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.).

[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 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.

[Efficacy and safety of the single pill combination of valsartan 80 mg plus amlodipine 5 mg in mild to moderate essential hypertensive patients without adequate blood pressure control by monotherapy].

OBJECTIVE: To evaluate the efficacy and safety of a once daily valsartan/amlodipine 80/5 mg combination tablet in Chinese mild to moderate hypertensive patients without adequate blood pressure control by monotherapy. METHODS: Two multicenter, randomized, double-blind, double dummy, active-controlled, parallel group trials were conducted. After a washout period (no medication) of 1-4 weeks, patients with Mean Sitting Diastolic Blood Pressure (MSDBP) > or = 95 mm Hg (1 mm Hg = 0.133 kPa) and < 110 mm Hg received a monotherapy of either Amlodipine 5 mg (in study 1) or valsartan 80 mg (in study 2) for 4 weeks. Patients with MSDBP > or = 90 mm Hg and < 110 mm Hg at the end of the monotherapy period were randomized to receive valsartan/amlodipine 80/5 mg treatment, or continue with the monotherapy. RESULTS: In study 1, compared with amlodipine 5 mg, valsartan/amlodipine 80/5 mg once daily further reduced mean sitting systolic blood pressure (MSSBP)/MSDBP 4.4/3 mm Hg (P < 0.0001). In study 2, compared with valsartan 80 mg, valsartan/amlodipine 80/5 mg once daily further reduced MSSBP/MSDBP 6.4/4.2 mm Hg (P < 0.0001). The blood pressure (BP) control rates (BP < 140/90 mm Hg) of combination treatment group were 71.0% and 71.2% respectively, and significantly higher than the monotherapy groups in both trials. Incidence of adverse events was comparable in monotherapy and combination therapy groups. CONCLUSION: Our results showed that valsartan/amlodipine 80/5 mg was superior to amlodipine 5 mg or valsartan 80 mg alone in lowering blood pressure and BP control in patients with mild to moderate hypertension not adequately controlled with amlodipine 5 mg or valsartan 80 mg monotherapy. No new or unexpected safety issues were identified with valsartan/amlodipine combination therapy compared with monotherapy.

[Differences in goal attainment in clinical management of dyslipidemia in China evaluated by different guidelines].

OBJECTIVE: To better understand the similarities and disparities between the newly issued Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults (CG) and exist relevant guidelines by comparing the actual effect on assessment of current clinical management of dyslipidemia in China, in order to promote the use of CG in clinical practice. METHODS: Study participants included 2094 patients from the Second Multi-center Survey of Dyslipidemia Management in China. The goal attainment rate was defined as the proportion of participants who achieved their target low-density lipoprotein cholesterol (LDL-C) levels specified by CG, the Chinese Expert Recommendations on Prevention and Treatment of Dyslipidemia (CR), the updated Adult Treatment Panel III of the National Cholesterol Education Program (ATP III), respectively. RESULTS: (1) The overall goal attainment rates were 62%, 34% and 50% according to CR, ATP III and CG, respectively. (2) With reference to the CG risk stratifications, the risk of nearly 40% of high risk patients and all very high risk patients were underestimated by CR, whereas the risk of more than 40% of patients in any risk groups were overestimated by ATP III. (3) The disparities in risk stratifications accounted for 90% of the difference in overall goal attainment rate (12%) between CR and CG, while the disparities in the risk stratifications and that in LDL-C target levels were responsible for 29% and 71% of the difference (16%) , respectively, between ATP III and CG. CONCLUSIONS: There were significant differences in goal attainment rates assessed by different clinical practice guidelines. CG is more aggressive in risk stratification than CR but simpler and easier to use than ATP III, and hence more appropriate to Chinese patients and should be widely promoted in China.

[Therapeutic efficacy of valsartan and valsartan/HCTZ in mild to moderate hypertensive patients].

