Telmisartan: a review of its use in hypertension

Telmisartan is an angiotensin II receptor antagonist that is highly selective for type 1 angiotensin II receptors. It was significantly more effective than placebo in large (n >100), double-blind, randomised, multicentre clinical trials in patients with mild to moderate hypertension. Telmisartan 20 to 160 mg once daily produced mean reductions in supine trough systolic blood pressure and diastolic blood pressure of up to 15.5 and 10.5 mm Hg, respectively. Maximum blood pressure reduction occurred with a dosage of 40 to 80 mg/day. Telmisartan 40 to 120 mg/day was as effective as amlodipine 5 to 10 mg/day or atenolol 50 to 100 mg/day in dose-titration studies. Telmisartan 20 to 160 mg/day was generally similar in efficacy to enalapril 5 to 20 mg/day or lisinopril 10 to 40 mg/day in both titration-to-response and other studies. Hydrochlorothiazide was coadministered in most of the titration-to-response studies if patients remained hypertensive. Telmisartan 80 mg/day was more effective than submaximal dosages of losartan (50 mg/day) or valsartan (80 mg/day) and was as effective as a fixed-dose combination of losartan 50 mg plus hydrochlorothiazide 12.5 mg over the last 6 hours of the dosage interval and the whole 24-hour postdose interval. In patients with severe hypertension, telmisartan 80 to 160 mg/day was as effective as enalapril 20 to 40 mg/day (both agents could be titrated and combined sequentially with hydrochlorothiazide 25 mg and amlodipine 5 mg). The addition of hydrochlorothiazide to telmisartan was more effective than each agent alone at lowering blood pressure in patients with hypertension. Telmisartan was well tolerated in patients with mild to moderate hypertension and was significantly less likely to cause persistent, dry cough than lisinopril. Conclusion: Telmisartan is an effective antihypertensive agent with a tolerability profile similar to that of placebo. Comparative data have shown telmisartan to be as effective as other major classes of antihypertensive agents at lowering blood pressure. Compared with lisinopril, telmisartan is associated with a significantly lower incidence of dry, persistent cough. Therefore, telmisartan is a useful therapeutic option in the management of patients with hypertension.     

Ramipril/felodipine extended-release fixed-dose combination: a review of its use in the management of essential hypertension

Ramipril/felodipine extended release (ER) [Triapin and Triapin Mite, Unimax] is a once-daily fixed-dose combination of the ACE inhibitor ramipril and the ER formulation of the dihydropyridine calcium channel antagonist felodipine. It is indicated in adult patients with essential hypertension whose blood pressure (BP) is inadequately controlled with ramipril or felodipine monotherapy. In this patient population, commercially available fixed-dose combinations (i.e. 2.5 mg/2.5 mg and 5 mg/5 mg) of ramipril and felodipine ER are more effective at controlling hypertension than the individual components used as monotherapy at the same dosages. Likewise, the 5 mg/5 mg combination is as effective as felodipine ER 10 mg, and more effective than ramipril 10 mg administered as monotherapy. The addition of low-dose ramipril plus felodipine ER (fixed-dose or combination of individual components) to the existing antihypertensive regimen also appears to provide adequate BP control and renal protection in hypertensive patients with non-diabetic chronic renal disease. In these patients, the low-dose combination of ramipril and felodipine ER was as effective as standard-dose felodipine ER, but more effective than standard-dose ramipril, in providing diastolic BP (DBP) control, and as effective as standard-dose ramipril, but more effective than standard-dose felodipine ER, in slowing the rate of regression of glomerular filtration. The ramipril/felodipine ER combination is as well tolerated as ramipril or felodipine ER monotherapy administered at the same dosages, and is better tolerated than felodipine ER monotherapy given at twice the dosage used in the combination. Overall, ramipril/felodipine ER appears to be an effective option for the treatment of adults with essential hypertension that is poorly controlled with monotherapy. In addition, a fixed, low-dose combination of ramipril/felodipine ER is a potential alternative to monotherapy for the initial management of essential hypertension.     

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.     

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.     

