Comparative antihypertensive efficacy of olmesartan: comparison with other angiotensin II receptor antagonists

Hypertension is a major risk factor for cardiovascular morbidity and mortality. Effective control of elevated blood pressure (BP) has been shown to reduce this risk. Early studies of risk reduction assumed that the mechanism by which BP was lowered had little impact on the benefit obtained. Recent evidence, however, suggests that agents that inhibit the renin-angiotensin system may be particularly beneficial. The results of the recent Heart Outcomes Prevention Evaluation (HOPE) trial suggest that angiotensin-converting enzyme (ACE) inhibitors have a greater impact on cardiovascular morbidity and mortality than would be anticipated from their antihypertensive effects alone. Angiotensin receptor blockers, the other major class of antihypertensive drugs that inhibit the renin-angiotensin system, have not been widely tested in outcomes trials, but early results suggest that they are beneficial for controlling target organ damage that is related to hypertension. Furthermore, unlike ACE inhibitors, these agents have a side-effect profile that is similar to that of placebo. Based on their efficacy in controlling hypertension and their wider health benefits, together with minimal side effects, angiotensin II (A II) receptor blockers should be considered as first-line agents for the treatment of hypertension, particularly in patients with other cardiovascular risk factors. Preliminary evidence suggests that olmesartan, an A II receptor blocker currently being evaluated for approval for clinical use, may provide antihypertensive efficacy that is superior to other members of the class.     

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in African-American patients with hypertension

African-American patients with hypertension are less responsive to blockers of the renin-angiotensin system than white patients. The relative efficacy of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers and the extent of cross-resistance to these agents has not been studied. Fifty-one African-American patients with stage 1-2 hypertension were randomly assigned to enalapril or candesartan cilexetil for 8 weeks and then crossed over to the other treatment. Nonresponders to enalapril and candesartan used a combination of the two. Of the 51 patients randomized (average age 61.2+/-9 years, blood pressure 148/100 mm Hg, heart rate 74 bpm, and body weight 92.8 kg), 44 completed the study. At Week 8, systolic blood pressure (SBP) was reduced by 4.8 mm Hg with enalapril and by 4.7 mm Hg with candesartan (p=NS), and diastolic blood pressure (DBP) was reduced by 4.4 mm Hg and 5.6 mm Hg, respectively (p<0.04). Of these 44 patients, 11 (25%) responded to enalapril by SBP criteria and 19 (43%) by DBP criteria. Seven patients (16%) responded by both SBP and DBP criteria, and 21 patients (48%) were nonresponders. With candesartan, 13 patients (29%) responded by SBP criteria, 20 (45%) by DBP criteria and 12 (27%) by both SBP and DBP criteria (p<0.04, compared with enalapril). Only six patients (14%) responded to both enalapril and candesartan by both SBP and DBP criteria. Of the 18 nonresponders to either enalapril or candesartan, the combination of the two had minimal additional effect. Significant changes in plasma-renin activity and angiotensin II levels were noted only with the high dose of each drug. In this small group of patients, treatment with candesartan resulted in slightly higher response and control rates than enalapril, more than 40% of patients who responded to enalapril did not respond to candesartan and vice versa, and in nonresponders, a combination of candesartan and enalapril offered little additional antihypertensive effect.     

Interaction between nonsteroidal anti-inflammatory drug intake and calcium-channel blocker-based antihypertensive treatment in the Syst-Eur trial

OBJECTIVE: To assess the relationship between chronic intake of nonsteroidal anti-inflammatory drugs (NSAID) and outcome, in particular (gastrointestinal) bleeding and to investigate whether the effect of chronic NSAID intake was similar in untreated and treated elderly hypertensives. METHODS: Eligible patients (> or = 60 years, with systolic blood pressure 160-219 mm Hg and diastolic blood pressure < 95 mm Hg) were randomised to active treatment or placebo. Active treatment consisted of nitrendipine, with the possible addition of enalapril, hydrochlorothiazide, or both, titrated or combined to reduce the sitting systolic blood pressure by at least 20 mm Hg to below 150 mm Hg. Patients never taking NSAIDs (n = 2882) were compared with patients on chronic NSAID intake (n = 861), defined as reporting NSAID intake on at least 50% of the patient forms. RESULTS: There was a tendency towards lower mortality (relative hazard rate (95% confidence interval (CI), 0.77 (0.56-1.06)) and higher incidence of bleeding (1.13 (0.63-2.05) with chronic NSAID intake. Although there was no significant interaction between calcium-channel blocker (CCB)-based treatment and chronic NSAID intake for any of the end points, chronic NSAID intake tended to be associated with a lower incidence of bleeding on active treatment as compared to placebo (P-value of the interaction term = 0.07). CONCLUSION: The effect of chronic NSAID intake on outcome was similar in patients on active treatment based on a dihydropyridine CCB or on placebo. However, chronic NSAID intake might have a less deleterious effect on bleeding on active treatment as compared to placebo.     