OBJECTIVE: To assess the efficacy and safety of valsartan/hydrochlorothiazide (HCTZ) 80/12.5 mg once daily (o.d.) in Chinese patients with mild to moderate essential hypertension who was not adequately controlled by valsartan 80 mg o.d. monotherapy. METHODS: In this multi-center, double-blind, randomized, active controlled, parallel group trial, 1051 out of 1175 Chinese patients with mild to moderate essential hypertension [DBP >or= 95 mm Hg and < 110 mm Hg (1 mm Hg = 0.133 kPa)] completed single-blind run-in period (valsartan 80 mg o.d. therapy for 4 weeks) after 2 week's wash-out period. At the end of the single-blind run-in period, those patients with DBP >or= 95 mm Hg (n = 864) were randomized in 1:1 ratio to Valsartan and Valsartan 80 mg (n = 429)/HCTZ80/12.5 mg (n = 435) treatment o.d. for 8 weeks. Safety and efficacy was assessed every 4 weeks during double blind phase. RESULTS: At the end of study, valsartan/HCTZ 80/12.5 mg combination treatment further reduced systolic (-3.5 mm Hg) and diastolic (-2.2 mm Hg) pressures and increased the rate of patients reaching goal BP level (53.9% vs. 40.9%) compared to valsartan 80 mg o.d. monotherapy. Incidence of side effects was similar between the combination therapy and monotherapy groups (8.9% vs. 5.1%, P > 0.05). CONCLUSION: Efficacy of Valsartan 80 mg/HCTZ 12.5 mg compound was superior to valsartan 80 mg on BP reduction and goal BP control rate in Chinese patients with mild to moderate essential hypertension. The combination of Valsartan 80 mg/hydrochlorothiazide (HCTZ) 12.5 mg provides a suitable treatment for Chinese patients who are not adequately controlled by valsartan 80 mg o.d. monotherapy.

[Cut offs and risk stratification of dyslipidemia in Chinese adults].

OBJECTIVE: To establish cut offs and risk stratification of dyslipidemia in Chinese adults. METHODS: Data from 2 widely cited studies: the PRC-US Collaborative Study of Cardiovascular and Cardiopulmonary Epidemiology and the China Multi-Provincial Cardiovascular Cohort Study, with a total of 40 719 Chinese adults, age 35 to 64 at baseline, about half men and half women, followed up for a total of 345 140.5 person years, were used to analyze the relationship between dyslipidemia and ischemic cardiovascular diseases (ICVD, including coronary heart events and ischemic stroke events) using a common data analysis protocol co-developed by the scientists from the 2 studies. The relative risk was estimated with the Cox proportional hazard model adjusting for other conventional cardiovascular risk factors. The 10-year absolute risk of ICVD for a 50 years-old person at different risk factor combinations was used to develop the risk stratification. RESULTS: (1) There was a continuous linear relationship between baseline TC (or LDL-C) and ICVD risk without a threshold; (2) The incidence (absolute risk) of ICVD was similar for LDL-C < 3.37 mmol/L (130 mg/dl) and for TC < 5.18 mmol/L (200 mg/dl); and similar for LDL-C < 4.14 mmol/L (160 mg/dl) and for TC < 6.22 mmol/L (240 mg/dl); (3) The absolute ICVD risk for TC > or = 6.22 mmol/L (240 mg/dl) was slightly less but close to that for grade 1 hypertension; (4) ICVD risk increased as HDL-C decreased; (5) No significant association was found between baseline TG and subsequent ICVD; (6) At any TC level, the absolute ICVD risk for those having only hypertension was higher than that for those having 3 other risk factors. CONCLUSION: The cut offs for diagnosis of dyslipidemia in Chinese adults can refer to those used in relevant international guidelines: TC < 5.18 mmol/L (200 mg/dl) [or LDL-C < 3.37 mmol/L (130 mg/dl)] as normal, TC 5.18 - 6.19 mmol/L (200 - 239 mg/dl) [or LDL-C 3.37 - 4.12 mmol/L (130 - 159 mg/dl)] as borderline high, and TC > or = 6.22 mmol/L (240 mg/dl) [or LDL-C > or = 4.14 mmol/L (160 mg/dl)] as high; HDL-C < 1.04 mmol/L (40 mg/dl) as low, 1.04 - 1.53 mmol/L (40 - 59 mg/dl) as normal and > or = 1.55 mmol/L (60 mg/dl) as optimal. In risk stratification scheme, hypertension plays a role that equals to that of any other 3 risk factors.

