Safety and Efficacy of a New Ultrathin Sirolimus-Eluting Stent with Abluminal Biodegradable Polymer in Real-World Practice

Background and Objectives: Recently, Genoss drug-eluting stent (DES)(TM) stent comprising cobalt-chromium platform with an ultrathin strut thickness, sirolimus, and an abluminal biodegradable polymer was developed. Owing to the lack of substantial evidence for the safety and efficacy of this stent, we report 12-month results of the Genoss DES (TM) stent. Methods: We analyzed subjects who were eligible for a 12-month follow-up from the ongoing Genoss DES (TM) registry, which is a prospective, single-arm, observational, multicenter trial to investigate the clinical outcomes after the successful Genoss DES (TM) stent implantation among all-comers. The primary endpoint was a device-oriented composite outcome, defined as cardiac death, target vessel-related myocardial infarction, and target lesion revascularization at 12-month follow-up. Results: Among 622 subjects, the mean age of subjects was 66.5 +/- 10.4 years, 70.6% were males, 67.5% had hypertension, and 38.3% had diabetes. The implanted stent number, diameter, and length per patient were 1.5 +/- 0.8, 3.1 +/- 0.4 mm, and 36.0 +/- 23.3 mm, respectively. At 12-month clinical follow-up, the primary endpoint occurred only in 4 (0.6%) subjects. Conclusions: The novel Genoss DES (TM) stent exhibited excellent safety and efficacy in real-world practice.ope

Cardiovascular safety of celecoxib on top of dual antiplatelet therapy.

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Efficacy and Safety of DP-R202 in Patients with Chronic Artery Occlusive Disease: Multicenter Randomized Double-blind Active-controlled Parallel Group Phase III Clinical Study.

PURPOSE: Sarpogrelate hydrochloride, a selective 5-hydroxytryptamine 2A antagonist, is a widely used antiplatelet agent for the treatment of peripheral arterial disease (PAD). DP-R202 is a new sarpogrelate hydrochloride product with an improved dosage regimen compared with the agent in current use. The aim of this study was to compare the efficacy and safety profile of DP-R202 and Anplag(⁎) Tab in patients with PAD. METHODS: This study was a 12-week, multicenter, randomized, double-blinded, active-controlled, parallel group comparative Phase III clinical trial. One hundred fifty-one volunteer patients with PAD were randomized to receive DP-R202 300 mg once daily or Anplag Table 100 mg TID for 12 weeks. The primary end point was a change in patient assessment of lower leg pain intensity with the use of a visual analog scale (VAS) after 12 weeks of treatment. Results after 4, 8, and 12 weeks of treatment were compared with baseline and between treatment groups, and all patients were assessed for adverse events (AEs), clinical laboratory data, and vital signs. FINDINGS: Two hundred thirty-one patients from 25 medical centers were assessed, and 151 were enrolled and randomly assigned to 1 of 2 treatment groups. Seventy-five patients received DP-R202 300 mg once daily and 76 patients received Anplag Table 100 mg TID for 12 weeks. Analysis of the change in lower leg pain intensity as determined by VAS score between baseline and week 12 (mean [SD], 20.72 [20.06] mm vs 15.55 [21.44] mm) suggested that DP-R202 was not inferior to Anplag Tab, and no significant differences were found in the secondary end points. No significant between-group differences were observed in the prevalence of drug-related clinical- or laboratory-determined AEs. For tolerability, no specific issue was found during the treatment period. IMPLICATION: The results of this study suggest that DP-R202 was not inferior to Anplag Tab for efficacy in patients with PAD and indicated a good safety profile.ope

Potential role of leptin in angiogenesis: leptin induces endothelial cell proliferation and expression of matrix metalloproteinases in vivo and in vitro

Leptin, the product of ob gene, is an endocrine hormone that regulates adipose tissue mass. Recently, leptin has been found to generate a growth signal involving a tyrosine kinase-dependent intracellular pathway and promote angiogenic processes via activation of leptin receptor (Ob-R) in endothelial cells. However, it is not clear how leptin functions to promote multi-step processes involved in the neovascularization at the atherosclerotic plaque. We have examined the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) and Ob-R in human atherosclerotic lesions, leptin-mediated angiogenesis in vivo and in vitro. Immunohistochemical analysis of human atherosclerotic aorta revealed an increased expression of Ob-R in the intima of neorevascularized regions and of both MMPs and TIMPs predominantly in the endothelial lining of intimal neovessels and macrophages/foam cells. In the rat corneal angiogenesis assay, leptin elicited a comparable sensitivity of angiogenic activity to those of vascular endothelial growth factor (VEGF). The immunohistological analysis of the leptin-treated rat cornea showed definitive rises in Ob-R, MMPs and TIMPs expression as well as those of VEGF receptor (VEGFR-1). Leptin (10-40 ng/ml) induced proliferation of the human umbilical vein endothelial cells (HUVECs) and elevation of MMP-2, MMP-9, TIMP-1, and TIMP-2 expression in a dose-dependent manner. Leptin also induced increases of MMP-2, MMP-9, TIMP-1, and Up-regulated the human coronary artery smooth muscle cells (HCASMCs). These findings suggest that leptin, a hormone with pluralistic properties including a mitogenic activity on vascular endothelial cells, plays a role in matrix remodeling by regulating the expression of MMPs and TIMPs. Taken together, our findings further provide evidences for leptin's role as an angiogenesis inducer in the normal organ (rat cornea) and in aberrant vasculature under duress like atherosclerosis.ope

