Introduction: The TAXUS Liberté Post-approval Study (TL-PAS) studied long-term clini- cal outcomes for the TL stent in conjunction with the use of prasugrel and aspirin. A portion of patients from TL-PAS contributed to the Dual Anti-Platelet Therapy (DAPT) trial. Methods: Eligible and consecutive patients in the United States treated with TL stents were enrolled into TL-PAS (N=4199). Those meeting inclusion and exclusion criteria were recruited for participation in the DAPT trial (N=3904). Patients received open-label prasugrel plus aspirin for 12 months after stent placement. At 12 months, patients without ischemic or bleeding events continued aspirin therapy and were randomized 1:1 to continued blinded treatment with either prasugrel or placebo for an additional 18 months (N=2202). At 30 months, study drugs were discontinued, and aspirin was continued through at least 33 months after stent placement. Events were adjudicated by a clinical events committee and monitored by the TL-PAS Data Monitoring Committee (DMC). Results: Nearly 3 years following randomization, the DMC noted a significant increase in spontaneous ischemic events following withdrawal of prasugrel therapy in randomized patients. This risk was observed in both random- ized arms: patients who switched to placebo after the first 12 months of unblinded DAPT and in patients randomized to blinded prasugrel who had completed an additional 18 months of drug therapy. In response, the DMC recommended that treatment be unblinded for TL-PAS patients when they completed 18 months of randomized drug treatment, to allow discussion of continuing prasugrel in those patients randomized to the active drug arm. Completed patient follow-up and the adjudicated death, unplanned revasularization, myocardial infarction, stroke and bleeding events will be available for presentation. Conclusion: An increased risk of ischemic events was observed after prasugrel cessation in patients randomized to either 12 months or 30 months of DAPT following placement of a TAXUS Liberté paclitaxel-eluting coronary stent and prompted the recommendation for unblinding of therapy by the DMC. A complete analysis of ischemic and bleeding events with the results of 12 versus 30 month treatment com- parisons will be presented. Introduction: The optimal duration of dual antiplatelet therapy (DAPT) after drug- eluting stent (DES) implantation is a question of debate. Hypothesis: We hypothesized that in patients with DES implantation a 6 month duration is not inferior to a 12 month duration of DAPT with aspirin and clopidogrel in terms of clinical Methods: ISAR-SAFE is a randomized, double-blind, multicenter trial comparing 6 versus 12 months of clopidogrel therapy duration in patients with DES implantation. Patients were enrolled at 6 months after DES implantation and randomly assigned to either 6 further months of clopidogrel therapy or placebo. Based on sample size calculations the planned total number of patients was 6,000. A blinded overall analysis showed lower than expected event rates. This along with slow recruitment induced the DSMB to recommend stopping the trial after inclusion of 4,000 patients. A total of 4,005 patients have been enrolled. Primary endpoint is the composite of death, myocardial infarction, stent thrombosis, stroke and major bleeding at 9 months after randomization. Results: Results for clinical endpoints will be in November 2014. Conclusions: ISAR-SAFE is the largest and the only double-blind, randomized clinical trial assessing the value of shortening DAPT duration from 12 to 6 months in patients with DES implantation. Although the trial was stopped prematurely after inclusion of two thirds of patients it has the potential to provide major insights into the optimal DAPT duration after DES implantation. The trial was supported by the BMBF (FKZ 01KG0901) and Abbott Vascular. recommended and 7( 0.4%) major bleeding. Conclusion: The risk benefit ratio (bleeding/stent thrombosis) of short/ long DAPT requires randomized trials. The primary endpoint of the ITALIC trial will be available at the meeting. ITALIC is the 1st randomized trial comparing 2 DAPT regimens in pts non resistant to aspirin. Background: Prevention of atherosclerotic cardiovascular diseases (ASCVD) has been an important public health priority due to the aging of the population and changes of lifestyle. We aimed to examine the efficacy of low-dose aspirin for primary prevention of cardiovascular events in Japanese elderly patients with multiple atherosclerotic risk factors who have no previous history of ASCVD. Methods: The Japanese Primary Prevention Projects (JPPP) is a multi- center, open-labelled, randomized, parallel-group trial which evaluates primary prevention with low-dose aspirin in Japanese patients aged 60 to 85 years with hypertension, dyslipidemia, or diabetes mellitus. Enrollment began in March 2005 and was completed in June 2007. A total of 14,466 individuals were randomly allocated to receive enteric-coated aspirin, 100mg/day or no aspirin. At randomization, study cohort had a mean age of 70.6 years. 