Efficacy and Tolerability of Telmisartan/Amlodipine + Hydrochlorothiazide Versus Telmisartan/Amlodipine Combination Therapy for Essential Hypertension Uncontrolled With Telmisartan/Amlodipine: The Phase III, Multicenter, Randomized, Double-blind TAHYTI Study

PURPOSE: This 8-week study in Korea aimed to evaluate the efficacy and tolerability of a telmisartan/amlodipine + hydrochlorothiazide (TAH) combination versus telmisartan/amlodipine (TA) combination in patients with essential hypertension that did not respond appropriately to 4-week treatment with TA. METHODS: All patients who met the inclusion criteria received TA (40/5 mg) during a 4-week run-in period (period 1). Patients who met the criteria for essential hypertension (mean sitting systolic blood pressure [MSSBP], >/=140 and /=130 and<200 mm Hg in those with diabetes mellitus or chronic kidney disease) after period 1 were randomly assigned to receive TA 40/5 mg + hydrochlorothiazide 12.5 mg (test group) or TA only (control group). The test and control drugs were administered in each group for 2 weeks (period 2). Patients who completed period 2 underwent 6-week treatment (period 3) with a TAH and TA dose twice that in period 2. The primary end point was the change in MSSBP at week 8 of treatment. Secondary end points were the change in MSSBP at week 2 and MS diastolic BP, BP control rate, and BP response rate at weeks 2 and 8. Treatment tolerability was assessed based on adverse events (AEs), laboratory evaluations (chemistry, hematology, and urinalysis), 12-lead ECG, and physical examination including vital sign measurements. FINDINGS: We randomized 310 patients to the treatment groups. The mean (SD) ages of the TAH and TA groups were 62.0 (10.8) and 63.4 (10.4) years, respectively. The least squares mean change in MSSBP was significantly greater in the TAH group than in the TA group after 8 weeks (-18.7 vs -12.2 mm Hg; P < 0.001). Similar results were obtained on changes in MSSBP after 2 weeks and changes in sitting diastolic BP, BP control rate, and BP response rate at weeks 2 and 8 compared with the respective baseline values. The prevalences of treatment-emergent AEs (29.0% vs 16.3%; P = 0.008) and adverse drug reactions (20.0% vs 10.5%; P = 0.020) were significantly greater in the TAH group than in the TA group. Most treatment-emergent AEs were mild or moderate; none were severe. The most frequently reported AEs were dizziness and headache. IMPLICATION: TAH triple therapy was more effective than was TA double therapy in reducing BP in these patients in Korea with essential hypertension that did not adequately respond to TA. ClinicalTrials.gov identifier: NCT02738632.ope

Quantitative coronary angiography versus intravascular ultrasound guidance for drug-eluting stent implantation (GUIDE-DES): study protocol for a randomised controlled non-inferiority trial

Introduction: Angiography remains the gold standard for guiding percutaneous coronary intervention (PCI). However, it is prone to suboptimal stent results due to the visual estimation of coronary measurements. Although the benefit of intravascular ultrasound (IVUS)-guided PCI is becoming increasingly recognised, IVUS is not affordable for many catheterisation laboratories. Thus, a more practical and standardised angiography-based approach is necessary to support stent implantation. Methods and analysis: The Quantitative Coronary Angiography versus Intravascular Ultrasound Guidance for Drug-Eluting Stent Implantation trial is a randomised, investigator-initiated, multicentre, open-label, non-inferiority trial comparing the quantitative coronary angiography (QCA)-guided PCI strategy with IVUS-guided PCI in all-comer patients with significant coronary artery disease. A novel, standardised, QCA-based PCI protocol for the QCA-guided group will be provided to all participating operators, while the PCI optimisation criteria will be predefined for both strategies. A total of 1528 patients will be randomised to either group at a 1:1 ratio. The primary endpoint is the 12-month cumulative incidence of target-lesion failure defined as a composite of cardiac death, target-vessel myocardial infarction or ischaemia-driven target-lesion revascularisation. Clinical follow-up assessments are scheduled at 1, 6 and 12 months for all patients enrolled in the study. Ethics and dissemination: Ethics approval for this study was granted by the Institutional Review Board of Asan Medical Center (no. 2017-0060). Informed consent will be obtained from every participant. The study findings will be published in peer-reviewed journal articles and disseminated through public forums and academic conference presentations. Cost-effectiveness and secondary imaging analyses will be shared in secondary papers. Trial registration number: NCT02978456.ope

