A candesartan cilexetil/hydrochlorothiazide combination tablet provides effective blood pressure control in hypertensive patients inadequately controlled on monotherapy

In this double-blind, placebo-controlled, randomised, parallel-group study, a combination tablet of candesartan cilexetil/hydrochlorothiazide (HCTZ), 16/12.5 mg once daily, reduced sitting diastolic blood pressure (DBP) significantly more (p = 0.037) than candesartan cilexetil/placebo, 16 mg once daily, in patients with mild to moderate primary hypertension (n = 328) who had not reached target blood pressure with candesartan cilexetil, 16 mg once daily. At the end of the 8-week double-blind treatment period, the adjusted mean reductions in sitting DBP, 24 h post dose, were 7.5 mm Hg in the candesartan cilexetil/HCTZ treatment group and 5.5 mm Hg in the candesartan cilexetil/placebo treatment group, corresponding to an adjusted mean difference between treatments of 2.0 mm Hg in favour of candesartan cilexetil/HCTZ (95% CI 0.1-3.8 mm Hg, p = 0.037). The adjusted mean reductions in sitting systolic blood pressure, 24 h post dose, were 12.0 mm Hg and 7.5 mm Hg, respectively, corresponding to an adjusted mean difference between treatments of 4.5 mm Hg (95% CI 1.1-8.0, p = 0.01). Consistent with the placebo-like tolerability of candesartan cilexetil reported in other studies, both treatments were very well tolerated, with a similar pattern and low frequency of adverse events in both treatment groups.     

Angiotensin II type 1 (AT1) receptor blockade in hypertensive women: benefits of candesartan cilexetil versus enalapril or hydrochlorothiazide

The aim of this large, randomized, double-blind, parallel-group study in hypertensive women was to compare the antihypertensive efficacy and effects on subjective symptoms and quality of life of the new angiotensin II type 1 (AT₁) receptor blocker candesartan cilexetil, the angiotensin-converting enzyme inhibitor enalapril, and the diuretic hydrochlorothiazide (HCTZ). Women, aged 40 to 69 years, with a seated diastolic blood pressure (DBP) of 95 to 115 mm Hg, were randomized to candesartan cilexetil, 8 to 16 mg (n = 140), enalapril, 10 to 20 mg (n = 146), or HCTZ, 12.5 to 25 mg (n = 143), for 12 weeks; the higher doses were used if DBP was greater than 90 mm Hg after 6 weeks. Candesartan cilexetil lowered seated blood pressure by 17/11 and 19/11 mm Hg after 6 and 12 weeks of treatment, respectively. This reduction was greater (P < .01) than with enalapril (12/8 and 13/9 mm Hg) or HCTZ (12/7 and 13/8 mm Hg). The proportions of patients with controlled DBP (< 90 mm Hg) after 12 weeks of treatment with candesartan cilexetil, enalapril, or HCTZ were 60%, 51%, and 43%, respectively. Patients experienced less dry cough (P < 0.001) with candesartan cilexetil or HCTZ than with enalapril. No treatment differences were found in the incidence of dizziness and quality of life was well maintained in all groups. Compared with candesartan cilexetil and enalapril, HCTZ increased uric acid and decreased serum potassium (P < .001). In conclusion, candesartan cilexetil reduced blood pressure more effectively and was better tolerated than enalapril or HCTZ in women with mild to moderate hypertension.     

Efficacy of candesartan cilexetil in hypertensive patients with or without diabetes

OBJECTIVE: To assess the effect of an ARB, candesartan cilexetil (CC), on blood pressure (BP) from 5 double-blind, randomised, studies in hypertensive patients. METHODS: Similar design was used in the 5 selected studies. Following 2-4 weeks run-in period with placebo, patients were randomised to receive the double-blind treatment. BP were assessed at inclusion, after 4-6 weeks and at the end (8-12 weeks). Depending on the BP response, dosage of CC 8 mg was doubled at the follow-up visit if BP >or=140/90 mmHg. RESULTS: 702 patients were randomised in CC group of whom 22% (153) were diabetic. Mean BP was 160 +/- 13/94 +/- 10/65 +/- 14 mmHg for SBP/DBP/PP at inclusion and were significantly reduced to 141 +/- 15/83 +/- 10/58 +/- 13 mmHg (p<0.001) after 8-12 weeks. The results according to the diabetes status are presented in the table below: [table: see text] CONCLUSION: Results of this meta analysis analysis performed on individual data show that CC reduces significantly BP in hypertensive population with a significant decrease in the diabetic patients.     

