Olmesartan,an angiotensin Ⅱ receptor blocker,is a commonly used antihypertensive drug.Several case reports and cohort studies in recent years have described a severe gastrointestinal adverse event with chronic diarrhea,intestinal malabsorption,and weight loss after the administration of olmesartan.In such cases,the patients recovered after discontinuing olmesartan.This adverse effect is called olmesartan-associated enteropathy(OAE).This article reviews the potential pathogenesis and clinical characteristics of OAE,which broadens the disease spectrum for the differential diagnosis of chronic diarrhea and intestinal malabsorption.
Angiotensin Receptor Antagonists ; Humans ; Imidazoles ; Intestinal Diseases/diagnosis* ; Tetrazoles/adverse effects*

OBJECTIVETo investigate the relationship between the dosage of irbesartan and the renal tissue structure in diabetic rats.

METHODSMale Wistar rats was given a single intraperitoneal dose (mg/kg) of streptozotocin to induce diabetes. The diabetic rats were randomized into 4 groups and received 4 weeks later 25 mg/kg (n=9), 50 mg/kg (n=9), 200 mg/kg (n=9) irbesartan intragastrically, or equal volume of water (model group, n=11) on a daily basis. Seven normal rats receiving with equal volume of water served as the normal control. All the rats were sacrificed after 8 weeks and the 24-hour albumin excretion, renal mass index and the volume of the glomerulus were measured.

RESULTSThe 24-hour albumin excretion, renal mass index and volume of the glomerulus in the 3 irbesartan groups were significantly decreased as compare with those in the model group; the reductions in 50 and 200 mg/kg irbesartan groups were significant greater than those in 25 mg/kg irbesartan group.

CONCLUSIONIrbesartan can decrease the 24-hour urinary albumin excretion and relive glomerulopathy in diabetic rats. Within a certain dose range, irbesartan produces a dose-dependent protective effect on the renal structures in the diabetic rats.

Animals ; Biphenyl Compounds ; adverse effects ; pharmacology ; Diabetes Mellitus, Experimental ; pathology ; Dose-Response Relationship, Drug ; Kidney ; pathology ; Male ; Rats ; Rats, Wistar ; Tetrazoles ; adverse effects ; pharmacology

OBJECTIVESTo analyse the control rate of irbesartan/hydrochlorothiazide (HCTZ) combination tablets (COAPROVEL) in the treatment of patients with mild to moderate primary hypertension.

METHODSIn this multi-center, open, single therapy trial, the enrolled patients aged 18-75 were treated with irbesartan/HCTZ combination tablets for 8 weeks. The initial dose comprised one tablet of irbesartan (150 mg)/HCTZ (12.5 mg) once a day during the first 2 weeks. If diastolic blood pressure was greater than 85 mm Hg at the end of the second or fourth weeks, irbesartan (300 mg)/HCTZ (12.5 mg) once a day or irbesartan (300 mg)/HCTZ (25 mg) once a day were added respectively.

RESULTSIn 968 patients with mild to moderate hypertension enrolled, 920 patients were followed up for 8 weeks. (1) After 1 week of treatment, irbesartan/HCTZ combination tablets lowered systolic blood pressure by 11.87 mm Hg and diastolic blood pressure by 8.54 mm Hg (P < 0.01). After 8 weeks of treatment, the corresponding decreases were 21.97 mm Hg and 16.08 mm Hg, respectively (P < 0.01). (2) After 2, 4 and 8 weeks of treatment, 526, 703 and 769 patients reached blood pressure target (diastolic blood pressure less than 85 mm Hg). The control rates were 57.17%, 76.41% and 83.59%, respectively. (3) Among the 920 patients who completed the trial, 637 patients took irbesartan (150 mg)/HCTZ (12.5mg) once a day (69.24%), 211 patients took irbesartan (300 mg)/HCTZ (12.5 mg) once a day (22.93%), and 72 patients took irbesartan (300 mg)/HCTZ (25 mg) once a day (7.82%). (4) In the intention-to-treat analysis, no adverse reaction was observed in 903 patients (93.29% of the patients enrolled).

CONCLUSIONSWhen irbesartan/HCTZ combination regimen are used in the treatment of patients with mild to moderate primary hypertension, the proportion of patients reaching blood pressure target is high and adverse reactions are rare.

