Utilization of peanut hull hydrochar /beta cyclodextrin/Fe3O4 magnetic composite for lead ion removal from water solution.

This study involves synthesizing peanut hull hydrochar (PHH) and a PHH/ß-CD/Fe3O4 magnetic composite through hydrothermal and chemical precipitation methods, respectively, to use as effective adsorbents for Pb2+ removal. Vibrating-sample magnetometry (VSM) and Brunauer-Emmett-Teller (BET) analyses revealed that the magnetic saturation value and specific active surface area of PHH/ß-CD/Fe3O4 are 31.543 emu/g and 32.123 m2/g, respectively. The impact of key variables on adsorption efficiency was evaluated using the response surface method - central composite design. ANOVA results (F-value: 166.22 and p-value: <0.05) demonstrated that the model effectively assesses the interaction of variables in the adsorption process. Additionally, R2, Adjusted R2, and Predicted R2 values were 0.999, 0.986, and 0.975, respectively, indicating the model's high adequacy in describing response changes. The maximum efficiency for Pb2+ adsorption was found to be 95.35% using PHH and 99.73% with the PHH/ß-CD/Fe3O4 magnetic composite. These measurements were taken at a temperature of 25°C, an adsorbent dose of 1 g/L, a pH of 6, and a Pb2+ concentration of 5 mg/L, with respective contact times of 130 minutes and 50 minutes. Thermodynamic analysis revealed negative enthalpy and Gibbs free energy values, indicating that the adsorption process is exothermic and spontaneous. The negative entropy parameter suggests a reduction in random interactions during the process. The Pb2+ adsorption data for both PHH (R2: 0.982) and PHH/ß-CD/Fe3O4 (R2: 0.985) were best described by the Pseudo 2nd order kinetic model. Equilibrium data followed the Freundlich model, with R2 values of 0.981 for PHH and 0.990 for PHH/ß-CD/Fe3O4, highlighting the importance of heterogeneous surfaces in the removal process. The maximum adsorption capacities for Pb2+ were 26.72 mg/g for PHH and 33.88 mg/g for PHH/ß-CD/Fe3O4. Reuse and stability tests confirmed the structural stability and reusability of the adsorbents. Therefore, the PHH/ß-CD/Fe3O4 magnetic composite is a promising option for removing Pb2+ from aqueous solutions.

Efficient removal of RR2 dye by electro- Ce(III) process with its elegant arts and attractive charm in performance, energy consumption and mechanism.

Reactive red 2 (RR2) azo dye wastewater poses a serious hazard to the water environment health, so using a novel and efficient Electro- Ce(III) (E- Ce(III)) process takes on a critical significance in treating RR2 dye wastewater. In this study, the effects of a variety of single-factor conditions on RR2 removal efficiency were evaluated in depth. The results indicated that the optimal experimental conditions are as reaction temperature of 25 °C, Na2SO4 concentration of 25 mM, Ce(III) concentration of 0.3 mM, pH of 4.0, and current density of 40.0 mA/cm2. When the RR2 dye wastewater was treated for 40 min under the optimal experimental conditions, a high removal rate of 99.8% for RR2 was obtained. It is suggested that the background ion PO43- in the dye wastewater inhibits the E-Ce (III) process, whereas Cl- facilitates this process. Moreover, the yield of Ce(IV) increases with the increase of the current density. At the current density of 40.0 mA/cm2, a reasonable energy consumption of 3.85 kW h/gTOC for the process was obtained after the 3-h treatment. The effects of different degradation processes (including Direct Electrooxidation (DEO), single Ce(III), and E-Ce (III)) on RR2 removal efficiency and TOC change were compared. The types of oxidizing substances in the E-Ce (III) process were detected, and the mechanism of RR2 oxidative degradation in the E-Ce (III) process was summarized. The result suggests that the E-Ce (III) process has low power consumption. Meanwhile, in the E-Ce (III) process, free reactive Ce(IV) with strong oxidation is continuously generated, RR2 can be efficiently degraded. And the continuous cycle transformation between Ce(III) and Ce(IV) maintains the strong oxidation of the process. The contribution of free reactive Ce(IV) and DEO to RR2 degradation was obtained as 58.8% and 39.8%, respectively. The combined effect of Ce(IV) and DEO played a major role in the E-Ce (III) process, while ·OH exhibited a relatively weak effect (nearly 1.4%). RR2 was comprised of 13 major intermediates, and the biodegradability of wastewater was improved significantly after treatment, thus facilitating the further mineralization and biodegradation of the products. The E- Ce(III) process is novel, efficient, and environment-friendly, and has a large market application space, suggesting that it can be applied as an efficient, economic, and sustainable water treatment process.