Additive beneficial effects of valsartan combined with rosuvastatin in the treatment of hypercholesterolemic hypertensive patients

BACKGROUND AND OBJECTIVES: We compared the efficacy and safety of valsartan and rosuvastatin combination therapy with each treatment alone in hypercholesterolemic hypertensive patients. SUBJECTS AND METHODS: Patients who met inclusion criteria were randomized to receive 1 of the following 2-month drug regimens: valsartan 160 mg plus rosuvastatin 20 mg, valsartan 160 mg plus placebo, or rosuvastatin 20 mg plus placebo. The primary efficacy variables were change in sitting diastolic blood pressure (sitDBP) and sitting systolic blood pressure (sitSBP), and percentage change in low-density lipoprotein-cholesterol (LDL-C) in the combination, valsartan, and rosuvastatin groups. Adverse events (AEs) during the study were analyzed. RESULTS: A total of 354 patients were screened and 123 of them were finally randomized. Changes of sitDBP by least squares mean (LSM) were -11.1, -7.2, and -3.6 mm Hg, respectively, and was greater in the combination, as compared to both valsartan (p=0.02) and rosuvastatin (p<0.001). Changes of sitSBP by LSM were -13.2, -10.8, and -4.9 mm Hg, and was greater in the combination, as compared to rosuvastatin (p=0.006) and not valsartan (p=0.42). Percentage changes of LDL-C by LSM were -52, -4, and -47% in each group, and was greater in the combination, as compared to valsartan (p<0.001), similar to rosuvastatin (p=0.16). Most AEs were mild and resolved by the end of the study. CONCLUSION: Combination treatment with valsartan and rosuvastatin exhibited an additive blood pressure-lowering effect with acceptable tolerability, as compared to valsartan monotherapy. Its lipid lowering effect was similar to rosuvatatin monotherapy.ope

Morphological Characteristics of Intimal Hyperplasia in Stented Coronary Arteries Assessed with Intravascular Ultrasound

Background Intravascular ultrasound(IVUS) provides high resolution cross-sectional images of the vessels and permits the quantiative and qualitative assessment of coronary artery disease. Stent is a figid endovascular lattice that effectively prevents elastic recoil at treated sites, but in-stent restenois is a major limitation. The purpose of thecurrent study is to assess the contribution of neointimal hyperplasia for in-stent restenosis and the distribution and morphological characteristics of neointimal hyperplasia in deployed stents. Methods Thirty patients(male 25 & female 5;31 leions) deployed with intracoronary stents underwent intravascular ultrasound imaging at follow-up at least 4 months after stenting ([mean±SD] 8.3±2.9 months). Results 1) In-stent restenosis occurred in 15 lesions out of 31 lesions at follow-up coronary angiography. There was no difference in clinical characteristics between the restenotic and the non-restenotic groups. 2) There was no difference in angiographic profiles between two groups. Deployed stents were as follows ; 16 Palmaz-Schatz(P-S) stents, 12 Gianturco-Roubin(G-R) stents, 2 Cordis stents, and 1 Microstent II. Average diameter of stents in the restenotic and the non-restenotic groups were 3.07±0.26mm and 3.16±0.30mm, respectively(p=0.38). 3) There was no difference of stent cross-sectional areas(CSA) between the non-restenotic and the restenotic groups(p=0.476), but luminal CSA of the restenotic group was significantly smaller than that of the non-restenotic group(p=0.006). 4) In the restenotic group, there were no differences of the maximal and the minimal diameters of stents, and the mean CSAs of stents among proximal, mid, and distal segments. But the mean CSA of neointimal hyperplasia at the mid segment was larger than that at the distal segment(p<0.05). There was a tendency that the mean CSA of neointimal hyperplasia at the mid segment was larger than that at the proximal segment(p=0.187). These findings were the same in the non-restenotic group. 5) In the restenotic group deployed with P-S stents, there were no differences of the maximal and the minimal diameters of stents, and the mean cross-sectional areas(CSA) of stents between each segment. But, the mean CSA of neointimal hyperplasia at the mid segment was larger than that at the distal segment(p<0.05) and there was a tendency that the mean CSA of neointimal hyperplasia at the mid segment was larger than that at the proximal segment(p=0.354). 6) In the morphology of neointimal hyperplasia of the restenotic group, eccentric form(77%) was more common than concentric form(22%). Neointimal hyperplasia occurred in focal or diffuse patterns(7 versus 8 cases). Conclusions In-stent restenosis resulted from neointimal hyperplasia which almost mainly occurred eccentrically at the mid segment of stents and in focal or diffuse patterns. Intravascular ultrasound imaging was a useful method for recognition of distribution and morphological characteristics of neointimal hyperplasia at follow-up of deployed stents.ope