Adolescent ; Adult ; Aged ; Antihypertensive Agents ; adverse effects ; therapeutic use ; Biphenyl Compounds ; adverse effects ; therapeutic use ; China ; Drug Combinations ; Humans ; Hydrochlorothiazide ; adverse effects ; therapeutic use ; Hypertension ; drug therapy ; Middle Aged ; Tablets ; Tetrazoles ; adverse effects ; therapeutic use ; Young Adult

OBJECTIVETo 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.

METHODSIn 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.

RESULTSAt 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).

CONCLUSIONEfficacy 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.

Adult ; Antihypertensive Agents ; adverse effects ; therapeutic use ; Double-Blind Method ; Drug Therapy, Combination ; Female ; Humans ; Hydrochlorothiazide ; adverse effects ; therapeutic use ; Hypertension ; drug therapy ; Male ; Middle Aged ; Tetrazoles ; adverse effects ; therapeutic use ; Valine ; adverse effects ; analogs & derivatives ; therapeutic use ; Valsartan

OBJECTIVETo investigate the effects of valsartan on cyclooxygenase-2 (COX-2) in cultured human umbilical vein endothelial cells (HUVECs) stimulated by ox-LDL.

METHODSHUVECs were cultured in endothelial basal medium and divided into four groups (n = 5 each): group I, control group without any treatment; group II: HUVECs stimulated with ox-LDL (100 mg/L) in endothelial basal medium for 24 hours; group III: HUVECs treated with ox-LDL (100 mg/L) and valsartan (10 µmol/L) in endothelial basal medium for 24 hours; group IV: HUVECs treated with ox-LDL (100 mg/L) and valsartan (30 µmol/L) in endothelial basal medium for 24 hours. Expression of COX-1 and COX-2 mRNA were determined by reverse transcription-polymerase chain reaction (RT-PCR).

RESULTSExpression of and COX-2 mRNA was significantly higher in ox-LDL-treated HUVECs than in control group (1.478 ± 0.104 vs. 0.366 ± 0.104, P < 0.05), while expression of COX-1 mRNA was similar between the 2 groups (P > 0.05). Valsartan dose-dependently decreased the COX-2 mRNA expression (group III vs. group II: 1.074 ± 0.112 vs. 1.478 ± 0.104, P < 0.05; group IV vs. group II: 0.664 ± 0.104 vs. 1.478 ± 0.104, P < 0.05). Expression of COX-1 mRNA in ox-LDL-treated HUVECs was not affected by valsartan.

CONCLUSIONSCOX-2 mRNA expression in ox-LDL-treated HUVECs could be reduced by valsartan suggesting valsartan might attenuate atherosclerosis by reducing ox-LDL-induced inflammatory responses.

Cells, Cultured ; Cyclooxygenase 2 ; metabolism ; Human Umbilical Vein Endothelial Cells ; drug effects ; metabolism ; Humans ; Lipoproteins, LDL ; adverse effects ; Tetrazoles ; pharmacology ; Valine ; analogs & derivatives ; pharmacology ; Valsartan

OBJECTIVETo evaluate the efficacy and safety of olmesartan medoxomil compared with losartan potassium in patients with mild to moderate essential hypertension.

METHODThis 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.

CONCLUSIONThis 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).

Adolescent ; Adult ; Aged ; Antihypertensive Agents ; administration & dosage ; China ; Double-Blind Method ; Female ; Humans ; Hypertension ; drug therapy ; physiopathology ; Imidazoles ; adverse effects ; therapeutic use ; Losartan ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Olmesartan Medoxomil ; Tetrazoles ; adverse effects ; therapeutic use

OBJECTIVETo compare effects of valsartan and benazepril on erythropoietin (EPO) levels in essential hypertensive patients with normal renal function.

METHODSSixty essential hypertensive patients were randomly divided into valsartan group (n=30, valsartan 80 mg/day) and benazepril group (n=30, benazepril 10 mg/day). Plasma EPO and hemoglobin (Hb) levels were measured at the start of and at 4 and 8 weeks during the treatments.