Improved neural network with least square support vector machine for wastewater treatment process.

This research offers a unique interval by using the predicting approach for discharge indicators of water quality data such as biochemical oxygen demand (BOD) and ammonia nitrogen (NH3-N). This is considered one of the significant quality metrics in wastewater treatment plants for water quality management as well as surveillance. To begin, the effluent information for BOD/NH3-N and their supplementary parameters are gathered. Hence BOD and NH3 are considered major feature sources for estimating water pollutants. BOD is high then oxygen level is very low in the water due to pollutants or algae. Ammonia nitrogen is an organic waste component in water from sewage. The significant characteristics with good correlation levels of BOD and NH3-N are examined and identified using a grey correlation analysis method after certain basic data pre-processing procedures. The BOD/NH3-N effluent information of a water treatment plant is predicted using an upgraded feed-forward neural network with the least square support vector machine (FFNN-LSSVM) method. An optimization approach for an enhanced feed-forward neural network (IFFNN) is built by Machine Learning Algorithms. The IFFNN used regular influent water quality, influent rate of flow, and Wastewater performance monitoring and operational conditions as input parameters. For future prediction, input variables were previous different wastewater quality measurements. Lastly, the analysis shows that, when compared to other current algorithms, the proposed methodology can forecast wastewater quality of water with high accuracy in predicting BOD and NH3 levels, limited computation duration, mean error less than 10% and R2 is 90% proves better than existing techniques.

Ambulatory arterial stiffness index correlates with ambulatory pulse pressure but not dipping status in patients with grade 1/grade 2 essential hypertension.

OBJECTIVE: To evaluate the relationship between ambulatory arterial stiffness index (AASI) and other parameters derived from ambulatory blood pressure (BP) monitoring, including dipping status, in patients with grade 1/grade 2 hypertension. METHODS: This retrospective analysis included baseline data from Chinese outpatients enrolled into a previous study, who had clinic diastolic BP of 90-109 mmHg and systolic BP <180 mmHg, had undergone 24-h ambulatory BP monitoring and routine blood chemistry investigations, and had estimated glomerular filtration rate (eGFR) data. RESULTS: Out of 120 patients screened, 87 were included. No significant difference in 24-h AASI was found between dippers and nondippers. The 24-h AASI significantly correlated with age, systolic BP and pulse pressure, and inversely correlated with 24-h diastolic BP variation and eGFR. In dippers and nondippers, AASI correlated with daytime pulse pressure, daytime diastolic BP variation and eGFR; in nondippers, AASI also correlated with 24-h systolic BP and 24-h pulse pressure. The 24-h AASI was significantly associated with 24-h pulse pressure and daytime pulse pressure. CONCLUSION: In patients with grade 1/grade 2 essential hypertension, AASI shows a significant correlation with ambulatory pulse pressure.

Efficacy and safety of olmesartan medoxomil/amlodipine fixed-dose combination for hypertensive patients uncontrolled with monotherapy.

This study aimed to evaluate the efficacy and safety of olmesartan medoxomil (OM)/amlodipine (AML) 20/5 mg fixed-dose combination tablet in Chinese mild to moderately hypertensive patients with inadequate blood pressure (BP) control on monotherapy. Two multicenter, randomized, double-blind, double-dummy, active-controlled, parallel group clinical trials were conducted. After screening and a 2-week placebo run-in period, patients with 95 mmHg ≤ seated diastolic blood pressure (SeDBP) < 110 mmHg received monotherapy with OM 20 mg (in Study 1) or AML 5 mg (in Study 2), once daily for 4 weeks. Patients with 90 mmHg ≤ mean SeDBP < 110 mmHg at the end of the monotherapy period were randomized to receive OM/AML 20/5 mg treatment or continue with the monotherapy, once daily for 8 weeks. OM/AML (20/5 mg) treatment significantly lowered both systolic and diastolic BP at 4 and 8 weeks compared to 40 mg olmesartan or 5 mg AML. The incidence of drug-related adverse effects did not differ significantly between the groups. OM/AML 20/5 mg was superior to OM 40 mg or AML 5 mg monotherapy in lowering BP in Chinese mild to moderately hypertensive patients with inadequate BP control on monotherapy. No new or unexpected safety issues were identified with OM/AML combination therapy compared to monotherapy.

