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: 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.     

Telmisartan: a review of its use in cardiovascular disease prevention

Telmisartan (Micardis?, Pritor?), a well established angiotensin type 1 receptor antagonist, is indicated in the EU for the reduction of cardiovascular morbidity in patients with manifest atherothrombotic cardiovascular disease (CVD) or type 2 diabetes mellitus with documented target organ damage, as well as for the treatment of hypertension. In the pivotal ONTARGET trial, which enrolled ACE inhibitor-tolerant patients at high vascular risk, telmisartan 80?mg once daily added to existing, proven therapy was noninferior to ramipril 10?mg once daily (the gold standard cardioprotective ACE inhibitor) in terms of CVD prevention. Moreover, telmisartan was better tolerated than ramipril, as reflected in, for example, lower incidences of permanent treatment discontinuations due to cough and angioedema. The placebo-controlled TRANSCEND and PRoFESS studies provided supporting evidence for the (time-dependent) effectiveness of telmisartan in preventing cardiovascular events, although the drug appeared to have neither a beneficial nor a harmful impact on cardiovascular mortality. The TRANSCEND trial also demonstrated that telmisartan was well tolerated in ACE inhibitor-intolerant patients at high vascular risk. On the basis of these findings, telmisartan can be considered an effective treatment option for CVD prevention in patients at high vascular risk. Consideration may be given to prescribing the drug as an alternative to ramipril in patients who are able to tolerate ACE inhibitors and, potentially, instead of ramipril in patients who are unable to tolerate ACE inhibitors.     

Lercanidipine: a review of its use in hypertension

Lercanidipine is a vasoselective dihydropyridine calcium antagonist which causes systemic vasodilation by blocking the influx of calcium ions through L-type calcium channels in cell membranes. It is a highly lipophilic drug and as such has a slower onset and longer duration of action than a number of other calcium antagonists. Preclinical evidence suggests that lercanidipine has antiatherogenic potential and it may also protect against end-organ damage. In well controlled clinical studies, once daily administration of lercanidipine 10 or 20mg effectively reduced blood pressure (BP) compared with placebo in patients with mild to moderate hypertension without affecting heart rate. Response rate (percentage of patients with diastolic BP < or =90mm Hg or reduced by > or =10mm Hg from baseline) ranged from 50 to 66% with lercanidipine 10 mg/day and up to 86% with lercanidipine 20 mg/day. The drug had a long duration of action: clinical measurements for diastolic BP yielded a trough/peak ratio of >0.8 for both lercanidipine dosages in 1 study. Comparative trials, either published in full or as abstracts, found lercanidipine 10mg once daily for > or =4 weeks to be at least as effective as atenolol 50mg once daily, candesartan cilexetil 16 mg/day, captopril 25mg twice daily, enalapril 20 mg/day, hydrochlorothiazide 12.5mg once daily, irbesartan 150 mg/day and slow release nifedipine 20mg twice daily in patients with mild to moderate hypertension. In addition, lercanidipine 20 mg/day was as effective as amlodipine 10 mg/day. Lercanidipine is effective in the treatment of elderly patients (aged 60 to 85 years) with mild to moderate essential hypertension and in those with isolated systolic hypertension. In addition, monotherapy with lercanidipine 20 or 40 mg/day has shown efficacy in patients with severe hypertension, and add-on therapy helped control BP in a large proportion of patients with severe hypertension not responding sufficiently to beta-blockers, diuretics or ACE inhibitors. Unpublished data indicate that the drug reduces blood pressure in patients with type 2 (non-insulin-dependent) diabetes mellitus, without adversely affecting glucose homeostasis. Lercanidipine was well tolerated in clinical trials, with most treatment-related adverse events typical of dihydropyridine calcium antagonists, namely headache, flushing, dizziness and ankle oedema. CONCLUSIONS: Lercanidipine is an effective and well tolerated once daily antihypertensive agent in patients with mild to moderate hypertension. In addition, the drug may reduce BP when used as monotherapy in patients with severe hypertension or when used adjunctively in patients with resistant hypertension. Importantly, lercanidipine appears to be at least as effective and well tolerated as other commonly used antihypertensive agents. The drug therefore represents a useful therapeutic option in the management of patients with hypertension and will be particularly useful in patients not responding to, or intolerant of, antihypertensive agents from other drug classes.     

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.     

