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.     

Telmisartan: a review of its use in the management of hypertension

Telmisartan (Micardis, Pritor), a highly selective angiotensin II (AII) type 1 (AT1) receptor antagonist, is approved for the treatment of hypertension, either as monotherapy or in combination with other antihypertensive agents. The long elimination half-life of telmisartan ensures the drug provides effective reductions in blood pressure (BP) across the entire 24-hour dosage interval. Extensive evidence from well designed clinical trials and the clinical practice setting indicates that telmisartan, either as monotherapy or in combination with other antihypertensive agents, provides long-term antihypertensive efficacy and is well tolerated in a broad spectrum of hypertensive patients, including the elderly and those with coexisting type 2 diabetes mellitus, metabolic syndrome and/or renal impairment. Notably, BP control is sustained throughout the 24-hour dosage interval, including during the last 6 hours of this period. Independent of its effect on BP, telmisartan displays favourable effects on insulin resistance, lipid levels, left ventricular hypertrophy (LVH) and renal function. The consistent antihypertensive efficacy during the entire 24-hour dosage interval and sustained BP-lowering effect in the long term, combined with its favourable tolerability profile, mean that telmisartan is a valuable first-line treatment option for the management of essential hypertension.     

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.     

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.     

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.     

Fixed-Dose Combination Antihypertensives and Reduction in Target Organ Damage

Hypertension is a multifactorial disorder leading to pathophysiologic changes in target organs over time through diverse mechanisms. In addition, hypertension frequently resists control with monotherapy, necessitating combination therapy with two or more antihypertensive agents. Many currently available fixed-dose antihypertensive combinations combine drugs with different, but complementary, mechanisms of action to improve overall efficacy and tolerability. In addition, it is possible to select drug combinations whereby one drug offsets the negative effects of the other drug. Fixed-dose antihypertensive combinations may provide significant advantages over high-dose monotherapy, such as improved BP-lowering efficacy, reduced adverse event frequency, improved patient compliance, potentially lower treatment costs, and shorter time to BP control. Combination therapy has been recommended as potential first-line therapy in recent consensus guideline statements, especially for higher-risk patients, such as those with stage 2 hypertension. The combination of a renin-angiotensin-aldosterone system-targeting agent, such as an ACE inhibitor or angiotensin II receptor antagonist (ARB), and a diuretic or calcium channel antagonist appears to provide synergy with regard to BP lowering. In addition, ACE inhibitors and ARBs have demonstrated beneficial effects beyond BP reduction, reducing cardiovascular morbidity and mortality, inhibiting development and progression of type 2 diabetes mellitus and the progression of renal disease. Preliminary studies of fixed-dose combinations have shown reductions in left ventricular hypertrophy and improvements in markers of renal function. Additional studies currently underway will compare the effects of available fixed-dose combinations on cardiovascular morbidity and mortality, and markers of renal dysfunction.     

Concomitant calcium entry blockade and inhibition of the renin-angiotensin system: a rational and effective means for treating hypertension.

Pharmacological treatment of hypertension is effective in preventing cardiovascular and renal complications. Calcium antagonists (CAs) and blockers of the renin-angiotensin system [angiotensin-converting enzyme (ACE) inhibitors and angiotensin II antagonists (ARBs)] are widely used today to initiate antihypertensive treatment but, when given as monotherapy, do not suffice in most patients to normalise blood pressure (BP). Combining a CA and either an ACE-inhibitor or an ARB considerably increases the antihypertensive efficacy, but not at the expense of a deterioration of tolerability. Several fixed-dose combinations are available (CA + ACE-inhibitors: amlodipine + benazepril, felodipine + ramipril, verapamil + trandolapril; CA + ARB: amlodipine + valsartan). They are expected not only to improve BP control, but also to facilitate long-term adherence with antihypertensive therapy, thereby providing maximal protection against the cardiovascular and renal damage caused by high BP.     

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.     

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.     

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.     

Amlodipine/Valsartan: fixed-dose combination in hypertension

Amlodipine, a dihydropyridine calcium channel blocker, and valsartan, an angiotensin II receptor blocker, are established antihypertensive agents. Fixed-dose combinations of amlodipine/valsartan are available in several European countries and in the US. Individual dose titration with amlodipine and valsartan is generally recommended before changing to the fixed-dose combination. Amlodipine/valsartan, at approved dosage regimens, achieved significantly greater reductions in mean sitting diastolic and systolic blood pressure (BP) than amlodipine or valsartan monotherapy, or placebo in two randomized, double-blind, factorial trials in patients with mild to moderate hypertension. Approximately 80-90% of patients receiving approved dosages of amlodipine/valsartan achieved a response, defined as a mean sitting diastolic BP <90 mmHg or a >or= 10 mmHg reduction from baseline. Subgroup analyses of data from the two trials showed that the antihypertensive efficacy of amlodipine/valsartan in the elderly, Black patients and those with stage 2 hypertension was consistent with that observed in the overall study population. Marked reductions in BP were also observed in patients whose BP was previously uncontrolled on monotherapy (with various antihypertensives) who were switched (without washout) to amlodipine/valsartan in a phase IIIb-IV study. Amlodipine/valsartan was generally well tolerated in clinical trials. In particular, the incidence of peripheral oedema was significantly lower in patients receiving amlodipine/valsartan than in those treated with amlodipine monotherapy.     