Time-Phasic Development of Nitrate Tolerance According to the Hemodynamic Responses and the Expression of Phosphodiesterase 1A1

Background and Objectives：Time-phasic development of nitrate tolerance in cardiovascular diseases is very important because it can contribute to the advent of blunted vasodilation or rebound ischemia even during continuous NTG treatment. In such a condition, we should change the therapeutic regimen of nitrate treatment to prevent the worsening of symptoms. Materials and Methods：We created a nitrate-tolerant rat model using an osmotic minipump, and we examined the hemodynamic response to bolus NTG infusion in vivo. We checked the phosphodiesterase (PDE)1A1 mRNA and protein level by relative quantitative RT-PCR and western blot analysis. We used 8-cpt-cGMP for investigating the development of a time-phasic nitrate tolerance mechanism after nitrate infusion. Results：NTG-treated rats revealed a significant decrease in NTG-induced MAP drop (nitrate tolerance) from 1-day and this continued to the third day. The mRNA and protein levels of PDE1A1 similarly increased during these periods. Conclusion：This study revealed the development of time-phasic nitrate tolerance from the the aspects of in vivo hemodynamic responses and PDE 1A1 gene expression, and our work supports the need for further investigation to come up with a different therapeutic strategy and new drugs.ope

Synephrine-containing dietary supplement precipitating apical ballooning syndrome in a young female

Apical ballooning syndrome (ABS) is a unique reversible cardiomyopathy that is frequently precipitated by emotional or physical stress. In addition, the few drugs reported to precipitate ABS were either illegal or strictly controlled for medical use. This paper reports a case of ABS precipitated by a dietary supplement. Our case accentuates the potential risk of dietary supplements containing synephrine, which is uncontrolled and available to the general public. Therefore, the Korea Food and Drug Administration should regulate these dietary supplements, and warn healthcare workers and the general public of the potential hazards of the indiscriminate abuse of dietary supplements.ope

AVE Micro-Ⅱ Stent：6-months Follow up Result

Background Several stents are now available for the treatment of failed or suboptimal angioplasty. However, one of the limitations of stents is difficult to deploy especially in tortuous vessels, lesions at a bend, and distal to previously deployed stents. The AVE Micro-II stent has a very low profile(1.65mm), optimum radio-opacity, and highly flexible properties. It is mounted on a semi-compliant balloon with a monorail delivery system. Therefore, it is easy to operate and feasible in tortuous, distal lesions and variety of lesion lengths. We report clinical outcomes and angiographic follow up results of AVE Micro-II stent. Methods Between January 1996 and September 1996, 77 patients were stented with the AVE Micro-II stent. Six-months follow-up angiogram was performed in 57 patients(64 lesions, follow-up rate : 74%). Results The overall angiographic restenosis rate was 26.6%. By univariable analysis, the rate of restenosis was significantly higher for stents in angulated lesions, in smaller post-stent luminal diameter, in the left anterior descending artery lesion than the right coronary artery, in ostial lesion(p=0.02), in peristent dissecting lesions(p=0.02), in tortuous proximal vessels(p=0.03). Stenting of angulated lesions(p=0.0001, Odds ratio=54.64), small post-stent luminal diameter(p=0.01, Odds ratio=5.46), and the left anterior descending artery than the right coronary artery(p=0.03, Odds ratio=17.2) were the strong independent predictors of restenosis in a multiple logistic regression analysis. Event-free survival(freedom from death, myocardial infarction or revascularization) was 80.7% at 6 months. Conclusions 1) The AVE Micro-II stent can be placed safely and efficiently. 2) The angiographic restenosis rate was 26.6%, and 80.7% of patients remained free of cardiovascular events at 6 months. 3) Stenting of angulated lesions, small post-stent luminal diameter, and the left anterior descending artery than the right coronary artery are associated with higher rates of restenosis.ope

Significance of small dense low-density lipoprotein as a risk factor for coronary artery disease and acute coronary syndrome

Small dense LDL (sd-LDL) has recently emerged as an important coronary artery disease (CAD) risk factor. This study was performed to investigate how LDL particle size is related to CAD and acute coronary syndrome (ACS). Blood samples were collected from 504 patients that underwent coronary angiography to evaluate chest pain. The LDL particle size of these samples was measured. The mean LDL particle size was smaller in patients with angiographically proven CAD than in the controls (26.41 ± 0.95 vs 26.73 ± 0.64 nm, p <0.001), and was negatively correlated with the Framingham risk score (r = -0.121, p = 0.007). Patients with more extensive CAD had smaller LDL particles. LDL particle size was also smaller in patients with acute coronary syndrome as compared to non-ACS patients (26.09 ± 1.42 vs 26.54 ± 0.63 nm, p = 0.011). These results suggest that sd-LDL is independently associated with the incidence and extent of CAD, and can be a risk factor for the development of ACS in the Korean population.ope