Efficacy and tolerability of a combination tablet of candesartan cilexetil and hydrochlorothiazide in insufficiently controlled primary hypertension--comparison with a combination of losartan and hydrochlorothiazide

This randomized, double-blind study compared the antihypertensive effect, safety and tolerability of a candesartan cilexetil/hydrochlorothiazide (candesartan/HCT; 16/12.5 mg) combination tablet with that of a losartan/HCT (50/12.5 mg) combination tablet in patients with mild-to-moderate primary hypertension insufficiently controlled on previous monotherapy. Men and women, aged 20-80 years, with a sitting diastolic blood pressure (DBP) > or = 90 and < or = 110 mmHg and sitting systolic blood pressure (SBP) < or = 200 mmHg during treatment with any kind of antihypertensive monotherapy for at least 4 weeks were randomized to candesartan/HCT or losartan/HCT once daily for 12 weeks. All BP measurements were performed 24 h after previous dose. Mean values and standard deviations (SD) or confidence intervals (CI) are given. A total of 340 patients were enrolled, of whom 299 (144 women and 155 men, mean age 59.5 [10.5] years) were randomized to candesartan/HCT (n = 151) or losartan/HCT (n = 148). BPs at randomization were 159.5 (15.4)/98.4 (5.8)mmHg and 160.5 (16.1)/98.5 (5.4)mmHg, respectively. There was a greater reduction in BP with candesartan/HCT than with losartan/HCT: DBP -10.4 (-11.8; -8.9) vs -7.8 (-9.3; -6.3) mmHg, difference between treatments -2.6 (-4.7; -0.5) mmHg (p = 0.016); SBP -19.4 (-22.1; -16.7) vs - 13.7 (-16.5; - 10.9) mmHg, difference between treatments -5.7 (-9.6; -1.8) mmHg (p = 0.004). The proportion of patients achieving a DBP < or = 90 mmHg was greater in the candesartan/HCT group: 60.9 (53.1; 68.7) vs 49.3 (41.3; 57.4)% (p = 0.044). There were 12 withdrawals in the candesartan/HCT group, of which 8 were due to adverse events, and 17 and 12, respectively in the losartan/HCT group. We conclude that the combination of candesartan and HCT reduces BP effectively and is well tolerated. BP was normalized in 61% of these patients who had insufficient response to previous monotherapy. The reduction in BP and the proportion of patients with normalized BP were greater with the candesartan/HCT 16/12.5 mg combination than with the losartan/ HCT 50/12.5 mg combination.     

Effects of candesartan and lisinopril on the fibrinolytic system in hypertensive patients

The effects of the angiotensin II receptor blocker candesartan and the angiotensin-converting enzyme inhibitor lisinopril on the fibrinolytic system were investigated in a double-blinded, prospective, randomized study. Seventy-seven hypertensive patients taking candesartan (n=41) and lisinopril (n=36) with a systolic blood pressure >130 mm Hg and/or a diastolic blood pressure >80 mm Hg obtained by 24-hour ambulatory blood pressure measurement were included in the study. Blood pressure, plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (tPA), and the molar ratio of PAI-1/tPA were determined before treatment and 6 weeks later. Blood pressure decreased in both groups (candesartan, 155/85 mm Hg to 140/84 mm Hg; P<.05; lisinopril, 152/85 mm Hg to 138/83 mm Hg; P<.05). The fibrinolytic balance was significantly different between treatment groups (molar ratio of PAI-1/tPA: candesartan, 3.66 [2.2;] lisinopril, 5.44 [2.6;] P<.05). In contrast to lisinopril, the balance between coagulation and fibrinolytic activity shifted toward fibrinolysis during candesartan treatment.     

