Olmesartan medoxomil

Olmesartan medoxomil is a nonpeptide angiotensin II receptor antagonist which selectively and competitively inhibits the type 1 angiotensin II receptor without affecting other receptors regulating the cardiovascular system. In well designed randomised trials, olmesartan medoxomil was significantly more effective than placebo, and at dosages of 10 to 20 mg/day was at least as effective as atenolol 50 to 100 mg/day in reducing diastolic blood pressure (DBP). At dosages of 5 to 20 mg/day, olmesartan medoxomil was more effective than captopril 12.5 to 50mg twice daily at lowering seated DBP in patients with mild to moderate hypertension in a dose titration study. Reductions in seated DBP were greater with olmesartan medoxomil 10 to 20 mg/day than losartan 50 to 100 mg/day. Olmesartan medoxomil at 20 mg/day was more effective in lowering seated DBP than losartan 50 mg/day, valsartan 80 mg/day or irbesartan 150 mg/day, and was more efficacious than losartan 50 mg/day or valsartan 80 mg/day at reducing 24-hour ambulatory systolic blood pressure. Olmesartan medoxomil has shown no clinically important pharmacokinetic interactions with digoxin, warfarin or antacid (aluminium magnesium hydroxide). Adverse events were infrequent in clinical studies of olmesartan medoxomil and were similar to those attributed to placebo. With olmesartan medoxomil, the frequency of dizziness was higher than with placebo but similar to that occurring with losartan, valsartan and irbesartan.     

Olmesartan medoxomil: a review of its use in the management of hypertension

Olmesartan medoxomil (Olmetec, Benicar) is an angiotensin II type 1 (AT(1)) receptor antagonist (angiotensin receptor blocker [ARB]) that inhibits the actions of angiotensin II on the renin-angiotensin-aldosterone system, which plays a key role in the pathogenesis of hypertension. Oral olmesartan medoxomil 10-40 mg once daily is recommended for the treatment of adult patients with hypertension. In those with inadequate BP control using monotherapy, fixed-dose olmesartan medoxomil/hydrochlorothiazide (HCTZ) [Olmetec plus, Benicar-HCT] combination therapy may be initiated. Extensive clinical evidence from several large well designed trials and the clinical practice setting has confirmed the antihypertensive efficacy and good tolerability profile of oral olmesartan medoxomil, as monotherapy or in combination with HCTZ, in patients with hypertension, including elderly patients with isolated systolic hypertension (ISH). Notably, BP control is sustained throughout the 24-hour dosage interval, including during the last 4 hours of this period. In clinical trials, olmesartan medoxomil monotherapy provided better antihypertensive efficacy than losartan, candesartan cilexetil or irbesartan monotherapy, and was at least as effective as valsartan treatment, with a faster onset of action than other ARBs in terms of reductions from baseline in diastolic BP (DBP) and, in most instances, systolic BP (SBP). Combination therapy with olmesartan medoxomil plus HCTZ was superior to that with benazepril plus amlodipine, as effective as that with losartan plus HCTZ, noninferior to that with atenolol plus HCTZ, but less effective than that with telmisartan plus HCTZ, in individual trials. Data from ongoing clinical outcome trials are required to more fully determine the relative position of olmesartan medoxomil therapy in the management of hypertension. In the meantime, the consistent antihypertensive efficacy during the entire 24-hour dosage interval and good tolerability profile of olmesartan medoxomil, with or without HCTZ, make it a valuable option for the treatment of adult patients with hypertension, including the elderly.     

