BACKGROUNDThere have been no mortality/morbidity endpoint studies with losartan in Chinese heart failure patients. The objective was to evaluate the effects of high-dose vs. low-dose losartan on clinical outcomes in Chinese subjects with heart failure.

METHODSThis study was a post hoc analysis of the Heart failure Endpoint evaluation of Angiotensin II Antagonist losartan (HEAAL) trial (n = 545). Chinese adults with symptomatic heart failure (New York Heart Association (NYHA) II-IV) intolerant of treatment with angiotensin converting enzyme (ACE) inhibitors were randomized to losartan 150 mg or 50 mg daily. The primary endpoint was the composite event rate of all-cause death or hospitalization for heart failure. Safety and tolerability were assessed.

RESULTSMedian follow-up was 4.8 years. Baseline characteristics were generally similar to the overall HEAAL cohort. Overall, 120 (44.1%) subjects in the losartan 150 mg group and 137 (50.2%) subjects in the losartan 50 mg group died (any cause) or were hospitalized for heart failure (hazard ratio (OR) 0.807, 95%CI 0.631 - 1.031). There were no notable differences between treatment groups in the proportion of subjects with adverse experiences.

CONCLUSIONThe results of this post hoc analysis in Chinese subjects, although not powered to show significance, were generally consistent with the main study results, which demonstrated a significantly reduced risk of all cause death or hospitalization for heart failure with daily losartan 150 mg vs. losartan 50 mg in subjects with symptomatic heart failure and intolerance to ACE inhibitors, supporting the use of the higher dose for optimum clinical benefit.

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Double-Blind Method ; Female ; Heart Failure ; drug therapy ; Humans ; Losartan ; adverse effects ; therapeutic use ; Male ; Middle Aged

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 results from the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) indicated that the angiotensin-receptor blocker telmisartan was not inferior to the angiotensin-converting-enzyme inhibitor ramipril in reducing the composite endpoint of cardiovascular death, myocardial infarction, stroke or hospitalization for congestive heart failure in high-risk patients, and telmisartan was associated with slightly superior tolerability. The combination of the two drugs was associated with more adverse events without an increase in benefit. This study aimed to analyze the data from ONTARGET obtained from a subgroup of patients enrolled in China and to evaluate the demographic and baseline characteristics, the compliance, efficacy, and safety of the different treatment strategies in randomized patients in China.

METHODSA total of 1159 high-risk patients were randomized into three treatment groups: with 390 assigned to receive 80 mg of telmisartan, 385 assigned to receive 10 mg of ramipril and 384 assigned to receive both study medications. The median follow-up period was 4.3 years.

RESULTSThe mean age of Chinese patients was 65.6 years, 73.6% of patients were male. The proportion of patients with stroke/transient ischemic attacks at baseline in China was two times more than the entire study population (47.7% vs. 20.9%). In Chinese patients the proportion of permanent discontinuation of study medication due to cough was 0.5% in the telmisartan group, which was much less than that in the combination or the ramipril group. There were no significant differences in the incidence of primary outcome among three treatment groups of Chinese patients. More strokes occurred in Chinese patients than in the entire study population (8.5% vs. 4.5%). Greater systolic blood pressure reduction (-9.8 mmHg), and more renal function failure were noted in the combination treatment group than in the ramipril or telmisartan group (2.6% vs. 1.6% and 1.0%).

CONCLUSIONSThere was no evidence that the results of ONTARGET differed between Chinese patients and the entire study population with respect to the incidence of primary outcome, particularly safety. Compliance with study medications was good. The evidence from ONTARGET indicated that the treatment strategies in ONTARGET were applicable to patients in China.

Aged ; Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Benzimidazoles ; administration & dosage ; adverse effects ; therapeutic use ; Benzoates ; administration & dosage ; adverse effects ; therapeutic use ; China ; Drug Therapy, Combination ; Female ; Heart Failure ; drug therapy ; Humans ; Male ; Middle Aged ; Ramipril ; administration & dosage ; adverse effects ; therapeutic use

BACKGROUNDCentral blood pressure (BP) is pathophysiologically more important than peripheral BP for the pathogenesis of cardiovascular disease. Arterial stiffness is also a good predictor of cardiovascular morbidity and mortality. The effects of benidipine, a unique dual L-/T-type calcium channel blocker, on central BP have not been reported. This study aimed to compare the effect of benidipine and losartan on the central BP and arterial stiffness in mild to moderate essential hypertensives.

METHODSThis 24 weeks, multi-center, open label, randomized, active drug comparative, parallel group study was designed as a non-inferiority study. The eligible patients (n = 200) were randomly assigned to receive benidipine (n = 101) or losartan (n = 99). Radial artery applanation tonometry and pulse wave analysis were used to measure the central BP, pulse wave velocity (PWV) and augmentation index (AIx). We also measured the metabolic and inflammatory markers.

RESULTSAfter 24 weeks, the central BP decreased significantly from baseline by (16.8 ± 14.0/10.5 ± 9.2) mmHg (1 mmHg = 0.133 kPa) (systolic/diastolic BP; P < 0.001) in benidipine group and (18.9 ± 14.7/12.1 ± 10.2) mmHg (P < 0.001) in losartan group respectively. Both benidipine and losartan groups significantly lowered peripheral BP (P < 0.001) and AIx (P < 0.05), but there were no significant differences between the two groups. The mean aortic, brachial and femoral PWV did not change in both groups after 24-week treatment. There were no significant changes of the blood metabolic and inflammatory biomarkers in each group.