AT1 receptor blocker added to ACE inhibitor provides benefits at advanced stage of hypertensive diastolic heart failure

Diastolic heart failure (DHF) has become a social burden; however, evidences leading to its therapeutic strategy are lacking. This study investigated effects of addition of angiotensin II type 1 receptor blocker (ARB) to angiotensin-converting enzyme inhibitor (ACEI) at advanced stage of DHF in hypertensive rats. Dahl salt-sensitive rats fed 8% NaCl diet from age 7 weeks served as DHF model, and those fed a normal chow served as control. The DHF model rats were arbitrarily assigned to 3 treatment regimens at age 17 weeks: ACEI (temocapril 0.4 mg/kg per day), combination of ACEI (temocapril 0.2 mg/kg per day) with ARB (olmesartan 0.3 mg/kg per day), or placebo. At age 17 weeks, this model represents progressive ventricular hypertrophy and fibrosis, relaxation abnormality, and myocardial stiffening. Data were collected at age 20 weeks. As compared with the monotherapy with ACEI, the addition of ARB induced more prominent suppression of ventricular hypertrophy and fibrosis, leading to suppression of myocardial stiffening, improvement of relaxation, and inhibition of hemodynamic deterioration. Such benefits were associated with greater decreases in reactive oxygen species (ROS) generation, macrophage infiltration, and gene expression of transforming growth factor (TGF)-beta(1) and interleukin (IL)-1beta, but not with changes in gene expression of monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor (TNF)-alpha. Thus, ARB added to ACEI provides more benefits as compared with ACEI alone in DHF when initiated at an advanced stage. The additive effects are likely provided through more prominent suppression of ROS generation and inflammatory changes without effects on expression of MCP-1 and TNF-alpha.     

Effect of telmisartan/hydrochlorothiazide vs lisinopril/hydrochlorothiazide combination on ambulatory blood pressure and cognitive function in elderly hypertensive patients

The aim of this study was to compare the effects of telmisartan/hydrochlorothiazide (HCTZ) vs lisinopril/HCTZ combination on ambulatory blood pressure and cognitive function in elderly hypertensive patients. A total of 160 patients, 76 men and 84 women, aged 61-75 years, with sitting diastolic blood pressure (DBP)>90 mmHg and <110 mmHg and systolic blood pressure (SBP)>140 mmHg were randomized to receive temisartan 80 mg/HCTZ 12.5 mg o.d. or lisinopril 20 mg/HCTZ 12.5 mg o.d. for 24 weeks, according to a prospective, open-label, blinded end point, parallel-group design. At the end of a 2-week wash-out period and after 12 and 24 weeks of active treatment, 24-h noninvasive ambulatory BP monitoring (ABPM) was performed and cognitive function was evaluated through six different tests (verbal fluency, Boston naming test, word-list memory, word-list recall, word-list recognition and Trails B). Both treatments significantly reduced ambulatory BP. However, the telmisartan/HCTZ combination produced a greater reduction in 24-h, day-time and night time ABPM values. Lisinopril/HCTZ did not induce significant changes in any of the cognitive function test scores at any time of the study, whereas at both 12 and 24 weeks telmisartan/HCTZ significantly improved the word-list memory score (+17.1 and +15.7%, respectively, P<0.05 vs baseline), the word-list recall score (+13.5 and +16.9%, P<0.05) and the Trails B score (-33 and -30.5%, P<0.05). These results suggest that in elderly hypertensive patients treatment with telmisartan/HCTZ produces a slightly greater reduction in ambulatory BP than lisinopril/HCTZ combination and, unlike this latter, improves some of the components of cognitive function, particularly episodic memory and visuospatial abilities.     