Azilsartan medoxomil: a review of its use in hypertension

Azilsartan medoxomil (Edarbi?; Ipreziv?) is an orally administered angiotensin II receptor type 1 antagonist (blocker) used in the treatment of adults with essential hypertension. This article reviews data on the clinical efficacy and tolerability of azilsartan medoxomil in adults with essential hypertension and provides a summary of its pharmacological properties. Azilsartan medoxomil is a prodrug that undergoes rapid hydrolysis in the gastrointestinal tract after oral administration to the bioactive moiety azilsartan, before systemic absorption. Azilsartan medoxomil produces antihypertensive effects by selectively blocking the binding of angiotensin II to the angiotensin type 1 (AT(1)) receptor, thereby antagonizing the pressor response activity of angiotensin II. In vitro, azilsartan produced greater and more sustained AT(1) receptor binding/blockade activity than several comparator angiotensin II receptor antagonists. Azilsartan medoxomil reduces blood pressure (BP) in hypertensive adults. In addition, the drug has been shown to have pleiotropic effects (i.e. effects beyond AT(1) receptor blockade). In adults with essential hypertension, azilsartan medoxomil 20, 40 or 80?mg effectively reduced BP over a 24-hour period with once-daily administration in three major, randomized, controlled trials in which the primary endpoints were changes from baseline in 24-hour mean systolic BP (SBP) at week 6 (two trials) or week 24, assessed by ambulatory BP monitoring (ABPM). In the two 6-week trials, azilsartan medoxomil showed dose-dependent efficacy over all evaluated dosages and was more effective than placebo in lowering SBP. At the maximum approved dosage of 80?mg once daily, azilsartan medoxomil was significantly more effective than maximum dosages of olmesartan medoxomil (40?mg once daily) or valsartan (320?mg once daily), based on primary endpoint assessments. Mean reductions in clinic measurements of SBP and diastolic BP (DBP) measurements were also generally greater with azilsartan medoxomil 80?mg once daily than with the comparator drugs in these 6-week studies. Over a longer treatment period of 24 weeks, azilsartan medoxomil showed sustained BP-lowering efficacy, with the reduction in 24-hour mean SBP at week 24 significantly greater with azilsartan medoxomil 40 or 80?mg once daily than with valsartan 320?mg once daily. Mean reductions from baseline in mean clinic SBP and DBP as well as DBP by ABPM were also significantly greater with azilsartan medoxomil 40 or 80?mg once daily than with valsartan. Azilsartan medoxomil was generally well tolerated, with a tolerability profile similar to that of placebo in the 6-week trials. Across the three major trials, headache and dizziness were among the most common adverse events. Overall, rates of treatment discontinuation as a result of adverse events were low in the 6-week and 24-week trials. In conclusion, once-daily azilsartan medoxomil effectively lowers BP in adults with essential hypertension and has shown better antihypertensive efficacy than maximum therapeutic dosages of olmesartan medoxomil or valsartan in major trials of up to 24 weeks' duration. Azilsartan medoxomil is generally well tolerated and the low rates of discontinuation due to adverse events suggest that patients are likely to persist with long-term treatment. Azilsartan medoxomil is therefore a useful and attractive new option for lowering BP in patients with essential hypertension, particularly for those not able to tolerate other antihypertensive drugs. Further studies are required to evaluate the effects of azilsartan medoxomil on cardiovascular morbidity and mortality.     

Olmesartan medoxomil/amlodipine/hydrochlorothiazide: fixed-dose combination in hypertension

The antihypertensive agents olmesartan medoxomil, amlodipine and hydrochlorothiazide (HCTZ) are now available as a fixed-dose combination tablet (olmesartan medoxomil/amlodipine/HCTZ). In a 12-week, randomized, double-blind, multicentre trial (TRINITY) in adults with moderate to severe hypertension, olmesartan medoxomil?+?amlodipine?+?HCTZ triple combination therapy produced significantly greater least squares mean reductions from baseline in seated diastolic blood pressure (BP) [primary endpoint] and seated systolic BP than olmesartan medoxomil/amlodipine, olmesartan medoxomil/HCTZ or amlodipine?+?HCTZ. Furthermore, significantly more patients achieved BP goals and targets with the triple combination regimen than with any of the dual combination regimens at week 12, with olmesartan medoxomil?+?amlodipine?+?HCTZ also demonstrating benefit over the dual regimens in terms of ambulatory BP control. According to subgroup analyses of the TRINITY trial, olmesartan medoxomil?+?amlodipine?+?HCTZ was more effective in reducing BP and achieving BP goals than each of the dual therapies, irrespective of hypertension severity, age, sex, race or diabetes mellitus status. Data from a number of smaller clinical studies indicated that olmesartan medoxomil?+?amlodipine?+?HCTZ triple combination therapy provides antihypertensive efficacy in patients whose BP is not adequately controlled with olmesartan medoxomil?+?amlodipine. Olmesartan medoxomil?+?amlodipine?+?HCTZ was generally well tolerated in the TRINITY study, with adverse events usually being mild or moderate in severity.     