Residual macrovascular risk in 2013: what have we learned?

Cardiovascular disease poses a major challenge for the 21st century, exacerbated by the pandemics of obesity, metabolic syndrome and type 2 diabetes. While best standards of care, including high-dose statins, can ameliorate the risk of vascular complications, patients remain at high risk of cardiovascular events. The Residual Risk Reduction Initiative (R3i) has previously highlighted atherogenic dyslipidaemia, defined as the imbalance between proatherogenic triglyceride-rich apolipoprotein B-containing-lipoproteins and antiatherogenic apolipoprotein A-I-lipoproteins (as in high-density lipoprotein, HDL), as an important modifiable contributor to lipid-related residual cardiovascular risk, especially in insulin-resistant conditions. As part of its mission to improve awareness and clinical management of atherogenic dyslipidaemia, the R3i has identified three key priorities for action: i) to improve recognition of atherogenic dyslipidaemia in patients at high cardiometabolic risk with or without diabetes; ii) to improve implementation and adherence to guideline-based therapies; and iii) to improve therapeutic strategies for managing atherogenic dyslipidaemia. The R3i believes that monitoring of non-HDL cholesterol provides a simple, practical tool for treatment decisions regarding the management of lipid-related residual cardiovascular risk. Addition of a fibrate, niacin (North and South America), omega-3 fatty acids or ezetimibe are all options for combination with a statin to further reduce non-HDL cholesterol, although lacking in hard evidence for cardiovascular outcome benefits. Several emerging treatments may offer promise. These include the next generation peroxisome proliferator-activated receptorα agonists, cholesteryl ester transfer protein inhibitors and monoclonal antibody therapy targeting proprotein convertase subtilisin/kexin type 9. However, long-term outcomes and safety data are clearly needed. In conclusion, the R3i believes that ongoing trials with these novel treatments may help to define the optimal management of atherogenic dyslipidaemia to reduce the clinical and socioeconomic burden of residual cardiovascular risk.

Preloading with atorvastatin before percutaneous coronary intervention in statin-naïve Asian patients with non-ST elevation acute coronary syndromes: A randomized study.

BACKGROUND: Data on atorvastatin pretreatment in Asian patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) are limited. However, there have been studies in other populations in Asia which demonstrated that statins can reduce the risk of periprocedural myocardial infarction (MI). METHODS AND RESULTS: Statin-naïve patients with non-ST-segment-elevation (NSTE)-ACS scheduled for PCI were randomized to usual care or atorvastatin preloading groups. All patients received usual care including atorvastatin 40 mg/day. The atorvastatin group received atorvastatin 80 mg 12 h and 40 mg 2 h pre-PCI. Of 499 patients randomized, 247 were assigned to atorvastatin preloading. Following coronary angiography, 335 patients (163 atorvastatin) received PCI. During the 30 days post-PCI, major adverse cardiac events (death, MI, and target vessel revascularization) occurred in 24 (15%) atorvastatin and 27 (16%) usual care patients (p=NS). Post hoc analyses showed that at 8 h post-PCI, 3.82% of the atorvastatin group and 7.22% of the usual care group had a post-procedural creatine kinase-myocardial band (CK-MB) above 3 times the upper limit of normal (p=0.27) and at 24 h post-PCI, the rate was 7.64% versus 9.47% (p=1.0). Safety profile suggests that high-dose atorvastatin (40 mg) for up to 1 month, in conjunction with usual care, is relatively safe and well tolerated. CONCLUSIONS: This study of statin-naïve Korean and Chinese patients with NSTE-ACS who received additional atorvastatin loading doses of 80 mg at 12 h, and 40 mg at 2 h, pre-PCI did not find a beneficial effect compared with usual post-PCI atorvastatin 40 mg/day treatment. Atorvastatin was found to be well tolerated in Asian patients with NSTE-ACS undergoing PCI. Results of the current study merit further investigation of the early use of statins in patients with NSTE-ACS to delineate patient subgroups who may benefit from this therapy.

Long-term efficacy of olmesartan medoxomil in Chinese hypertensive patients as assessed by clinic, ambulatory and home blood pressure measurements.