Effect of the alpha 1-receptor blocker prazosin and the beta 1-receptor blocker acebutolol and their combination on blood pressure and pressure rate product. Ergometric studies of hypertensive patients

The cardiovascular risk of hypertension depends not only on blood pressure under resting conditions, but particularly on blood pressure increases induced by daily physical and emotional activity. Therefore, the ability of the beta 1-receptor antagonist acebutolol (400 mg/day) and of the alpha 1-receptor antagonist prazosin (4 mg/day) to reduce exercise-induced increases in blood pressure and pressure-rate product during and after standardized ergometric work (50-100 W) was compared in an intrapatient study including 20 outpatients with arterial hypertension (WHO stage 1-2) aged 29-55 years. Both drugs resulted in a significant reduction of systolic (p less than 0.01) and diastolic (p less than 0.001) blood pressure at rest. However, systolic blood pressure (p less than 0.001) and pressure-rate product (p less than 0.001) during exercise were only significantly reduced by acebutolol. The strongest blood pressure lowering effect under all conditions could be achieved by the combination of prazosin and acebutolol. From these findings it is concluded that: (1) beta-adrenoreceptor-blocking agents are the drugs of first choice in the baseline therapy of mild to moderate arterial hypertension, and (2) prazosin potentiates the antihypertensive effect of beta-blocking agents. This therapeutic regimen is recommended especially for hypertensives with ischemic heart disease, because prazosin fails to reduce pressure-rate product as a measure of myocardial O2-consumption.     

Efficacy of candesartan cilexetil alone or in combination with amlodipine and hydrochlorothiazide in moderate-to-severe hypertension. UK and Israel Candesartan Investigators

This multicenter study evaluated the efficacy of candesartan cilexetil, an angiotensin II type 1 receptor antagonist, used alone or in combination with amlodipine or in combination with amlodipine and hydrochlorothiazide in the treatment of patients with moderate-to-severe essential hypertension. After a 2-week, single-blind, placebo run-in period, patients entered a 12-week, open-label, dose-titration period. The candesartan cilexetil dose was increased from 8 to 16 mg once daily; amlodipine (5 mg once daily), hydrochlorothiazide (25 mg once daily), and additional medication were also added sequentially if necessary. Patients then entered a final 4-week, parallel-group, double-blind, randomized, placebo-controlled withdrawal period of candesartan alone. A total of 216 patients were recruited. After a 2-week run-in period on placebo tablets, mean sitting blood pressure (BP) was 175/108 mm Hg. At the end of the 12-week dose-titration/maintenance period, mean sitting BP fell to 141/88 mm Hg. In 67 patients who were randomized to placebo and had their candesartan withdrawn, there was a highly significant increase in mean systolic/diastolic BP (13/6 mm Hg) compared with those patients who continued with candesartan (ANCOVA, P:<0.0001). In conclusion, candesartan cilexetil is an effective BP-lowering drug when used alone or in combination with amlodipine or amlodipine plus hydrochlorothiazide in the treatment of moderate-to-severe essential hypertension. The drug was well tolerated throughout the investigation period.     

Comparative metabolic effects of hydrochlorothiazide and indapamide in hypertensive diabetic patients receiving ACE inhibitor therapy.

BACKGROUND: ACE inhibitors, when used as monotherapy, are frequently unable to adequately control blood pressure in diabetic patients. A diuretic may be added; however, thiazide diuretics, but not indapamide, have been associated with adverse metabolic effects. Whether these effects also apply to thiazides when administered in the currently used lower doses, and whether they differ from indapamide in their metabolic effects, particularly when used in combination with an ACE inhibitor in diabetic patients, has not been previously studied. METHODS: We conducted a prospective, randomized, open-label, blinded endpoint crossover study comparing the metabolic responses to the addition of either hydrochlorothiazide (HCTZ) or indapamide, in 18 diabetic hypertensive patients receiving ACE inhibitor monotherapy for hypertension. Patients stabilized on fosinopril 20 mg/day were randomized to receive either HCTZ 12.5 mg od or indapamide 2.5 mg od for 8 weeks, then crossed over to the alternate therapy for a further 8-week period. Blood pressure, heart rate and metabolic assessments were performed at the end of each 8-week treatment period. RESULTS: Seated and standing systolic and diastolic blood pressures were not different between HCTZ or indapamide when added to fosinopril, nor was the fasting lipid profile or urinary albumin : creatinine ratio. Plasma potassium was lower with indapamide compared with HCTZ treatment (indapamide 4.3+/-0.1 mmol/l; HCTZ 4.5+/-0.1 mmol/l, P<0.01) and HbA1c was higher with indapamide than with HCTZ therapy (indapamide 7.8+/-0.4%; HCTZ 7.2+/-0.3%, P<0.01). CONCLUSIONS: Hydrochlorothiazide 12.5 mg/day, when added to background ACE inhibitor therapy with fosinopril in hypertensive diabetic patients, resulted in a metabolic profile that was similar, if not superior on certain parameters, in comparison with indapamide 2.5 mg/day.     