Clinical and experimental aspects of olmesartan medoxomil, a new angiotensin II receptor antagonist

Olmesartan medoxomil is a new orally active angiotensin II (Ang II) type 1 receptor antagonist. It is a prodrug and is rapidly de-esterified during absorption to form olmesartan, the active metabolite. Olmesartan is a potent, competitive and selective Ang II type 1 receptor antagonist. Olmesartan is not metabolized by the cytochrome P-450 and has a dual route of elimination, by kidneys and liver. In patients with essential hypertension olmesartan medoxomil administered once daily at doses of 10-80 mg dose-dependently reduced diastolic blood pressure (DBP). Troughto-peak ratios for both DBP and systolic blood pressure (SBP) were above 50%. At the recommended once-daily starting doses, olmesartan medoxomil (20 mg) was more effective than losartan (50 mg), valsartan (80 mg) or irbesartan (150 mg) in reducing cuff DBP in patients with essential hypertension. The results of cuff SBP and mean 24-h DBP and SBP were similar to those of cuff DBP measurement. In mild-to-moderate hypertensive patients the recommended starting dose of olmesartan medoxomil was as effective as that of amlodipine besylate (5 mg/day) in reducing both cuff and 24-h blood pressure. In lowering DBP olmesartan medoxomil, at 10-20 mg/day, was as effective as atenolol at 50-100 mg/day. In mild-to-moderate hypertensive patients, olmesartan medoxomil, at 5-20 mg once daily, was more effective than captopril at 12.5-50 mg twice daily. At 20-40 mg once daily olmesartan medoxomil was as effective as felodipine, at 5-10 mg once daily. Olmesartan medoxomil has minimal adverse effects with no clinically important drug interactions. Animal studies have shown that olmesartan medoxomil provides a wide range of organ protection. Olmesartan medoxomil ameliorated atherosclerosis in hyperlipidemic animals and ameliorated cardiac remodeling and improved survival in rats with myocardial infarction. Olmesartan medoxomil has renoprotective effects in a remnant kidney model and type 2 diabetes models. Future investigation should reveal whether these beneficial effects of olmesartan medoxomil are applicable to human diseases.     

奥美沙坦酯与缬沙坦治疗中度原发性高血压临床研究

目的比较奥美沙坦酯和缬沙坦治疗中度原发性高血压的疗效和安全性。方法入选482例中度原发性高血压患者,按照1∶1随机分组,分别接受奥美沙坦酯20～40 mg/d或缬沙坦80～160 mg/d治疗,共8周。观察并比较其降压效果。结果治疗4周后,奥美沙坦酯组SeDBP平均下降了(10.58±6.82)mmHg,缬沙坦组下降了(9.38±7.16)mmHg;两组比较,P=0.004。奥美沙坦组与缬沙坦组分别有60%、61.74%的患者剂量加倍,加量有效率分别为52.22%、51.85%;治疗8周后,两组SeDBP平均下降(15.72±6.03)mmHg及(14.12±6.79)mmHg;治疗4周后,两组的药物不良反应发生率分别为3.33%、7.5%(P>0.05)。结论口服奥美沙坦酯胶囊20～40 mg/d,1次/d,能保持24 h平稳降压,8周总有效率为79.65%;与缬沙坦80～160 mg/d的降压疗效相近。而两组药物不良反应发生率差异无统计学意义。     

Use of 24-Hour Ambulatory Blood Pressure Monitoring to Assess Antihypertensive Efficacy