Assessing the extent of social exclusion by the analysis of trip-making behavior

학위논문 (석사)-- 서울대학교 환경대학원 : 환경계획학과(교통관리전공), 2014. 2. 장수은.본 연구의 목적은 사회적 배제 해소를 목적으로 하는 교통정책의 기반이 되는 기초현황분석이다. 본 연구는 향후 사회적 배제 해소를 목적으로 하는 새로운 교통정책 수립을 위한 객관적이고 미시적인 현황 분석을 수행하였다. 이를 위해 통행발생모형을 통한 수도권지역 거주민의 통행행태를 분석하였으며, 순서형 프로빗 모형을 활용하였다. 통행발생량은 일정 시간동안 나타나는 통행주체와 교통체계, 토지이용 특성간의 함수로 볼 수 있으며 이를 반영하기 위해 다음과 같은 변수를 고려하였다. 통행주체의 특성은 나이, 성별, 운전면허 취득여부와 같은 개인특성 변수와 가구원 수, 가구 내 미취학 아동 유무, 가구 내 고령자 유무, 가구소득, 차량 보유여부 등의 가구특성 변수를 고려하였으며, 교통체계특성을 반영하기 위해 읍·면·동 버스 정류장 밀도, 지하철역 유무를, 토지이용 특성을 반영하기 위해 읍·면·동 인구 1명당 쇼핑시설의 수, 미취학 아동 인구 1명당 보육시설 수, 종합병원 유무, 종사자 밀도 등을 변수로 고려하였다. 분석 결과 여성은 남성에 비해 통행에 더 큰 제약을 받고 있었다. 나이의 증가는 36-50세 이후 통행에 음의 영향을 미치고 있었으며, 고령자로 분류되는 65세 이상 계층에서 매우 뚜렷하게 나타났다. 소득의 증가는 통행에 양의 영향을 미치고 있었으며, 가구 내 미취학 아동과 고령자는 통행에 음의 영향을 미치고 있었다. 교통특성 변수는 모두 통행에 양의 영향을 미치고 있었으며, 차량 보유여부가 가장 큰 영향을 미치는 것으로 나타났으며 토지이용 변수 역시 통행에 양의 영향을 미치는 것으로 타나났다.Ⅰ. 서론 1 1. 연구의 배경 및 목적 1 2. 연구의 범위 2 3. 연구의 방법 3 Ⅱ. 이론적 배경 및 선행연구 고찰 6 1. 형평성과 사회적 배제 6 2. 교통과 사회적 배제 13 Ⅲ. 연구방법론 19 Ⅳ. 자료구축 및 모형추정 23 1. 자료구축 23 2. 기초현황분석 28 3. 모형추정 결과 45 Ⅴ. 결론 54 1. 결론 54 2. 정책제언 57 참고문헌 59Maste

The efficacy and safety of co-administration of fimasartan and rosuvastatin to patients with hypertension and dyslipidemia