Effects of ACE inhibitor and AT1 blocker on dystrophin-related proteins and calpain in failing heart

OBJECTIVES: Genetic depletion of dystrophin-related protein (DRP) complex causes cardiomyopathy in animals and humans. We found in a previous study that some types of DRP were degraded and that calpain content was increased in rats with non-genetically induced heart failure. The present study was aimed at examining the effects of an angiotensin-I-converting enzyme inhibitor (ACEI) trandolapril (Tra) or an angiotensin II type 1 receptor blocker (ARB) candesartan (Can), both of which are known to improve the pathophysiology of chronic heart failure (CHF) on degradation of DRP in failing hearts. METHODS: Coronary artery-ligated (CAL) and sham-operated rats (Sham rats) were treated orally with 3 mg/kg/day trandolapril (Tra) or 1 mg/kg/day candesartan (Can) from the 2nd to 8th week after surgery. RESULTS: Hemodynamic parameters of CAL rats at the 8th week after CAL (8w-CAL) indicated heart failure. alpha-Sarcoglycan (SG) and dystrophin in the surviving left ventricle (surviving LV) of 8w-CAL rats decreased, whereas beta-, gamma-, and delta-SGs remained unchanged. Calcium-activated neutral proteases mu-calpain and m-calpain increased in the surviving LV at the 8th week of postmyocardial infarction. Proteolytic activity in the presence of 5 mM Ca2+ markedly increased at the 2nd and 8th weeks, whereas 50 microM Ca2+ slightly but significantly increased proteolysis of casein. Tra or Can treatment improved the hemodynamic parameters, attenuated changes in alpha-SG and dystrophin, and reversed both calpain contents and activities of the failing heart back to sham levels. CONCLUSION: These results suggest that attenuation in calpain-induced degradation of DRP complex is a possible mechanism for the Tra- or Can-mediated improvement of the pathogenesis of CHF following myocardial infarction.     

Valsartan in combination with lisinopril versus the respective high dose monotherapies in hypertensive patients with microalbuminuria: the VALERIA trial

OBJECTIVES: Microalbuminuria is known as an independent predictor for stroke, myocardial infarction, and death. The purpose of the VALERIA trial was a comparison of the efficacy and safety of combination therapy of valsartan and lisinopril with valsartan and lisinopril high-dose monotherapy in patients with hypertension and microalbuminuria. METHODS: This was a randomized, double-blind, interventional, parallel-group study. After a washout/placebo-run-in phase of 3 weeks, 133 patients were randomized to treatment (1: 1:1) with either lisinopril 40 mg, valsartan 320 mg, or a combination of valsartan/lisinopril 320/20 mg for 30 weeks. RESULTS: At baseline, the urine albumin creatinine ratio was similar for the three treatment groups (geometric means, lisinopril 9.6 mg/mmol, valsartan 9.1 mg/mmol, and valsartan/lisinopril 9.5 mg/mmol). After 30 weeks of treatment, the geometric mean urine albumin creatinine ratio had decreased in all three groups by 41, 51, and 62% to 5.7 mg/mmol (lisinopril), 4.5 mg/mmol (valsartan), and 3.6 mg/mmol (valsartan/lisinopril). The decrease for valsartan/lisinopril was statistically significantly greater compared with lisinopril [adjusted ratio 60%, confidence interval (38-94%), P = 0.029]. Normalization of microalbuminuria was greatest with valsartan and valsartan/lisinopril (lisinopril 17%, valsartan 31%, and valsartan/lisinopril 38% of patients) and was statistically significant for lisinopril in contrast with valsartan/lisinopril (P = 0.034). Differences in blood pressure reduction between the groups were not statistically significant. All treatments were safe and well tolerated. CONCLUSION: The combination of valsartan and lisinopril provided a significantly better reduction of urine albumin creatinine ratio and more than doubled the rate of patients with normalized urine albumin creatinine ratio compared with lisinopril alone. All treatments were safe and well tolerated.     