[The angiographic features of exercise-induced ST-segment elevation in patients without myocardial infarction].

OBJECTIVE: To explore the incidence and angiographic features of exercise-induced ST-segment elevation in patients without prior myocardial infarction. METHODS: Exercise-induced ST-segment elevation occurred in 15 out of 4601 consecutive patients without prior myocardial infarction underwent treadmill exercise testing during a 2-year period. The coronary angiographic features of the 15 patients (13 males, aged between 40 - 75 years) were analyzed. RESULTS: Coronary angiography revealed one hemodynamically relevant stenotic vessel in 6 patients, two hemodynamically relevant stenotic vessels in 6 patients, three hemodynamically relevant stenotic vessels in 3 patients. Left anterior descending (LAD) coronary artery was affected in 12 patients. Left main coronary artery (LMCA) stenosis was evidenced in 1 patient and right coronary artery stenosis in 7 patients. Severe (90% - 100%) occlusions were visualized in 8 out of 13 patients with LAD or LMCA lesions. Elevated ST-segment leads were consistent with the ischemic area where the blood supply of myocardium was affected by diseased vessels. CONCLUSIONS: The incidence of exercise induced ST-segment elevation in patients without prior myocardial infarction is very low and mostly due to severe fixed coronary artery stenosis, especially in LAD. The location of ischemic myocardium can be suggested by ST-segment elevation leads during exercise.

Tolerability of beta-blockers in elderly patients with chronic heart failure: the COLA II study.

BACKGROUND: Beta-blockers are recommended therapy for patients with chronic heart failure (CHF). However, there remains concern regarding tolerability of these agents in the elderly, which has contributed to the limited uptake of these agents in clinical practice. AIMS: We conducted a multi-national, prospective evaluation of tolerability to carvedilol in 1030 CHF patients aged >70 years selected by their treating physician to receive this agent in everyday practice. METHODS AND RESULTS: NYHA Class II-IV CHF patients were assessed at baseline for key demographic parameters that may predict tolerability, then followed for 6 months after starting carvedilol. Tolerability was defined as being on >or=6.25 mg bd of carvedilol at 6 months having received a total of >or=3 months therapy. Tolerability overall was 80% with age 70-75 years 84.3%, 76-80 years 76.8% and >80 years 76.8%. Mean carvedilol dose achieved was 31.2 mg. In multivariate analysis, advanced age, low diastolic BP, LVEF, obstructive airways disease and presence of diabetes were predictors of tolerability. CONCLUSIONS: Carvedilol appears to be well tolerated in this elderly CHF patient cohort. Therefore, elderly CHF patients should not be denied treatment with carvedilol because of concerns regarding tolerability.

[Efficacy and safety of olmesartan medoxomil versus losartan potassium in Chinese patients with mild to moderate essential hypertension].

