Efficacy and tolerability of candesartan cilexetil/hydrochlorothiazide and amlodipine in patients with poorly controlled mild-to-moderate essential hypertension.

The antihypertensive efficacy and tolerability of combination therapy with candesartan cilexetil, 16 mg plus hydrochlorothiazide (CC/HCTZ), 12.5 mg was compared with that of amlodipine, in a multicentre, double-blind, randomised, parallel-group study in patients with mild-to-moderate essential hypertension inadequately controlled by monotherapy. After a two week run-in period on existing therapy, patients with a sitting diastolic blood pressure (DBP) of 90-110 mmHg and a sitting systolic blood pressure (SBP) 相似文献   

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.     

Efficacy and tolerability of valsartan in combination with hydrochlorothiazide in essential hypertension

OBJECTIVE: This study compared the efficacy and tolerability of two combination regimens of valsartan and hydrochlorothiazide (HCTZ) with valsartan monotherapy in patients with essential hypertension inadequately controlled with valsartan 80mg once daily. PATIENTS AND METHODS: A total of 708 patients with inadequately controlled blood pressure after 4 weeks' treatment with valsartan 80mg once daily participated in this double-blind comparative trial. Patients were randomly allocated once-daily treatment with valsartan 80mg, valsartan 160mg, valsartan 80mg + HCTZ 12.5mg or valsartan 80mg + HCTZ 25mg for 8 weeks. RESULTS: Statistically significant decreases in mean sitting diastolic blood pressure (SDBP) and mean sitting systolic blood pressure (SSBP) from baseline were seen in all treatment groups (least squares mean change from baseline SDBP: -5.1mm Hg, -6.2mm Hg, -8.2mm Hg, -10.8mm Hg; SSBP: -3.9mm Hg, -6.5mm Hg, -9.8mm Hg, -16.0mm Hg for valsartan 80mg, valsartan 160mg, HCTZ 12.5mg combination, HCTZ 25mg combination, respectively). A significant difference for mean SDBP, SSBP and responder rates in favour of the combination regimens was observed compared with either valsartan monotherapy. All treatments were well tolerated with the percentage of patients reporting treatment-related adverse experiences at any time ranging from 9.9% (valsartan 160mg) to 21.0% (HCTZ 25mg combination). CONCLUSION: The study demonstrated that a combination of valsartan 80mg and HCTZ 12.5mg or 25mg provides an effective and well tolerated treatment in patients who need additional blood pressure control beyond valsartan monotherapy.     

坎地沙坦酯片治疗原发性高血压118例

目的:比较国产坎地沙坦酯片与氯沙坦治疗轻、中度原发性高血压的疗效和安全性。方法:多中心、随机、双盲、双模拟、阳性药平行对照试验。经2 wk安慰剂导入期,238例原发性高血压病人进入8 wk治疗期,每日1次服用坎地沙坦酯片8 mg(n=118),或氯沙坦片50 mg(n=120),2 wk后如舒张压≥12 kPa则剂量加倍。结果:2组病人的血压均得到明显地降低(P<0.01);坎地沙坦酯组总有效率为82.2%,氯沙坦组为84.2%,2组间没有显著差异。坎地沙坦酯组和氯沙坦组收缩压和舒张压的降压谷峰(T/P)比值分别为0.75,0.71和0.76,0.94。结论:对轻、中度原发性高血压病人坎地沙坦酯片是一种有效、安全且易耐受的降压药,每日1次能维持24 h降压效应。     

Candesartan Cilexetil

Candesartan cilexetil is the orally administered prodrug of candesartan, an angiotensin II subtype 1 receptor antagonist. The pharmacokinetics (area under the plasma concentration-time curve and maximum plasma concentration) of candesartan do not appear to be affected by age, sex, or weight, with a similar exposure observed in children aged 1 to <6 years or >6 years and adults. Therapy with candesartan cilexetil 0.05, 0.20, and 0.40 mg/kg/day for 4 weeks was effective in the treatment of hypertension in children aged 1 to <6 years, inducing significant dose-dependent reductions from baseline in sitting SBP (SSBP) [primary endpoint] and sitting DBP (SDBP) in the double-blind phase of a randomized, parallel-group, multinational, dose-ranging clinical study. The criteria for antihypertensive response (SBP and DBP values that were less than the 95th percentile) were met by 28–66% of patients. The beneficial antihypertensive effects of candesartan cilexetil therapy were sustained for up to 160 weeks. No significant difference from zero in the slope of the placebo-adjusted change in SSBP (primary endpoint) and SDBP was observed across the three candesartan cilexetil treatment groups (candesartan cilexetil 2,8, or 16 mg/day in patients weighing <50 kg and candesartan cilexetil 4, 16, or 32 mg/day in patients weighing ≥50 kg) during the double-blind phase of a randomized, double-blind, parallel-group, placebo-controlled, multinational, dose-ranging study in children and adolescents aged 6 to <17 years. Nonetheless, candesartan cilexetil demonstrated significantly greater changes from baseline to the end of the double-blind phase than placebo in SSBP and SDBP, with a significantly higher proportion of patients receiving candesartan cilexetil meeting the criteria for antihypertensive response than those receiving placebo. Antihypertensive response rates were sustained for 52 weeks. Candesartan cilexetil therapy for up to 160 weeks was generally well tolerated in clinical studies in children and adolescents aged 1 to <17 years with hypertension.     