Moxonidine: a review of its use in essential hypertension

Moxonidine (Physiotens, Moxon, Cynt) is an orally administered imidazoline compound with selective agonist activity at imidazoline I1 receptors and only minor activity at alpha2-adrenoceptors. Moxonidine acts centrally to reduce peripheral sympathetic activity, thus decreasing peripheral vascular resistance. In patients with mild to moderate hypertension, moxonidine reduces blood pressure (BP) as effectively as most first-line antihypertensives when used as monotherapy and is also an effective adjunctive therapy in combination with other antihypertensive agents. It improves the metabolic profile in patients with hypertension and diabetes mellitus or impaired glucose tolerance, is well tolerated, has a low potential for drug interactions and may be administered once daily in most patients. Thus, moxonidine is a good option in the treatment of patients with mild to moderate hypertension, particularly as adjunctive therapy in patients with the metabolic syndrome.     

Manidipine: a review of its use in hypertension.

Manidipine is a dihydropyridine calcium antagonist, which causes systemic vasodilation by inhibiting the voltage-dependent calcium inward currents in smooth muscle cells. The resulting reduction in blood pressure (BP) in patients with hypertension is maintained over 24 hours. Manidipine 10 to 40 mg once daily for 4 weeks significantly lowered office BP from baseline and compared with placebo, and significantly reduced 24-hour BP compared with placebo in patients with essential hypertension in a well controlled trial. The decline in BP was maintained over 24 hours (trough to peak BP ratios were >50%) without disturbing the circadian BP pattern. BP reductions with therapeutic dosages of manidipine were maintained for up to 1 year in noncomparative trials. The BP-lowering capacity of manidipine 5 to 20 mg/day appears to be similar to that of other calcium antagonists with which it has been compared in randomised double-blind and nonblind trial. In a well controlled short term trial, manidipine 10 mg daily significantly decreased trough sitting BP compared with placebo in elderly patients with mild to moderate essential hypertension. Decreases in BP were maintained for up to 3 years of treatment. The drug (10 or 20 mglday) also significantly lowered sitting BP from baseline in patients with hypertension and type 2 diabetes mellitus in randomised, long term comparative trials. In general, the observed reduction in BP with manidipine was similar to that observed with amlodipine, enalapril or delapril. The effects of manidipine on urinary albumin excretion (UAE) have not been clearly demonstrated in clinical trials in this patient group. BP was also reduced with manidipine in patients with impaired glucose tolerance. Manidipine was well tolerated in clinical trials, with most adverse effects related to vasodilation. Commonly reported events included ankle oedema, headache. palpitation. flushing, dizziness, rash and fatigue. Manidipine appears to have less potential for pedal oedema than amlodipine. CONCLUSIONS: Manidipine has shown antihypertensive efficacy and appears to be well tolerated in adult and elderly patients with mild or moderate essential hypertension. The BP-lowering effects of the drug in patients with hypertension and type 2 diabetes mellitus or impaired glucose tolerance were not associated with any adverse metabolic effects. The effects of manidipine on UAE in this patient group remain unclear. Manidipine provides an additional treatment option for patients for whom dihydropyridine calcium antagonists are appropriate. Manidipine is a dihydropyridine calcium antagonist, which causes systemic vasodilation by inhibiting the voltage-dependent calcium inward currents in smooth muscle cells. The resulting reduction in blood pressure (BP) in patients with hypertension is maintained over 24 hours. Manidipine 10 to 40mg once daily for 4 weeks significantly lowered office BP from baseline and compared with placebo, and significantly reduced 24-hour BP compared with placebo in patients with essential hypertension in a well controlled trial. The decline in BP was maintained over 24 hours (trough to peak BP ratios were >50%) without disturbing the circadian BP pattern. BP reductions with therapeutic dosages of manidipine were maintained for up to 1 year in non-comparative trials. The BP-lowering capacity of manidipine 5 to 20 mg/day appears to be similar to that of other calcium antagonists with which it has been compared in randomised double-blind and nonblind trial. In a well controlled short term trial, manidipine 10 mg daily significantly decreased trough sitting BP compared with placebo in elderly patients with mild to moderate essential hypertension. Decreases in BP were maintained for up to 3 years of treatment. The drug (10 or 20 mg/day) also significantly lowered sitting BP from baseline in patients with hypertension and type 2 diabetes mellitus in randomised, long term comparative trials. In general, the observed reduction in BP with manidipine was similar to that observed with amlodipine, enalapril or delapril. The effects of manidipine on urinary albumin excretion (UAE) have not been clearly demonstrated in clinical trials in this patient group. BP was also reduced with manidipine in patients with impaired glucose tolerance. Manidipine was well tolerated in clinical trials, with most adverse effects related to vasodilation. Commonly reported events included ankle oedema, headache. palpitation. flushing, dizziness, rash and fatigue. Manidipine appears to have less potential for pedal oedema than amlodipine. CONCLUSIONS: Manidipine has shown antihypertensive efficacy and appears to be well tolerated in adult and elderly patients with mild or mo     