OBJECTIVE: To evaluate the efficacy and safety of olmesartan medoxomil compared with losartan potassium in patients with mild to moderate essential hypertension. METHOD: This is a randomized, double-blind, double-dummy, active-controlled, parallel, multi-center study. After a 2-week placebo run-in period, a total of 287 eligible subjects were randomized at 1:1 ratio to receive olmesartan medoxomil 20 mg or losartan potassium 50 mg, once daily for 8 weeks. The blood pressure was assessed after 4 weeks treatment. If the subject's seating diastolic blood pressure (SeDBP) was still >or=90 mm Hg, the dosage was doubled for another 4 weeks; for those subjects whose SeDBP was <90 mm Hg after 4-week treatment, the initial dosage remained unchanged and the treatment continued until completion of the study. RESULTS: (1) The mean trough reduction in SeDBP from baseline in olmesartan group was significantly greater than that in losartan group after 4 weeks (11.72 mm Hg vs 9.23 mm Hg, P=0.004) and 8 weeks treatment (12.94 mm Hg vs 11.01 mm Hg, P=0.035). (2) The number and percentage of responders in olmesartan group (81, 65.3%) were statistically higher than those (68, 52.7%) in losartan group (P=0.028) after 4 weeks treatment and were similar between the two groups after 8 weeks treatment (P>0.05). (3) Individual and overall trough/peak ratios of DBP and SBP in 24-hour ambulatory blood pressure monitoring were higher in olmesartan group than losartan group. The hypotensive effect of olmesartan was more durable than losartan at 24 hour interval. (4) The incidence of study drug-related adverse events (AEs) in olmesartan group (10.5%) was similar as that in losartan group (13.9%, P>0.05). Most of these AEs were mild and transient. CONCLUSION: This study shows that olmesartan medoxomil, at oral dose of 20 mg-40 mg once daily was effective and safe for hypertension treatment and the hypotensive effect was superior to losartan potassium (50 mg-100 mg once daily).

Efficacy and safety of simvastatin in Asian and non-Asian coronary heart disease patients: a comparison of the GOALLS and STATT studies.

BACKGROUND: Asians are thought to be more responsive to the lipid-lowering effects of statins than non-Asians although there are no head-to-head trials that examine this perception. OBJECTIVE: To compare the results of the GOALLS and STATT studies that used similar titrate-to-goal protocols with 20 mg up to 80 mg simvastatin in Asian and non-Asian coronary heart disease (CHD) patients. METHODS: GOALLS (N = 198; included non-Asians and Asians) and STATT (N = 133; included Asians only) were both multi-center, open-label 14-week studies in CHD patients with serum low density lipoprotein cholesterol (LDL-C) levels 115 mg/dL-180 mg/dL and triglycerides (TG) levels < or = 400 mg/dL. Simvastatin was titrated from 20 mg/day up to 80 mg/day in order to achieve the National Cholesterol Education Program (NCEP) LDL-C target < or = 100 mg/dL. The primary efficacy variable was the percentage of patients attaining the NCEP LDL-C target at Week 14. Secondary endpoints included proportion of patients achieving the European Society of Cardiology/European Atherosclerosis Society/European Society of Hypertension (European) LDL-C target < or = 115 mg/dL at Week 14 and percentage change in lipid parameters. Safety and tolerability were assessed by monitoring adverse experiences and safety laboratory tests. Fifteen Asian patients were part of the GOALLS cohort and their data were compared separately with results of non-Asians from GOALLS and Asians from the STATT study. RESULTS: After 14 weeks of simvastatin treatment, 87.1% of GOALLS non-Asians, 85.7% of GOALLS Asians, and 78.2% of STATT patients attained the NCEP LDL-C target. At Week 14, 94.4%, 92.9%, and 91.7% of the GOALLS non-Asians, GOALLS Asians, and STATT patients achieved the European LDL-C target, respectively. The average treatment doses to attain NCEP and European targets were comparable among groups. The percentage reductions in lipid parameters from baseline to week 14 were similar among groups except, changes in high density lipoprotein cholesterol and apolipoprotein A-I favored Asian subjects. There was also a greater reduction in TG in the STATT study, but this was not consistent with TG reductions experienced by Asians in the GOALLS study. In both studies, simvastatin was generally well tolerated by all patients across the dosage range of 20 mg-80 mg. No cases of rhabdomyolysis or myopathy were reported in either study. CONCLUSIONS: A great majority of CHD patients is able to achieve LDL-C treatment goals (up to 90%) on simvastatin regardless of racial background. Simvastatin treatment at doses of 20 mg-80 mg is well-tolerated in Asian and non-Asian CHD patients. This side-by-side comparison provides evidence that Asian and non-Asian CHD populations respond similarly to comparable doses of simvastatin.

