Stent thrombosis and drug-eluting stents

SummaryCoronary stents have been used for the treatment of patients with coronary artery disease (CAD), and significantly improved procedural safety and are associated with a lower rate of restenosis compared with balloon angioplasty alone. Drug-eluting stents (DES) have been dominant for the treatment of CAD with efficacy in significantly reducing both restenosis and target lesion revascularization. However, late and very late stent thrombosis have become a major concern in DES-implanted arteries compared with those treated with bare-metal stents (BMS). This review focuses on the feature of DES thrombosis and pathological examination and dual antiplatelet therapy for prevention of stent thrombosis.Currently, the incidence of stent thrombosis associated with first-generation and second-generation DES remains unclear in data from real-world cohort registry studies. Further studies of larger multicenter trials would give us insight into the specific mechanisms of stent thrombosis among different generations of DES

Association between plasma concentration of tolvaptan and urine volume in acute decompensated heart failure patients with fluid overload

Background: Tolvaptan (TLV) is a useful diuretic for acute decompensated heart failure (ADHF) with fluid overload, but its clinical response varies between patients. The aim of this study is to investigate whether plasma TLV concentrations correlate with the urine volume. Methods: ADHF inpatients with evidence of fluid overload and total urine volume < 1,500 mL 24 h after initial intravenous administration of 40 mg furosemide were included in the study. On days 1–7, 7.5 mg oral TLV was added. The plasma TLV concentration, plasma renin activity (PRA), and plasma aldosterone concentration (PAC) were measured on days 1, 3 and 7. Results: In the 52 patients who completed the protocol, the TLV concentration increased significantly from 67.6 ± 30.1 ng/mL on day 1 to 98.3 ± 39.6 ng/mL on day 3 to 144.8 ± 44.2 ng/mL on day 7, and the TLV concentration correlated with total urine volume on days 3 and 7 (r = 0.392, p < 0.01; r = 0.639, p < 0.001, respectively) but not on day 1. The urine volume correlated inversely with PRA and PAC (r = −0.618, p < 0.05; r = −0.547, p < 0.05, respectively). Conclusions: Plasma TLV concentrations correlated with the urine volume in late phase of treatment but not in early phase, which suggests that the effect of TLV may possibly be inhibited by renin–angiotensin–aldosterone system activity.

SERCA2aの持続的過剰発現は、生理的条件下では膀胱機能に影響を及ぼすが、膀胱出口部閉塞亜急性期の病的条件下では膀胱機能に影響しない

A functional impairment of the bladder and heart in a decompensated state caused by a pressure overload is accompanied by a decrease in the sarcoplasmic reticulum Ca2+-ATPase (SERCA2). The beneficial effects of SERCA2 overexpression in preserving cardiac functions have been previously reported. The aim of the present study was to investigate the effects of overexpressed SERCA2 on bladder functions under physiological and pathological conditions using partial bladder outlet obstruction (BOO) in SERCA2a transgenic Wistar rats (TG). Bladder cystometry and western blot analysis were performed using the wild-type Wistar rats (WT), TG, and BOO models (WTBOO and TGBOO). Persistent overexpression of SERCA2 induces reduced bladder compliance without hypertrophy in TG. BOO induces reduced bladder compliance and hypertrophy in WT and TG in the sub-acute phase, but persistent overexpression of SERCA2a in TG does not aggravate the bladder compliance and hypertrophy. In conclusion, SERCA2a overexpression affects bladder functions under physiological conditions, but not in BOO-induced sub-acute pathological conditions.博士（医学）・甲第623号・平成26年5月28

飲水指導は夜間頻尿患者の頻尿症状を有効に改善する

OBJECTIVES: To evaluate how guidance on water-intake impacts the degree of nocturia. METHODS: A total of 67 male patients were enrolled in the present study. Patients were asked to adjust their water and food intakes so that their 24-h urine production/bodyweight would be equal or lower than 30 mL/kg. One month after the treatment, the therapeutic gain from and adverse effects of fluid restriction were examined by comparing the pretreatment and post-treatment value of various parameters. RESULTS: Overall, 65 eligible patients were evaluated. In 44 patients (67%), the frequency of nocturia was improved to one or more times. The change in frequency of nocturia showed a positive correlation with the change in nocturnal urine volume. The change in nocturnal urine volume showed a positive correlation with the changes in 24-h urine production/bodyweight, 24-h drinking volume and daytime drinking volume. The changes in 24-h urine production/bodyweight and daytime drinking volume were independent factors influencing therapeutic effect. None of the participants reported any adverse event. CONCLUSIONS: In patients with a 24-h urine production/bodyweight equal or higher than 30 mL/kg, guidance on water intake might be considered effective and safe as a lifestyle therapy. Water restriction should be carried out not only in the evening, but also during daytime.博士（医学）・乙第1348号・平成26年12月3日© 2014 The Japanese Urological Associatio

A Phase 3 Study of Evolocumab (AMG 145) in Statin-Treated Japanese Patients at High Cardiovascular Risk

Evolocumab (AMG 145), a fully human monoclonal antibody against PCSK9, significantly reduced low-density lipoprotein cholesterol (LDL-C) levels in phase 2 and 3 studies. This phase 3 study evaluated the efficacy and safety of evolocumab plus atorvastatin in Japanese patients with hyperlipidemia or mixed dyslipidemia and high cardiovascular risk. Patients were randomized to atorvastatin 5 or 20 mg/day for 4 weeks. Subsequently, patients underwent second randomization to evolocumab 140 mg biweekly (Q2W) or 420 mg monthly (QM) or placebo Q2W or QM. Coprimary end points were % change from baseline in LDL-C at week 12 and mean of weeks 10 and 12. Secondary end points included change and % change in other lipids and proportion of patients reaching LDL-C <70 mg/dl. Adverse events and laboratory values were recorded. Four hundred four patients were randomized to study drug. At baseline, the mean (SD) age was 61 (10) years (placebo) and 62 (11) years (evolocumab); 39% and 40% were women; 14% and 12% had cerebrovascular or peripheral arterial disease; and 51% and 47% had diabetes. At entry, mean (SD) calculated LDL-C was 128 (23) mg/dL; after stabilization on atorvastatin 5 and 20 mg/day, baseline LDL-C levels were 118 (35) and 94 (24) mg/dL, respectively. Mean LDL-C reductions at week 12 for evolocumab versus placebo ranged from 67% to 76%. No imbalances were observed in adverse events between treatment groups. Efficacy and safety for Q2W or QM evolocumab dosing were similar. In conclusion, in high-risk Japanese patients receiving stable statin therapy, evolocumab markedly reduced LDL-C and was well tolerated