The importance of early antihypertensive efficacy: the role of angiotensin II receptor blocker therapy

Desirable features of antihypertensive agents include efficacy, tolerability, prolonged duration of action and rapid achievement of target blood pressure (BP). Recent studies have examined the relationship between the onset of antihypertensive effect and cardiovascular events. Data from the Valsartan Antihypertensive Long-term Use Evaluation (VALUE), the Study on Cognition and Prognosis in the Elderly (SCOPE), and the Systolic Hypertension in Europe (Syst-Eur) trials support the hypothesis that the time it takes to reach target BP influences cardiovascular outcomes. VALUE, which compared BP-lowering and clinical event rates between patients treated with the angiotensin II receptor blocker (ARB) valsartan or the calcium channel blocker (CCB) amlodipine as well as between those who achieved immediate or delayed BP control, provides the strongest evidence of this to date. Additional data from SCOPE and Syst-Eur suggest that delays of 3 months to 2 years in starting antihypertensive therapy can increase the risk of certain cardiovascular end points, especially stroke. These data suggest that it may be beneficial to examine the efficacy of antihypertensive agents, not only long term, but also at earlier times to assess the onset and impact of early antihypertensive effect. The ARB olmesartan medoxomil (olmesartan) and the CCB amlodipine were compared in a randomized, double-blind, placebo-controlled clinical trial, which demonstrated that the onset of antihypertensive effect of olmesartan is comparable with that of amlodipine. Another study demonstrated that more patients treated with olmesartan achieved target BPs within 2 weeks of treatment compared with the ARBs losartan, valsartan and irbesartan.     

A home blood pressure monitoring study comparing the antihypertensive efficacy of two angiotensin II receptor antagonist fixed combinations

BACKGROUND: The objective of this prospective, randomized, open-label, blinded-endpoint study was to compare the antihypertensive efficacy of valsartan 80 mg v irbesartan 150 mg when combined with hydrochlorothiazide (HCTZ) 12.5 mg. METHODS: Untreated or uncontrolled hypertensive adults (n = 800) were enrolled by primary care physicians. After a 5-week open-label lead-in phase in which all patients received 12.5 mg HCTZ once daily, subjects whose blood pressure (BP) remained uncontrolled were randomized (n = 464) to valsartan/HCTZ (80/12.5 mg) or irbesartan/HCTZ (150/12.5 mg) for 8 weeks. Home BP monitoring (HBPM) was performed in the morning and in the evening for 5 days, at baseline, and after 8 weeks. Office BP measurements were obtained at baseline and after 8 weeks. RESULTS: Irbesartan/HCTZ produced greater reductions in average systolic BP (SBP) and diastolic BP (DBP) measured by HBPM than valsartan/HCTZ (SBP: -13.0 v -10.6 mm Hg, P = .0094; DBP: -9.5 v -7.4 mm Hg, P = .0007). These differences were more pronounced in the morning (trough) than in the evening. Office BP measurements also showed greater reductions in trough seated SBP and DBP with irbesartan/HCTZ compared with valsartan/HCTZ. Normalization rates observed with HBPM (SBP <135 mm Hg and DBP <85 mm Hg) were significantly greater with irbesartan/HCTZ than with valsartan/HCTZ (50.2 v 33.2%; P = .0003). The overall safety was similar in the two groups. CONCLUSIONS: The superior BP-lowering potency of the fixed combination irbesartan/HCTZ (150/12.5 mg) over valsartan/HCTZ (80/12.5 mg), evidenced independently from the investigators by HBPM, supports the use of this technique in trials with prospective, randomized, open-label, blinded-endpoint designs.     