Sildenafil: a review of its use in pulmonary arterial hypertension

Sildenafil citrate (Revatio), an inhibitor of phosphodiesterase type 5 (PDE5), is approved for use in the US, Europe and other countries for the treatment of pulmonary arterial hypertension (PAH). Oral sildenafil 20 mg three times daily added to conventional background therapy was significantly more effective than placebo at increasing exercise capacity in patients with idiopathic PAH or PAH associated with connective tissue diseases or repaired congenital systemic-to-pulmonary shunts. Sildenafil was also associated with improvements in WHO functional class and haemodynamic parameters, and was generally well tolerated. Sildenafil provides benefits in terms of exercise capacity when added to epoprostenol; however, these findings come from a trial that did not use the approved dosage of sildenafil. In conclusion, sildenafil is an effective oral treatment option for patients with PAH.     

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

Eprosartan is a potent and selective angiotensin II subtype 1 receptor antagonist. Results of large (n > 100) randomised double-blind studies in patients with mild, moderate or severe hypertension demonstrated that the antihypertensive efficacy of eprosartan (usually 400 to 800 mg/day as a single daily dose or in 2 divided doses) is significantly greater than that of placebo and at least as good as that of enalapril. In placebo-controlled trials, eprosartan achieved mean reductions from baseline in trough sitting systolic blood pressure of 6.3 to 15 mm Hg and in diastolic blood pressure of 4.1 to 9.7 mm Hg. Response rates associated with once daily administration of eprosartan 400 to 800 mg were approximately double those with placebo. Overall, eprosartan was well tolerated with a similar tolerability profile to that of placebo. In comparative trials, in which the incidence of persistent dry cough was evaluated as the primary end-point, enalapril was several-fold more likely to induce this adverse event than eprosartan (the difference being statistically significant regardless of study population and definition of cough). In conclusion, the angiotensin II receptor antagonist eprosartan is a well tolerated and effective antihypertensive agent that is administered once or twice daily without regard to meals. Eprosartan has a low potential for serious adverse events, and the drug has not been associated with clinically significant drug interactions. Unlike ACE inhibitors such as enalapril, eprosartan does not have a high propensity to cause persistent nonproductive cough. Thus, eprosartan represents a useful therapeutic option in the management of patients with hypertension.     

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

The angiotensin II receptor antagonist eprosartan is approved for the treatment of essential hypertension and may be administered using a convenient once-daily regimen. The drug is a well tolerated and effective antihypertensive agent with benefit in the secondary prevention of cerebrovascular events, independent of blood pressure (BP)-lowering effects. Eprosartan has a low potential for serious adverse events and has not been associated with clinically significant drug interactions, establishing it as a promising agent for combination antihypertensive strategies. Unlike ACE inhibitors such as enalapril, eprosartan does not have a tendency to cause persistent nonproductive cough. Accordingly, eprosartan represents a useful therapeutic option in the management of patients with hypertension, including those who have had a stroke and those with co-morbid type 2 diabetes mellitus.     

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

Aliskiren (Tekturna) is an orally active, nonpeptidic inhibitor of renin, the enzyme involved in the initial and rate-limiting step of the renin-angiotensin system (RAS). In the US, aliskiren is approved for the treatment of hypertension and may be used alone or in combination with other antihypertensive agents.Monotherapy with aliskiren 150-300mg once daily was effective in lowering blood pressure (BP) and providing 24-hour BP control; it was generally well tolerated when administered for up to 1 year to patients with mild to moderate hypertension. In the short term (1-3 months), the BP-lowering effect of aliskiren 150-300mg once daily was significantly greater than that of hydrochlorothiazide (HCTZ) 12.5-25mg once daily and noninferior to, or significantly greater than, that of ramipril 5-10mg once daily. It was similar to that of valsartan 160-320mg once daily and losartan 100mg once daily, and similar to, or significantly greater than, that of irbesartan 150mg once daily. Aliskiren provided significant additional BP-lowering effects when combined with HCTZ 12.5-25 mg/day, ramipril 5-10 mg/day, amlodipine 5mg once daily or valsartan 160-320 mg/day; combination therapy was well tolerated. Long-term administration of aliskiren-based therapy was superior to HCTZ- and ramipril-based therapies in lowering BP after 6 months, and was similarly well tolerated.The ultimate role of aliskiren will be determined by the results of target organ protection studies, which are ongoing, and a cardiovascular outcome trial, which is planned. Nonetheless, by offering a new approach to the blockade of the RAS, aliskiren provides a useful addition to the therapeutic options available to treat patients with mild to moderate hypertension.     