Fixed combination trandolapril/verapamil sustained-release: a review of its use in essential hypertension

In well designed studies in patients with mild to moderate hypertension, combinations of the sustained-release (SR) formulation of the nondihydropyridine calcium channel antagonist verapamil 120 to 240 mg/day and the ACE inhibitor trandolapril 0.5 to 8 mg/day were significantly more effective in reducing sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline than placebo. In most randomised studies, combinations of verapamil SR 120 to 240 mg/day and trandolapril 0.5 to 8 mg/day were significantly more effective in lowering sitting DBP and SBP than the corresponding monotherapies administered at the same dosage. Trandolapril/verapamil SR 2/180 mg/day provided significantly more effective 24-hour ambulatory blood pressure (BP) control than of the corresponding monotherapies. Moreover, trandolapril/verapamil SR reduced BP in patients inadequately controlled with either of the corresponding monotherapies. The antihypertensive efficacy of trandolapril/verapamil SR 2/180 mg/day was generally similar to that of other combinations of antihypertensive agents (metoprolol/hydrochlorothiazide, atenolol/chlorthalidone, lisinopril/hydrochlorothiazide, enalapril/hydrochlorothiazide) in patients with hypertension, including those with type 2 diabetes mellitus. Trandolapril/verapamil SR reduced BP in patients with hypertension and type 2 diabetes or primary renal disease, Black patients and elderly patients. Trandolapril/verapamil SR was more effective than the individual components administered as monotherapy in reducing proteinuria in patients with type 2 diabetes or primary renal disease. Trandolapril/verapamil SR had a neutral or beneficial effect on metabolic parameters (glucose, insulin, lipids) in patients with hypertension, including those with type 2 diabetes. Trandolapril/verapamil SR preserved left ventricular function in patients with heart failure. Fewer cardiac events occurred after therapy with trandolapril/verapamil SR than after trandolapril alone in post-myocardial infarction patients with congestive heart failure. The incidence of adverse events in recipients of trandolapril/verapamil SR was similar to that of the individual components, and that of other combination therapies. In placebo-controlled trials conducted in the US, headache, upper respiratory tract infections, cough, constipation, atrioventricular block (first degree) and dizziness were the most commonly reported adverse events in recipients of combinations of verapamil SR (120 to 240 mg/day) and trandolapril (0.5 to 8 mg/day). In conclusion, the fixed-dose combination of trandolapril/verapamil SR is an effective treatment for patients with hypertension, including those with type 2 diabetes. Trandolapril/verapamil SR tended to be more effective than monotherapy with either verapamil SR or trandolapril, and generally showed antihypertensive efficacy similar to that of other combination antihypertensive therapies. Current data support the use of trandolapril/verapamil SR as an alternative treatment when monotherapy with either agent is not effective. Data from large clinical trials currently being conducted will assist in fully defining the role of trandolapril/verapamil SR as a cardio- and renoprotective agent.     

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: 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.     

Trandolapril/verapamil sustained release: a review of its use in the treatment of essential hypertension

Trandolapril/verapamil sustained release (SR) [Tarka] is an oral, fixed-dose combination of the ACE inhibitor trandolapril and the SR formulation of the phenylalkylamine calcium channel antagonist verapamil. It is indicated for the treatment of hypertension in patients who require more than one agent to achieve blood pressure (BP) targets. In the large, randomised, multicentre INVEST (INternational VErapamil SR/trandolapril STudy), a verapamil SR-based treatment strategy that included trandolapril in most patients was as effective as an atenolol-based treatment strategy in reducing the risk of the primary outcome (first occurrence of death [all-cause], nonfatal myocardial infarction [MI] or nonfatal stroke) in patients with hypertension and coronary artery disease (CAD) and was as well tolerated. Trandolapril/verapamil SR is generally more effective at controlling hypertension than either component as monotherapy, and is as effective as a number of other fixed-dose combination therapies. The combination is as well tolerated as trandolapril monotherapy and is at least as well tolerated as verapamil SR monotherapy. In hypertensive patients with type 2 diabetes mellitus in the BENEDICT (BErgamo NEphrologic DIabetes Complications Trial), trandolapril/verapamil SR prolonged the time to the onset of persistent microalbuminuria compared with placebo, as did trandolapril monotherapy. Thus, trandolapril/verapamil SR is an effective option for the treatment of essential hypertension in patients requiring more than one agent to achieve BP targets, including those with compelling indications, such as CAD or type 2 diabetes.     