INTRODUCTION: Goal rates, the percentage of patients with hypertension achieving recommended SBP/DBP, are a clinically important assessment of an antihypertensive agent's efficacy. Twenty-four-hour ambulatory blood pressure monitoring (ABPM) allows accurate assessment of a patient's hypertension and risk for cardiovascular events, and provides the most accurate measure of an antihypertensive agent's efficacy throughout a 24-hour dosing interval. METHODS: A 12-week (4-week single-blind placebo run-in phase followed by an 8-week double-blind active treatment phase) randomized, parallel-group study reported that the recommended starting dose of the angiotensin II receptor antagonist (angiotensin receptor blocker; ARB) olmesartan medoxomil (Benicar(trade mark)) 20 mg/day was more effective than starting doses of losartan potassium (Cozaar) 50 mg/day, valsartan (Diovan) 80 mg/day, or irbesartan (Avapro) 150 mg/day in reducing cuff DBP in patients with essential hypertension. The present report includes analyses of secondary efficacy variables from this 12-week trial. RESULTS: The mean reduction in blood pressure from baseline to week 8 (end of treatment) was significantly greater with olmesartan medoxomil than with valsartan for all ABPM times analyzed (24 hours, daytime, night-time, and last 2 and 4 hours of monitoring). Statistical significance was reached for comparisons of olmesartan medoxomil with losartan potassium for a majority of times analyzed and with irbesartan for SBP in the last 4 hours of monitoring. Goal rates for accepted critical ambulatory blood pressure (ABP) values of <130/80 mm Hg for mean 24-hour ABP, <135/85 mm Hg for mean daytime ABP, and <120/75 mm Hg for mean night-time ABP were significantly greater for patients receiving olmesartan medoxomil than for those receiving losartan potassium or valsartan. Goal rates were numerically superior, but not statistically significant, to those achieved with irbesartan. Compared with losartan potassium or valsartan recipients, a significantly higher percentage of patients treated with olmesartan medoxomil achieved the 24-hour ABP goal of <130/85 mm Hg. The last 2 and 4 hours of ABPM indicated that olmesartan medoxomil maintained larger mean decreases in blood pressure through the morning surge. DISCUSSION/CONCLUSION: ABP goal rates are a meaningful measure of antihypertensive efficacy. The effects on mean change from baseline in ABP and ABP goal rates after 8 weeks of treatment were numerically better, but not statistically significant, for olmesartan medoxomil than for irbesartan. However, olmesartan medoxomil was significantly more effective than losartan potassium or valsartan.     

Antihypertensive, insulin-sensitising and renoprotective effects of a novel, potent and long-acting angiotensin II type 1 receptor blocker, azilsartan medoxomil, in rat and dog models

The pharmacological profile of a novel angiotensin II type 1 receptor blocker, azilsartan medoxomil, was compared with that of the potent angiotensin II receptor blocker olmesartan medoxomil. Azilsartan, the active metabolite of azilsartan medoxomil, inhibited the binding of [(125)I]-Sar(1)-I1e(8)-angiotensin II to angiotensin II type 1 receptors. Azilsartan medoxomil inhibited angiotensin II-induced pressor responses in rats, and its inhibitory effects lasted 24h after oral administration. The inhibitory effects of olmesartan medoxomil disappeared within 24h. ID(50) values were 0.12 and 0.55 mg/kg for azilsartan medoxomil and olmesartan medoxomil, respectively. In conscious spontaneously hypertensive rats (SHRs), oral administration of 0.1-1mg/kg azilsartan medoxomil significantly reduced blood pressure at all doses even 24h after dosing. Oral administration of 0.1-3mg/kg olmesartan medoxomil also reduced blood pressure; however, only the two highest doses significantly reduced blood pressure 24h after dosing. ED(25) values were 0.41 and 1.3mg/kg for azilsartan medoxomil and olmesartan medoxomil, respectively. In renal hypertensive dogs, oral administration of 0.1-1mg/kg azilsartan medoxomil reduced blood pressure more potently and persistently than that of 0.3-3mg/kg olmesartan medoxomil. In a 2-week study in SHRs, azilsartan medoxomil showed more stable antihypertensive effects than olmesartan medoxomil and improved the glucose infusion rate, an indicator of insulin sensitivity, more potently (≥ 10 times) than olmesartan medoxomil. Azilsartan medoxomil also exerted more potent antiproteinuric effects than olmesartan medoxomil in Wistar fatty rats. These results suggest that azilsartan medoxomil is a potent angiotensin II receptor blocker that has an attractive pharmacological profile as an antihypertensive agent.     

