The safety of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) used in hemodialysis (HD) patients was evaluated. Medline, Embase, the Cochrane Library, some databases of clinical trial registries, grey literatures, other reference lists of eligible articles and review articles for the randomized clinical trials (RCTs) on comparison of ACEIs/ARBs or placebo in HD patients were retrieved. RCTs reporting the risk of hyperkalemia by using ACEIs/ARBs in HD patients were selected. Eight articles met the eligibility criteria and were subjected to meta-analysis by using the Cochrane Collaboration's RevMan 4.2 software package. The results showed that there was no significant difference in hyperkalemia in HD patients between ACEIs or ARBs group and control group (ACEIs vs. control: RD=0.03, 95% CI=-0.13-0.18, Z=0.34, P=0.73; ARBs vs. control: RD=-0.02, 95% CI=-0.07-0.03, Z=0.75, P=0.45). However, there was no significant difference in the serum potassium between ACEIs or ARBs group and control group in HD patients (ACEIs vs. control: WMD=0.10, 95% CI=0.06-0.15, Z=4.64, P<0.00001; ARBs vs. control: WMD=-0.24, 95% CI=-0.37-0.11, Z=3.58, P=0.0003). The use of ACEIs or ARBs could not cause an increased risk of hyperkalemia in HD patients, however the serum potassium could be increased with use of ACEIs in HD patients. Therefore the serum potassium concentration should still be closely monitored when ACEIs are taken during the maintenance HD.
Aged ; Angiotensin Receptor Antagonists ; adverse effects ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; adverse effects ; therapeutic use ; Female ; Humans ; Hyperkalemia ; chemically induced ; Male ; Middle Aged ; Renal Dialysis

OBJECTIVE: To evaluate the efficacy and safety of combined treatment with angiotensin II receptor blocker (ARB) and angiotensin converting enzyme inhibitor (ACEI) on diabetic kidney disease. METHODS: Randomized controlled trials (RCTs) were identified from CoChrane library, PubMed, EMbase, CNKI and VIP. Eleven RCTs involving 602 patients were included and analyzed with Rev Man 5.1 software. RESULTS: Compared with ACEI alone, combined treatment with ARB and ACEI was more effective on decreasing 24 h albuminuria, systolic pressure, average 24 h systolic pressure, diastolic pressure, and average 24 h diastolic pressure but with a high level of serum potassium. Compared with ARB alone, combined treatment with ARB and ACEI was more effective on decreasing systolic pressure and diastolic pressure. Compared with ACEI or ARB alone, we didn't get a definite conclusion that whether combined treatment with ARB and ACEI was more effective on decreasing 24 h proteinuria. CONCLUSION Based on this Meta analysis, combined treatment with ARB and ACEI is safer and has positive effect on diabetic kidney disease. However, small sample size and low methodological quality appeared in most of the trials included in this systematic review. Therefore, available evidence is insufficient to recommend a routine clinical application of combined treatment with ARB and ACEI on diabetic kidney disease.
Angiotensin Receptor Antagonists ; adverse effects ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; adverse effects ; therapeutic use ; Diabetic Nephropathies ; drug therapy ; Drug Therapy, Combination ; Humans ; Randomized Controlled Trials as Topic

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 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

BACKGROUNDThe role of angiotensin-converting enzyme inhibitors (ACEI) in contrast-induced acute kidney injury (CI-AKI) is controversial. Some studies pointed out that it was effective in the prevention of CI-AKI, while some concluded that it was one risk for CI-AKI, especially for patients with pre-existing renal impairment. The purpose of this study was to assess the influence of benazepril administration on the development of CI-AKI in patients with mild to moderate renal insufficiency undergoing coronary intervention.

METHODSOne hundred and fourteen patients with mild to moderate impairment of renal function were enrolled before coronary angioplasty, who were randomly assigned to benazepril group (n = 52) and control group (n = 62). In the benazepril group, the patients received benazepril tablets 10 mg per day at least for 3 days before procedure. CI-AKI was defined as an increase of ≥ 25% in creatinine over the baseline value or increase of 0.5 mg/L within 72 hours of angioplasty.

