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.     

A Review of the Efficacy of Fixed-Dose Combinations Olmesartan Medoxomil/ Hydrochlorothiazide and Amlodipine Besylate/ Benazepril in Factorial Design Studies

In order to adequately control hypertension, the majority of patients will require treatment with more than one antihypertensive agent. Fixed-dose combination therapy offers several advantages, including improved efficacy, tolerability, and treatment compliance. Certain combinations have benefits in specific patient populations, such as the elderly or those with comorbidities. In this review, we evaluate the BP-lowering efficacy of olmesartan medoxomil/hydrochlorothiazide (HCTZ) and amlodipine besylate/benazepril in similarly designed, randomized, placebo-controlled studies in similar patient populations. This indirect comparison showed that both combinations significantly improve both systolic and diastolic BP compared with monotherapy with the individual agents or placebo; it also demonstrated that the combinations were well tolerated. Both combination therapies significantly improved response rates, but olmesartan medoxomil/HCTZ achieved the highest control rates compared with the individual agents. On the basis of an indirect comparison of published factorial design studies, olmesartan medoxomil/HCTZ appears to be at least as effective as amlodipine besylate/benazepril and may provide quantitatively greater reductions in diastolic BP at commonly used dosages. A randomized clinical trial comparing the two combinations is needed to confirm these findings.     

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.     

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.     

Telmisartan/Hydrochlorothiazide: a review of its use as fixed-dose combinations in essential hypertension

Fixed-dose combinations of telmisartan and hydrochlorothiazide (HCTZ) [Micardis Plus((R)), Micardis((R)) HCT, PritorPlus((R))] are available in many countries for the treatment of patients with essential hypertension. Combining the angiotensin II receptor antagonist (angiotensin II receptor blocker [ARB]) telmisartan with the thiazide diuretic HCTZ provides antihypertensive therapy with complementary mechanisms of action. In the US and EU, telmisartan/HCTZ is approved for patients whose hypertension is not adequately controlled with telmisartan monotherapy; US labelling for the fixed-dose combination also includes inadequate control of blood pressure (BP) with HCTZ monotherapy.The antihypertensive efficacy of once-daily telmisartan/HCTZ has been demonstrated in several large, randomized trials in patients with stages 1 and 2 hypertension. The addition of HCTZ to telmisartan achieved significant reductions in BP in nonresponders to telmisartan monotherapy, and the antihypertensive efficacy of telmisartan/HCTZ was similar to or significantly greater than that of various comparator agents. Moreover, in studies that used ambulatory BP monitoring, telmisartan/HCTZ provided consistent 24-hour BP reductions throughout morning, daytime and night-time periods. The BP-lowering efficacy over the entire 24-hour dose administration interval is consistent with the pharmacokinetic profile of telmisartan, which has the longest elimination half-life among currently available ARBs and a unique chemical structure. Adverse events with telmisartan/HCTZ in clinical trials were typically mild and transient, and no unexpected events occurred that had not been previously reported with either telmisartan or HCTZ. Extensive tolerability data are available for telmisartan, in particular from the ONTARGET study, the largest clinical outcomes trial with an ARB. As such, fixed-dose combinations of telmisartan/HCTZ provide an effective, rational and generally well tolerated treatment option for the management of patients with hypertension.     

Combination delapril/manidipine as antihypertensive therapy in high-risk patients

The majority of patients with hypertension, and in particular high-risk patients or those with diabetes mellitus or renal dysfunction, are likely to require combination therapy with at least two antihypertensive agents (from different classes) to achieve their blood pressure (BP) target. The delapril/manidipine fixed-dose combination consists of two antihypertensive agents with different, yet complementary, mechanisms of action. Delapril/manidipine has demonstrated short- and long-term antihypertensive efficacy in a number of clinical studies in patients with hypertension with an inadequate response to monotherapy. Comparative studies have demonstrated that delapril/manidipine is as effective as enalapril/hydrochlorothiazide (HCTZ) in patients with hypertension with an inadequate response to monotherapy, and as effective as irbesartan/HCTZ, losartan/HCTZ, olmesartan medoxomil/HCTZ, ramipril/HCTZ and valsartan/HCTZ in reducing BP in patients with hypertension and diabetes, or in obese patients with hypertension. Therapy with delapril/manidipine also appears to exert beneficial effects that extend beyond a reduction in BP, including nephroprotective activity and an improvement in fibrinolytic balance, supporting its value as a treatment option in these patient populations at high or very high cardiovascular risk because of the presence of organ damage, diabetes or renal disease.     