Amlodipine/Valsartan/Hydrochlorothiazide

Amlodipine/valsartan/hydrochlorothiazide (HCTZ) is a fixed-dose combination of the well established antihypertensive agents amlodipine (a calcium channel antagonist), valsartan (an angiotensin II receptor antagonist), and HCTZ (a thiazide diuretic). In patients with moderate or severe hypertension, triple combination therapy with amlodipine + valsartan + HCTZ produced significantly greater reductions from baseline in mean sitting systolic and diastolic BP (msSBP and msDBP) than either valsartan + HCTZ, amlodipine + HCTZ, or amlodipine + valsartan in a large, 8-week, randomized, double-blind, multinational, phase III trial. Furthermore, the proportion of patients achieving overall BP control at endpoint was significantly greater with the triple combination regimen than with any of the dual regimens, with significantly more triple combination recipients achieving msSBP and msDBP control at each assessment throughout the trial. Subgroup analyses of this study suggested that amlodipine + valsartan + HCTZ was generally more effective in reducing BP and providing overall BP control than the dual combination therapies, irrespective of age, race, gender, ethnicity, or hypertension severity. Several smaller studies provide data that support the efficacy of amlodipine + valsartan + HCTZ in patients whose BP is inadequately controlled with amlodipine + valsartan, amlodipine + HCTZ, or valsartan + HCTZ dual combination therapy. Treatment with amlodipine + valsartan + HCTZ for up to 8 weeks was generally well tolerated in the large, phase III trial, with most adverse events being transient and of mild to moderate severity.     

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.     

Single-pill telmisartan and amlodipine: a rational combination for the treatment of hypertension

Despite the well documented benefits conferred by adequate control of hypertension, the majority of hypertensive patients display suboptimal control and few patients achieve blood pressure (BP) levels <140/90?mmHg. As a consequence, combination therapy will be required in the majority of patients to achieve target BP. Fixed-dose combinations of antihypertensives not only simplify treatment regimens, contributing to enhanced patient adherence, they provide superior BP-lowering efficacy and an improved tolerability profile. Fixed-dose combinations have become the strategy of choice in high-risk patients or those with stage 2-3 hypertension. The combination of a renin-angiotensin system inhibitor (RASI) with a calcium channel blocker (CCB) is a first-line combination that, in addition to its antihypertensive efficacy, reduces oedema, the main adverse effect of the dihydropyridine CCB and the main factor limiting their use. In morbidity/mortality studies, this fixed-dose combination has also demonstrated superiority over a RASI combined with a diuretic. The single-pill combination of telmisartan and amlodipine has been shown to produce a dose-dependent BP-lowering effect significantly greater than that of either agent administered as monotherapy. These findings have been confirmed by ambulatory BP monitoring in patients with stage 1 and 2 hypertension, which demonstrated that single-pill telmisartan/amlodipine provides substantial 24-hour BP-lowering efficacy. A higher proportion of patients achieved 24-hour BP goals of <130/80?mm?Hg on combination therapy. The superior efficacy of combination therapy has been demonstrated across a broad range of patients, including those with moderate-to-severe hypertension, diabetes mellitus and obesity. Moreover, combined use of telmisartan and amlodipine reduces the incidence of amlodipine-induced oedema, making it a preferred combination for the treatment of hypertension.     

Fixed-dose combination enalapril/nitrendipine: a review of its use in mild-to-moderate hypertension

The fixed-dose combination of enalapril 10mg with nitrendipine 20mg combines an ACE inhibitor with a calcium channel antagonist (CCA) and is indicated for the treatment of patients with mild-to-moderate hypertension whose blood pressure (BP) is inadequately controlled with enalapril or nitrendipine monotherapy. In randomised, double-blind clinical trials, enalapril/nitrendipine 10/20 mg/day was significantly more effective than its individual components in reducing diastolic BP (DBP) in patients with mild-to-moderate hypertension inadequately controlled with enalapril 10 mg/day or nitrendipine 20 mg/day. The fixed-dose combination was similar in efficacy at reducing DBP to amlodipine 10 mg/day in patients who failed to achieve BP control with amlodipine 5 mg/day, and to losartan/hydrochlorothiazide 50/12.5 mg/day in patients who received the combinations as first-line therapy. Enalapril/nitrendipine 10/20 mg produced a consistent antihypertensive effect that persisted for the entire 24-hour dosage interval as shown by ambulatory BP monitoring. Enalapril/nitrendipine 10/20 mg was well tolerated in clinical trials where it was administered to patients with mild-to-moderate hypertension for up to 12 weeks. The adverse events were those expected of ACE inhibitors and CCAs and included cough, headache and flushing. Evidence from clinical trials, including a pooled analysis, suggests that the incidence of oedema may be significantly lower with the fixed-dose combination than with CCA monotherapy.In conclusion, enalapril/nitrendipine 10/20 mg is a well tolerated fixed-dose combination of two established antihypertensive agents administered once daily that effectively lowers BP throughout the 24-hour dosage interval. Importantly, the fixed-dose combination may have a lower incidence of oedema than CCA monotherapy. Enalapril/nitrendipine 10/20 mg provides an additional treatment option for patients with mild-to-moderate hypertension for whom combination therapy is appropriate.     