RESULTSPatients were well matched with no significant differences at baseline in all measured parameters between two groups. The incidence of CI-AKI was lower by 64% in the benazepril group compared with control group but without statistical significance (3.45% vs. 9.68%, P = 0.506). Compared with benazepril group, estimated glomerular filtration rate (eGFR) level significantly decreased from (70.64 ± 16.38) ml · min⁻¹·1.73 m⁻² to (67.30 ± 11.99) ml · min⁻¹·1.73 m⁻² in control group (P = 0.038). There was no significant difference for the post-procedure decreased eGFR from baseline (ΔeGFR) between two groups (benazepril group (0.67 ± 12.67) ml · min⁻¹·1.73 m⁻² vs. control group (-3.33 ± 12.39) ml · min⁻¹·1.73 m⁻², P = 0.092). In diabetic subgroup analysis, ΔeGFR in benazepril group was slightly lower than that in the control group, but the difference was not statistically significant.

CONCLUSIONSBenazepril has a protective effect on mild to moderate impairment of renal function during coronary angioplasty. It is safe to use benazepril for treatment of patients with mild to moderate impairment of renal function before coronary intervention.

Acute Kidney Injury ; chemically induced ; prevention & control ; Aged ; Angioplasty, Balloon, Coronary ; adverse effects ; Angiotensin-Converting Enzyme Inhibitors ; Benzazepines ; therapeutic use ; Contrast Media ; adverse effects ; Coronary Angiography ; Female ; Humans ; Male ; Middle Aged ; Renal Insufficiency ; complications

Angiogenesis Inhibitors ; adverse effects ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Antibodies, Monoclonal ; adverse effects ; therapeutic use ; Antibodies, Monoclonal, Humanized ; Aspirin ; administration & dosage ; therapeutic use ; Bevacizumab ; Hemorrhage ; chemically induced ; Humans ; Hypertension ; chemically induced ; drug therapy ; Intestinal Perforation ; chemically induced ; surgery ; Neoplasms ; drug therapy ; Proteinuria ; chemically induced ; Thromboembolism ; chemically induced ; drug therapy

BACKGROUNDAntihypertensive drugs have been linked to new-onset osteoporotic fracture (NOF), and different classes of antihypertensive drugs may alter the risk for the development of NOF; however, the classic effect of different antihypertensive drugs on the development of NOF in the elderly has not been well studied during long-term follow-up.

METHODSIn this study, we investigated the association between different classic antihypertensives and the development of NOF in the elderly. This was a longitudinal cohort study performed using data from claim forms submitted to the Taiwan Bureau of National Health Insurance in Central Taiwan, China including case patients with NOF aged 65-80 years from January 2002 to December 2012 and non-NOF controls. Prescriptions for antihypertensives before the index date were retrieved from a prescription database. We estimated the hazard ratios (HR s) of NOF associated with antihypertensive use. Non-NOF controls served as the reference group.

RESULTSA total of 128 patients with NOF were identified from among 1144 patients with hypertension during the study period. The risk of NOF after adjusting age, sex, comorbidities, and concurrent medications was higher among the users of angiotensin-converting enzyme (ACE) inhibitors (HR, 1.64; 95% confidence interval [CI], 1.01-2.66) than among nonusers. Patients who took calcium channel blockers (CCBs) (HR, 0.70; 95% CI, 0.49-0.99) were at a lower risk of developing NOF than nonusers. Loop diuretics, thiazide diuretics, angiotensin receptor blocker, beta-blocker, and alpha-blocker were not associated with the risk of NOF.

CONCLUSIONSElderly with hypertension who take CCBs are at a lower risk of NOF and that the use of ACE inhibitors was associated with a significantly increased risk of developing NOF during the 11-year follow-up.

Aged ; Aged, 80 and over ; Angiotensin-Converting Enzyme Inhibitors ; adverse effects ; therapeutic use ; Antihypertensive Agents ; adverse effects ; therapeutic use ; Calcium Channel Blockers ; adverse effects ; therapeutic use ; Cohort Studies ; Female ; Humans ; Hypertension ; drug therapy ; Longitudinal Studies ; Male ; Osteoporotic Fractures ; chemically induced ; epidemiology ; Retrospective Studies ; Risk Factors ; Taiwan ; epidemiology

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

BACKGROUNDCombination therapy is an effective method to reduce the blood pressure (BP) for patients with hypertension. This study was performed to evaluate the efficacy and safety of benazepril/lercanidipine compared with benazepril alone in patients with mild-to-moderate hypertension.

