Rivastigmine Patch in Chinese Patients with Probable Alzheimer's disease: A 24-week, Randomized, Double-Blind Parallel-Group Study Comparing Rivastigmine Patch (9.5 mg/24 h) with Capsule (6 mg Twice Daily).

AIMS: To compare the once-daily rivastigmine patch 9.5 mg/24 h (10 cm(2) ) versus twice-daily capsule (12 mg/day) in Chinese patients with probable Alzheimer's disease (AD) (mini-mental state examination [MMSE] scores of 10-20). METHODS: The primary objective was to demonstrate the noninferiority of patch to capsule in Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) change from baseline to 24 week. Secondary endpoints included cognition (MMSE), overall clinical response (Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change [ADCS-CGIC]), activities of daily living (Alzheimer's Disease Cooperative Study-Activities of Daily Living [ADCS-ADL]), behavior (Neuropsychiatric Inventory [NPI-12]), and safety. RESULTS: Similar cognitive improvement was observed in both patch (n = 248) and capsule (n = 253) groups. Statistical noninferiority for ADAS-Cog was not established (least-square means difference, 0.1; 95% confidence interval, -1.2; 1.5). Considering all efficacy parameters into account, both treatments showed similar performance at Week 24. Treatment-related adverse events (AEs) were lower for patch (39.7%) compared with capsule (49.8%). Application site pruritus was reported in 10.9% of patients receiving patch; most cases were mild. Gastrointestinal AEs including nausea, vomiting, and diarrhea occurred less frequently in the patch group (15.8% vs. 28.7%). CONCLUSION: Rivastigmine patch 9.5 mg/24 h is effective and well tolerated in Chinese patients with probable AD.

A 1-year randomized controlled trial of deferasirox vs deferoxamine for myocardial iron removal in ß-thalassemia major (CORDELIA).

Randomized comparison data on the efficacy and safety of deferasirox for myocardial iron removal in transfusion dependent patients are lacking. CORDELIA was a prospective, randomized comparison of deferasirox (target dose 40 mg/kg per day) vs subcutaneous deferoxamine (50-60 mg/kg per day for 5-7 days/week) for myocardial iron removal in 197 ß-thalassemia major patients with myocardial siderosis (T2* 6-20 milliseconds) and no signs of cardiac dysfunction (mean age, 19.8 years). Primary objective was to demonstrate noninferiority of deferasirox for myocardial iron removal, assessed by changes in myocardial T2* after 1 year using a per-protocol analysis. Geometric mean (Gmean) myocardial T2* improved with deferasirox from 11.2 milliseconds at baseline to 12.6 milliseconds at 1 year (Gmeans ratio, 1.12) and with deferoxamine (11.6 milliseconds to 12.3 milliseconds; Gmeans ratio, 1.07). The between-arm Gmeans ratio was 1.056 (95% confidence interval [CI], 0.998, 1.133). The lower 95% CI boundary was greater than the prespecified margin of 0.9, establishing noninferiority of deferasirox vs deferoxamine (P = .057 for superiority of deferasirox). Left ventricular ejection fraction remained stable in both arms. Frequency of drug-related adverse events was comparable between deferasirox (35.4%) and deferoxamine (30.8%). CORDELIA demonstrated the noninferiority of deferasirox compared with deferoxamine for myocardial iron removal. This trial is registered at www.clinicaltrials.gov as #NCT00600938.

A randomized, double-blind, placebo-controlled study to determine the effects of valsartan on exercise time in patients with symptomatic heart failure with preserved ejection fraction.

