Koichi Miyazaki

A Double-Blind, Dose-Response Study of the Efficacy and Safety of Olmesartan Medoxomil in Children and Adolescents with Hypertension

The current study investigated the efficacy and safety of olmesartan medoxomil in children with hypertension, defined as systolic blood pressure measured at or above the 95th percentile (90th percentile for patients with diabetes, glomerular kidney disease, or family history of hypertension) for age, gender, and height while off any antihypertensive medication. The active treatment phase was conducted in 2 periods, with 2 cohorts in each period (cohort A, 62% white; cohort B, 100% Black). In period 1, patients stratified by weight received low-dose (2.5 or 5 mg) or high-dose (20 or 40 mg) olmesartan medoxomil daily for 3 weeks. In period 2, patients maintained their olmesartan medoxomil dose or initiated placebo washout for an additional 2 weeks. Period 1 efficacy results showed a dose-dependent, statistically significant reduction in seated trough systolic and diastolic blood pressure for both cohorts, with mean blood pressure reductions numerically smaller in cohort B than in cohort A. The olmesartan medoxomil dose response remained statistically significant when adjusted for body weight. In period 2, blood pressure control decreased in those patients switching to placebo, whereas patients continuing to receive olmesartan medoxomil therapy maintained consistent blood pressure reduction. Adverse events were generally mild and unrelated to study medication. Olmesartan medoxomil was safe and efficacious in children with hypertension, resulting in significant blood pressure reductions.

Edoxaban vs. Warfarin in East Asian Patients With Atrial Fibrillation – An ENGAGE AF-TIMI 48 Subanalysis –

BACKGROUND In the multinational, double-blind, double-dummy ENGAGE AF-TIMI 48 phase 3 study, once-daily edoxaban was non-inferior to warfarin for prevention of stroke or systemic embolism event (SEE) in patients with non-valvular atrial fibrillation (AF). Here, we evaluated the efficacy and safety of edoxaban in patients from East Asia. METHODSANDRESULTS Patients aged ≥21 years with documented AF and CHADS score ≥2 were randomized to receive once-daily edoxaban higher-dose (60 mg) or lower-dose (30 mg) regimen or warfarin dose-adjusted to an international normalized ratio of 2.0-3.0. Patients with a creatinine clearance of 30-50 ml/min, weighing ≤60 kg, or receiving strong p-glycoprotein inhibitors at randomization or during the study received a 50% dose reduction of edoxaban or matched placebo. This prespecified subanalysis included 1,943 patients from Japan, China, Taiwan, and South Korea. The annualized rate of stroke/SEE for higher-dose edoxaban was 1.34% vs. 2.62% for warfarin (hazard ratio [HR], 0.53; 95% confidence interval [CI]: 0.31-0.90, P=0.02) and 2.52% for lower-dose edoxaban (HR, 0.98; 95% CI: 0.63-1.54, P=0.93). Compared with warfarin (4.80%), major bleeding was significantly reduced for the higher-dose (2.86%; HR, 0.61; 95% CI: 0.41-0.89, P=0.011) and lower-dose regimens (1.59%; HR, 0.34; 95% CI: 0.21-0.54, P<0.001). CONCLUSIONS Once-daily edoxaban provided similar efficacy to warfarin while reducing major bleeding risk in the East Asian population.

Quantitative Assessment of Fluid Accumulation Using Bioelectrical Impedance Analysis in Patients With Acute Decompensated Heart Failure

BACKGROUND Acute decompensated heart failure (ADHF) is generally considered to be a problem of fluid volume overload, therefore accurately quantifying the degree of fluid accumulation is of critical importance in assessing whether adequate decongestion has been achieved. The aim of this study was to develop and validate a method to quantify the degree of fluid accumulation in patients with ADHF. METHODSANDRESULTS Using multi-frequency bioelectrical impedance analysis (BIA), we measured extracellular water (ECW) volume in 130 ADHF patients on admission and at discharge. We also predicted optimal ECW volume using original equations based on data from 60 control subjects without the signs of HF. Measured/predicted (M/P) ratio of ECW in ADHF patients was observed to decrease from 1.26±0.25 to 1.04±0.17 during hospitalization (P<0.001). The amount of ECW volume reduction was significantly correlated with reduction in body weight (r=0.766, P<0.001). On multivariate analysis, higher M/P ratio of ECW at discharge was associated with increased risk of ADHF readmission or cardiac death within 6 months after discharge. CONCLUSIONS Multi-frequency BIA-measured ECW was found to offer valuable information for analyzing the pathophysiology of ADHF, and may be a useful guide in the management of this disease.

Current Status and Open Issues Concerning Global Clinical Trials (GCTs) in Japan and East Asia

When global clinical trials are carried out, it is important to consider the influence of racial and ethnic differences on the outcome. From this viewpoint, global clinical trials in East Asia, where racial differences are estimated to be small, are now attracting close attention. Under such circumstances, we conducted a survey using the data registered with ClinicalTrial.gov to investigate the status of participation of East Asian countries in global clinical trials and differences in the regions selected for drug development between Japanese enterprises and non‐Japanese enterprises. This survey revealed that about 90% of all global clinical trials and those involving East Asian countries were sponsored by non‐Japanese enterprises. Global clinical trials involving only East Asia have been accepted as one of the development strategies by Japanese enterprises, but this strategy has not spread widely among non‐Japanese enterprises.

Response to Pharmacological Therapy for Hypertensive Children: An “Additional Bypass” of Lifestyle Interventions

In response to the queries raised by Thomopoulos et al1 regarding our pediatric publication,2 we wanted to first clarify that we are certainly in agreement that diet and lifestyle modifications should be the initial strategy in treating obese children with hypertension. However, it must be conceded that lifestyle modifications are not always successful in reducing body mass index to recommended levels and, despite the introduction of new pediatric guidelines over the last few years for the treatment of obesity, childhood obesity continues to be a national health issue. Furthermore, although there are some comprehensive pediatric weight-loss programs in the United States, they remain very limited in number, which …