Patterns of activation and deposition of platelets exposed to the polymeric surface of the paclitaxel eluting stent.

The interaction of platelets with the polymeric surface of drug eluting stents has not been fully described in the literature. Our aim was to analyze the patterns of activation and deposition of platelets exposed to two different stent platforms; (a) the polymeric surface of the paclitaxel eluting stent (Taxus((R)) stent, PES,) and (b) the metallic surface of a stent with identical structural design (Express((R)) stent, BMS). Platelet activation was tested by deploying stents in an in vitro flow chamber model. Anticoagulated blood of 25 healthy volunteers was circulated (flow rate 10 ml/min for 60 min) into the flow chamber system. P-selectin expression, glycoprotein IIb/IIIa activation (PAC-1 binding) and platelet-monocyte complexes (PMC) formation were evaluated at 0, 10, 30 and 60 min. Surface platelet deposition was assessed by surface electron microscopy in stents implanted in the in vitro system for 60 min and in stents implanted in normal porcine coronary arteries for 24 h. Platelet activation evaluation showed a higher P-Selectin expression (92.9% of baseline in PES versus 68.3 % in BMS, P = 0.01) and higher PMC formation (125.7 % of baseline in PES versus 75.6% in BMS, P < 0.01) in the PES compared to the BMS control group. PAC-1 binding levels did not differ among groups. In the in vitro study, SEM analysis of the stent surface showed no statistical differences on platelet deposition between the groups. In addition, presence of proteinaceous material was more frequently seen on the BMS group (moderate to complete coverage = 80% in BMS versus 26% in PES, P < 0.01). In the in vivo study, complete platelet coverage was similar between groups (PES = 7% versus BMS = 8%, P = NS). However, there was an overall trend towards less platelet deposition on the BMS surface (mild and moderate coverage = 83%, 9% in BMS versus 49%, 44% in PES, P < 0.001 for both) but thrombus formation was not observed in either group. The polymeric surface of the PES appears to induce a higher degree of platelet activation and deposition compared to the BMS surface. The biological implications of these findings on the patterns of vascular healing need to be further studied in vivo. Condensed Abstract The interaction of human platelets with the surface of drug eluting stents has not been fully characterized. Patterns of platelet activation and adhesion were evaluated in vitro and in vivo after exposing platelets to the surface of the paclitaxel-eluting stent and identical bare metal stent. The degree of PMC formation and P-selectin expression was increased in PES compared to BMS. In the in vivo study, complete platelet coverage was similar between groups. There was an overall trend towards less platelet deposition on the BMS surface, however, thrombus formation was not observed on either surface. The polymeric surface of the PES appears to induce a higher degree of platelet activation and deposition compared to the BMS surface.

Clinical outcomes and stent thrombosis following off-label use of drug-eluting stents.

CONTEXT: Clinical trials that have excluded patients at high risk for cardiac events have led to commercial labeling approval of drug-eluting stents; nevertheless, such high-risk patients commonly undergo stent placement in clinical practice. The degree to which they experience cardiac events at a higher rate than non-high-risk patients is unclear. OBJECTIVE: To assess the rates of major adverse cardiac events during the index admission and 1 year after the implantation of drug-eluting stents in patients with high-risk angiographic and clinical features. DESIGN, SETTING, AND PATIENTS: From July 2004 to September 2005, consecutive patients who underwent attempted stent placement at 42 different hospitals throughout the United States were enrolled in a prospective multicenter registry. We analyzed outcomes of 3323 patients who received at least 1 drug-eluting stent for a reason other than acute ST-segment elevation myocardial infarction. The study population was divided into 2 groups based on presence of at least 1 of 9 off-label characteristics based on the current US Food and Drug Administration-approved indications for sirolimus- and paclitaxel-eluting stents. MAIN OUTCOME MEASURES: The composite clinical outcomes of death, myocardial infarction, or target vessel revascularization during the index admission and death, myocardial infarction, or target lesion revascularization at 1 year were evaluated. RESULTS: Of the 3323 patients, 1817 (54.7%) had at least 1 off-label characteristic. During the index hospitalization, the composite clinical outcome occurred in 198 (10.9%) of patients in the off-label group and 76 (5.0%) of patients in the on-label group (adjusted odds ratio, 2.32; 95% confidence interval [CI], 1.75-3.07; P<.001). At 1 year, the composite clinical outcome occurred more often in the off-label group compared with the on-label group; 309 (17.5%) vs 131 (8.9%) (adjusted hazard ratio [HR], 2.16; 95% CI, 1.74-2.67; P<.001). Stent thrombosis also occurred more frequently among patients in the off-label group during the initial hospitalization (8 [0.4%] vs 0) and at 1 year: 29 (1.6%) vs 13 (0.9%), adjusted HR, 2.29 (95% CI, 1.02-5.16; P = .05). CONCLUSIONS: Compared with on-label use, off-label use of drug-eluting stents is associated with a higher rate of adverse outcomes during the index admission and at 1 year. Stent thrombosis occurred predominantly in patients who underwent off-label drug-eluting stent implantation. Clinicians should be cautious about extrapolating the benefits of drug-eluting stents over bare-metal stents observed in randomized clinical trials to higher-risk clinical settings that have not been assessed.

In vivo plaque characterization using intravascular ultrasound-virtual histology in a porcine model of complex coronary lesions.

OBJECTIVE: To determine the accuracy of detection of different tissue types of intravascular ultrasound-virtual histology (IVUS-VH) in a porcine model of complex coronary lesions. METHODS AND RESULTS: Coronary lesions were induced by injecting liposomes containing human oxidized low-density lipoprotein into the adventitia of the arteries. IVUS-VH imaging was performed in vivo at 8.2+/-1.6 weeks after injection. A total of 60 vascular lesions were analyzed and compared with their correspondent IVUS-VH images. Correlation analysis was performed using linear regression models. Compared with histology, IVUS-VH correctly identified the presence of fibrous, fibro-fatty, and necrotic tissue in 58.33%, 38.33%, and 38.33% of lesions, respectively. The sensitivity of IVUS-VH for the detection of fibrous, fibro-fatty, and necrotic core tissue was 76.1%, 46%, and 41.1% respectively. A linear regression analysis performed for each individual plaque component did not show strong correlation that would allow significant prediction of individual values. CONCLUSIONS: In a porcine model of complex coronary lesions, IVUS-VH was not accurate in detecting the relative amount of specific plaque components within each individual corresponding histological specimen.