Anti-albuminuric effects of the angiotensin AT1 receptor blocker telmisartan in hypertensive patients

We evaluated the anti-hypertensive and anti-albuminuric effect of the angiotensin receptor blocker telmisartan alone and in combination with torasemide and amlodipine. Patients were hypertensive, both diabetics and non-diabetics with persistent microalbuminuria. Our primary endpoint was a change in microalbuminuria levels, while the secondary endpoints were changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), serum creatinine levels, and glomerular filtration rate.After the 16-week treatment period, the patients significantly reduced microalbuminuria levels (76.4 ± 52.4 μg/min; p < 0.001), SBP (16.4 ± 8.7 mmHg; p < 0.001) and DBP (17.7 ± 5.9 mmHg; p < 0.001). Both diabetics and non-diabetics showed an identical pattern of significance with respect to the whole population. Systolic blood pressure, DBP, and microalbuminuria were significantly reduced as a consequence of therapy, both in diabetics and non-diabetics.     

An alpha1-receptor blocker reduces plasma leptin levels in hypertensive patients with obesity and hyperleptinemia.

Obesity is often complicated by hypertension, and both conditions are risk factors for atherosclerosis. Leptin has attracted attention as a possible cause of hypertension in obese persons. We investigated the effect of a slow-release alpha1-receptor blocker, bunazosin hydrochloride, on leptin levels and insulin resistance in obese hypertensive patients with hyperleptinemia. The subjects were 17 patients (12 men and 5 women aged 56.1 +/- 12.2 years) with essential hypertension who were not receiving alpha1-receptor blockers. They had a body mass index (BMI) > or = 25 kg/m2 and a plasma leptin concentration > or = 5 ng/ml. They received oral therapy with bunazosin hydrochloride at doses of up to 9 mg/day. The plasma leptin concentration, body weight, blood pressure, heart rate, fasting blood glucose, plasma insulin concentration, and free fatty acid level were compared between before and after treatment. Although there was no significant change of BMI, there was a significant decrease of plasma leptin after treatment (10.6 +/- 5.4 ng/ml vs. 8.7 +/- 3.4 ng/ml, p = 0.0128), as well as a significant decrease of plasma insulin (9.8 +/- 4.8 microU/ml vs. 8.1 +/- 4.6 microU/ml, p = 0.0494) and HOMA-R (2.9 +/- 2.1 vs. 2.2 +/- 1.5, p = 0.0237). In conclusion, bunazosin hydrochloride reduced the plasma leptin level and improved insulin resistance in hypertensive patients with obesity and hyperleptinemia.     

赖诺普利氢氯噻嗪片治疗轻中度原发性高血压的疗效和安全性的多中心观察性临床研究

目的评价真实世界中赖诺普利氢氯噻嗪片治疗轻中度原发性高血压的疗效和安全性。方法本研究为多中心回顾性调查。入选2015年6月至2016年8月期间就诊于国内16所二级或三级医院心内科门诊的1～2级原发性高血压、且已连续服用赖诺普利氢氯噻嗪片至少8周的患者,由经过统一培训的调查医生与患者进行面对面访谈完成调查问卷,并查阅病历收集资料,评估真实世界中赖诺普利氢氯噻嗪片治疗轻中度原发性高血压的疗效和安全性。结果共入选1 017例患者,男性509例(50.1%),女性508例(49.9%),年龄平均为(59.8±12.0)岁。(1)降压疗效评价:治疗4周,血压平均降幅为(25.3±10.9)/(13.1±6.5) mmHg,血压达标率为72.7%;治疗8周,血压平均降幅为(30.3±9.7)/(15.7±6.2) mmHg,血压达标率为96.7%。(2)安全性评价:最常见的不良反应为干咳(5.9%),其他依次为头晕(0.7%)、乏力(0.5%)、头痛(0.5%)、心悸(0.1%)和症状性低血压(0.1%)。结论赖诺普利氢氯噻嗪片治疗轻中度高血压疗效确切,且安全性良好。     