Dose-Response Characteristics of Olmesartan Medoxomil and Other Angiotensin Receptor Antagonists

Angiotensin receptor antagonists (angiotensin receptor blockers; ARBs) are an effective initial antihypertensive monotherapy in many patients. However, when initial ARB monotherapy fails to achieve the recommended BP goal, there is some controversy as to whether dose uptitration or the addition of a diuretic is more appropriate. This article addresses this issue by reviewing the dose-response characteristics of olmesartan medoxomil and other ARBs, as well as the relationship between ARB uptitration and BP goal attainment. Two types of trial designs are used to assess dose response: dose-ranging studies (usually a parallel design using different doses across different patient groups), which are used to establish the optimal dose for US FDA registration purposes, and dose-titration studies (increased dosing within the same patients and treating to goal BP). Since dose titration is within the same patient, it may be considered more appropriate for demonstrating dose-response characteristics and demonstration of BP goal attainment. While results from dose-ranging studies suggest that the dose-response curve for some ARBs may be flat, dose-titration studies indicate that significant improvements in BP control and BP goal attainment can be achieved with ARB uptitration. In an integrated analysis of seven US and European randomized, placebo-controlled, dose-ranging trials involving 3055 patients with stage 2 hypertension treated with olmesartan medoxomil 2.5-80 mg/day or placebo for 8 weeks, all olmesartan medoxomil doses were significantly more effective than placebo in lowering the mean DBP and mean SBP (p相似文献   

Pharmacological profiles and clinical effects of olmesartan medoxomil, a novel angiotensin II receptor blocker

Olmesartan medoxomil is a new angiotensin II receptor blocker (ARB) indicated for the treatment of hypertension. Olmesartan medoxomil is a pro-drug that is converted to the active metabolite olmesartan. Olmesartan does not undergo further metabolism and does not interact with cytochrome P450 enzymes. Olmesartan is a potent ARB with high selectivity for the type 1 (AT(1)) receptor subtype and shows insurmountable antagonism against the AT(1) receptor in vascular tissues. This antagonistic mode, which could be attributed to tight binding of this drug to the receptor, would underlie the potent and persistent action of olmesartan medoxomil in vivo. In fact, oral administration of olmesartan medoxomil produces a potent and long-lasting antihypertensive action without inducing tachycardia. The preventive effects of olmesartan medoxomil on end-organ damage in the kidney, heart, and blood vessels have been demonstrated in various animal models. In clinical studies, olmesartan medoxomil is shown to be well tolerated and have an excellent safety profile that is comparable to that of placebo. Head-to-head comparisons with other ARBs (losartan, valsartan, irbesartan, and candesartan cilexetil) conducted in the United States and Europe have revealed that olmesartan medoxomil is superior to these other ARBs in lowering blood pressure. These facts suggest that olmesartan medoxomil would be beneficial for the treatment of hypertension and other end-organ diseases.     

Valsartan: in children and adolescents with hypertension

Valsartan is an oral angiotensin II subtype 1 receptor antagonist with well established antihypertensive efficacy in adults. It is now approved in the EU and the US for the treatment of hypertension in children and adolescents. In two, randomized, double-blind trials, a once-daily regimen of valsartan reduced the blood pressure (BP) of children and adolescents with hypertension. In one trial in hypertensive children and adolescents aged 6-16 years, significant dose-dependent reductions from baseline in mean sitting systolic BP (msSBP) were observed for recipients of valsartan following 2 weeks' treatment (primary endpoint). There were corresponding dose-dependent and significant reductions in mean sitting diastolic BP. Following 2 further weeks of treatment, the reduction in msSBP was maintained in patients who were re-randomized to continue receiving the same dosage of valsartan but not in those re-randomized to placebo. In the other trial in hypertensive children and adolescents aged 6-17 years, valsartan was no less effective than enalapril in reducing BP. Following 12 weeks' treatment, the least square mean reduction from baseline in msSBP (primary endpoint) in recipients of valsartan was noninferior to that in recipients of enalapril. In addition, the proportion of patients achieving an msSBP <95th percentile for age, sex, and height at week 12 was not significantly different between recipients of valsartan and enalapril (67% vs 70%). Treatment with valsartan for up to 52 weeks was well tolerated in children and adolescents with hypertension.     