57.8 % of the patients were women, 85.0% had hypertension, 71.7% had dyslipidemia, and 33.9% had diabetes. 80.4% of enrolled patients had ≥ 3 conventional risk factors. The primary endpoints were atherosclerotic events including fatal or nonfatal myocardial infarction, fatal or nonfatal stroke and other cardiovascular death. Secondary endpoints included each and combinations of primary and other cardiovascular endpoints as well as death from any cause. Endpoint assessment was done by a central adjudication committee blinded to treatment assignments. Results: The final analysis was done at a median follow-up time of 5.02 years (Quartiles: 4.55-5.33) according to the recommendation in Data Safety Monitoring Board. The number of eligible patients in aspirin and non-aspirin group was 7,220 and 7,244, respectively. There was no significant difference between two groups (P=0.544) while we observed 193 and 207 primary events in each group and the estimated hazard ratio was 0.941 (95%CI 0.774-1.145). The 5 year cumulative event rates were also 2.772% (95%CI 2.400%-3.201% Background: Coronary artery disease (CAD) is the major cause of mortality and mor- bidity in pts with diabetes mellitus (DM). It is proposed that 64-slice coronary CT angiography (CCTA) may provide early CAD information on both myocardial ischemia and plaque burden, which could guide preventative therapy and reduce future cardiovascular events in high-risk otherwise asymptomatic DM patients. Methods: A total of 900 participants with high risk DM (males ≥ 50 yrs / females ≥ 55 yrs with DM ≥ 3 years on DM medication ≥ 1 yr, or males ≥ 40 yrs / females ≥ 45 yrs with DM ≥ 5 yrs on medication ≥ 1 yr) and no symptoms of CAD were randomly assigned to be assessed by CCTA or not. Pts randomized to CCTA (n=452) were managed by their physicians according to pre-specified trial recommendations based on the results of CCTA screening. Those randomized to the control arm (n=448) received standard medical therapy. Participants were monitored for procedures performed and changes in medical therapy accomplished at one year, and prospectively followed up for 4.0 ± 1.7 years for the combined primary clinical endpoint of death, MI and unstable angina. Results: Major baseline characteristics included age = 61 ± 8 years, males = 52%, DM duration = 13 ± 10 years, Type I DM = 12%, Insulin requiring = 43%, systolic BP = 130 ± 12 mm Hg, HgA1C = 7.5 ± 1.4% and LDL cholesterol = 87 ± 32 mg/dL. Of those randomized to the screening arm 285(63%) had at least some degree of atherosclerosis and 21 (4.7%) had severe (>70% stenosis) proximal vessel CAD. This resulted in 26 (5.8%) protocol coronary revascularization procedures, more use of statin therapy (83.1% versus 75.7%; p=0.008) and a significant reduction in blood pressure and LDL levels at one year compared to those randomized to control. The primary event rate was 7.6% and 6.2% for non-screened and screened groups respectively (Hazard ratio (HR) = 0.80, p=0.38). Conclusions: In this contemporary study population of patients with high risk, but well medically managed, asymptomatic diabetes, randomization to screening with CCTA resulted in a modest number of protocol recommended coronary revascularization procedures and a significant increase in the use of statin therapy. However, it did not result in a significant reduction in the primary clinical endpoint by 4.0 years. Background: Statin intolerance (SI) limits many patients (pts) from taking statins and achieving LDL-C goals. Ezetimibe (EZE) is a recommended option for SI pts. ODYSSEY ALTERNATIVE (NCT01709513) compared alirocumab (ALI) vs. EZE in pts with history of SI due to muscle symptoms (inability to tolerate ≥ 2 statins, 1 at lowest approved starting dose). The novel study design included a placebo (PBO) run-in period and statin rechallenge arm to SI. Methods: SI pts (with CHD/other CV risk factors) first received single-blind subcutaneous and oral PBO for 4 weeks (W), and were excluded if muscle-related adverse events (AEs) were reported with PBOs. Continuing pts were randomized (2:2:1 ratio) to ALI 75 mg self-administered via 1 - mL pre-filled pen every 2 weeks (Q2W) or EZE 10 mg/day or atorvastatin (ATV) 20 mg/day for 24 W. ALI dose was increased to 150 mg Q2W (also 1-mL) at W12 depending on CV risk and W8 LDL-C level. Primary endpoint was % change in LDL-C from baseline to W24 (intent-to-treat analysis). Pts could enter an open-label extension (OLE) and receive ALI 75/150 mg Q2W. Results: PBO run-in was completed by 87.0% (314/361) pts, 6.9% (25) discontinued due to muscle AE. Baseline mean LDL-C levels were 191–194 mg/dL (Table), 15% of pts had HeFH. ALI produced significant LDL-C reductions vs. EZE at W24 (Table). Although treatment-emergent adverse events (TEAEs) were generally comparable between groups, the rate of skeletal muscle related TEAEs