Effects of candesartan cilexetil and enalapril on inflammatory markers of atherosclerosis in hypertensive patients with non-insulin-dependent diabetes mellitus

OBJECTIVE: Circulating adhesion molecules may have a prognostic significance as markers of endothelial damage. Drugs which inhibit the renin-angiotensin system may be effective in reducing circulating or tissue adhesion molecules, albeit data available are scarce. The aim of the study was to investigate the effects of an angiotensin-converting enzyme (ACE) inhibitor, enalapril and a highly selective angiotensin receptor blocker, candesartan cilexetil, on circulating adhesion molecules in a large sample of patients with non-insulin-dependent diabetes mellitus (NIDDM). The study was comparative, multicenter, randomized and double blind, with two parallel groups. PATIENTS AND METHODS: NIDDM patients with a diagnosis of mild (grade 1) essential hypertension were included in the study, at the end of a 2-week placebo run-in period. The primary end-point of the study was to evaluate changes of intercellular adhesion molecule-1 (ICAM-1) plasma levels during treatment. The secondary end-points were: changes in vascular cells adhesion molecule-1 (VCAM-1), von Willebrand factor (vWF), fibrinogen and plasminogen activator inhibitor-1 (PAI-1) circulating levels and of urinary albumin excretion rate (AER) as well; 129 patients were randomized: 66 in the candesartan group and 63 in the enalapril group, 118 of them completed the scheduled 24-week treatment period. RESULTS: Candesartan and enalapril equally reduced circulating level of ICAM-1 and exerted comparable effects on changes of other adhesion molecules and coagulation factors. A similar blood pressure-lowering effect was observed with the two drugs (candesartan: from 148/90 +/- 11/8 to 132/82 +/- 12/7 mmHg, P < 0.01, enalapril: from 148/91 +/- 12/8 to 131/85 +/- 14/6 mmHg, P < 0.01). Candesartan was more effective than enalapril in the reduction of albuminuria (P < 0.05 between treatments), although urinary protein excretion can be considered normal in the majority of patients. The two drugs were comparable in terms of adverse events reported. CONCLUSION: Candesartan and enalapril showed similar effects on blood pressure and on circulating adhesion molecules. In this study urinary protein excretion was reduced more by candesartan.     

Comparative efficacy of fixed dose combinations of enalapril with hydrochlorothiazide and captopril with hydrochlorothiazide in patients with high risk hypertension

Clinical effectiveness and tolerability of o.d. use of fixed dose combinations of enalapril (10 mg) with hydrochlorothiazide (25 mg) (Enap H) and captopril (50 mg) with hydrochlorothiazide (25 mg) (Capozide) were compared in a randomized study on 60 patients with I-II degree high and very high risk hypertension. Study duration was 6 months, number of patients in each of parallel groups -- 30. Antihypertensive activity, ability to improve arterial elasticity and T/P parameter, cost/efficacy index of enalapril (10 mg) plus hydrochlorothiazide (25 mg) combination was found to be superior to those of captopril (50 mg) plus hydrochlorothiazide (25 mg) combination.     

