis upon the WATCHMAN device.

PURPOSE OF REVIEW: Stroke is a leading cause of death and disability worldwide. Many strokes occur in patients with atrial fibrillation. Current guidelines recommend an antithrombotic regimen with warfarin to prevent thromboembolism in atrial fibrillation; however, a substantial number of patients are not eligible for this therapy. The exclusion of the left atrial appendage from circulation seems to be an alternative strategy for stroke prevention in atrial fibrillation. The review focuses on the different devices for stroke prevention in patients with atrial fibrillation. RECENT FINDINGS: Recently, two devices developed for percutaneous transcatheter occlusion of the left atrial appendage have been studied: the PLAATO (Percutaneous Left Atrial Appendage Transcatheter Occlusion) device and the WATCHMAN device. Safety and feasibility data are available for both devices. About 200 patients have received a PLAATO device. These patients were at high risk for thrombembolic stroke and were not candidates for oral anticoagulation therapy. The WATCHMAN device was implanted in 75 patients that were eligible for long-term anticoagulation therapy with a moderate risk for thrombembolic stroke due to nonvalvular atrial fibrillation. SUMMARY: For both devices, a reduction in the risk of stroke was documented, and device implantation was shown to be safe and feasible. Provided the ongoing trials show noninferiority to oral anticoagulation, another therapeutic option will become available to prevent ischemic strokes.

Initial worldwide experience with the WATCHMAN left atrial appendage system for stroke prevention in atrial fibrillation.

OBJECTIVES: This study assessed the feasibility of implanting a device in the left atrial appendage (LAA) in patients with atrial fibrillation (AF) to prevent thromboembolic stroke. BACKGROUND: Meta-analyses confirmed that in cases of left atrial thrombus in nonrheumatic AF patients approximately 90% of them are in the LAA. METHODS: The WATCHMAN Left Atrial Appendage System (Atritech Inc., Plymouth, Minnesota) is a nitinol device implanted percutaneously to seal the LAA. Patients were followed by clinical and transesophageal echocardiography at 45 days and 6 months with annual clinical follow-up thereafter. RESULTS: Sixty-six patients underwent device implantation. Mean follow-up was 740 +/- 341 days. At 45 days, 93% (54 of 58) devices showed successful sealing of LAA according to protocol. Two patients experienced device embolization, both successfully retrieved percutaneously. No embolizations occurred in 53 patients enrolled after modification of fixation barbs. There were 2 cardiac tamponades, 1 air embolism, and 1 delivery wire fracture (first generation) with surgical explantation but no long-term sequelae for the patient. Four patients developed a flat thrombus layer on the device at 6 months that resolved with additional anticoagulation. Two patients experienced transient ischemic attack, 1 without visible thrombus. There were 2 deaths, neither device related. Autopsy documented a stable, fully endothelialized device 9 months after implantation. No strokes occurred during follow-up despite >90% of patients with discontinuation of anticoagulation. CONCLUSIONS: Preliminary data suggest LAA occlusion with the WATCHMAN System to be safe and feasible. A randomized study is ongoing comparing oral anticoagulation with percutaneous closure.

Neointima formation after stent implantation in an experimental model of restenosis: polytetrafluoroethylene-covered versus uncovered stainless steel stents.

The aim of the study was to assess whether stents covered with a membrane of polytetrafluoroethylene spanned over the mashes of a sandwich-configured double stent (n = 15) prevent migration of smooth muscle cells through stent spaces, leading to less neointima formation compared with uncovered stainless steel stents (n = 14) in iliac arteries of male Chinchilla Bastard rabbits (n = 18). Lumen stenosis was assessed by quantitative angiography immediately before the animals were killed 5 weeks after stent deployment. Neointima formation was quantified by histomorphometric analysis. There were large regional and individual differences in neointima formation, leading locally to a significantly higher degree of stenosis in covered stents (histologically, 76.0 +/- 13.7 vs. 62.9 +/- 12.9%; angiographically, 33.5 +/- 21.1 vs. 7.8 +/- 8.8%) compared with uncovered stents, though mean neointimal and lumen area values were not significantly different. In conclusion, polytetrafluoroethylene-covered stents do not prevent neointima formation compared with uncovered stents. Although the membrane reduces local smooth muscle cell migration, the neointima hyperplasia at the proximal and distal ends of a covered stent stimulates migration along its longitudinal axis. In this stent-restenosis model, regional and individual proliferation processes and not the membrane-covering strut-to-strut distances determine lumen restenosis.