Zwei Patienten (m,37; w 43J) prästentierten sich mit starken akuten Oberbauchbeschwerden. Bei beiden Patienten war eine äthyltoxische chronische Pankreatitis mit Pseudozysten bekannt. Die Entzündungsparameter waren bei beiden Patienten nur mäßig erhöht, die Lipase bei der Patientin massiv (6000 U/L), bei dem Patienten mit 236U/l nur mäßig erhöht. Abdomensonographisch zeigte sich bei beiden Patienten in der Duplexsonographie ein arterielles Flusssignal in jeweils einer der Pankreaspseudozysten im Sinne eines Pseudoaneurysma der A. gastroduodenalis. Zur Planung des weiteren Procedere wurde eine erweiterte Bildgebung mittels Endosonographie und Angio-CT durchgeführt. Hierbei zeigte sich, dass Teile der jeweiligen Zyste, die in einem Fall 5cm, im anderen Fall 6cm maß, aus der arrodierten A. gastroduodenalis gespeist wurden. Bei beiden Patienten wurde unmittelbar eine selektive Angiographie durchgeführt. Die arrodierte A. Gastroduodenalis sowie die arteriell perfundierte Pseudozyste wurde in beiden Fällen dargestellt und jeweils mittels eines PTFE-ummantelter Graft-Stents (3mm DM, 12mm Länge; 3mm DM, 18mm Länge) direktgestentet. Nach der Stentplatzierung war in beiden Fällen das Pseudoaneurysma komplett verschlossen. Die Beschwerden des Patienten sistierten unmittelbar, die Schmerzen der Patientin nach 24 Stunden. Entzündungswerte und Lipase waren rückläufig, der klinische Zustand beider Patienten verbesserte sich schnell. Abdomen- und duplexsonographische Kontrollen zeigten den perfundierten Stent in der A. gastroduodenalis sowie die hämatomgefüllte Pseudozyste ohne Flusssignal. Es erfolgte eine Thrombozystenaggregationshemmung zur Prävention einer Stentthrombose mit Clopidogrel 75mg und Acetylsalicylsäure 100mg für 3 Monate, dann für weitere 3 Monate die Therapie mit ASS 100mg. Die Patienten konnten jeweils 4 Tage nach Aufnahme beschwerdefrei nach Hause entlassen werden. Die hier vorgestellten Fälle zeigen eine erfolgreiche internistische Therapie einer schwerwiegenden Komplikation der chronischen Pankreatitis. Die beiden Fälle demonstrieren, dass ummantelte PTFE-Graft-Stents eine mögliche minimal invasive therapeutische Alternative bei Arrosionsblutungen im Gastrointestinaltrakt darstellen und langfristig einen sicheren Therapieerfolg gewährleisten können.

Fallvorstellung: Bis heute sind Ösophagusrupturen mit Eröffnung des Mediastinums eine Domäne der Viszeralchirurgie, eine konservative Behandlung ist bisher nur selten beschrieben. Eine 72-jährige Patientin ohne Vorerkrankungen und Dauermedikation stellte sich mit starken thorakalen Schmerzen nach massivem Erbrechen, zuletzt blutig, vor. Kardiopulmonal und abdominell keine Auffälligkeiten. LEU 17,3/nl, LDH 347 U/l, CRP 8,36mg/dl, EKG und Herzecho o.B.

AIMS:In the Intracoronary Stenting and Antithrombotic Regimen-Rapid Early Action for Coronary Treatment Trial, the use of abciximab in patients undergoing percutaneous coronary intervention (PCI) after pretreatment with 600 mg clopidogrel for >2 h was associated with no clinically measurable benefit at 30 days. We assessed whether there was any clinical benefit from abciximab at 1 year follow-up.METHODS AND RESULTS:After pre-treatment with 600 mg clopidogrel, a total of 2159 patients undergoing PCI for stable or unstable angina without marked ST-segment shifts or positive biomarkers were randomly assigned to receive abciximab or placebo. The occurrence of the composite endpoint of death, myocardial infarction, or target vessel revascularization was assessed at 1 year after randomization. At 1 year, the composite endpoint occurred in 23.8% of the patients in each group [relative risk (RR), 1.01; 95% confidence interval (CI), 0.85-1.20; P=0.92]. The combined incidence of death and myocardial infarction was 6.0% in the abciximab group and 6.4% in the placebo group (RR, 0.94; 95% CI, 0.67-1.32; P=0.73). The mortality rate was 2.1% in the abciximab group and 2.4% in the placebo group (RR, 0.88; 95% CI, 0.50-1.54; P=0.66). No trend towards clinical benefit was observed with abciximab at 1 year in any subgroup analysed.CONCLUSION:In patients with a low-to-intermediate risk profile undergoing PCI after pre-treatment with a 600 mg clopidogrel for at least 2 h, the use of abciximab offers no additional clinical benefit at 1 year.