BACKGROUND AND OBJECTIVES: There is limited information on the long-term efficacy and safety of olmesartan medoxomil in the management of hypertension in Chinese patients. We therefore conducted the present multicentre, single-arm, prospective, observational study to investigate the 24-week efficacy and safety of olmesartan medoxomil in patients with mild to moderate hypertension. METHODS: Eligible patients (diastolic blood pressure [BP] 90-109 mmHg and systolic BP <180 mmHg off antihypertensive medication) were started on olmesartan medoxomil 20 mg once daily, with the possible up-titration to 40 mg once daily during 24 weeks of follow-up, to control clinic BP to the target level (<140/90 and <130/80 mmHg in diabetes mellitus). In a subset of enrolled patients, 24-h ambulatory and home BP monitoring were also performed. RESULTS: In the intent-to-treat analysis (n = 348), at 24 weeks of follow-up, the mean ± SD changes from baseline in clinic systolic/diastolic BP were 21.2 ± 14.2/16.0 ± 8.8 mmHg (p < 0.001). The proportions of patients who achieved the goal BP for systolic, diastolic and both were 81, 80 and 75 %, respectively. Olmesartan medoxomil also significantly (p < 0.001) reduced systolic/diastolic BP measured at patients' homes by 17.7 ± 13.1/12.1 ± 7.9 mmHg from baseline (n = 109), and reduced mean 24-h, daytime and night-time ambulatory BP by 13.3 ± 16.3/7.6 ± 9.5 mmHg, 13.9 ± 17.4/8.0 ± 10.4 mmHg and 12.3 ± 18.1/6.8 ± 10.2 mmHg, respectively (n = 87). Seven (2.0 %) serious adverse events were reported during follow-up. CONCLUSION: In Chinese hypertensive patients, olmesartan medoxomil is efficacious in lowering BP as assessed by three different BP-measuring methods and has an acceptable long-term safety and tolerability profile.

Using different methods to evaluate the efficacy of olmesartan medoxomil in Chinese patients with mild to moderate essential hypertension according to ambulatory blood pressure monitoring.

OBJECTIVE: To evaluate the efficacy of olmesartan medoxomil in Chinese patients with mild to moderate essential hypertension using different methods according to ambulatory blood pressure monitoring. METHODS: Chinese patients 18-75 years of age with clinic diastolic blood pressure (BP) 90-109 mmHg and systolic BP less than 180 mmHg were treated with olmesartan medoxomil 20-40 mg once daily for 24 weeks to reach the goal BP (< 140/90 and < 130/80 mmHg in diabetes) in a multicenter study. The trough-to-peak ratio (T/P ratio) and the smoothness index (SI) for systolic/diastolic BP were calculated using different methods according to ambulatory blood pressure monitoring. RESULT: Olmesartan medoxomil 20-40 mg once daily reduced the systolic/diastolic ambulatory BP for 24-h, daytime, and night-time by 13.3 ± 16.3/7.6 ± 9.5, 13.9 ± 17.4/8.0 ± 10.4, and 12.3 ± 18.1/6.8 ± 10.2 mmHg in all eligible patients at week 24 from baseline (n = 87, P < 0.0001). The global and individual T/P ratios were 0.64/0.62 and 0.32/0.30 (n = 87) for systolic/diastolic BP, whereas these were 0.71/0.70 and 0.31/0.39 in fair responders (n = 71). Global and individual SI were 6.81/5.37 and 0.92/0.67 (n = 87) for systolic/diastolic BP, whereas these were 7.04/5.44 and 1.03/1.03 in fair responders (n = 71). Global and individual T/P ratios for systolic/diastolic BP were 0.75/0.82 and 0.45/0.46 in the 20 mg subgroup (n = 41), whereas these were 0.44/0.59 and 0.30/0.29 in the 40 mg subgroup (n = 30). Global and individual SI were 5.70/5.32 and 1.03/0.87 for systolic/diastolic BP in the 20 mg subgroup (n = 41), but these were 3.64/2.46 and 1.01/0.60 in the 40 mg subgroup (n = 30). CONCLUSION: The duration of the antihypertensive action of olmesartan medoxomil with 20-40 mg once daily can be assessed by the global T/P ratio and SI rather than the individual values, even in different populations and dosages.

Reduction of the morning blood pressure surge treated with olmesartan in Chinese patients with mild to moderate essential hypertension--a multicenter, open-label, single treatment group clinical study.

