Beneficial Effect of Efonidipine, an L- and T-Type Dual Calcium Channel Blocker, on Heart Rate and Blood Pressure in Patients With Mild-to-Moderate Essential Hypertension

Background and Objectives: Efonidipine hydrochloride, an L- and T-type dual calcium channel blocker, is suggested to have a heart rate (HR)-slowing action in addition to a blood pressure (BP)-lowering effect. The aim of this study was to determine the effect of efonidipine on HR and BP in patients with mild-to-moderate hypertension. Subjects and Methods: In a multi-center, prospective, open-labeled, single-armed study, we enrolled 53 patients who had mild-to-moderate hypertension {sitting diastolic BP (SiDBP) 90-110 mmHg}. After a 2-week washout, eligible patients were treated with efonidipine (40 mg once daily for 12 weeks). The primary end point was the change in HR from baseline to week 12. The secondary end-point included the change in trough sitting BP and 24-hour mean BP between baseline and week 12. Laboratory and clinical adverse events were monitored at each study visit (4, 8, and 12 weeks). Results: Fifty-two patients were included in the intention-to-treat analysis. After 12 weeks of treatment with efonidipine, the resting HR decreased significantly from baseline to week 12 (from 81.5??5.3 to 71.8??9.9 beats/minute (difference, -9.9??9.0 beats/minute), p<0.0001}. The trough BP {sitting systolic blood pressure (SiSBP) and SiDBP} and 24-hour mean BP also decreased significantly (SiSBP: from 144.6??8.2 to 132.9??13.5 mmHg, p<0.0001; SiDBP: from 96.9??5.4 to 88.3??8.6 mmHg, p<0.0001, 24-hour mean systolic BP: from 140.4??13.5 to 133.8??11.6 mmHg, p<0.0001; 24-hour mean diastolic BP: from 91.7??8.7 to 87.5??9.5 mmHg, p<0.0001). Conclusion: Efonidipine was effective in controlling both HR and BP in patients with mild-to-moderate hypertension. Copyright ?? 2010 The Korean Society of Cardiology

Progression of Prostate Cancer Despite an Extremely Low Serum Level of Prostate-Specific Antigen

A 61-year-old man who had been diagnosed with prostate cancer 9 years ago and had been treated with pelvic irradiation and intermittent androgen deprivation therapy visited the emergency room because of back pain and weakness in both legs. Spine magnetic resonance imaging showed a lumbar epidural mass and spine metastasis. The whole-body workup revealed multiple metastases to the lymph nodes, bone, liver, and lung. The serum prostate-specific antigen was 0.02 ng/ml. He underwent laminectomy, posterior fixation, and epidural mass excision, and metastatic adenocarcinoma from the prostate was diagnosed. The patient underwent 1 cycle of docetaxel-based chemotherapy. More chemotherapy could not be done because of his general weakness. The patient died one month later of multiple organ failure

A Randomized, Double-Blind, Placebo-Controlled, Bridging Study to Evaluate the Efficacy and Safety of Vibegron in Treating Korean Patients With Overactive Bladder

Purpose Vibegron, a novel, potent β3 agonist, has been approved for clinical use in overactive bladder (OAB) treatment in Japan and the Unites States. We performed a bridging study to investigate the efficacy and safety of a daily 50-mg vibegron (code name JLP-2002) dose in Korean patients with OAB. Methods A multicenter, randomized, double-blind, placebo-controlled study was conducted from September 2020 to August 2021. Adult patients with OAB with a symptom duration of more than 6 months entered a 2-week placebo run-in phase. Eligibility was assessed at the end of this phase and selected patients entered a double-blind treatment phase after 1:1 randomization to either the placebo or vibegron (50 mg) group. The study drug was administered once daily for 12 weeks and follow-up visits were scheduled at weeks 4, 8, and 12. The primary endpoint was the change in mean daily micturition at the end of treatment. The secondary endpoints included changes in OAB symptoms (daily micturition, nocturia, urgency, urgency incontinence, and incontinence episodes, and mean voided volume per micturition) and safety. A constrained longitudinal data model was used for statistical analysis. Results Patients who took daily vibegron had significant improvements over the placebo group in both primary and secondary endpoints, except for daily nocturia episodes. The proportions of patients with normalized micturition and resolution of urgency incontinence and incontinence episodes were significantly higher in vibegron group than in the placebo. Vibegron also improved the patients’ quality of life with higher satisfaction rates. The incidence of adverse events in the vibegron and placebo groups was similar with no serious, unexpected adverse drug reactions. No abnormality in electrocardiographs was observed as well as no significant increase in postvoid residual volume. Conclusions Once daily vibegron (50 mg) for 12 weeks was effective, safe, and well-tolerated in Korean patients with OAB

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Low Dietary Inorganic Phosphate Stimulates Lung Tumorigenesis Through Altering Protein Translation and Cell Cycle in K-ras(LA1) Mice

Recent surveys indicate that Pi intake has increased steadily as Pi-containing foods have increased. Our previous study demonstrated that high dietary Pi strongly stimulated lung tumorigeneis. In order to answer the issue whether low Pi may be chemopreventive, we examined the effects of low Pi on lung cancer. Eighteen 5-wk-old male K-ras(LA1) lung cancer model mice were randomly allocated to 2 groups. One group was fed a normal diet (0.5% Pi) and other group was fed low Pi (0.1% Pi) diet for 4 wk. Lung cancer development was evaluated by histopathological examination, Western blot, kinase assay, and immunohistochemistry. Low Pi increased the expression of sodium-dependent phosphate cotransporter 2b, and activated Akt signal with decreased PTEN expression in the lungs of K-ras(LA1) mice. Low Pi increased the Akt/mTOR-mediated protein translation through upregulating the phosphorylation of p70S6K and 4E-BP1. In addition, low Pi stimulated cell cycling as evidenced by altered cell cycle regulators such as cyclin D1 and D3. Finally, low Pi increased lung tumorigenesis in K-ras(LA1) mice compared to the normal diet group. Our results clearly demonstrated that low Pi also promoted lung tumorigenesis, thus suggesting that an appropriate intake of dietary Pi may be critical for lung cancer prevention as well as treatment