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   

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.     

Telmisartan/hydrochlorothiazide: in the treatment of essential hypertension

Oral telmisartan/hydrochlorothiazide (HCTZ) combines two antihypertensive agents, a selective angiotensin II receptor antagonist with a long half-life and once-daily administration, and a thiazide diuretic. In two large, 8-week, double-blind trials, patients with hypertension unresponsive to monotherapy who received combined telmisartan/HCTZ 80/12.5 or 40/12.5 mg/day, achieved significantly larger reductions in diastolic and systolic blood pressure (BP), than recipients of continued telmisartan monotherapy (p < 0.05 for all). Compliance with telmisartan/HCTZ 80/12.5 mg/day was 98.9%. In patients with hypertension, telmisartan/HCTZ resulted in similar BP reductions to oral enalapril/HCTZ and atenolol/HCTZ in 26-week double-blind trials and greater reductions than oral losartan/HCTZ 50/12.5 mg/day in a 6-week randomised open-label trial (p < 0.001). Up to one-third of patients with hypertension initially responsive to telmisartan 40 or 80 mg/day in a 4-year study required the eventual addition of HCTZ 12.5 or 25 mg/day and/or another agent to maintain BP control. BP was controlled in about 75% of these by adding only HCTZ. In clinical trials of up to 4 years, including elderly patients, telmisartan/HCTZ had similar tolerability to placebo, with few reports of hypokalaemia. Most adverse events were mild to moderate.     

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.     

Comparison of angiotensin II type 1 receptor antagonists in the treatment of essential hypertension

Hypertension is a major health problem worldwide, yet remains under-diagnosed and under-treated. Angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) are highly effective at reducing blood pressure (BP), exhibit renoprotective properties and have placebo-like tolerability. However, it is unclear whether there are clinical differences in efficacy and tolerability between the available ARBs. A review of published, randomized, comparative clinical trials suggests that differences in BP-lowering efficacy and 24-hour BP control may exist between ARBs, although it appears that there is no evidence for important differences in tolerability between ARBs. Few studies have assessed attainment rates for important combined systolic BP (SBP)/diastolic BP (DBP) goals recommended in treatment guidelines. Likewise, few studies have directly compared more than two agents or ARB/hydrochlorothiazide fixed-dose combinations, and most ARBs have not been compared across their full recommended dosage ranges. Overall, there is insufficient weight of evidence to allow definitive conclusions to be drawn regarding the comparative efficacy of the available ARBs. However, newer ARBs (e.g. olmesartan medoxomil and telmisartan) appear to be more effective than older ARBs (e.g. losartan and valsartan) in reducing DBP and/or SBP in some trials. In addition, olmesartan medoxomil treatment regimens resulted in high BP control rates in several trials, but head-to-head trials with other ARBs are required to put these control rates into perspective, especially for SBP control with various agents. The purpose of this review is to present published data from ARB efficacy trials for a comparison of various efficacy parameters among the agents within this drug class.     

Zofenopril plus hydrochlorothiazide: Combination therapy for the treatment of mild to moderate hypertension