RESULTSEPO and Hb levels were all in normal range in the two groups. Valsartan decreased EPO levels from 14.179∓3.214 U/L (baseline) to 12.138∓2.926 U/L (P<0.05) and Hb levels from 144.32∓13.84 g/L (baseline) to 135.16∓14.78 U/L (P<0.05). Benazepril treatment did not resulted in any obvious changes in EPO or Hb levels (P>0.05).

CONCLUSIONValsartan may lower EPO and Hb levels in patients with essential hypertension, while benazepril does not have such effects. The safety of valsartan in anemic hypertensive patients should be further investigated.

Adult ; Aged ; Aged, 80 and over ; Benzazepines ; adverse effects ; therapeutic use ; Erythropoietin ; blood ; Female ; Hemoglobins ; analysis ; Humans ; Hypertension ; blood ; drug therapy ; Male ; Middle Aged ; Tetrazoles ; adverse effects ; therapeutic use ; Valine ; adverse effects ; analogs & derivatives ; therapeutic use ; Valsartan

OBJECTIVETo investigate the effects and safety of Western medicine combined with Chinese medicine (CM) based on syndrome differentiation in the treatment of elderly polarized hypertension (PHPT), or isolated systolic hypertension with low diastolic blood pressure (DBP).

METHODSA total of 125 elderly patients with PHPT were randomly assigned to two groups: 59 in the control group treated by Western medicine and 66 in the intervention group treated by Western medicine combined with CM treatment. Based on syndrome differentiation, the patients in the intervention group were further divided into subgroups of yang-qi deficiency and yin-qi deficiency. All subjects were treated with Western medicine of Amlodipine Besylate Tablets and Irbesartan Tablets (or Irbesartan and Hydrochlorothiazide Tablets), to decrease their systolic blood pressure (SBP) slowly to 125-135 mm Hg in 2-6 weeks. In the intervention group, Shiyiwei Shenqi Capsule was given additionally to the subgroup of yang-qi deficiency at the dosage of 3-5 capsules, thrice a day, while Dengzhan Shengmai Capsule was given additionally to the subgroup of yin-qi deficiency at the dosage of 2 capsules, 2-3 times per day. For all subjects, SBP, pulse pressure (PP), and DBP were measured before treatment and at the terminal of a 6-week treatment. For subjects in the intervention group, left ventricular ejection fraction (LVEF) was also recorded.

RESULTSAfter a 6-week treatment, the SBP in the two groups and the PP in the intervention group decreased significantly compared to those before treatment (P<0.05), while the PP in the control group showed no significant difference between prior and post-treatment (P>0.05). After treatment, the DBP in the control group decreased (P>0.05), while the DBP and LVEF in the intervention group showed an increase tendency although it had no statistical significance (P>0.05). When subjects in the intervention group were classified further by the course of disease, the DBP and LVEF of subjects whose course of disease were less than 2 years, increased significantly after treatment (P<0.05).

CONCLUSIONWestern medicine combined with CM treatment based on syndrome differentiation was safer and more effective than Western medicine alone in the treatment of elderly PHPT, because it not only reduced SBP but also improved DBP, which might lower the incidence of the cardiovascular and cerebrovascular events.

Aged ; Amlodipine ; adverse effects ; pharmacology ; therapeutic use ; Antihypertensive Agents ; adverse effects ; pharmacology ; therapeutic use ; Biphenyl Compounds ; adverse effects ; pharmacology ; therapeutic use ; Blood Pressure ; drug effects ; Diastole ; drug effects ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; therapeutic use ; Female ; Humans ; Hypertension ; drug therapy ; physiopathology ; Male ; Stroke Volume ; drug effects ; Syndrome ; Tetrazoles ; adverse effects ; pharmacology ; therapeutic use

BACKGROUNDThe non-hemodynamic effects of angiotensin receptor blocker (ARB) in the delay of progression of chronic kidney disease (CKD) remain unclear. In this study, we investigated the influence of irbesartan on the urinary excretion of cytokines in patients with CKD.

METHODSIn this randomized perspective clinical trial, different doses of irbesartan (150 mg/d and 300 mg/d) were given to two groups of patients in a cross-over design. Blood pressure (BP), creatinine clearance (Ccr) and 24-hour proteinuria were examined. Urinary excretion of cytokines was determined by human inflammatory cytokine antibody array. A two-fold change in spot intensity was considered significant.