BACKGROUND: Hypertension and dyslipidemia are major risk factors of cardiovascular disease (CVD) events. The objective of this study was to evaluate the efficacy and safety of the co-administration of fimasartan and rosuvastatin in patients with hypertension and hypercholesterolemia. METHODS: We conducted a randomized double-blind and parallel-group trial. Patients who met eligible criteria after 4 weeks of therapeutic life change were randomly assigned to the following groups. 1) co-administration of fimasartan 120 mg/rosuvastatin 20 mg (FMS/RSV), 2) fimasartan 120 mg (FMS) alone 3) rosuvastatin 20 mg (RSV) alone. Drugs were administered once daily for 8 weeks. RESULTS: Of 140 randomized patients, 135 for whom efficacy data were available were analyzed. After 8 weeks of treatment, the FMS/RSV treatment group showed greater reductions in sitting systolic (siSBP) and diastolic (siDBP) blood pressures than those in the group receiving RSV alone (both p < 0.001). Reductions in siSBP and siDBP were not significantly different between the FMS/RSV and FMS alone groups (p = 0.500 and p = 0.734, respectively). After 8 weeks of treatment, FMS/RSV treatment showed greater efficacy in percentage reduction of low-density lipoprotein cholesterol (LDL-C) level from baseline than that shown by FMS alone treatment (p < 0.001). The response rates of siSBP with FMS/RSV, FMS alone, and RSV alone treatments were 65.22, 55.56, and 34.09%, respectively (FMS/RSV vs. RSV, p = 0.006). The LDL-C goal attainment rates with FMS/RSV, RSV alone, and FMS alone treatments were 80.43%, 81.82%, and 15.56%, respectively (FMS/RSV vs. FMS, p < 0.001). Incidence of adverse drug reactions with FMS/RSV treatment was 8.33%, which was similar to those associated with FMS and RSV alone treatments. CONCLUSION: This study demonstrated that the co-administration of fimasartan and rosuvastatin to patients with both hypertension and hypercholesterolemia was efficacious and safe.ope

Antiplatelet Effect of Clopidogrel Can Be Reduced by Calcium-Channel Blockers

PURPOSE: Clopidogrel is metabolized by the hepatic cytochrome P450 (CYP) system into its active thiol metabolite. CYP3A4 is involved in the metabolism of both clopidogrel and dihydropyridine calcium channel blockers (CCBs). A few reports have suggested an inhibitory interaction between CCBs and clopidogrel. Accordingly, the aim of this study was to determine the effect of CCBs on the antiplatelet activity of clopidogrel by serial P2Y12 reaction unit (PRU) measurements. MATERIALS AND METHODS: We assessed changes in antiplatelet activity in patients receiving both clopidogrel and CCBs for at least 2 months prior to enrollment in the study. The antiplatelet activity of clopidogrel was measured by VerifyNow P2Y12 assay in the same patient while medicated with CCBs and at 8 weeks after discontinuation of CCBs. After discontinuation of the CCBs, angiotensin receptor blockers were newly administered to the patients or dosed up for control of blood pressure. RESULTS: Thirty patients finished this study. PRU significantly decreased after discontinuation of CCBs (238.1±74.1 vs. 215.0±69.3; p=0.001). Of the 11 patients with high post-treatment platelet reactivity to clopidogrel (PRU≥275), PRU decreased in nine patients, decreasing below the cut-off value in seven of these nine patients after 8 weeks. Decrease in PRU was not related to CYP2C19 genotype.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

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

Diagnostic accuracy of low-radiation coronary computed tomography angiography with low tube voltage and knowledge-based model reconstruction

We aimed to evaluate the accuracy of coronary computed tomography angiography (CCTA) with a low-radiation protocol and iterative model reconstruction (IMR), in comparison with invasive coronary angiography (ICA). Sixty-one patients (45 males; mean age, 61.9 ± 9.2 years) with suspected coronary artery disease who underwent CCTA and ICA were retrospectively enrolled. CCTA was performed with low tube voltage (80 or 100 kVp), low tube current (100-200 mAs), prospective ECG triggering, and IMR using a 64-slice computed tomography scanner. Coronary artery disease was defined as luminal narrowing of >50%, as assessed using CCTA and ICA. The sensitivity, specificity, positive (PPV) and negative (NPV) predictive value, and accuracy of CCTA were examined. The mean radiation dose of CCTA was 1.05 ± 0.36 mSv. No non-diagnostic segment was noted. The sensitivity, specificity, PPV, NPV, and accuracy of CCTA were 86.4%, 96.1%, 80.3%, 97.5%, and 94.6% on a per segment basis, 93.1%, 94.7%, 88.3%, 97.0%, and 94.2% on a per vessel basis, and 100%, 83.3%, 93.5%, 100%, and 95.1% on a per patient basis, respectively. In conclusion, a low-radiation CCTA protocol with IMR may be useful for diagnosing coronary artery disease, as it reduces the radiation dose while maintaining diagnostic accuracy.ope