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

Lacidipine (Caldine, Lacimen, Lacipil, Midotens, Motens) is a once-daily, orally-administered, lipophilic dihydropyridine calcium antagonist with an intrinsically slow onset of activity, resulting in a lack of reflex tachycardia. It has a long duration of action and a high degree of vascular selectivity. In addition to calcium channel-modulated vasodilation, lacidipine displays antioxidant activity greater than that of other dihydropyridine calcium antagonists. In randomised, well-controlled trials, lacidipine 2-6 mg orally once daily had antihypertensive efficacy similar to that of other long-acting dihydropyridine calcium antagonists, thiazide diuretics, atenolol (a beta-blocker) and enalapril (an ACE inhibitor). Lacidipine was effective in elderly patients (including those with isolated systolic hypertension), African Nigerian patients and patients with concurrent type 2 diabetes mellitus. During long-term treatment for 4 or 5 years in patients with isolated systolic hypertension or essential hypertension, the incidence of cardiovascular events and mortality with lacidipine was similar to that with chlorthalidone or atenolol. The European Lacidipine Study on Atherosclerosis (ELSA), in which 2334 patients with hypertension were randomised to 4 years of therapy with lacidipine 4-6 mg/day or the beta-blocker atenolol 50-100 mg/day, demonstrated significantly lower atherosclerotic progression and plaque formation with lacidipine compared with atenolol in patients completing the full 4 years of the study. Between-group differences in favour of lacidipine for the primary efficacy variable (mean change in carotid artery intima-media thickness) did not reach statistical significance in the intent-to-treat population. The tolerability profile of lacidipine (headache, flushing, pedal oedema, dizziness and palpitations) is similar to that of other dihydropyridine calcium antagonists, but with a lower incidence of peripheral oedema. Data from the ELSA study suggest that the incidence of serious adverse events during long-term lacidipine therapy is similar to that with atenolol. CONCLUSION: Lacidipine is an effective, well tolerated, once-daily, oral antihypertensive agent that can be used in a wide variety of patients. As with other members of its class, lacidipine has shown potentially beneficial antiatherosclerotic effects, although definitive data with respect to possible superiority over other drug classes are still required. Therefore, lacidipine is an attractive therapy for the long-term management of essential hypertension.     

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

Manidipine is a lipophilic, third-generation dihydropyridine calcium channel antagonist with a high degree of selectivity for the vasculature, thereby inducing marked peripheral vasodilation with negligible cardiodepression. In addition, manidipine does not significantly affect norepinephrine levels, suggesting a lack of sympathetic activation. It has a gradual onset of action and a long duration of action enabling once daily administration. Furthermore, manidipine dilates both the efferent and the afferent renal arterioles and appears to have beneficial renal effects unrelated to its antihypertensive effect. Once-daily oral manidipine is an effective and generally well tolerated antihypertensive agent for younger and elderly adult patients with mild-to-moderate hypertension. In particular, in a large double-blind trial, the incidence of ankle oedema was significantly lower in manidipine than in amlodipine recipients. Manidipine is also effective in hypertensive patients with comorbidities, such as type 2 diabetes mellitus and/or renal impairment, and appears to improve insulin sensitivity without affecting metabolic function. Thus, manidipine represents a first-line treatment option for patients with essential mild-to-moderate hypertension.     

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

Irbesartan (Aprovel, Avapro, Irbetan, Karvea), an angiotensin II receptor type 1 antagonist, is approved in many countries worldwide for the treatment of hypertension. It is also approved in some regions for the treatment of nephropathy in patients with hypertension and type 2 diabetes mellitus. In adults with essential hypertension, irbesartan is effective at reducing blood pressure (BP) over a 24-hour period with once-daily administration. Irbesartan also slows the progression of renal disease in hypertensive patients with type 2 diabetes, with this effect partly independent of its BP-lowering effect. In addition, irbesartan was generally well tolerated in clinical trials. Thus, irbesartan is a useful treatment option for patients with hypertension, including those with type 2 diabetes and nephropathy.     