OBJECTIVE: To investigate the morning blood pressure surge (MBPS) in Chinese patients with mild to moderate essential hypertension treated with long-term administration of olmesartan, an angiotensin II receptor antagonist according to ambulatory blood pressure monitoring (ABPM). MATERIALS AND METHODS: In a multi-center, prospective study, we investigated the long-term efficacy of olmesartan by ABPM in 18-75 years-old Chinese patients with mild to moderate hypertension (clinic diastolic blood pressure [DBP] 90-109 mm Hg and systolic blood pressure [SBP] < 180 mmHg). After a 1 week placebo runin, 87 patients were treated with olmesartan 20 mg once daily in the morning for 24 weeks. Ambulatory blood pressure monitoring was conducted at baseline and at the end of 24 weeks. At baseline, patients with an MBPS > or = 23 mmHg were classified as the MBPS group (n = 41), and all other patients were classified as the non-MBPS group (n = 46). RESULTS: The mean systolic and diastolic blood pressures (SBP/DBP) over 24 hours were reduced from 141.78 +/- 12.8/91.17 +/- 7.34 to 128.35 +/- 15.86/83.58 +/- 9.53 mmHg (p < 0.01). The mean blood pressure in the final 6 hours of the dosing interval dropped from 135.75 +/- 5.84/87.29 +/- 4.80 mmHg to 122.98 +/- 6.46/80.49 +/- 4.31 mmHg (p < 0.01). The MBPS for SBP/ DBP were reduced from 35.68 +/- 8.85/29.77 +/- 17.19 mmHg to 28.62 +/- 15.08/19.08 +/- 11.01 mmHg in the MBPS group (p < 0.05). The reductions in MBPS after treament with olmesartan were significantly different between the two groups (p < 0.01). CONCLUSIONS: Olmesartan effectively reduces blood pressure in patients with essential hypertension, and olmesartan especially reduces the MBPS in MBPS-prone patients.

[Ultraviolet-initiated synthesis and characterization of anionic polyacrylamide].

APAM was prepared under the action of composite initiator and UV irradiation, using acryl amide (AM), 2-acrylamido-2-methyl propane sulfonic acid (AMPS) and acrylic acid (AA) as raw materials. The paper studied the effect of proportion between monomers, monomer ratio, initiator concentration and other factors on intrinsic viscosity of the polymer, and optimized preparation conditions. The chemical structure and thermal stability of APAM were characterized by UV, FTIR, SEM and DTA-TGA respectively. The results showed that the APAM with the intrinsic viscosity 1.6 x 10(3) mL x g(-1) can prepared when the proportion between monomers was 70 : 10 : 10, the monomer ratio was 40%, initiator concentration was 0.20%, pH was 9 and the illumination time was 60 min.

Efficacy and safety of aliskiren, a direct renin inhibitor, compared with ramipril in Asian patients with mild to moderate hypertension.

This 8-week, randomized, double-blind, parallel-group study compared the efficacy and safety of aliskiren with ramipril in Asian patients with mild to moderate hypertension. Following a 2- to 3-week placebo run-in period, patients with mean sitting diastolic blood pressure (msDBP) ≥95 and <110 mm Hg were randomized to receive once daily dose of either aliskiren 75, 150, 300 mg or ramipril 5 mg for 8 weeks. Efficacy variables were the changes in msDBP and mean sitting systolic BP (msSBP) and BP control rates (<140/90 mm Hg). Safety was assessed by recording adverse events (AEs) and serious AEs (SAEs). Of 1316 randomized patients, 1160 (88.1%) completed the study. At the study endpoint, patients on aliskiren had greater mean BP reductions (14.39/11.63 mm Hg for 300 mg; 12.16/10.04 mm Hg for 150 mg; 12.24/10.66 mm Hg for 75 mg) than those on 5 mg ramipril (11.46/9.19 mm Hg). All aliskiren doses were statistically non-inferior (P<0.0001) to ramipril in reducing msDBP. The reduction in BP for aliskiren 300 mg was statistically superior vs. ramipril (P<0.002). Blood pressure control rates were higher for aliskiren (300 mg, 52.29%; 150 mg, 48.11%; 75 mg, 45.68%) than for ramipril (5 mg, 43.7%); the difference for aliskiren 300 mg vs. ramipril 5 mg was statistically significant (P<0.05). Aliskiren was well tolerated with a fourfold lower incidence of cough (0.6-1.2%) compared with ramipril (5.2%). SAEs were rare in this study (0.5%). Aliskiren produced greater BP reductions with a lower incidence of cough than ramipril in Asian patients with mild to moderate hypertension.

Dronedarone in high-risk permanent atrial fibrillation.