Context The optimal pharmacological strategy for bridging the delay between admission and performance of percutaneous coronary intervention (PCl) in patients with acute myocardial infarction (Ml) is not known.Objective To assess whether early administration of reteplase plus abciximab produces better results compared with abciximab alone in patients with acute MI referred for PCl.Design, Setting, and Patients Open-label, randomized controlled study conducted from May 3, 2001, through June 2, 2003, of 253 patients who were admitted to 13 community hospitals without catheterization facilities (n= 186) and to 5 hospitals with catheterization facilities (M=67), with the diagnosis of an ST-segment elevation acute MI within 12 hours from onset of symptoms.Interventions Patients received intravenously either the combination of a half-dose reteplase (two 5-U boluses, 30 minutes apart) with a standard dose of abciximab (0.25 mg/kg bolus, 0.1-25 mug/kg per minute infusion [maximum 10 mug/min for 12 hours]) or the standard dose of abciximab alone; all patients were then transferred for PCl.Main Outcome Measure Final infarct size according to a single-photon emission computed tomography study with technetium Tc 99m sestamibi performed between 5 and 10 days after randomization in 228 patients (90.1 % of entire sample).Results Of the 253 patients enrolled, 125 were assigned to reteplase plus abciximab and 128 to abciximab alone. The median (interquartile range) of the final infarct size of the left ventricle was 13.0% (3.0%-28.0%) in the reteplase plus abciximab group and 11.5% (3.0%-26.3%) in the abciximab-alone group (P=.81). The mean difference in final infarct size of left ventricle between the reteplase plus abciximab group and the abciximab group was 1.3 % (95% confidence interval [CI], -3.1 % to 5.7%). Within 6 months after randomization, the composite secondary end point of death, recurrent Ml, or stroke occurred in 8 patients (6.4%) in the reteplase plus abciximab group and 6 patients (4.7%) in the abciximab group (relative risk, 1.4; 95% Cl, 0.5-3.9; log-rank P=.56). Major bleeding complications were observed in 7 patients (5.6%) in the reteplase plus abciximab group and 2 patients (1.6%) in the abciximab group (P=16).Conclusion Early administration of reteplase plus abciximab does not lead to a reduction of infarct size compared with abciximab alone in patients with acute MI referred for PCl.

BACKGROUND:Despite recent advances in interventional cardiology, including the introduction of drug-eluting stents for de novo coronary lesions, the treatment of in-stent restenosis (ISR) remains a challenging clinical issue. Given the efficacy of systemic sirolimus administration to prevent neointimal hyperplasia in animal models and to halt and even reverse the progression of allograft vasculopathy, the aim of the present double-blind, placebo-controlled study was to evaluate the efficacy of a 10-day oral sirolimus treatment with 2 different loading regimens for the prevention of recurrent restenosis in patients with ISR.METHODS AND RESULTS:Three hundred symptomatic patients with ISR were randomly assigned to 1 of 3 treatment arms: placebo or usual-dose or high-dose sirolimus. Patients received a cumulative loading dose of 0, 8, or 24 mg of sirolimus 2 days before and the day of repeat intervention followed by maintenance therapy of 2 mg/d for 7 days. Angiographic restenosis at 6-month angiography was the primary end point of the study. Restenosis was significantly reduced from 42.2% to 38.6% and to 22.1% in the placebo, usual-dose, and high-dose sirolimus groups, respectively (P=0.005). Similarly, the need for target vessel revascularization was reduced from 25.5% to 24.2% and to 15.2% in the placebo, usual-dose, and high-dose groups, respectively (P=0.08). The sirolimus blood concentration on the day of the procedure correlated significantly with the late lumen loss at follow-up (P<0.001).CONCLUSIONS:In patients with ISR, an oral adjunctive sirolimus treatment with an intensified loading regimen before coronary intervention resulted in a significant improvement in the angiographic parameters of restenosis.