Telmisartan 80 mg/hydrochlorothiazide 25 mg single-pill combination in the treatment of hypertension

Introduction: International guidelines emphasize the importance of blood pressure (BP) control to reduce cardiovascular risk. Telmisartan, an angiotensin II receptor blocker, provides large BP reductions and also prevents cardiovascular events in patients at high risk. The thiazide diuretic, hydrochlorothiazide (HCTZ), has a complementary mode of action, and combination with telmisartan is an established and rational treatment option for patients uncontrolled on monotherapy. A single-pill combination (SPC) of telmisartan 80 mg with high-strength HCTZ 25 mg (T80/H25) is widely available.

Area covered: Clinical data on T80/H25 SPC for the management of hypertension was identified via MEDLINE searches. T80/H25 SPC provides greater BP reductions and higher goal achievement rates in patients who cannot achieve BP goal with T80/HCTZ 12.5 mg SPC, and also as initial therapy compared with T80 monotherapy. T80/H25 also reduced BP significantly more than valsartan 160 mg/H25 combination, and demonstrated favorable tolerability in clinical trials.

Expert opinion: Patients with hypertension often do not achieve BP goal, even when treated, leaving them at increased cardiovascular risk. In part this is due to poor adherence, which can be exacerbated by treatment side effects. High BP goal achievement with SPC T80/H25, with maintained tolerability, provides a treatment option for increasing BP control.     

Angiotensin II Receptor Antagonists Alone and Combined with Hydrochlorothiazide

Angiotensin II receptor antagonists (angiotensin receptor blockers; ARBs) and thiazide diuretics have an accepted place in the management of hypertension. Most patients require combination therapy with two or more drugs to adequately control blood pressure to targets recommended by European and international guidelines. ARBs and the thiazide diuretic hydrochlorothiazide have complementary modes of action. Fixed-dose combinations of an ARB and low-dose hydrochlorothiazide provide a convenient and effective treatment option for patients who do not achieve blood pressure targets on monotherapy, without compromising the placebo-like tolerability of ARBs. In Europe, fixed-dose combinations with hydrochlorothiazide currently are available for the ARBs candesartan, eprosartan, irbesartan, losartan, telmisartan, and valsartan. Recently, a number of studies have focused on the use of ARBs in monotherapy and in combination therapy, in conditions including congestive heart failure, post-myocardial infarction management, hypertension with cardiovascular risk factors, and diabetic and non-diabetic nephropathy. Evidence from these studies suggests a beneficial role beyond the antihypertensive effect of these therapies in providing protection against cardiovascular, renovascular, and cerebrovascular events.     

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/Hydrochlorothiazide : in moderate to severe hypertension

* The fixed-dose combination of irbesartan/hydrochlorothiazide (HCTZ) is approved in the US for use as initial therapy in patients who are likely to need multiple agents to achieve their blood pressure (BP) goals. * In a 12-week, randomized, double-blind, multicentre trial in 538 patients with moderate hypertension that was untreated or uncontrolled by monotherapy, the mean reduction from baseline in seated systolic BP (SeSBP) at week 8 (primary endpoint) was significantly greater with irbesartan/HCTZ than with either irbesartan or HCTZ as monotherapy. * In addition, the proportion of patients with moderate hypertension achieving controlled BP (SeSBP < 140 mmHg/seated diastolic BP [SeDBP] < 90 mmHg) at 12 weeks was significantly greater with irbesartan/HCTZ combination therapy than with irbesartan or HCTZ monotherapy. * In a 7-week, randomized, double-blind, multicentre trial in 697 patients with severe hypertension that was untreated or uncontrolled by monotherapy, a significantly greater proportion achieved a trough SeDBP of < 90 mmHg following 5 weeks of combination therapy with irbesartan/HCTZ compared with irbesartan monotherapy (primary endpoint). * Furthermore, the proportion of patients with severe hypertension achieving controlled BP of < 140/90 mmHg was significantly greater at all timepoints of the trial compared with irbesartan monotherapy. * Irbesartan/HCTZ combination therapy had a similar tolerability profile to irbesartan and HCTZ monotherapy. Most adverse events were of mild to moderate intensity.     

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.