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 effect of low-dose carvedilol combined with candesartan in the prevention of acute and chronic cardiotoxicity of anthracycline drugs in adjuvant chemotherapy of breast cancer.

METHODSForty patients were randomly divided into two groups: the experimental group with chemotherapy plus low-dose carvedilol combined with candesartan (20 cases) and control group with chemotherapy alone (20 cases). The same chemotherapy was given to the two groups. All the 40 patients had no contraindication for carvedilol and candesartan. Patients of the experimental group received low-dose carvedilol from 2.5 mg orally twice a day at first cycle to 5 mg twice a day gradually if no side reactions, and candesartan 2.5 mg orally once a day. Electrocardiogram, ultrasonic cardiogram, arrhythmia, troponin and non-hematologic toxicity were recorded and compared after the second, forth and sixth cycle of chemotherapy. Each cycle included 21 days.

RESULTSLVEF was decreased along with the prolongation of chemotherapy in the experimental group and control group. LVEDD and LVESD showed no significant changes in the experimental group, but gradually increased in the control group. After four and six cycles of chemotherapy, LVEF were (57.00 ± 5.13)% and (45.95 ± 3.68)%, respectively, in the control group, significantly lower than that of (67.00 ± 5.13)% and (57.50 ± 2.57)%, respectively, in the experimental group (P < 0.05). After six cycles of chemotherapy, LVEDD and LVESD were (50.00 ± 10.48) mm and (35.01 ± 2.99) mm, respectively, in the control group, significantly higher than those before chemotherapy (P < 0.05) and experimental group (P < 0.001). The rate of ST segment and T wave abnormalities was 80.0% in the control group after six cycles of chemotherapy, significantly higher than that of 25.0% after four cycles of chemotherapy (P = 0.001) and 10.0% after two cycles of chemotherapy (P < 0.001). The reduction of QRS voltage, arrhythmia and abnormal troponin were 55.0%, 45.0% and 45.0%, respectively, in the control group, significantly higher than those in the experimental group (20.0%, P < 0.05), (10.0%, P = 0.010) and (10.0%, P < 0.05), respectively. The rate of abnormal expression of troponin was 45.0% in the control group, significantly higher than the 10.0% in the experimental group (P < 0.05).

CONCLUSIONSThe use of low-dose carvedilol combined with candesartan can reduce the acute and chronic cardiotoxicity of anthracycline drugs, and with tolerable toxicities. This may provide a new approach to prevent cardiotoxicity of anthracycline drugs in adjuvant chemotherapy of breast cancer.

Adrenergic beta-Antagonists ; administration & dosage ; pharmacology ; Adult ; Aged ; Angiotensin II Type 1 Receptor Blockers ; administration & dosage ; pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Arrhythmias, Cardiac ; chemically induced ; Benzimidazoles ; administration & dosage ; pharmacology ; Breast Neoplasms ; drug therapy ; surgery ; Carbazoles ; administration & dosage ; pharmacology ; Chemotherapy, Adjuvant ; Cyclophosphamide ; adverse effects ; therapeutic use ; Electrocardiography ; drug effects ; Epirubicin ; adverse effects ; therapeutic use ; Female ; Fluorouracil ; adverse effects ; therapeutic use ; Humans ; Mastectomy, Radical ; Middle Aged ; Propanolamines ; administration & dosage ; pharmacology ; Stroke Volume ; drug effects ; Tetrazoles ; administration & dosage ; pharmacology ; Troponin ; metabolism

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

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

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

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

PURPOSE: It is unknown whether cilostazol pretreatment reduces postprocedural myonecrosis (PPMN). Cilostazol pretreatment reduces PPMN after percutaneous coronary intervention (PCI). MATERIALS AND METHODS: A total of 120 patients with stable angina scheduled for elective PCI were randomly assigned to a 7-day pretreatment with Cilostazol (200 mg/day) or to a control group. Creatine kinase-MB (CK-MB) and cardiac troponin I (cTnI) levels were measured at baseline and at 6 and 24 hours after PCI. The primary end-point was the occurrence of PPMN, defined as any CK-MB elevation above the upper normal limit (UNL). Aspirin and clopidogrel were co-administered for 7 days before PCI, and resistance to these agents was then assayed using the VerifyNow System. RESULTS: There was no difference in baseline characteristics between the final analyzable cilostazol (n=54) and the control group (n=56). Despite a significantly greater % inhibition of clopidogrel in the cilostazol group (39+/-23% versus 25+/-22%, p=0.003), the incidence of PPMN was similar between the cilostazol group (24%) and the control group (25%, p=1.000). The rate of CK-MB elevation at > or =3 times UNL was also similar between the two groups (6% versus 5%, p=0.583). The incidence of cTnI increase over the UNL or to 3 times the UNL was not different between the two groups. There was no significant difference in terms of the rate of adverse events during follow-up, although the cilostazol group showed a tendency to have a slightly higher incidence of entry site hematoma. CONCLUSION: This trial demonstrated that adjunctive cilostazol pretreatment might not significantly reduce PPMN after elective PCI in patients with stable angina.
Aged ; Angina, Stable/drug therapy/enzymology/therapy ; Angioplasty, Balloon, Coronary/*adverse effects ; Creatine Kinase, MB Form/blood ; Female ; Heart Injuries/etiology/prevention & control ; Humans ; Male ; Middle Aged ; Myocardium/pathology ; Necrosis ; Phosphodiesterase 3 Inhibitors/*administration & dosage ; Prospective Studies ; Tetrazoles/*administration & dosage