Effect of combination therapy of benidipine hydrochloride and candesartan cilexetil on serum lipid metabolism and blood pressure in elderly hypertensive patients with type 2 diabetes mellitus

The effects of combination therapy of angiotensin II receptor blockers (ARBs) and a calcium antagonist, benidipine hydrochloride, on glucose and lipid metabolism and pulse pressure were studied in elderly hypertensive patients with type 2 diabetes mellitus. Twenty-five hypertensive diabetic patients aged 65 years or older, who had been receiving candesartan cilexetil, were administered benidipine hydrochloride (4 mg/day) and followed for 4 months. After 4 months, systolic and diastolic blood pressure decreased significantly from 154/91 mmHg to 139/78 mmHg (p<0.01 versus before benidipine hydrochloride administration). Body mass index (BMI) and glycosylated hemoglobin (HbA1c) were apparently reduced but the changes were not statistically significant. The serum lipid profile showed no significant changes in serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Serum lipoprotein lipase mass levels (preheparin LPL mass) increased significantly from 51 to 59 ng/dl (p<0.01 versus before benidipine hydrochloride administration), and the LDL/HDL motility ratio calculated from PAG disc electrophoresis decreased significantly (p<0.05 versus before benidipine hydrochloride administration). When patients were divided into a systolic hypertension group (systolic blood pressure > or =140 mmHg and diastolic blood pressure <90 mmHg) and non-systolic hypertension group (others), preheparin LPL mass was significantly lower in the systolic hypertension group, and the decrease in pulse pressure and increase in preheparin LPL mass were significantly greater in the systolic hypertension group. Stepwise regression analysis showed that low preheparin LPL mass at baseline was associated with a decrease in pulse pressure. Add-on benidipine hydrochloride therapy in elderly hypertensive patients with type 2 diabetes mellitus significantly decreases the LDL/HDL motility ratio and pulse pressure, and significantly increases preheparin LPL mass, in addition to improving blood pressure control. These findings suggest that combination therapy with benidipine hydrochloride and candesartan cilexetil may contribute to the suppression of arteriosclerosis and may be useful for elderly hypertensive patients with diabetes mellitus.     

Comparison of candesartan with lisinopril on ambulatory blood pressure and morning surge in patients with systemic hypertension

We performed a prospective crossover study in 73 essential hypertensives to compare the effects of candesartan and lisinopril on ambulatory blood pressure (BP) and early-morning BP. Twenty-four-hour ambulatory BP monitoring was performed at baseline and for each active treatment. Small doses of thiazide diuretic were added as needed. The effects of both drugs on 24-hour BP were almost identical and satisfactory. When we classified patients into the morning surge group (the highest quartile of morning systolic BP surge >36 mm Hg) and the non-morning surge group (the remaining 3 quartiles of morning BP surge), candesartan was superior in decreasing morning BP and morning BP surge.     

ACE inhibitor and angiotensin II type 1 receptor blocker differently regulate ventricular fibrosis in hypertensive diastolic heart failure

BACKGROUND: Promoted myocardial stiffening has a crucial role in the transition to overt diastolic heart failure (DHF) in hypertensive hearts and is attributed to progressive ventricular fibrosis. Previous studies revealed the effects of an angiotensin II type 1 receptor blocker (ARB) and an angiotensin-converting enzyme inhibitor (ACEI) on the synthesis and degradation of collagens in the other phenotype of heart failure, systolic heart failure, which has a different pathophysiology; however, little is known about their effects in DHF. OBJECTIVE: To investigate effects of an ACEI and an ARB on the regulatory system of ventricular fibrosis in hypertensive DHF. DESIGN AND METHODS: Dahl salt-sensitive rats fed a diet containing 8% NaCl from age 7 weeks (DHF model) were divided into three groups: six untreated rats, six rats treated with a subdepressor dose of an ARB, candesartan cilexetil (1 mg/kg per day), from age 8 weeks, and six rats treated with a subdepress or dose of an ACEI, temocapril hydrochloride (0.2 mg/kg per day), from age 8 weeks. Six Dahl salt-sensitive rats fed on normal chow served as controls. Data were collected when animals were aged 20 weeks. RESULTS: The administration of an ARB or an ACEI inhibited ventricular fibrosis to the same degree. The ACEI decreased the level of type I collagen mRNA, but the decrease was less than that induced by the ARB. The difference in collagen synthesis was probably cancelled out by that in degradation: both in-vitro and in-situ zymography showed that gelatinase activity was greater in the rats treated with the ACEI than in those treated with the ARB. CONCLUSIONS: An ARB and an ACEI inhibited ventricular fibrosis through different mechanisms in hypertensive DHF.