RESULTSUrinary excretion of cytokines (granulocyte colony stimulating factor (GCSF), intercellular cell adhesion molecule-1 (ICAM-1), interferon γ (IFN-γ), interleukin 1β (IL-1b), IL-2, IL-6, IL-8, IL-11, IL-15 and macrophage inflammatory protein 1d (MIP-1d)) in group B (irbesartan 300 mg/d) was significantly decreased in comparison to group A (irbesartan 150 mg/d) after 8-week treatment. In group A, 8 weeks of treatment induced a two- to nine-fold reduction in urinary cytokine levels (GCSF, GM-CSF, IFN-γ, IL-1a, IL-11, IL-12p40, MCP-2, MIP-1a), while increasing the dosage to 300 mg/d further decreased the excretion of GCSF, GM-CSF, IL-12p40, MCP-2 and MIP-1a by week 18. There was no significant difference in BP or Ccr between the two groups. However, 24-hour proteinuria was significantly reduced in both groups, and in group A the reduction was dose dependent.

CONCLUSIONIrbesartan offers additional renoprotection in a dose-dependent manner by reducing pro-inflammatory cytokines excretion in the urine of CKD patients.

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Biphenyl Compounds ; adverse effects ; therapeutic use ; Chronic Disease ; Creatinine ; metabolism ; Cross-Over Studies ; Cytokines ; urine ; Humans ; Kidney Diseases ; drug therapy ; immunology ; Prospective Studies ; Tetrazoles ; adverse effects ; therapeutic use

BACKGROUNDThe combination of cilostazol, aspirin and clopidogrel (triple antiplatelet therapy, TAT) after a percutaneous coronary intervention has been used as an alternative therapy. We performed a meta-analysis to evaluate the efficacy and safety of TAT for patients after percutaneous coronary intervention (PCI).

METHODSWe systematically searched Pubmed, Embase and Web of Science databases to identify all randomized controlled trials (RCTs) that compared dual antiplatelet therapy (DAT) with and without cilostazol after PCI. All analyses were conducted using Review Manager 5.0.

RESULTSThe final analysis consisted of 4474 patients from ten studies. The combined results suggested that there was a lower risk of cardiac death (relative risk (RR) = 0.55, 95% confidence interval (CI): 0.31 - 0.98, P < 0.05) and major adverse cardiac events (MACEs) (RR = 0.63, 95% CI: 0.54 - 0.74, P < 0.05) in patients treated with TAT as compared to those with DAT follow-ups after six months to one year; no significant difference was observed in bleeding and non-fatal myocardial infarction (MI) (RR = 1.14, 95% CI: 0.80 - 1.64, P > 0.05; RR = 0.87, 95% CI: 0.42 - 1.83, P > 0.05). However, the rate of adverse drug reaction was higher in patients receiving TAT than in patients receiving DAT (RR = 2.21, 95% CI: 1.84 - 2.66, P < 0.05). Moreover, there was a lower risk of stent thrombosis in patients treated with TAT as compared to those treated with DAT (RR = 0.44, 95% CI: 0.21 - 0.94, P < 0.05). The TAT group had a reduced risk of target lesion revascularization (TLR) (RR = 0.60, 95% CI: 0.43 - 0.82, P = 0.001) and target vessel revascularization (TVR) than the DAT group (RR = 0.56, 95% CI: 0.45 - 0.71, P < 0.05). The number of MACEs was lower for patients in the TAT group than in the DAT group with diabetes mellitus sub-analysis (RR = 0.41, 95% CI: 0.28 - 0.61, P < 0.05). But no significant difference was observed between the two groups regarding MACEs in patients with drug-eluting stent implantations (RR = 0.82, 95% CI: 0.65 - 1.03, P > 0.05).

CONCLUSIONTAT could significantly reduce the rates of MACEs and cardiac death in comparison to DAT, but more attention should be paid to adverse side effects of the drugs.

Aspirin ; administration & dosage ; Drug Therapy, Combination ; Humans ; Percutaneous Coronary Intervention ; Platelet Aggregation Inhibitors ; administration & dosage ; adverse effects ; Publication Bias ; Stents ; adverse effects ; Tetrazoles ; administration & dosage ; Ticlopidine ; administration & dosage ; analogs & derivatives