Achieving target blood pressure (BP) levels in clinical practice is one of the main challenges for physicians in the management of patients with hypertension. It is now recognised that the majority of patients will require at least two antihypertensive drugs to achieve optimal BP control; the use of combination therapy as first-line treatment is also increasing as BP goals of antihypertensive therapy become more ambitious. The fixed combination of zofenopril/hydrochlorothiazide (HCTZ) 30/12.5 mg/day is approved in Italy, France, Switzerland and Greece for the management of mild to moderate hypertension. In clinical trials comparing zofenopril/HCTZ with each agent administered as monotherapy, combination therapy was more effective in normalising BP. This effect was particularly evident in one trial in which patients who were nonresponsive to zofenopril monotherapy were studied. In addition, in clinical trials to date, combination therapy provided sustained and consistent BP control over the entire 24-hour dose interval. Despite the greater efficacy of zofenopril/HCTZ 30/12.5 mg/day, when directly compared with each agent administered as monotherapy, there were no significant differences in the nature, severity or incidence of treatment-related adverse events; headache, dizziness, cough and polyuria were most frequently reported. Notably, in one study, fewer patients discontinued treatment with combination therapy than with zofenopril monotherapy due to adverse events. In conclusion, zofenopril/HCTZ 30/12.5 mg/day provides more optimal BP control in a larger proportion of patients than would be achievable with monotherapy, while maintaining the tolerability profile observed with each individual agent, and thereby potentially enhancing patient compliance. The efficacy and safety profiles of this combination shown in clinical trials to date indicate that it will be a useful addition to currently available therapy for patients who have mild to moderate hypertension that is not adequately controlled by monotherapy, as well as for patients who require more rapid, intensive BP control.     

Aliskiren: a review of its use as monotherapy and as combination therapy in the management of hypertension

Aliskiren is an orally administered, nonpeptide direct renin inhibitor indicated for the management of hypertension. Aliskiren was effective in controlling blood pressure (BP) as monotherapy and in combination with other antihypertensives, in large, randomized trials. Aliskiren 150-300?mg/day as monotherapy was effective in lowering BP across short- (≤12 weeks) and longer-term (up to 54 weeks) periods, providing sustained and consistent effects with 24-hour BP control. Compared with other antihypertensives, aliskiren was generally as effective as hydrochlorothiazide (HCTZ), valsartan, losartan, irbesartan and lisinopril in reducing BP. Furthermore, short-term aliskiren was noninferior to ramipril in reducing BP, but with a longer treatment duration, a greater efficacy of aliskiren-based therapy over ramipril-based therapy was demonstrated. Additional BP-lowering effects occurred when aliskiren was coadministered (as a fixed-dose combination or separate tablets) with other antihypertensives, including HCTZ, valsartan and amlodipine, according to large, randomized trials of short- (≤12 weeks) and longer-term (up to 54 weeks) duration. Combination therapy with aliskiren plus HCTZ was effective in hypertensive patients when administered as initial therapy or to patients previously treated with HCTZ or aliskiren monotherapy. Aliskiren-based therapy was also effective in lowering BP in obese patients, patients with type 1 or 2 diabetes mellitus, patients with metabolic syndrome and the elderly. Aliskiren efficacy was observed irrespective of patient age, sex or ethnicity. Aliskiren monotherapy or combination therapy was generally well tolerated over short- and longer-term study durations in large, randomized clinical trials. Clinical trials to evaluate the effects of aliskiren on clinical outcomes, including renoprotective and cardioprotective effects, are currently ongoing. Thus, aliskiren is a useful option for the treatment of patients with stage 1 to stage 2 (mild to moderate) hypertension, alone or in combination with other antihypertensives, including HCTZ, valsartan or amlodipine.     

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.     

Combination Therapy with Olmesartan Medoxomil and Hydrochlorothiazide

Background

The combination of olmesartan medoxomil and hydrochlorothiazide (HCTZ) [olmesartan medoxomil/HCTZ] has previously been shown to produce significantly greater SBP/DBP reductions than monotherapy with either agent alone in a randomized, double-blind, factorial study in patients with stage 2 hypertension. Compared with the evaluation of a single mean BP reduction in a patient population, determining the efficacy of an antihypertensive agent in achieving multiple BP targets provides additional information about the range of BP reductions attainable within this study population.

Objective

To conduct a secondary analysis of this study to evaluate the proportion of patients achieving combined SBP/DBP targets recommended in current hypertension treatment guidelines as well as individual SBP and DBP targets.

Methods

A total of 502 patients with DBP ≥100 and ≤115 mmHg were randomized to 8 weeks of treatment with placebo, HCTZ 12.5 or 25 mg/day, olmesartan medoxomil 10, 20, or 40 mg/day, or olmesartan medoxomil/HCTZ 10/12.5, 10/25, 20/12.5, 20/25, 40/12.5, or 40/25 mg/day. Mean baseline SBP ranged from 151.9 to 156.6 mmHg and mean baseline DBP ranged from 102.6 to 104.4 mmHg across the twelve treatment arms. The chi-squared test was used to compare the proportion of patients achieving each BP goal in each of the 11 active treatment regimens with that in the placebo group.