Therapeutic efficacy of an angiotensin II receptor antagonist in patients with nonalcoholic steatohepatitis

The therapeutic efficacy of angiotensin II receptor antagonist, losartan, was studied in patients with nonalcoholic steatohepatitis (NASH). Seven patients with both NASH and hypertension were treated with losartan (50 mg/d) for 48 weeks. Treatment with losartan resulted in a significant decrease in blood markers of hepatic fibrosis, plasma TGF-beta1 and serum ferritin concentration concurrently with an improvement in serum aminotransferase levels. Histological assessment showed improvement of hepatic necroinflammation in five patients, reduction of hepatic fibrosis in four patients, and disappearance of iron deposition in two patients. No side effect of treatment was noted at any time during the study. In conclusion, the present data raise the possibility that an angiotensin II receptor antagonist may be therapeutically efficacious for NASH.     

An ambulatory blood pressure monitoring study of the comparative antihypertensive efficacy of two angiotensin II receptor antagonists,irbesartan and valsartan

BACKGROUND: The primary objective of this study was to compare the change from baseline in mean diastolic ambulatory blood pressure (ABP) at 24 h post dose (trough measurement) after 8 weeks of treatment with irbesartan or valsartan in subjects with mild-to-moderate hypertension. Secondary objectives included comparing the mean changes from baseline in systolic ABP at trough; 24-h ABP; morning and night-time ABP; self-measured systolic blood pressure (SBP) and diastolic blood pressure (DBP); and office-measured SBP and DBP at trough. DESIGN: After a 3-week, single blind, placebo lead-in period, 426 subjects were randomized to receive either irbesartan 150 mg or valsartan 80 mg for 8 weeks. METHODS: Ambulatory blood pressure measurements were obtained at baseline and at week 8. Self-measured morning and evening DBP and SBP readings were obtained at home over a 7-day period at baseline and at week 8. Office-measured seated DBP and SBP measurements were obtained at trough, at baseline, and at week 8. RESULTS: Irbesartan demonstrated significantly greater reductions than valsartan for mean change from baseline in diastolic ABP at trough (-6.73 versus -4.84 mmHg, respectively; P = 0.035). Irbesartan produced significantly greater reductions than valsartan for mean systolic ABP at trough (-11.62 versus -7.5 mmHg, respectively; P < 0.01) and for mean 24-h diastolic ABP (-6.38 versus -4.82 mmHg, respectively; P = 0.023) and systolic ABP (-10.24 versus -7.76 mmHg; P < 0.01). Irbesartan also produced significantly greater reductions than valsartan for office-measured seated DBP (-10.46 versus 7.28 mmHg, respectively; P < 0.01) and SBP (-16.23 versus -9.96 mmHg, respectively; P < 0.01) and for self-measured morning DBP (-6.28 versus -3.75 mmHg, respectively; P < 0.01) and SBP (-10.21 versus -6.97 mmHg, respectively; P < 0.01). Both drugs were well tolerated. CONCLUSION: Irbesartan was more effective than valsartan in reducing DBP and SBP at trough and in providing greater overall 24-h blood pressure-lowering efficacy.     

Nonpeptide angiotensin II receptor antagonists: a novel class of antihypertensive agents

The most direct approach to block the function of the renin-angiotensin system would be to antagonize angiotensin II (AII) at the level of its receptor. However, the AII receptor antagonists currently available, such as saralasin, are peptides which still retain agonistic activity and lack oral bioavailability. We have identified the N-benzylimidazoles, S-8307 and S-8308, as weak, but selective nonpeptide AII receptor antagonists. These initial leads were subsequently converted into more potent compounds, such as EXP6155, EXP6803 and EXP7711, while maintaining the selectivity. The compounds displace 3H-AII from its specific binding sites in adrenal cortical membranes and smooth muscle cells. They competitively inhibit the vasoconstrictor response to AII in various in vivo and in vitro preparations, but do not influence those to KCl, norepinephrine, and vasopressin. Converting enzyme and renin are not affected by these agents. In renal hypertensive rats and sodium-depleted dogs our compounds cause a sustained decrease in arterial pressure following intravenous and oral (EXP7711) administration, and are devoid of agonistic properties. Taken together, these nonpeptide structures are true competitive AII receptor antagonists and represent a new class of effective antihypertensive agents.     