Perindopril: an updated review of its use in hypertension

Perindopril erbumine (perindopril) is a prodrug ester of perindoprilat, an angiotensin converting enzyme (ACE) inhibitor. Perindopril 4 to 8 mg once daily significantly reduces supine systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline values in hypertensive patients. These reductions are maintained for at least 24 hours, as evidenced by trough/peak ratios of >50%. Vascular abnormalities associated with hypertension were improved or normalised during perindopril treatment. Perindopril 4 to 8 mg once daily significantly decreased carotid-femoral aortic pulse wave velocity (PWV), improved arterial compliance, reduced left ventricular mass index and, in patients with recent cerebral ischaemia and/or stroke, preserved cerebral blood flow despite significantly reducing SBP and DBP. Further research is needed to establish the significance of promising results showing that reductions in aortic PWV were associated with reduced mortality in patients with end-stage renal failure, a third of whom received perindopril. Response rates (numbers of patients with supine DBP < or = 90 mm Hg) were significantly higher with perindopril 4 to 8 mg once daily (67 to 80%) than with captopril 25 to 50 mg twice daily (44 to 57%) in 3 randomised double-blind trials. In other clinical trials, the antihypertensive effects of perindopril were similar to those of other ACE inhibitors (including enalapril) and calcium-channel antagonists. Combination treatment with perindopril and an antihypertensive agent from another treatment class provided additional benefits, either as first-line treatment or in patients failing to respond to monotherapy. Perindopril monotherapy was also effective in the elderly and in patients with hypertension and concomitant disease. Perindopril has a similar adverse event profile to that of other ACE inhibitors; cough is the most common event reported during treatment, and is also the most common adverse event responsible for treatment withdrawal. Conclusions: Perindopril is a well tolerated ACE inhibitor that is significantly better than captopril (in terms of response rates) in the treatment of hypertension, and as effective as other ACE inhibitors. Perindopril appears to reverse some of the vascular abnormalities associated with hypertension, including arterial stiffness and left ventricular hypertrophy, although further research is needed to confirm promising results regarding its ability to decrease associated cardiovascular morbidity and mortality. Results from ongoing studies will help confirm the place of perindopril in the treatment of hypertension; currently, it is an effective and well tolerated treatment for patients with mild to moderate essential hypertension.     

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.     

Labetalol: a review of its pharmacology and therapeutic use in hypertension.

Labetalol is an orally active adrenoceptor blocking drug which is a competitive antagonist at both alpha- and beta-adrenoceptor sites. Its beta-blocking effects resemble those of propranolol, but its overall haemodynamic effects are akin to those of a comination of propranolol and an alpha-adrenoceptor blocking drugs such as phenoxybenzamine. Unlike with conventional beta-adrenoceptor blocking drugs, acute administration of labetalol reduces peripheral vascular resistance and blood pressure and has little effect on cardiac output. Theoretically, labetalol has advantages over beta-adrenoceptor blocking drugs alone in the treatment of hypertension, but any real advantage, particulary in mild or moderate hypertension, has yet to be conclusively demonstrated in therapeutic trials. Labetalol may be particularly useful in some patients whose blood pressure is not adequately controlled by beta-adrenoceptor blocking drugs alone or combined with a diuretic, but possibly at the expense of a postural hypotensive effect. Postural hypotension is the most troublesome side-effect, occasionally necessitating withdrawal of therapy, but severe side-effects such as are seen with effective antihypertensive dosages of phenoxybenzamine do not occur with labetalol.     

Candesartan cilexetil plus hydrochlorothiazide combination: a review of its use in hypertension