Results

The proportion of patients achieving an SBP <140 or <130 mmHg, DBP <90, <85, or <80 mmHg and combined SBP/DBP <140/90, <130/85, <130/80, or <120/80 mmHg typically increased with escalating dosages of olmesartan medoxomil and HCTZ when administered alone or in combination, but was always highest in those treated with the combination. As the BP goal became progressively more stringent, the proportion of patients achieving the BP goal decreased in each treatment group, although the trend toward greater reductions in patients treated with combination therapy remained intact. All combined SBP/DBP goals were achieved by a statistically significant proportion of patients (p<0.05) in the olmesartan medoxomil/HCTZ 20/25, 40/12.5, and 40/25 treatment groups.

Conclusions

A majority of patients with uncomplicated stage 2 hypertension can achieve recommended BP goals when treated with the combination of olmesartan medoxomil and HCTZ.     

Olmesartan medoxomil: in children and adolescents with hypertension

Olmesartan medoxomil is an orally administered angiotensin II receptor antagonist, selective for the angiotensin II type 1 receptor, which has established antihypertensive efficacy in adults. In children and adolescents with hypertension (n?=?302), oral olmesartan medoxomil significantly and dose-dependently reduced seated systolic blood pressure (BP) and seated dystolic BP from baseline (the primary endpoint) in a 3-week, dose-response period in a well designed phase II/III clinical trial. Patients received olmesartan medoxomil high dose (20 or 40?mg once daily depending on bodyweight) or low dose (2.5 or 5.0?mg once daily depending on bodyweight). The response was significant for both cohorts, which were stratified by race (cohort A was mixed race [62% White] and cohort B was 100% Black). In addition, BP control was maintained in olmesartan recipients relative to placebo recipients in cohort A and the combined cohort A?+?B, but not for patients in cohort B, during a placebo-controlled withdrawal period of this trial. Oral olmesartan medoxomil was generally well tolerated in children and adolescents with hypertension. The majority of adverse events were of mild to moderate intensity.     

奥美沙坦酯片治疗轻、中度原发性高血压的疗效和安全性

目的观察奥美沙坦酯片治疗轻、中度原发性高血压的疗效和安全性。方法61例轻、中度原发性高血压患者随机分为奥美沙坦酯组(n=30)和氯沙坦组(n=31),治疗8wk,观察2组治疗前后的血压、心率、心电图和血、尿实验室检查的变化。结果奥美沙坦酯组与氯沙坦组比较,坐位收缩压和舒张压降低程度都有显著差异,分别为(132±13 vs 139±13)mmHg(P<0.01)和(85±9 vs 87±9)mmHg(P<0.05)。奥美沙坦酯组降压有效率为83%;每日1次服用奥美沙坦酯作用可持续24h,药物降低收缩压和舒张压的谷峰比值均>50%。2组药物不良反应发生分别为1例和3例,2组比较无显著差别。结论奥美沙坦酯治疗轻、中度原发性高血压患者,能24h平稳降压,谷峰比满意,且耐受性较好。     

奥美沙坦酯治疗轻中度原发性高血压的疗效和安全性

目的评价奥美沙坦酯治疗轻中度原发性高血压的疗效和安全性。方法随机、双盲、双模拟、阳性药物(氯沙坦钾)平行对照。40例轻中度原发性高血压患者随机分为奥美沙坦酯或氯沙坦钾组,均治疗8周,观察两组治疗前后的血压、心率、心电图和血、尿常规等实验室检查结果的变化。结果奥美沙坦酯组与氯沙坦钾组比较,患者平均坐位收缩压和舒张压的降低程度均有显著性差异,分别为(18.9±8.7)mmHg和(12.6±7.6)mmHg(P<0.01);(13.8±3.5)mmHg和(11.7±3.3)mmHg(P<0.05)。治疗前后两组血压降低幅度均有显著差异,心率无明显变化。奥美沙坦酯和氯沙坦钾组降压显效率分别为63.2%和57.9%,总有效率分别为84.2%和68.4%,组间无显著差异。两组共出现3例头晕,实验室检查无异常改变。结论奥美沙坦酯治疗轻中度原发性高血压的疗效良好,不良反应发生率低。     