BACKGROUND: Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular antiarrhythmic effects. We hypothesized that dronedarone would reduce major vascular events in high-risk permanent atrial fibrillation. METHODS: We assigned patients who were at least 65 years of age with at least a 6-month history of permanent atrial fibrillation and risk factors for major vascular events to receive dronedarone or placebo. The first coprimary outcome was stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes. The second coprimary outcome was unplanned hospitalization for a cardiovascular cause or death. RESULTS: After the enrollment of 3236 patients, the study was stopped for safety reasons. The first coprimary outcome occurred in 43 patients receiving dronedarone and 19 receiving placebo (hazard ratio, 2.29; 95% confidence interval [CI], 1.34 to 3.94; P=0.002). There were 21 deaths from cardiovascular causes in the dronedarone group and 10 in the placebo group (hazard ratio, 2.11; 95% CI, 1.00 to 4.49; P=0.046), including death from arrhythmia in 13 patients and 4 patients, respectively (hazard ratio, 3.26; 95% CI, 1.06 to 10.00; P=0.03). Stroke occurred in 23 patients in the dronedarone group and 10 in the placebo group (hazard ratio, 2.32; 95% CI, 1.11 to 4.88; P=0.02). Hospitalization for heart failure occurred in 43 patients in the dronedarone group and 24 in the placebo group (hazard ratio, 1.81; 95% CI, 1.10 to 2.99; P=0.02). CONCLUSIONS: Dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent atrial fibrillation who were at risk for major vascular events. Our data show that this drug should not be used in such patients. (Funded by Sanofi-Aventis; PALLAS ClinicalTrials.gov number, NCT01151137.).

Efficacy and tolerability of a single-pill combination of amlodipine/valsartan in Asian hypertensive patients not adequately controlled with valsartan monotherapy.

This randomized, double-blind study evaluated efficacy of a single-pill combination of amlodipine/valsartan (Aml/Val) in Asian patients with hypertension not responding to Val 80 mg. Patients with mean sitting diastolic blood pressure (DBP) ≥90-≤110 mmHg were randomized to Aml/Val 5/80, Val 80, or Val 160 mg for 8 weeks. At week-8 endpoint, significantly greater reductions in BP were seen with Aml/Val 5/80 mg than valsartan monotherapies (p < 0.0001). The BP control was greater with Aml/Val 5/80 (70.5%) than Val (44.1-58.6%) monotherapies. The combination was well tolerated. In conclusion, single-pill combination with Aml/Val provided significant additional BP reduction and control in hypertensive patients not responding to Val 80 mg.

Prasugrel versus clopidogrel in Asian patients with acute coronary syndromes: design and rationale of a multi-dose, pharmacodynamic, phase 3 clinical trial.

BACKGROUND: Prasugrel is a third generation thienopyridine that is more potent, rapid in onset, and consistent in inhibition of platelets than clopidogrel. However, early prasugrel dose-ranging studies and the subsequent phase 3 TRITON-TIMI 38 trial were conducted primarily in Caucasian populations. OBJECTIVES: The current clinical study is designed to confirm superior inhibition of platelet aggregation with prasugrel versus clopidogrel in the treatment of Asian subjects with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). RESEARCH DESIGN AND METHODS: This is a phase 3, randomized, double-blind, multi-dose, four-arm parallel, multinational clinical trial. East and Southeast Asian patients (N = 715) with moderate- to high-risk ACS undergoing PCI will be randomized to one of three prasugrel dosing regimens (60 mg LD/10 mg MD; 30 mg LD/7.5 mg MD; 30 mg LD/5 mg MD) or clopidogrel (300 mg LD/75 mg MD) for 90 days. MAIN OUTCOME MEASURES: The primary endpoint is inhibition of platelet aggregation measured by the point-of-care Accumetrics VerifyNow P2Y12 device, and the primary analysis will be performed in a hierarchical manner for descending doses of prasugrel. Additional key endpoints include major adverse cardiovascular events, non-coronary artery bypass-graft (CABG) surgery-related TIMI bleeding, and genetic analyses of cytochrome P450 polymorphisms. CONCLUSIONS: This study is a phase 3, multi-dose, pharmacodynamic comparison of prasugrel versus clopidogrel in Asian patients with ACS undergoing PCI. It is the first study designed to investigate prasugrel therapy specifically in Asian ACS subjects, and will inform which doses of prasugrel are effective and safe for patients of Asian ethnicity.

Efficacy and safety of a single-pill combination of amlodipine/valsartan in Asian hypertensive patients inadequately controlled with amlodipine monotherapy.