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.

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.

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.

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.

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.

A randomised study comparing the efficacy and safety of rosuvastatin with atorvastatin for achieving lipid goals in clinical practice in Asian patients at high risk of cardiovascular disease (DISCOVERY-Asia study).

BACKGROUND: Most studies investigating the benefits of statins have focused on North American and European populations. This study focuses on evaluating the lipid-lowering effects of rosuvastatin and atorvastatin in Asian patients. OBJECTIVES: The DIrect Statin COmparison of LDL-C Values: an Evaluation of Rosuvastatin therapY (DISCOVERY)-Asia study is one of nine independently powered studies assessing the efficacy of starting doses of statins in achieving target lipid levels in different countries worldwide. DISCOVERY-Asia was a 12-week, randomised, open-label, parallel-group study conducted in China, Hong Kong, Korea, Malaysia, Taiwan, and Thailand. RESULTS: A total of 1482 adults with primary hypercholesterolaemia and high cardiovascular risk (> 20%/10 years, type 2 diabetes, or a history of coronary heart disease) were randomised in a 2 : 1 ratio to receive rosuvastatin 10 mg once daily (o.d.) or atorvastatin 10 mg o.d. The percentage of patients achieving the 1998 European Joint Task Force low-density lipoprotein cholesterol (LDL-C) goal of < 3.0 mmol/L at 12 weeks was significantly higher in the rosuvastatin group (n = 950) compared with the atorvastatin group (n = 471) (79.5 vs. 69.4%, respectively; p < 0.0001). Similar results were observed for 1998 European goals for total cholesterol (TC), and the 2003 European goals for LDL-C and TC. LDL-C and TC levels were reduced significantly more with rosuvastatin compared with atorvastatin. Both drugs were well-tolerated and the incidence and type of adverse events were similar in each group. TRIALS REGISTRATION: The trial registry summary is available at http://www.clinicaltrials.gov/; ClinicalTrials.gov Identifier: NCT00241488 CONCLUSIONS: This 12-week study showed that the starting dose of rosuvastatin 10 mg o.d. was significantly more effective than the starting dose of natorvastatin 10 mg o.d. at enabling patients with primary hypercholesterolaemia to achieve European goals for LDL-C and TC in a largely Asian population in real-life clinical practice. The safety profile of rosuvastatin 10 mg is similar to that of atorvastatin 10 mg in the Asian population studied here, and is consistent with the known safety profile of rosuvastatin in the white population.

The Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial: outcomes in patients receiving monotherapy.

In the main Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) report, we investigated outcomes in 15 245 high-risk hypertensive subjects treated with valsartan- or amlodipine-based regimens. In this report, we analyzed outcomes in 7080 patients (46.4%) who, at the end of the initial drug adjustment period (6 months), remained on monotherapy. Baseline characteristics were similar in the valsartan (N=3263) and amlodipine (N=3817) groups. Time on monotherapy was 3.2 years (78% of treatment exposure time). The average in-trial blood pressure was similar in both groups. Event rates in the monotherapy group were 16% to 39% lower than in the main VALUE trial. In the first analysis, we censored patients when they discontinued monotherapy ("censored"); in the second, we counted events regardless of subsequent therapy (intention-to-treat principle). We also assessed the impact of duration of monotherapy on outcomes. No difference was found in primary composite cardiac end points, strokes, myocardial infarctions, and all-cause deaths with both analyses. Heart failure in the valsartan group was lower both in the censored and intention-to-treat analyses (hazard ratios: 0.63, P=0.004 and 0.78, P=0.045, respectively). Longer duration of monotherapy amplified between-group differences in heart failure. New-onset diabetes was lower in the valsartan group with both analyses (odds ratios: 0.78, P=0.012 and 0.82, P=0.034). Thus, despite lower absolute event rates in monotherapy patients, the relative risks of heart failure and new-onset diabetes favored valsartan. Moreover, these findings support the feasibility of comparative prospective trials in lower-risk hypertensive patients.