METHODSOne hundred and eighty-one patients with mild-to-moderate primary hypertension were assigned in this randomized, single-blind, parallel-group study and were randomly divided into group A (benazepril 10 mg/lercanidipine 10 mg) and group B (benazepril 10 mg) for 8 weeks. At 4 weeks, the dosage of Benazepril was titrated up to 20 mg if the diastolic blood pressure (DBP) remained ≥ 90 mmHg. BP control and side effects were evaluated at the end of 1, 4 and 8 weeks.

RESULTSThe baseline characteristics of the two groups were similar. The BP in both groups decreased from the baseline (P < 0.05). At the end of 4 and 8 weeks, Benazepril/Lercanidipine produced greater BP reduction than Benazepril alone (P < 0.05). The comparison of the rate of BP control for the benazepril/lercanidipine and benazepril groups at the end of 1, 4, and 8 weeks were 41.2% vs. 37.6% (P > 0.05), 67.1% vs. 44.7% (P < 0.05), and 71.8% vs. 45.9% (P < 0.05). There was no significant difference of side effects between the two groups.

CONCLUSIONThe benazepril/lercanidipine combination is more effective in reducing BP than benazepril alone, while it does not increase the incidence of side effects.

Aged ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Benzazepines ; administration & dosage ; adverse effects ; therapeutic use ; Blood Pressure ; drug effects ; Calcium Channel Blockers ; administration & dosage ; Dihydropyridines ; administration & dosage ; adverse effects ; Drug Therapy, Combination ; Female ; Humans ; Hypertension ; drug therapy ; Male ; Middle Aged ; Single-Blind Method

Previous studies have demonstrated that enalapril and verapamil seem to attenuate the cyclosporine nephrotoxicity. However, the mechanisms have not been completely understood, especially on molecular events. The aim of this study was to examine the effect of individual or combined treatment on osteopontin, TGF-beta, endothelin-1 and procollagen alpha 1(I) mRNA expressions. Enalapril (50 mg/L in drinking water) and verapamil (0.5 mg/kg/day, subcutaneously), alone or in combination, were administered to rats with chronic cyclosporine nephrotoxicity (cyclosporine, 25 mg/kg/day, subcutaneously) (n = 5 each). Five rats treated with olive oil vehicle were used as control. After 4 weeks, biochemical parameters were measured, and renal cortical mRNA levels were evaluated by Northern blot analysis. Cyclosporine reduced renal creatinine clearance significantly and induced renal cortical osteopontin, TGF-beta, endothelin-1 and procollagen alpha 1(I) gene expressions around 13.5 +/- 1.3, 2.4 +/- 0.2, 1.5 +/- 0.1, 1.9 +/- 0.1 folds, respectively. Individual treatment with enalapril or verapamil significantly suppressed the osteopontin and TGF-beta mRNA expression, but not endothelin-1 and procollagen alpha 1(I). Combined treatment also inhibited the osteopontin and TGF-beta mRNA expression but there was no difference between combined and individual treatment. In conclusion, enalapril or verapamil significantly blunted the cyclosporine-induced osteopontin and TGF-beta gene expressions. However, combined treatment did not show any additive effect.
Angiotensin-Converting Enzyme Inhibitors/therapeutic use* ; Animal ; Calcium Channel Blockers/therapeutic use* ; Cyclosporine/adverse effects ; Drug Therapy, Combination ; Enalapril/therapeutic use* ; Enalapril/administration & dosage ; Endothelin-1/metabolism ; Endothelin-1/genetics ; Gene Expression Regulation/drug effects ; Immunosuppressive Agents/adverse effects ; Kidney Cortex/metabolism ; Male ; Nephritis/drug therapy* ; Nephritis/chemically induced ; Procollagen/metabolism ; Procollagen/genetics ; RNA, Messenger/analysis ; Rats ; Rats, Wistar ; Sialoglycoproteins/metabolism ; Sialoglycoproteins/genetics ; Transforming Growth Factor beta/metabolism ; Transforming Growth Factor beta/genetics ; Verapamil/therapeutic use* ; Verapamil/administration & dosage