CONCLUSIONBenidipine is as effective as losartan in lowering the central and peripheral BP, and improving arterial stiffness.

Adolescent ; Adult ; Aged ; Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Blood Pressure ; drug effects ; Calcium Channel Blockers ; therapeutic use ; Dihydropyridines ; adverse effects ; therapeutic use ; Essential Hypertension ; Female ; Humans ; Hypertension ; drug therapy ; physiopathology ; Losartan ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Vascular Stiffness ; drug effects

OBJECTIVETo evaluate the efficacy and safety of a fixed dose combination of telmisartan 80 mg plus hydrochlorothiazide (HCTZ) 12.5 mg (TH) to telmisartan 80 mg (T) in Chinese patients who failed to respond adequately to treatment with T.

METHODThis is a multi-center, randomized, double-blind, double-dummy clinical study. A total of 699 eligible hypertensive patients entered a one-week screening phase prior to the eight-week open-label T period. At the end of eight weeks, 345 patients who failed to respond to T (DBP > or = 90 mm Hg, 1 mm Hg = 0.133 kPa) were randomized to receive either TH (175 patients) or T (170 patients) for another eight weeks. Sitting and standing BP were taken 24 hours post-dose and adverse events were documented at visit with 4 weeks interval. Laboratory, ECG and physical examination were performed at screening, at baseline and at the final visit.

RESULTSAfter 8 weeks treatment, (1) The mean trough reduction in sitting diastolic blood pressure (SiDBP) from baseline in TH group was greater than that in T group (10.1 mm Hg vs 7.7 mm Hg, P = 0.0017). The mean trough reduction in sitting systolic blood pressure (SiSBP) from baseline was 14.2 mm Hg in TH group and 7.4 mm Hg in T group (P < 0.0001). (2) The mean trough reduction in standing DBP and standing SBP from baseline were significantly greater in TH group (8.7 mm Hg and 12.9 mm Hg) compared those in T group (7.3 mm Hg and 7.0 mmHg, P = 0.0350, P < 0.0001). (3) The number and percentage of responders in TH group (129, 74.6%) were significantly higher than in T group (100, 59.2%, P = 0.0016). (4) The incidence of the study drug-related adverse events was similar between TH and T group (3.5% vs. 3.6%, P > 0.05).

CONCLUSIONTH was more effective than T in patients not responded adequately to T in Chinese hypertensive patients.

Adult ; Aged ; Aged, 80 and over ; Angiotensin II Type 1 Receptor Blockers ; adverse effects ; therapeutic use ; Benzimidazoles ; adverse effects ; therapeutic use ; Benzoates ; adverse effects ; therapeutic use ; Double-Blind Method ; Drug Therapy, Combination ; Female ; Humans ; Hydrochlorothiazide ; adverse effects ; therapeutic use ; Hypertension ; drug therapy ; Male ; Middle Aged ; Treatment Outcome

BACKGROUND/AIMS: Angiotensin II type 1 receptor blockers (ARBs) have not been adequately evaluated in patients without left ventricular (LV) dysfunction or heart failure after acute myocardial infarction (AMI). METHODS: Between November 2005 and January 2008, 6,781 patients who were not receiving angiotensin-converting enzyme inhibitors (ACEIs) or ARBs were selected from the Korean AMI Registry. The primary endpoints were 12-month major adverse cardiac events (MACEs) including death and recurrent AMI. RESULTS: Seventy percent of the patients were Killip class 1 and had a LV ejection fraction > or = 40%. The prescription rate of ARBs was 12.2%. For each patient, a propensity score, indicating the likelihood of using ARBs during hospitalization or at discharge, was calculated using a non-parsimonious multivariable logistic regression model, and was used to match the patients 1:4, yielding 715 ARB users versus 2,860 ACEI users. The effect of ARBs on in-hospital mortality and 12-month MACE occurrence was assessed using matched logistic and Cox regression models. Compared with ACEIs, ARBs significantly reduced in-hospital mortality(1.3% vs. 3.3%; hazard ratio [HR], 0.379; 95% confidence interval [CI], 0.190 to0.756; p = 0.006) and 12-month MACE occurrence (4.6% vs. 6.9%; HR, 0.661; 95% CI, 0.457 to 0.956; p = 0.028). However, the benefit of ARBs on 12-month mortality compared with ACEIs was marginal (4.3% vs. 6.2%; HR, 0.684; 95% CI, 0.467 to 1.002; p = 0.051). CONCLUSIONS: Our results suggest that ARBs are not inferior to, and may actually be better than ACEIs in Korean patients with AMI.
Angiotensin II Type 1 Receptor Blockers/adverse effects/*therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/adverse effects/*therapeutic use ; Chi-Square Distribution ; Hospital Mortality ; Humans ; Kaplan-Meier Estimate ; Logistic Models ; Multivariate Analysis ; Myocardial Infarction/diagnosis/*drug therapy/mortality/physiopathology ; Proportional Hazards Models ; Prospective Studies ; Recurrence ; Registries ; Republic of Korea ; Risk Factors ; Secondary Prevention/*methods ; Stroke Volume ; Time Factors ; Treatment Outcome ; Ventricular Function, Left

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