Evaluation of olmesartan medoxomil in the rat monocrotaline model of pulmonary hypertension

It is suggested that angiotensin II is involved in the pathogenesis of pulmonary hypertension and subsequent right ventricular hypertrophy; therefore, an angiotensin AT1 receptor antagonist could be beneficial for the treatment of this disease. We tested the effect of the new AT1 receptor antagonist olmesartan medoxomil on monocrotaline-induced pulmonary hypertension in rats. At 3 weeks after a single subcutaneous injection of monocrotaline (50 mg/kg), the lung/body weight ratio, the right ventricle/(left ventricle plus septum) weight ratio [RV/(LV+S)], and right ventricular systolic pressure were increased, indicating establishment of pulmonary hypertension and right ventricular hypertrophy. Oral administration of olmesartan medoxomil (2 or 5 mg/kg/day for 3 weeks) restored RV/(LV+S) and right ventricular systolic pressure, and a higher dose (5 mg/kg/day) improved the lung/body weight ratio. Pulmonary arteries isolated from monocrotaline-treated rats exhibited an increase in basal tone in the resting state, indicating that they had intrinsic tone. Three weeks of treatment with olmesartan decreased this intrinsic tone. These data suggest that long-term treatment with olmesartan has beneficial effects on monocrotaline-induced pulmonary hypertension and subsequent right ventricular hypertrophy.     

Population pharmacokinetics of olmesartan following oral administration of its prodrug, olmesartan medoxomil: in healthy volunteers and hypertensive patients

BACKGROUND: Olmesartan medoxomil (CS-866) is a new orally active angiotensin II receptor antagonist that is highly selective for the AT1 receptor subtype. OBJECTIVE: To develop a population pharmacokinetic model for olmesartan (RNH-6270), the active metabolite of olmesartan medoxomil, in healthy volunteers and hypertensive patients, and to evaluate effects of covariates on the apparent oral clearance (CL/F), with particular emphasis on the effect of race. DESIGN: Retrospective analysis of data from 12 phase I-III trials in the US, Europe and Japan. PARTICIPANTS: Eighty-nine healthy volunteers and 383 hypertensive patients. METHODS: Nonlinear mixed-effects modelling was used to evaluate 7911 olmesartan plasma sample concentrations. The covariates included age, bodyweight, sex, race (Westerners [including Caucasians and Hispanics] versus Japanese), patient status (hypertensive patients versus healthy volunteers), serum creatinine level as an index of renal function and serum chemistry data as indices of hepatic function. RESULTS: The pharmacokinetic data of olmesartan were well described by a two-compartment linear model with first-order absorption and an absorption lag-time, parameterised in terms of CL/F (6.66 L/h for a typical male Western hypertensive patient), absorption rate constant (1.46h-1), elimination rate constant (0.193h-1), rate constant from the central to peripheral compartment (0.061h-1), rate constant from the peripheral to central compartment (0.079h-1) and absorption lag-time (0.427h). Analysis of covariates showed that age, bodyweight, sex, patient status and renal function were factors influencing the clearance of olmesartan. CONCLUSION: The population pharmacokinetic analysis of olmesartan showed that: (i) severe renal impairment (serum creatinine >265 micromol/L [approximately 3 mg/dL]) could cause a clearance decrease of > or =30%; (ii) older age, lower bodyweight and being female were determinants of lower clearance but their effects on olmesartan clearance were within 20%; (iii) no statistically significant difference in clearance was found between Westerners and Japanese.     