BACKGROUND/AIMS: Impaired responsiveness to clopidogrel is common in patients with type 2 diabetes mellitus (DM). The aim of this study was to evaluate the clinical application of a point-of-care assay to detect impaired responsiveness to clopidogrel after coronary stent implantation in patients with type 2 DM. METHODS: We measured P2Y12 reaction units (PRU) with the VerifyNow point-of-care assay in 544 consecutive patients undergoing dual or triple (i.e., dual plus cilostazol) anti-platelet therapy after coronary stent implantation. High platelet reactivity (HPR) was defined as a PRU value > or = 240. RESULTS: The mean PRU values were 233.5 +/- 83.2 and 190.3 +/- 85.5 in patients undergoing dual or triple anti-platelet therapy, respectively (p < 0.001). Patients with DM manifested higher post treatment PRU values (238.3 +/- 82.4 vs. 210.8 +/- 86.8, p = 0.001) and a higher frequency of HPR (44.8% vs. 31.0%, p = 0.003) as compared to patients without DM. We also found that higher PRU values and a higher frequency of HPR were present in patients with DM who were undergoing both triple and dual anti-platelet therapy. However, the higher post-treatment PRU values observed in patients with DM decreased with triple anti-platelet therapy (219.4 +/- 82.5 vs. 247.9 +/- 81.1, p = 0.044). CONCLUSIONS: A point-of-care assay can detect elevated platelet reactivity and impaired responsiveness to clopidogrel in patients with type 2 DM. The addition of cilostazol to dual anti-platelet therapy may decrease post-treatment PRU values in patients with type 2 DM.
Aged ; Angioplasty, Balloon, Coronary/adverse effects/*instrumentation ; Aspirin/administration & dosage ; Chi-Square Distribution ; Coronary Disease/blood/*therapy ; Diabetes Mellitus, Type 2/*blood ; Drug Therapy, Combination ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Platelet Activation/*drug effects ; Platelet Aggregation Inhibitors/*administration & dosage/adverse effects ; *Platelet Function Tests ; *Point-of-Care Systems ; Predictive Value of Tests ; Purinergic P2Y Receptor Antagonists/*administration & dosage/adverse effects ; Registries ; Republic of Korea ; Risk Assessment ; Risk Factors ; *Stents ; Tetrazoles/*administration & dosage/adverse effects ; Ticlopidine/administration & dosage/adverse effects/*analogs & derivatives ; Treatment Outcome

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

OBJECTIVETo observe the effect of combined therapy with Xuezhikang Capsule (XZK) and Valsartan on left ventricular hypertrophy (LVH) and heart rate turbulence (HRT) in hypertensive patients.

METHODSNinety primary hypertensive patients with LVH were randomly assigned to three groups. Basic treatment, including aspirin, beta-blockers, calcium antagonists, etc. were administered to all patients. Additionally, Valsartan (VS, 80 mg once a day) was given to the 30 patients in the VS group. Valsartan (in the same dosage) and XZK (600 mg, twice a day) were given to the 32 patients in the Chinese medicine (CM) group, while none was given to the 28 patients in the control group. The therapeutic course lasted for 24 months. Changes in left ventricular mass index (LVMI) measured by cardiac ultrasonic indices, HRT parameters, including the original heart rate (TO) and slope coeffificient (TS), systolic and diastolic blood pressures (SBP and DBP), as well as blood cholesterol level (TC) were measured before and after treatment.

RESULTSAfter treatment, TO and LVMI were lowered, while TS increased in both the VS group and the CM group (P<0.01), but changed insignificantly in the control group. Significant differences between the CM group and the control group were shown in terms of TO, LVMI, SBP, DBP and TS (P<0.01); and between the CM group and the VS group in terms of TO, LVMI and TS (P<0.01). Moreover, HRT parameters showed an evident correlation with LVMI (r=0.519-0.635, P<0.01).

CONCLUSIONCombined therapy with XZK and Valsartan can improve hypertensive LVH and HRT parameters, and lessen the damage on the autonomous nervous system.

Administration, Oral ; Aged ; Antihypertensive Agents ; administration & dosage ; adverse effects ; Arrhythmias, Cardiac ; drug therapy ; etiology ; Capsules ; Combined Modality Therapy ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; adverse effects ; Female ; Heart Rate ; drug effects ; Humans ; Hypertension ; complications ; drug therapy ; Hypertrophy, Left Ventricular ; drug therapy ; etiology ; Hypolipidemic Agents ; administration & dosage ; adverse effects ; Integrative Medicine ; methods ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Tetrazoles ; administration & dosage ; adverse effects ; Treatment Outcome ; Valine ; administration & dosage ; adverse effects ; analogs & derivatives ; Valsartan