AIMS: To determine whether valsartan improves treadmill exercise time, in patients with symptomatic heart failure with a preserved ejection fraction (HFPEF), compared with placebo. METHODS AND RESULTS: In this multicentred, double-blind, 14-week study, patients were randomized to receive valsartan (V) 80 mg or placebo (P) once daily on top of background medications. The dose of valsartan was force-titrated up to 320 mg. A total of 152 patients were randomized (V = 70, P = 82). Most patients had well-controlled hypertension (V = 91.2%, P = 89.0%) (mean baseline systolic BP approximately 130 mmHg) and >50% were receiving an angiotensin-converting enzyme inhibitor and/or beta-blocker (V = 57.4%, P = 54.9%). The mean ejection fraction at baseline was 70.48% in the placebo group (n = 64) and 71.52% in the valsartan group (n = 79). Valsartan had no significant effect on exercise time (primary variable), gas exchange variables, 6 min walk test distance, exertion-related symptoms, brain natriuretic peptide levels, echocardiographic parameters, or quality-of-life scores. Valsartan significantly lowered peak exercise systolic BP (-13.1 mmHg vs. placebo; P < 0.001) and improved ratings of perceived exertion (Borg score) (-0.69 vs. placebo; P = 0.008). CONCLUSION: In this population, which predominantly included patients with well-controlled hypertension and symptomatic HFPEF, addition of valsartan did not increase exercise time within 14 weeks. However, valsartan 320 mg reduced blood pressure and improved symptoms of perceived exertion (Borg score) during exercise and was generally well-tolerated.

Coadministration of valsartan 160 and 320 mg and simvastatin 20 and 40 mg in patients with hypertension and hypercholesterolemia: a multicenter, 12-week, double-blind, double-dummy, parallel-group superiority study.

BACKGROUND: Together, high blood pressure (BP) and high cholesterol levels constitute a cumulative risk for coronary heart disease (CHD). Elevations in cholesterol increase BP through upregulation of angiotensin type 1 receptors, with a corresponding increase in cholesterol oxidation due to elevations in BP. Hence, control of low-density lipoprotein cholesterol (LDL-C) and BP through coadministration of an antihypertensive and a statin have potential benefit in the management of CHD. OBJECTIVES: This study examined the dose response to simvastatin 20 and 40 mg in reducing LDL-C and the efficacy and tolerability of a high dose of valsartan (320 mg) when administered with simvastatin. METHODS: In this multicenter, 12-week, double-blind, double-dummy, parallel-group superiority study, patients with hypertension and hypercholesterolemia were randomized to receive valsartan 160 mg along with simvastatin 20 or 40 mg. At week 6, valsartan was titrated upward to 320 mg in both groups. The primary efficacy variable was the change in LDL-C, calculated using the Friedewald formula or measured directly (depending on triglyceride levels) and analyzed for superiority. Secondary efficacy variables were the change in LDL-C and the proportion of patients achieving LDL-C and BP control. Safety assessments included the occurrence of adverse events (AEs) and serious AEs, and changes in hematology and biochemistry variables, vital signs, and findings on physical examinations. RESULTS: Eight hundred seventy-two patients were randomized to receive double-blind treatment, and the intent-to-treat population included 838 patients. The combination of valsartan 160 mg + simvastatin 40 mg was statistically superior to that of valsartan 160 mg + simvastatin 20 mg in reducing LDL-C at week 6 (least squares mean percent change from baseline: -38.5% vs -33.6%, respectively; P < 0.001); at week 12, the corresponding values were -36.8% in the valsartan 320 mg + simvastatin 40 mg group and -32.7% in the valsartan 320 mg + simvastatin 20 mg group (P = 0.002). Rates of combined LDL-C and BP control at week 6 were 35.1% (146/416) in the valsartan 160 mg + simvastatin 20 mg group and 37.4% (154/412) in the valsartan 160 mg + simvastatin 40 mg group; at week 12, rates of combined control were 50.7% (212/418) in the valsartan 320 mg + simvastatin 20 mg group and 50.0% (206/412) in the valsartan 320 mg + simvastatin 40 mg group. AEs occurred in 24.3% (102/420) of the valsartan 160/320 mg + simvastatin 20 mg group and 22.2% (93/419) of the valsartan 160/320 mg + simvastatin 40 mg group. CONCLUSIONS: In these patients with hypertension and hypercholesterolemia, coadministration of valsartan and simvastatin was well tolerated and was associated with significant reductions from baseline in BP and LDL-C. Coadministered with valsartan 160/320 mg in the evening, simvastatin 40 mg had superior LDL-C-lowering efficacy to simvastatin 20 mg.