Efficacy and Safety of Olmesartan Medoxomil and Hydrochlorothiazide Compared with Benazepril and Amlodipine Besylate

BACKGROUND: Most patients with stage 2 hypertension require two or more antihypertensive agents in order to achieve the BP goals recommended in current treatment guidelines. Accordingly, combinations of two drugs with different mechanisms of antihypertensive action are widely used. OBJECTIVE: The aim of this randomized, double-blind, multicenter 12-week study was to compare the efficacy, safety, and tolerability of a combination of olmesartan medoxomil/hydrochlorothiazide (HCTZ) with that of benazepril plus amlodipine besylate in patients with stage 2 hypertension. METHODS: Patients were eligible for randomization following a 3- to 4-week placebo run-in period if they had either (i) mean seated DBP>or=90 mm Hg but<115 mm Hg and mean seated SBP>or=160 mm Hg but <200 mm Hg, or (ii) mean seated DBP>or=100 mm Hg but<115 mm Hg. The difference in mean seated SBP measured on two separate visits during the run-in period was required to beor=95 mm Hg and<115 mm Hg or SBP>145 mm Hg and相似文献   

奥美沙坦酯治疗老年高血压的疗效及安全性观察

目的：评价奥美沙坦酯治疗老年高血压的疗效和安全性。方法：选取2009年1-8月我院42例老年高血压患者,随机分为两组。治疗组（21例）服用奥美沙坦酯每次20mg,每日1次;对照组（21例）服用氯沙坦每次50mg,每日1次。总疗程均为8周。结果：奥美沙坦酯组和氯沙坦组治疗前后血压下降幅度差异均有统计学意义（P〈0.01）。奥美沙坦酯组和氯沙坦组降压显效率分别为69.0%和68.4%,总有效率分别为90.4%和89.7%,两组间差异无统计学意义（P〉0.05）。奥美沙坦酯组和氯沙坦组均未出现药品不良反应。结论：奥美沙坦酯治疗老年高血压效果明显,安全性好。     

Olmesartan medoxomil-based therapy for the management of hypertension

Contemporary practice guidelines for hypertension recommend a goal systolic/diastolic blood pressure (BP) of less than 140/90 mmHg for patients with hypertension and less than 130/80 mmHg for patients with diabetes mellitus or chronic kidney disease. Current guidelines recognize that most patients will require combination therapy to achieve these BP goals and recommend that the agents used in such therapy should have complementary mechanisms of action. Olmesartan medoxomil is an angiotensin receptor blocker approved for the treatment of hypertension as monotherapy or in combination with antihypertensive agents. It is also approved in a fixed-dose combination with hydrochlorothiazide or amlodipine. Olmesartan medoxomil-based therapy can manage hypertension across a range of patient types and has demonstrated good BP-lowering efficacy and goal attainment in individuals with stage 1 or stage 2 hypertension. The comparative antihypertensive efficacy and safety of olmesartan medoxomil, as monotherapy and as part of combination therapy, has been established in several large, randomized clinical trials. This review evaluates the chemistry, efficacy and safety of olmesartan medoxomil-based therapy and its expanding role in hypertension management.     

Irbesartan: a review of its use in hypertension and in the management of diabetic nephropathy