혈중 Adiponectin과 Resistin의 농도가 안정형 협심증 환자의 표적 병변에서 관상동맥 죽상판의 조성과 관상동맥 재형성에 미치는 영향

Objective : The purpose of this study was to investigate the effect of adiponectin and resistin on coronary plaque composition determined by virtual histology (VH) intravascular ultrasound (IVUS) and coronary artery remodeling of target lesion in patients with stable angina. Methods : We prospectively enrolled 48 patients who underwent coronary angiography and VH IVUS for stable angina (27 men, 61±9 years of age). Preintervention grayscale and VH IVUS analysis was done across the target lesion. Planar VH IVUS analysis at the minimum luminal site and volumetric analysis over a 10-mm-long segment centered at the minimum luminal site were performed. The subjects were divided into 2 groups based on remodeling index (RI): positive remodeling (PR) defined as RI>1.0 and non-PR as RI≤1.0. Blood samples for analysis of adiponectin and resistin were obtained from the femoral artery before coronary angioplasty. Results : Of the 48 patients enrolled, 23 (48%) had PR in their target lesion and 25 (52%) were non-PR group. Clinical and angiographic characteristics, VH IVUS parameters were not different between the PR and the non-PR groups. Adiponectin and resistin levels showed no significant correlations with coronary plaque composition evaluated with VH IVUS. Adiponectin showed no significant difference between the two groups. However, resistin showed trend toward higher level in non-PR group (4.17±2.18 ng/mL vs. 6.11±4.26 ng/mL, P=0.056) and a significant negative correlation with RI (r=-0.303, P=0.036). Conclusion : We found a negative correlation between the resistin level and RI of a de-novo target lesion in patients with stable angina.ope

Delayed Stent Fracture after Successful Sirolimus-Eluting Stent(Cypher®) Implantation

Background and Objectives: Sirolimus-eluting stent (SES) is very effective for preventing in-stent restenosis through the suppression of neointimal proliferation. Treatment failure cases related to stent fracture have recently been reported on, but any studies concerning the pattern or mechanism of SES fracture are very rare. Subjects and Methods: Between December 2003 to January 2005, 457 patients underwent follow-up coronary angiography after SES implantation at three referral center. We reviewed the angiographic and procedural data for eleven of theses patients [6 males (55%), mean age: 60 year-old age, range: 43-74 years] who were proven to have experience complete SES fracture. Results: The left anterior descending artery (LAD) and right coronary artery (RCA) stent fracture were 7 cases (63%) and 4 cases (37%), respectively. Myocardial bridge was shown in 6 cases with LAD fracture (86%). Overlapping stent implantation was performed in 5 cases (45%). The mean value of the maximal angulations at the fracture site before intervention was 50° (range; 39-70°) and the mean change between the maximal and minimal angulations was 13.2° (range; 2-28°). The mean stent diameter and length were 3.0 mm (range; 2.75-3.50 mm) and 40 mm (range; 23-52 mm). Stent inflation with high pressure was performed on 6 cases (54%) and it's frequency was higher in the RCA than the LAD (3 cases, 75%, mean inflation pressure: 13.1 mmHg). The mean follow-up duration was 7.2 month and only 2 cases were admitted due to the recurrent chest pain. The binary restenosis rate was 55% (6 cases) and the restenotic lesions were treated by balloon angioplasty in 2 cases and additional stenting was done in 2 cases. Conclusion: Our results demonstrated that SES fracture occurred in 7 cases with LAD lesion and in 4 cases with RCA lesion. Long stenting including overlapping implantation and more than 40° angulated long stent implantation may be the factors for SES fracture. Our results also showed high pressure stent inflation was performed more frequently at the RCA lesion, and myocardial bridge and kinking motion was detected more frequently at the LAD lesions.ope