Telmisartan/hydrochlorothiazide combination therapy in the treatment of essential hypertension

Telmisartan is an angiotensin-II receptor blocker that has demonstrated efficacy in the reduction of blood pressure in patients with hypertension. Patients with hypertension commonly require two or more antihypertensives to reduce their blood pressure to safe levels, and the choice of combination therapy should be informed by clinical trial data. Telmisartan is available in fixed-dose combination with hydrochlorothiazide (telmisartan/HCTZ) in doses of 40 mg/12.5 mg and 80 mg/12.5 mg. Telmisartan/HCTZ has been studied in a number of clinical trials in essential hypertension, for the most part using ambulatory blood pressure monitoring. It has been compared with monotherapy in full patient populations and in non-responders, and has been compared with other drug combinations. Telmisartan/HCTZ provides significantly greater reductions in blood pressure than monotherapy, and significantly increases the percentage of patients who achieve target blood pressure. The reduction in blood pressure achieved by adding HCTZ to telmisartan is greater than that achieved by adding HCTZ to atenolol, despite the fact that telmisartan and atenolol monotherapy had similar efficacy. Telmisartan/HCTZ provides significantly greater reductions than losartan plus HCTZ in 24-h mean blood pressure, primarily due to a significantly greater effect in the risky, early morning hours. Telmisartan/HCTZ is effective and well-tolerated in the elderly, diabetics and African-American patients. Ongoing studies are comparing the efficacy of telmisartan/HCTZ with valsartan plus HCTZ and amlodipine plus HCTZ in overweight, hypertensive diabetics and in patients with isolated systolic hypertension – two patient groups who are particularly at risk of target organ damage.     

Olmesartan Medoxomil-Based Antihypertensive Therapy Evaluated by Ambulatory Blood Pressure Monitoring

Hypertension affects approximately 26% of the world’s adult population and is a recognized major risk factor for morbidity and mortality associated with cardiovascular, cerebrovascular, and renal diseases. However, despite the availability of a range of effective antihypertensive agents and a growing awareness of the consequences of high blood pressure (BP), the treatment and control of hypertension remains sub-optimal. A number of patient subgroups are categorized as ‘high risk’ and may have hypertension that is more difficult to treat, including obese individuals, patients with stage 2 hypertension, those with type 2 diabetes mellitus (T2DM), patients with coronary artery disease or a history of stroke, and Black patients. As the benefits of lowering BP in patients with hypertension are unequivocal, particularly in high-risk patients, treating high-risk patients with hypertension to BP goals and maintaining 24-hour BP control is important to help reduce cardiovascular risk and improve outcomes. Although the BP goals recommended in current consensus guidelines for the management of patients with hypertension are based on cuff BP measurements, ambulatory BP monitoring (ABPM) provides a valuable diagnostic tool and allows a more accurate assessment of BP levels throughout the 24-hour dosing period. ABPM is a better predictor of prognosis than office BP measurement and is also useful for assessing whether antihypertensive therapy remains effective in the critical last few hours of the dosing period, which usually coincides with the morning BP surge associated with arousal and arising. ABPM has been adopted by new evidence-based guidelines in the United Kingdom to confirm a suspected diagnosis of hypertension, which is an indication of the growing importance of ABPM in the management of hypertension. This review provides an overview of the efficacy and safety of anti-hypertensive therapy based on olmesartan medoxomil ± hydrochlorothiazide and amlodipine/olmesartan medoxomil in high-risk patient populations enrolled in studies that reported ambulatory BP endpoints. The studies identified in this review showed that a titrate-to-BP goal strategy using olmesartan medoxomil- or amlodipine/olmesartan medoxomil-based antihypertensive therapy was an effective and well-tolerated approach for maintaining BP control throughout the full 24-hour dosing period in high-risk patients with difficult-to-treat hypertension.