Irbesartan (Avapro, Aprovel) is a potent and selective angiotensin II subtype 1 receptor antagonist indicated for use in patients with hypertension, including those with type 2 diabetes mellitus and nephropathy. Once-daily administration of irbesartan provided 24-hour control of blood pressure (BP). In patients with mild-to-moderate hypertension irbesartan was as effective as enalapril, atenolol and amlodipine, and more effective than valsartan in terms of absolute reduction in BP and response rates. Irbesartan produced a greater reduction in diastolic BP at trough than once-daily losartan, but had a smaller effect than olmesartan; the reduction in systolic BP achieved with irbesartan was similar or greater than that with losartan and similar to that seen with olmesartan. The combination of irbesartan with hydrochlorothiazide produced additive effects on BP reduction. Irbesartan also induced regression of left ventricular mass in patients with hypertension and left ventricular hypertrophy. In two large studies (IRbesartan MicroAlbuminuria type 2 diabetes mellitus in hypertensive patients [IRMA 2] and the Irbesartan Diabetic Nephropathy Trial [IDNT]) irbesartan exerted a renoprotective effect in hypertensive patients with type 2 diabetes at both the early and later stages of diabetic nephropathy. The renoprotective effect was at least partly independent of the BP-lowering effect. In the IRMA 2 trial, the proportion of patients progressing to overt nephropathy was significantly lower for recipients of irbesartan 300mg once daily than placebo. In patients with overt nephropathy in the IDNT, irbesartan 300mg once daily provided significantly greater renoprotection than amlodipine 10mg once daily or placebo. The relative risk of doubling of serum creatinine was significantly lower with irbesartan than amlodipine or placebo. Irbesartan is well tolerated in hypertensive patients, including those with type 2 diabetes and incipient or overt nephropathy. The overall incidence of adverse events with irbesartan was similar to that with placebo. Irbesartan was associated with a lower incidence of cough than enalapril and was not associated with ankle oedema or with any clinically significant drug interactions. In conclusion, irbesartan is a well tolerated and effective antihypertensive agent. It also slows the progression of renal disease in hypertensive patients with type 2 diabetes at both the early and later stages of diabetic nephropathy. Thus, irbesartan is a valuable agent in the management of patients with these indications.     

A review of the structural and functional features of olmesartan medoxomil, an angiotensin receptor blocker

The angiotensin II (A-II) type 1 (AT1) receptor-mediated effects of A-II play a key role in the pathophysiology of hypertension. Effective inhibition of A-II is provided by the latest class of antihypertensive medications, the AT1 receptor blockers (ARBs). These orally available agents were developed around a common imidazole-based structural core. The most recent member of this drug class to be approved by the Food and Drug Administration, olmesartan medoxomil, contains unique features that may explain its clinical efficacy. Key structural elements of olmesartan medoxomil include a hydroxyalkyl substituent at the imidazole 4-position and a hydrolyzable ester group at the imidazole 5-position. Inter- and intramolecular hydrogen bonding involving these groups may contribute to the potentiation of antagonist activity. After oral administration, olmesartan medoxomil is deesterified in the intestinal tract to produce the active metabolite olmesartan, which undergoes no additional metabolic change. The marked antihypertensive efficacy of olmesartan medoxomil may result from a unique pharmacological interaction of the drug with the AT1 receptor, resulting in a potent, long-lasting, dose-dependent blockade of A-II. This review article characterizes the structural features of olmesartan that may be responsible for its clinical efficacy. Inferential pharmacological studies compare and contrast the effects of olmesartan to those of other ARBs in comparable preclinical animal models.     

Combination therapy for hypertension: focus on high-dose olmesartan medoxomil (40 mg) plus hydrochlorothiazide

Importance of the field: Cardiovascular disease is a major cause of premature death and disability worldwide, and effective blood pressure (BP) control is crucial for the reduction of cardiovascular risk in patients with hypertension. Despite this, many will fail to attain recommended BP goals. A reappraisal of European guidelines led to revised recommendations for BP reduction to values within the SBP/DBP range of 130 – 139/80 – 85 mmHg in all patients with hypertension, including higher-risk groups such as those with diabetes.

Areas covered in this review: The majority of hypertensive patients will require the enhanced blood-pressure-lowering effects of at least two antihypertensive drugs with complementary mechanisms of action to achieve these goals.

What the reader will gain: The angiotensin II receptor blocker (ARB) olmesartan medoxomil and the thiazide diuretic hydrochlorothiazide (HCTZ) provide greater antihypertensive efficacy when used in combination than as monotherapy with either component, with a similar tolerability profile. In addition, there is evidence that higher doses of olmesartan may prolong the antihypertensive effect of this ARB, and a number of US ‘treat-to-target’ and European add-on clinical trials have been conducted to assess the efficacy and safety of high-dose olmesartan plus HCTZ in a wide range of patients with mild-to-severe hypertension.

Take home message: Combination therapy with olmesartan, including the high 40-mg dose, plus HCTZ is an effective and safe treatment option for controlling BP in patients with mild-to-severe hypertension, particularly those who fail to achieve recommended BP goals with monotherapy.