The combination of candesartan cilexetil [an angiotensin II type 1 (AT(1)) receptor antagonist] plus hydrochlorothiazide (a thiazide diuretic), has been used in the treatment of patients with hypertension. The blood pressure (BP) lowering effect of various doses of this combination, administered orally once a day for 4 to 52 weeks, has been demonstrated in clinical trials. These studies showed that combinations of candesartan cilexetil 4 to 16 mg with hydrochlorothiazide 12.5 or 25 mg induced significant reductions reductions in systolic (S) BP and diastolic (D) BP from baseline in patients with mild to severe hypertension. Data from clinical trials indicated that reductions in BP induced by candesartan cilexetil 4 to 32 mg/hydrochlorothiazide 12.5 mg combinations were significantly greater than those observed after monotherapy with either drug. Treatment for 8 weeks with candesartan cilexetil 16 mg/hydrochlorothiazide 12.5 mg or candesartan cilexetil 16 mg induced SBP/DBP reductions of 12.0/7.5 mm Hg and 7.5/5.5mm Hg, respectively (p < 0.05 both comparisons). Moreover, data from a randomised, double-blind, placebo-controlled, dose-finding study in 1038 patients with mild to moderate hypertension showed that the greatest reductions in SBP/DBP were achieved by candesartan cilexetil 16 mg/hydrochlorothiazide 12.5 mg. Significant differences in BP reduction in favour of the combination were observed when hypertensive patients were given candesartan cilexetil 4 or 8 mg/hydrochlorothiazide 12.5 mg or hydrochlorothiazide monotherapy for 8 weeks. Additionally, greater efficacy of the combination compared to monotherapy with either drug was demonstrated by response rates to treatment. Moreover, a fixed combination of candesartan cilexetil 16 mg/hydrochlorothiazide 12.5 mg demonstrated a greater antihypertensive effect than losartan 50 mg/hydrochlorothiazide 12.5 mg in two clinical trials. Candesartan cilexetil 8 mg/hydrochlorothiazide 12.5 mg showed a similar antihypertensive effect compared with that of combined lisinopril 10 mg/hydrochlorothiazide 12.5 mg. Candesartan cilexetil/hydrochlorothiazide combination was well tolerated in patients with hypertension. Combined data from placebo-controlled trials showed that most adverse events were uncommon and not serious. Patients receiving combination therapy exhibited, among other adverse events, headache (3.2 vs 5.5% for candesartan cilexetil/hydrochlorothiazide and placebo, respectively), back pain (3.0 vs 2.4%), dizziness (2.6 vs 1.2%) and respiratory infection (2.5 vs 1.4%). Moreover, 3.3 and 2.7% of patients receiving candesartan cilexetil/hydrochlorothiazide or placebo, respectively, discontinued treatment because of adverse events. CONCLUSION: The combination of candesartan cilexetil and hydrochlorothiazide (AT(1)-receptor antagonist and thiazide diuretic, respectively) is an effective treatment for patients with hypertension. Data from randomised, double-blind, placebo-controlled clinical trials showed that this combination is significantly more efficacious than either agent alone. Moreover, the combination of these two agents showed an excellent adverse event profile. Current data support the use of this combination as an alternative when monotherapy with either agent is not effective, and there are no compelling or specific indications for other drugs. However, data from large clinical trials, evaluating morbidity and mortality outcomes, are needed to determine the precise role of candesartan cilexetil/hydrochlorothiazide combination in the treatment of patients with hypertension.     

Valsartan/hydrochlorothiazide: a review of its use in the management of hypertension

Valsartan/hydrochlorothiazide is a fixed-dose (valsartan 80, 160 or 320mg plus hydrochlorothiazide 12.5 or 25mg) angiotensin II receptor blocker/diuretic drug combination indicated for the treatment of patients with essential hypertension not adequately controlled by monotherapy.There is ample evidence that valsartan/hydrochlorothiazide is an effective fixed-dose combination antihypertensive agent. However, efficacy and tolerability data pertaining to the 320mg dose of valsartan in the combination are currently relatively few. There is also some evidence of potential benefits associated with the relatively favourable tolerability profile of the combination, the low occurrence of new-onset diabetes mellitus versus amlodipine and the valsartan-associated improvements in cardiac and endothelial function.     

Indapamide sustained release: a review of its use in the treatment of hypertension

A low-dose sustained-release (SR) formulation of the thiazide-type diuretic indapamide, indapamide SR (Natrilix SR), retains the antihypertensive activity of the immediate-release (IR) formulation, with a smoother pharmacokinetic profile. In well controlled 12- to 52-week clinical trials, indapamide SR 1.5 mg/day was well tolerated and reduced blood pressure as effectively as therapeutic dosages of amlodipine, candesartan, enalapril, hydrochlorothiazide or indapamide IR. Indapamide SR was also more effective than enalapril in reducing left ventricular hypertrophy (LVH), and similar reductions in renal end-organ damage, assessed by microalbuminuria, were seen with indapamide SR- and enalapril-based antihypertensive strategies. Indapamide SR provides an effective option for initial antihypertensive monotherapy and a basis for multidrug antihypertensive strategies.