Comparative efficacy and adverse effects of the addition of ezetimibe to statin versus statin titration in chronic kidney disease patients.

BACKGROUND AND OBJECTIVES: The recent SHARP trial clearly demonstrated that a reduction in low-density lipoprotein (LDL) cholesterol with a daily regimen of simvastatin plus ezetimibe safely reduced the incidence of major atherosclerotic events in patients with chronic kidney disease (CKD). We aimed to compare the efficacy of and adverse effects from statin uptitration versus statin in combination with ezetimibe since only a few studies have addressed this question. METHODS: This was a randomized, open-label, multicenter trial that included 286 patients with CKD whose LDL cholesterol levels were not reduced below 120 mg/dl despite a minimum dose of statin therapy. Patients received double doses of statin or usual statin dose with the addition of ezetimibe 10 mg daily. The observation period was 1 year during which time patients were checked regularly in clinic for adverse effects as well as for usual laboratory examinations. The key prespecified outcome was the incidence of adverse effects, which included skeletal muscle complaints, myalgia, muscle weakness, and muscle cramps with and without elevated CK levels. Increases in alanine transaminase (ALT) or aspartate transaminase (AST) levels >2 times the upper limit of normal (ULN) were considered clinically significant adverse effects. RESULTS: Adverse events occurred in 9/145 in the combination group and in 24/141 in the statin uptitration group (p < 0.01). Moreover, in patients with CKD of stages 3-5, rates were 6/58 in the combination group versus 20/52 in the statin uptitration group (p < 0.01). No serious adverse effects such as rhabdomyolysis were noted in either group. Serum creatinine levels remained essentially unchanged in both groups except in CKD stages 4 and 5. Reductions in LDL cholesterol were similar between the two groups at the start of and at the end of the study. During the study, no atherosclerotic events were reported in either group. CONCLUSION: When statin uptitration produces adverse effects such as myopathy, combination therapy with ezetimibe is recommended instead of statin alone.

Eplerenone, an aldosterone blocker, is more effective in reducing blood pressure in patients with, than without, metabolic syndrome.

BACKGROUND: Recently, the role of aldosterone in metabolic syndrome (MS) has aroused interest and several reports have suggested that aldosterone blockade could be beneficial in reducing blood pressure (BP). METHODS: To examine the add-on effects of eplerenone (EP) on BP in patients with MS, 54 hypertensive patients with MS and 44 without MS were recruited. Systolic and diastolic BPs in mmHg before the initiation of EP was 144/84 ± 13/12 (MS group) and 147/85 ± 12/14 (non-MS group). Before the start of EP, all patients in both groups were treated with at least one antihypertensive drug. BPs were checked on every visit (at least every 2 months) and serum chemistries were measured every 4 months. The levels of microalbuminuria and aminoterminal pro-brain natriuretic peptide (NT pro-BNP) were determined before the start of and at the end of the study. Patients were followed for 1 year. If adverse effects were reported by patients or found in laboratory studies, EP was withdrawn. RESULTS: One month after the start of EP, BPs were decreased to 140/80 ± 12/12 mmHg (MS group) versus 142/82 ± 11/12 mmHg (non-MS group) and there was no difference between the two groups. Towards the end of the study, BPs of both groups gradually decreased. At the end of the study, BPs of both groups were 129/76 ± 15/13 mmHg (MS group) versus 133/78 ± 13/11 mmHg (non-MS group). There was a significant difference in reduction of systolic BP between the two groups (p < 0.05). Add-on EP significantly decreased the levels of urinary excretion of albumin in MS patients but not in non-MS patients (p < 0.05). There was a significant correlation between reduction of systolic BP and NT pro-BNP but not microalbuminuria in the MS group (p < 0.05). There were no serious adverse effects in both groups. CONCLUSION: EP may have some beneficial effects in lowering BP in patients with reduction of microalbuminuria.

Indenyl-functionalised triethylborane adduct of N-heterocyclic carbene: stepwise coordination of indenyl and NHC ligands toward molybdenum fragment.

Indenyl-functionalised BEt(3)-adduct NHCs were prepared by the reaction of imidazolium pro-ligands with LiBEt(3)H. This compound was converted into the indenyl-coordinate molybdenum complex dangling the NHC·BEt(3) moiety as a substituent. The stepwise coordination of NHC afforded a chelate-type mononuclear complex as well as a bimetallic complex.

[A case of the esophageal candidiasis supposedly caused by rhinenchysis steroid chronic administration before sleep].