OBJECTIVE: The antihypertensive efficacy of amlodipine/valsartan combination has not been evaluated in Asian patients as previous large-scale studies enrolled very few patients. This multicentre, randomised, double-blind study assessed the efficacy and safety of a single-pill combination of amlodipine/valsartan versus amlodipine in Asian hypertensive patients. METHODS: After a 1-4-week washout period, patients (mean sitting diastolic BP [msDBP]: >or=95-<110 mmHg) were treated with amlodipine 5 mg for 4 weeks. Patients inadequately controlled on amlodipine (msDBP >or=90 and <110 mmHg) were randomised to receive amlodipine/valsartan 5/80 mg (n = 349) or amlodipine 5 mg (n = 349) for 8 weeks. Efficacy variables were change in msDBP, mean sitting systolic BP (msSBP) from baseline (at randomisation) to week 8 endpoint, and BP control rate (<140/90 mmHg) at week 8 endpoint. Safety assessments included monitoring and recording of adverse events (AEs). RESULTS: Baseline characteristics were comparable between the groups. Most patients were Chinese (86.4%), men (65.1%), with a baseline BP 139.5/94.5 mmHg. At week 8 endpoint, the least square mean reduction in BP was significantly greater with amlodipine/valsartan combination than amlodipine monotherapy (-11.4/-9.7 vs. -7.4/-7.1 mmHg; p < 0.0001) with a higher BP control rate (69.2 vs. 57.6%; p = 0.0013). Ambulatory BP monitoring in a subgroup of patients (n = 82), showed a significant 24-h mean BP reduction from baseline with amlodipine/valsartan (-7.3/-6.3 mmHg; p < 0.0001), whereas the reduction was not significant with amlodipine (-0.2/+0.3 mmHg; p > 0.05). The overall incidence of AEs was similar in both groups. Peripheral oedema occurred only in the amlodipine group n = 4 (1.1%) and not in the amlodipine/valsartan combination. Hypotension was reported in only one patient in the amlodipine/valsartan combination. Six patients (0.9%) experienced serious AEs, of which only one SAE, i.e. gastric ulcer, was reported to be related to amlodipine treatment. CONCLUSION: The single-pill combination of amlodipine/valsartan was efficacious and well-tolerated in Asian hypertensive patients who were inadequately controlled on amlodipine alone. As with all clinical trials, the entry criteria may limit the extrapolation of these results to a broader population. ClinicalTrials.gov Identifier: NCT00413049.

A short-term, randomized, double-blind, parallel-group study to evaluate the efficacy and safety of dronedarone versus amiodarone in patients with persistent atrial fibrillation: the DIONYSOS study.

INTRODUCTION: We compared the efficacy and safety of amiodarone and dronedarone in patients with persistent atrial fibrillation (AF). METHODS: Five hundred and four amiodarone-naïve patients were randomized to receive dronedarone 400 mg bid (n = 249) or amiodarone 600 mg qd for 28 days then 200 mg qd (n = 255) for at least 6 months. Primary composite endpoint was recurrence of AF (including unsuccessful electrical cardioversion, no spontaneous conversion and no electrical cardioversion) or premature study discontinuation. Main safety endpoint (MSE) was occurrence of thyroid-, hepatic-, pulmonary-, neurologic-, skin-, eye-, or gastrointestinal-specific events, or premature study drug discontinuation following an adverse event. RESULTS: Median treatment duration was 7 months. The primary composite endpoint was 75.1 and 58.8% with dronedarone and amiodarone, respectively, at 12 months (hazard ratio [HR] 1.59; 95% confidence interval [CI] 1.28-1.98; P < 0.0001), mainly driven by AF recurrence with dronedarone compared with amiodarone (63.5 vs 42.0%). AF recurrence after successful cardioversion was 36.5 and 24.3% with dronedarone and amiodarone, respectively. Premature drug discontinuation tended to be less frequent with dronedarone (10.4 vs 13.3%). MSE was 39.3 and 44.5% with dronedarone and amiodarone, respectively, at 12 months (HR = 0.80; 95% CI 0.60-1.07; P = 0.129), and mainly driven by fewer thyroid, neurologic, skin, and ocular events in the dronedarone group. CONCLUSION: In this short-term study, dronedarone was less effective than amiodarone in decreasing AF recurrence, but had a better safety profile, specifically with regard to thyroid and neurologic events and a lack of interaction with oral anticoagulants.

Pharmacokinetics of rosuvastatin in healthy Chinese volunteers living in China: a randomized, open-label, ascending single- and multiple-dose study.