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.     

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.     

Amlodipine/ARB fixed-dose combinations for the treatment of hypertension: focus on amlodipine/olmesartan combination

The incidence of hypertension continues to increase worldwide and, according to recent estimates, its incidence is approximately 30% of the U.S. population. However, the control of blood pressure (BP) to recommended levels of < 140/90 mmHg for uncomplicated hypertension, recommended in the 7th Report of the Joint National Committee (JNC-7) on Prevention, Detection, Evaluation and Treatment of High Blood Pressure, remains low at 36.8%. Because the level of BP is directly related to cardiovascular and stroke morbidity and mortality, aggressive treatment and control of hypertension are strongly indicated. Since monotherapy alone is not effective for the control of stage 2 hypertension, fixed-dose combination therapy with two complementary drugs has been recommended by the JNC-7 guidelines as initial therapy for subjects with diastolic BP > or = 100 mmHg and systolic BP > or = 160 mmHg. There are several fixed-dose combination preparations already available, each with its individual indications. The recently FDA-approved fixed-dose combinations of amlodipine with either olmesartan or valsartan are very effective in treating hypertension and are safe and well tolerated. In addition to reducing BP, these new fixed-dose combinations have also demonstrated significant reductions in the inciendence of edema associated with amlodipine monotherapy, which makes them more acceptable to patients. In addition, due to the metabolic neutrality of both component drugs, these preparations are preferable for the treatment of hypertensive patients with diabetes or the metabolic syndrome, in addition to other cardiovascular risk factors.     

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     

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.     

复方替米沙坦胶囊中替米沙坦和氢氯噻嗪的HPLC测定

建立了HPLC法同时测定复方替米沙坦胶囊中替米沙坦和氢氯噻嗪的含量.采用Hypersil-BDS C18色谱柱,以氢氧化四丁铵磷酸盐缓冲液(pH 2.26)-乙腈(78:22)为流动相,检测波长230nm,柱温30C.替米沙坦在5～200μg/ml(r=0.9999)、氢氯噻嗪在1.6～64μg/ml(r=0.9998)浓度范围内线性关系良好.回收率分别为98.8%～99.8%和99.6%～99.9%.检测限分别为2.5和3.9ng.     

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.     

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.     

Triple-drug, fixed-dose combinations for the treatment of hypertension: focus on olmesartan/amlodipine/hydrochlorothiazide combination

Hypertension is a major risk factor for cardiovascular, renal and stroke complications. Its incidence continues to rise worldwide, and it is projected that by the year 2025, 1 billion people will be hypertensive. Despite the enormity of the high blood pressure burden, its control to < 140/90 mmHg for uncomplicated hypertensives and < 130/80 mmHg for patients with diabetes mellitus, chronic kidney disease or coronary artery disease remains poor and currently stands at approximately 50%. Reasons for this poor control include physician inertia and poor patient compliance and adherence due mostly to complicated drug regimens. Since hypertension is a multifactorial condition, its control will require the administration of multiple drugs with complimentary mechanisms of action. Several studies have shown that the patient's compliance and adherence to treatment is inversely related with the number of drugs administered. It is, therefore, important to combine different drugs with complimentary mechanisms of action into a single pill. Recent studies have shown that triple-drug combinations are very effective, safe and well tolerated by the patients. Three different triple-drug, fixed-dose combinations have recently been approved by the FDA for the treatment of hypertension, including, olmesartan medoxomil/amlodipine besylate/hydrochlorothiazide. These studies with collateral literature will be discussed in this concise review.     

The role of fixed-dose combinations in the management of hypertension: focus on lercanidipine-enalapril

Achieving optimal blood pressure (BP) control is the most important single issue in the management of hypertension, and in most patients, it is difficult or impossible to achieve target levels with one drug. Blocking two or more regulatory systems provides a more effective and more physiologic reduction in BP, and current guidelines have recommended the use of combination therapy as first-line treatment, or early in the management of hypertension. Fixed-dose combination therapy is an efficacious, relatively safe and cost-effective treatment option in most patients with essential hypertension. Of note, the once-daily administration of a fixed-dose enalapril/lercanidipine, by bringing together two distinct and complementary mechanisms of action, reduces BP effectively and has the potential for improved target organ protection relative to either class agent alone.