UNLABELLED: In general, steroid is mainly used as anti-inflammatory action in case of allergic diseases. As one of the side effects of inhalation steroid, a report is given below regarding buccal capsule/esophageal candidiasis. The patient came to the hospital with the chief complaint regarding passage dysphagia in the time of deglutition; pharyngitis and esophageal candidiasis were found by endoscopy of upper gastrointestinal tract.The interview after the endoscopy revealed that the patient, a 69-year-old female was diagnosed as chronic perennial allergic rhinitis a few years ago, and had been inhaling rhinenchysis Beclometasone dipropionate (BDP) before sleep every day for the past two years because using this collunarium seemed to mitigate the nasal obstruction and mucus during sleep. The patient did not report this fact before the endocsopy because she did not associate it with her subjective symptom. In this case, it was assumed that nebulized rhinenchysis BDP was accidentally swallowed to the pharynx and esophagus during sleep. As a treatment, rhinenchysis BDP was canceled and instead Azunol mouth washing (gargling/nasal douche) was used. No antifungal agent was used. In two weeks, the patient reported some improvement, and this was confirmed by reexamination of the upper gastrointestinal tract using endoscope in one month and a half. Pharyngitis was improved, and in the digital endoscopic assessment of esophageal candidiasis complicating inhaled steroid therapy the esophageal candidiasis became Grade I (mild grade). As for the later progress, the patient did not report any subjective symptoms such as nasal obstruction and dysphagia. In addition, the inflammation caused by candidiasis and found in the early examination was improved. The patient in this case was under treatment for thrombosis in the vein of lower extremity, but no complications such as diabetes mellitus or immune deficiency syndrome were observed. DISCUSSION: Esophageal candidiasis by chronic administration of inhalation of steroid before sleep for asthmatic patients has been reported. However, there has not been a report of esophageal candidiasis by chronic administration of rhinenchysis steroid before sleep for patients with allergic rhinitis. Similarly, in the case of the use of steroid in the form of collunarium before sleep, steroid stayed in the esophagus via the transendothelial nasal cavity, and that seemed to cause, in the long run, to develop esophageal candidiasis. CONCLUSIONS: One of the implications of the above case is that collunarium can go down, even when it is nebulized in the nasal cavity, to the esophagus via the nasal cavity to buccal capsule. This suggests the necessity for preventative measures in the case of chronic administration of steroid as follows. A. Blowing of the nose just after the use of collunarium B. Daily rinsing (gargling and nasal douche).

[Esophageal candidiasis as complication of inhaled steroid therapy].

UNLABELLED: Gastrointestinal endoscopy was performed in two bronchial asthma patients using inhaled corticosteroid who complained of odynophagia. The endoscopic finding was high grade with white moss (Grade III) in both patients. Esophageal candidiasis is often recognized in bronchial asthmatic patients receiving long-term fluticasone propionate (FP) dry powder (Diskhaler) inhalation. We therefore examined the complicated context of esophageal candidiasis in patients with long-term FP inhalation. Out of 20 bronchial asthmatic patients who had been using FP inhalation long-term, seven showed signs of esophageal candidiasis. Three patients had mild grade (Grade I), one middle grade (Grade II) and three high grade (Grade III) candidiasis, with a frequency of 35%. This rate is higher than the usual spontaneous occurrence rate of esophageal candidiasis, and it is suggested that inhalation of corticosteroid medication can penetrate into the esophagus after deep inhalation. We tested this hypothesis in two studies. 1) To measure the esophageal concentration of FP, four healthy adults inhaled 200 microg FP once. Right after inhalation, FP concentration in the esophageal washing fluid was 3.3 microg. On another day, 30 minutes after the same dose of inhaled FP, one FP concentration in the esophageal washing fluid was 0.67 microg (immediately laydown), and another was 0.11 microg (remained standing). This indicates that even though FP dissipates quickly, it remains in the esophagus 30 minutes after inhalation. 2) We observed the process in one patient with high grade (Grade III) esophageal candidiasis. The time of inhalation was changed from just after getting up and just before going to bed to before breakfast and before dinner. Under this regimen, the signs of esophageal candidiasis improved from high to middle grade. CONCLUSION: If asthmatic patients do not go to sleep immediately after FP inhalation, the remaining FP in the esophagus decreases rapidly, thereby decreasing the risk of esophageal candidiasis. In addition, by changing the FP inhalation times to before breakfast and dinner, the remaining FP in the esophagus is washed away and does not remain in the esophagus. Therefore, this study, which avoided inhalation before going to bed, provides useful information for the prevention and improvement of esophageal candidiasis.