BACKGROUND: Cross-study comparisons suggest that systemic exposure (AUC) to rosuvastatin calcium, a 3-hydroxy-3-methylglutaryl coenzyme A-reductase inhibitor, may be approximately 2-fold higher in Asian subjects living in Asian countries than in white subjects living in Western countries. OBJECTIVE: This study was conducted to determine the pharmacokinetic characteristics of rosuvastatin and its metabolites after single and multiple doses of rosuvastatin in healthy Chinese subjects living in China. METHODS: This was an open-label, ascending single- and multiple-dose study. Subjects were randomly assigned to receive rosuvastatin 5, 10, or 20 mg. Each subject received 1 tablet of the assigned treatment on day 1 and days 4 through 10. Plasma concentrations of rosuvastatin, N-desmethyl rosuvastatin, and rosuvastatin lactone were measured through 72 hours after administration of single doses and through 96 hours after administration of multiple doses. Blood samples were obtained within 30 minutes before dosing on days 7, 8, and 9 for the assessment of pharmacokinetic parameters at steady state. Noncompartmental pharmacokinetic analysis was performed to determine the C(max) and AUC(0-t) for rosuvastatin, N-desmethyl rosuvastatin, and rosuvastatin lactone after single and multiple doses of rosuvastatin. Tolerability assessments were conducted throughout the study. RESULTS: Of the 36 enrolled subjects, only 1 was female. The mean age of subjects in the rosuvastatin 5-, 10-, and 20-mg groups was 22.4, 21.3, and 22.4 years, respectively. Weight and height ranged from 54 to 85 kg and from 161 to 189 cm, respectively. Geometric mean C(max) values for rosuvastatin after administration of single doses of rosuvastatin 5, 10, and 20 mg were 8.33, 10.76, and 19.17 ng/mL, respectively; the corresponding geometric mean AUC(0-t) values were 57.63, 88.89, and 163.87 ng . h/mL. At steady state, values for C(max) were 8.31, 8.41, and 20.73 ng/mL; the corresponding geometric mean AUC values were 64.87, 77.29, and 178.64 ng . h/mL. After administration of multiple doses of rosuvastatin 5, 10, and 20 mg, the accumulation ratios were 1.23, 0.95, and 1.23, respectively, indicating minimal accumulation of rosuvastatin. Circulating concentrations of N-desmethyl rosuvastatin and rosuvastatin lactone were well below those of rosuvastatin after administration of single and multiple doses of rosuvastatin. CONCLUSIONS: Increases in C(max), AUC(0-t), C(max,ss), and AUC(ss) were observed with increasing single and multiple doses of rosuvastatin 5, 10, and 20 mg. The increase in exposure with increasing doses was lower than would be expected under conditions of strict proportionality. Rosuvastatin exhibited little accumulation on repeated administration. All rosuvastatin doses were well tolerated in these Chinese subjects.

Design and rationale of a study in Asia of atorvastatin pretreatment in patients undergoing percutaneous coronary intervention for non-ST elevation acute coronary syndromes.

BACKGROUND: Studies in Western populations have shown the benefits of pretreatment with atorvastatin in preventing cardiovascular events in patients, including those with acute coronary syndromes (ACS), undergoing percutaneous coronary intervention (PCI). However, data concerning the value of such therapy in Asian patients are limited. The primary objective of the present study is to evaluate the efficacy of atorvastatin in reducing cardiovascular outcomes in Asian patients with non-ST-segment elevation (NSTE)-ACS following hospital admission for early PCI (within 72 h of the onset of symptoms). Secondary objectives are to assess the effects of atorvastatin on cardiac biomarker levels, and the safety and tolerability profile of atorvastatin. METHODS: This study is a prospective, multicenter, open-label trial designed to enroll 350 statin-naïve patients with NSTE-ACS scheduled for PCI in China and the Republic of Korea. Patients are randomized to either usual care or atorvastatin treatment groups, with patients in both treatment groups receiving usual care including atorvastatin 40 mg/day for 30 days post-PCI. Patients in the atorvastatin group receive additional doses of atorvastatin 80 mg at 12 h pre-PCI and 40 mg at 2 h pre-PCI. The primary end point is the incidence of major adverse cardiac events (death, myocardial infarction, and target vessel revascularization) at 30 days post-PCI. CONCLUSIONS: The present study will provide valuable insights into whether the benefits of atorvastatin pretreatment extend to Asian patients with ACS undergoing interventions. Enhanced treatment of these patients will be an important contribution towards alleviating the increasing burden of cardiovascular disease in Asian countries.