Electrocardiographic left ventricular hypertrophy regression induced by an angiotensin receptor blocker-based regimen in hypertensive patients with the metabolic syndrome: data from the SARA Study

The authors assessed the effect of an angiotensin receptor blocker (candesartan)-based regimen on electrocardiographic left ventricular hypertrophy (ECG-LVH) in 276 patients with hypertension, including 141 with the metabolic syndrome (MS). Baseline blood pressure (BP) and ECG-LVH parameters did not differ in patients with and without MS. At the study's end, BP had decreased similarly in both groups. At baseline, 26.1% of patients with MS and 24.7% without MS exhibited ECG-LVH by Cornell product (CorP) criteria (P=NS); 26.8% and 17.2%, respectively, by Sokolow-Lyon product (SokP) (P=.01); 11.4%and 11.8% by Cornell voltage (CorV) (P=NS); and 12.4% and 6.5% by Sokolow-Lyon voltage (SokV) (P=.01). At the study's end, in the MS group, prevalence of ECG-LVH was reduced to 19.5% from 26.1% (P=.001), to 8.5% from 11.4% (P=.01), and to 24.4% from 26.8%(P=.03) by CorP, CorV, and SokP, respectively. In patients without MS, only the CorP criterion showed a significant decrease in ECG-LVH prevalence, declining to 20.5% (P=.01). The relative risk reduction of ECG-LVH was higher in patients with MS according to CorV and SokP criteria (P<.01).     

动态血压评价替米沙坦、氯沙坦治疗轻、中度高血压的临床疗效

目的　比较选择性血管紧张素Ⅱ受体拮抗剂替米沙坦、氯沙坦治疗轻、中度原发性高血压的疗效及安全性。方法　对 77例原发性高血压患者分成两组 ,分别予以替米沙坦 80mg,氯沙坦 5 0mg ,每日一次 ,6周后观察动态血压 (ABPM)评价降压效果。结果　替米沙坦和氯沙坦两组 2 4小时平均动态收缩压 (SBP)、舒张压 (DBP)均明显降低 ,替米沙坦 80mg的降压效果比氯沙坦 5 0mg更好 (P <0 .0 5 ) ,特别是在给药间期的最后 4～ 6小时 ,SBP/DBP替米沙坦降低了12 .3± 14 /7.2± 0 .9mmHg ,氯沙坦降低了 6.0± 1.6/3 .8± 0 .9mmHg(P <0 .0 5 )。结论　替米沙坦 80mg每日用药一次 ,可以保持正常的血压昼夜节律 ,提供 2 4小时血压控制的效果     

Beneficial effect of angiotensin II type 1 receptor blocker antihypertensive treatment on arterial stiffness: the role of smoking

The purpose of the present study was to assess angiotensin receptor blocker (ARB) treatment on arterial stiffness in select hypertensive patients and define possible differences between smokers and nonsmokers. The authors evaluated 81 consecutive, nondiabetic patients (mean age, 52 years; 47 men) with uncomplicated essential hypertension with high plasma renin activity who were administered monotherapy with irbesartan, an ARB, at maximal dose. Patients were divided into smokers (n=24) and nonsmokers (n=57). Carotid-radial pulse wave velocity (PWVc-r), carotid-femoral pulse wave velocity (PWVc-f), and augmentation index (AIx) were measured before and 6 months after ARB antihypertensive treatment. All mean values of elastic effect indices were decreased after irbesartan monotherapy (AIx, from 26.3%to 21.2% [P<.01;] PWVc-f, from 7.7 m/s to 7.3 m/s [P<.05], and PWVc-r, from 8.9 m/s to 8.3 m/s [P<.001]). When comparing smokers vs nonsmokers, no difference was noted in AIx and PWVc-f change (P=not significant), while PWVc-r change was greater in smokers compared with nonsmokers (P<.05). Chronic ARB treatment may favorably affect arterial stiffness and wave reflections in hypertensive chronic smokers with elevated plasma renin levels.     

Beneficial effects of angiotensin II type 1 receptor blocker antihypertensive treatment on inflammation indices: the effect of smoking

The effect of long-term angiotensin II type 1 receptor blocker (ARB) therapy on inflammation indices has not been fully investigated in a hypertensive population. The authors evaluated 323 consecutive nondiabetic patients (mean age, 57 years; 176 men; 92 smokers) with high renin activity and uncomplicated essential hypertension whose blood pressure levels normalized (from 163.9/100.7 mm Hg to 131.6/82.8 mm Hg) after 4 weeks of ARB or ARB/diuretic treatment. All patients underwent full laboratory evaluation (routine examination of blood and urine, liver, kidney, thyroid function, and lipid and glucose profiles), including measurement of high-sensitivity C-reactive protein and serum amyloid A levels, at drug-free baseline, which was repeated after 6 months of ARB or ARB/diuretic treatment. A significant (P<.001) overall decrease was noted in both high-sensitivity C-reactive protein (-0.41+/-1.56 mg/dL) and serum amyloid A (-0.62+/-2.03 mg/dL), but a smaller decrease in high-sensitivity C-reactive protein and serum amyloid A change was seen in the smoker subgroup compared with nonsmokers (P<.05), indicating that the ARB or ARB/diuretic anti-inflammatory effect may be adversely affected by smoking status.     