OBJECTIVES We examined clinical outcomes in the lntracoronary Stenting and Antithrombotic RegimenRapid Early Action for Coronary Treatment (ISAR-REACT) trial based on the duration of pretreatment with a 600-mg loading dose of clopidogrel.BACKGROUND The influence of the treatment duration with a 600-mg dose of clopidogrel before percutaneous coronary revascularization on early outcomes remains uncertain.METHODS Among 2,159 patients with coronary disease who underwent percutaneous coronary intervention (PCI) in the ISAR-REACT trial, we examined clinical outcomes relative to the duration of pretreatment with a 600-mg dose of clopidogrel: (2 to 3 h, 3 to 6 h, 6 to 12 h, or >12 h). Patients were randomly assigned to adjunctive therapy with abciximab or placebo at the beginning of the study. The primary end point was a composite of death, myocardial infarction, or urgent revascularization within 30 days after randomization.RESULTS No significant differences were observed between patient groups regarding the duration of pretreatment, irrespective of assignment to abciximab or placebo (p = 0.27 for interaction among abciximab/clopidogrel and placebo/clopidogrel treatment at each time interval). Occurrence of major bleeding also did not differ according to time of initial clopidogrel dosing.CONCLUSIONS For low-to-intermediate risk patients treated with a 600-mg loading dose of clopidogrel before PCI, incremental clinical benefit within the first 30 days from durations of pretreatment >2 to 3 h was not evident. (C) 2004 by the American College of Cardiology Foundation.

Objective. The objective of this randomized trial was to assess the antirestenotic effects of phosphorylcholine (PC)-coated stents as well as of abciximab in small coronary arteries when compared with percutaneous transluminal coronary angioplasty (PTCA) and placebo respectively.Background. Stent coating with PC has been shown to reduce protein absorption and platelet activation which may reduce the risk of restenosis. Furthermore, on the basis of nondedicated studies abciximab is believed to reduce the risk of restenosis after coronary interventions.Methods. A total of 502 patients with lesions situated in small coronary arteries (vessel diameter less than or equal to2.5 mm) were randomly assigned to be treated with either PC-coated stents (n = 253) or PTCA (n = 249) and with either abciximab (n = 251) or placebo (n = 2 5 1) with the use of a 2 x 2 factorial design. All patients were pretreated with 600 mg clopidogrel. The primary end-point was the incidence of angiographic restenosis (greater than or equal to50% diameter stenosis) at follow-up; death or myocardial infarction, and target vessel revascularization (TVR), were assessed as secondary end-points.Results. Angiographic restenosis did not differ between patients treated with PC-coated stents or with PTCA (39.0% vs. 34.2%; P = 0.30) and between patients receiving abciximab or placebo (39.3% vs. 34.3%; P = 0.2 9). Similarly, the need for TVR at I-year follow-up did not differ between patients receiving PC-coated stents or PTCA (20.2% vs. 20.5%; P = 0.98) as well as between patients treated with abciximab or placebo (18.7% vs. 21.9%; P = 0.44).Conclusions. PC-coated stents and abciximab failed to reduce the incidence of angiographic restenosis after percutaneous coronary intervention of small coronary arteries. These data strengthen the belief that future studies on prevention of restenosis in small coronary arteries should focus on drug-eluting stents.

Background A number of stent-versus-stent trials have not been able to disclose differences in stent performance. It has been hypothesized that the selection of patient subsets with simple lesion morphologies may have masked differences among the stent designs under testing. The randomized Intracoronary Stenting and Angiographic Results Strut Thickness Effect on Restenosis Outcome (ISAR-STEREO) trial has shown that a reduced stent strut thickness is associated with a reduced risk for restenosis. The rationale of this study was to investigate the role of lesion complexity on the capacity of a stent-versus-stent trial to distinguish between superior and inferior stents.Methods In the ISAR-STEREO trial, 651 patients were randomly assigned to receive either a thin-strut (n=326) or a thick-strut stent (n=325) with a comparable stent design. Restenosis, defined as a greater than or equal to50% diameter stenosis at follow-up angiography, was analyzed according to the lesion complexity, which was assessed with the use of the American College of Cardiology/American Heart Association classification system.Results The restenosis rate did not differ between stent designs in patients with noncomplex lesions (type A or B-1; restenosis rate: 16.7% vs 16.7%, P=1.0 for thin-strut vs thick-strut stents). In patients with complex lesions (type B-2 or C), there was a significant reduction in restenosis in the thin-strut stent group (restenosis rate: 14.5% vs 29.0%; P<.01 for thin-strut vs thick-strut stents).Conclusions The results of this study suggest that the potential to detect differences in the risk for restenosis in stent-versus-stent trials is strongly dependent on the inclusion of patients with complex lesions. These findings may be relevant when planning new stent-versus-stent trials.