Comparative effectiveness of an angiotensin receptor blocker,olmesartan medoxomil,in older hypertensive patients

The efficacy and safety of olmesartan medoxomil (OM) vs active control (AC) monotherapy among elderly patients aged 60‐79 years (N = 4487) was evaluated by meta‐analysis (25 studies). In all patients, change from baseline to end point in blood pressure (BP) was significantly greater with OM vs AC (−19.5/−11.9 vs −16.8/−10.7 mm Hg). Greater proportions of OM‐ vs AC‐treated patients achieved BP goals. In patients with impaired renal function (estimated glomerular filtration rate <60 mL/min/1.73 m²), OM treatment resulted in a greater mean change from baseline in systolic BP vs AC (−21.2 vs −18.7 mm Hg, respectively) and a greater proportion of patients achieving BP goals. These parameters were similar in both groups for elderly patients with diabetes. OM was well tolerated with few adverse events. OM monotherapy can be used as an initial treatment for hypertension in elderly patients, including those with renal impairment or diabetes.     

The choice of antihypertensive drugs in patients with diabetes: angiotensin II and beyond

Affecting over 16 million individuals, diabetes mellitus is among the leading causes of mortality in the United States. Hypertension is a common finding among diabetic patients and increases their morbidity and mortality. Control of blood pressure in this population has been shown to improve outcomes. Recent randomized trials have proven the benefit of lower blood pressure goals in the treatment of hypertensive patients as compared with nondiabetic patients. Randomized controlled trials have also demonstrated that the selection of the antihypertensive agent used to treat hypertension in diabetic patients is as important as the reduction of blood pressure levels to the recommended levels. In this article, we first focus on the importance of the renin angiotensin system in the development of diabetic complications, and then we review the results of the recent studies that have had a major impact on the treatment of hypertension in diabetes.     

ABPM comparison of the antihypertensive profiles of the selective angiotensin II receptor antagonists telmisartan and losartan in patients with mild-to-moderate hypertension.

The antihypertensive efficacy and tolerability profiles of the selective AT1 receptor antagonists telmisartan and losartan were compared with placebo in a 6-week, multinational, multicentre, randomised, double-blind, double-dummy, parallel-group study of 223 patients with mild-to-moderate hypertension, defined as clinic diastolic blood pressure (DBP) >/=95 and /=140 and /=85 mm Hg. After a 4-week single-blind placebo run-in, eligible patients were randomised to receive telmisartan 40 mg, telmisartan 80 mg, losartan 50 mg, or placebo. Ambulatory blood pressure monitoring (ABPM) after 6 weeks of double-blind therapy showed that all active treatments produced significant (P < 0.01) reductions from baseline in 24-h mean SBP and DBP compared with placebo. During the 18-to-24 h period after dosing, the reductions in SBP/DBP with telmisartan 40 mg (10.7/6.8 mm Hg) and 80 mg (12.2/7. 1 mm Hg) were each significantly (P <0.05) greater than those observed for losartan 50 mg (6.0/3.7 mm Hg), and losartan was no better than placebo. Also for the 24-h mean blood pressure, telmisartan 40 mg and 80 mg were significantly (P< 0.05) better than losartan 50 mg. Compared with losartan, telmisartan 80 mg produced significantly (P < 0.05) greater reductions in both SBP and DBP during all monitored periods of the 24-h period, while telmisartan 40 mg produced significantly greater reductions in SBP and DBP in the night-time period (10.01 pm to 5.59 am) (P < 0.05) and in DBP in the morning period (6.00 am to 11.59 am) (P < 0.05). All treatments were comparably well tolerated. Telmisartan 40 mg and 80 mg once daily were effective and well tolerated in the treatment of mild-to-moderate hypertension, producing sustained 24-h blood pressure control which compared favourably with losartan.