Switch from ABCD pretreatment to A-II-A treatment: a multinational, open, centrally randomized, prospective parallel group comparison

The aim of this trial was to evaluate the efficacy and safety of switching antihypertensive monotherapy from a non-angiotensin II receptor blocker treatment, i.e., angiotensin-converting enzyme (ACE) inhibitor, beta-blocker, calcium (Ca2+) channel blocker or diuretic, to monotherapy with candesartan cilexetil 8 or 16 mg once daily. Patients (age 18-74 years) with mild to moderate essential hypertension were enrolled in this multinational, open-label, centrally randomized, prospective parallel group study. Previous antihypertensive treatment, with either an ACE inhibitor, a beta-blocker, a Ca2+ channel blocker or a diuretic, was maintained for a run-in period of 4 weeks and was then substituted at the baseline visit where patients were randomized into two groups to receive either candesartan cilexetil 8 mg (n = 985) or 16 mg (n = 982) once daily for an 8-week treatment period. Blood pressure (BP) reduction was the primary endpoint after 4 weeks of therapy and the secondary endpoint after 8 weeks of therapy. Results of the first 4 weeks of therapy are presented here. A total of 1,967 patients were included: 985 received candesartan cilexetil 8 mg and 982 candesartan cilexetil 16 mg once daily; 1,879 patients were included in the intention-to-treat analysis. The percentages of patients receiving an ACE inhibitor, a beta-blocker, a Ca2+ channel blocker or a diuretic as previous antihypertensive treatment were 44.7, 18.8, 30.6 and 5.9%, respectively. After 4 weeks of treatment with candesartan cilexetil 8 and 16 mg, sitting diastolic and systolic BP were reduced (mean +/- SD): -7 +/- 10 and -14 +/- 17 mmHg, and -8 +/- 10 and -16 +/- 16 mmHg, respectively. The percentage of patients who were still borderline hypertensive or hypertensive after 4 weeks of substitute treatment was lower in the candesartan cilexetil 16 mg group than in the 8 mg group: 7.1 and 5.3%, respectively, versus 9 and 7.4%, respectively. Reported adverse events were mild or moderate in intensity and in accordance with those reported in the literature. Candesartan cilexetil can be considered an effective and safe alternative to other common antihypertensive monotherapies in a large spectrum of patients with mild and moderate hypertension.     

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

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

与氯少坦对照评价坎地沙坦西酯治疗轻 中度高血压的疗效和安全性

目的评价坎地沙坦西酯对轻、中度原发性高血压的降压疗效及安全性。方法采用随机双盲研究方法,坎地沙坦西酯和氯沙坦随机、双盲治疗轻、中度原发性高血压患者40例,男性30例,女性10例,年龄(46±6)岁,各组20例,给予双盲药坎地沙坦西酯8mg口服,每日1次,或氯沙坦50mg口服,每日1次;4周后根据血压情况决定维持原剂量或分别增加到12mg口服,每日1次,或100mg口服,每日1次;总疗程8周。结果坎地沙坦西酯治疗原发性轻、中度高血压8周末的显效率55%,总有效率75%,收缩压下降(20.0±12.5)mmHg,下降幅度为15.2%;舒张压下降(10.0±2.4)mmHg,下降幅度为10.8%,出现不良反应的发生率为5%。结论坎地沙坦西酯治疗轻、中度原发性高血压的短期疗效明显,每日1次,疗效持久稳定,不良反应少。     

A 52-week comparison of lisinopril, hydrochlorothiazide, and their combination in hypertension

Lisinopril is a long-acting converting-enzyme inhibitor. A 52-week study was undertaken to compare the antihypertensive efficacy and safety of lisinopril, hydrochlorothiazide (HCTZ), and a combination of the two drugs in 24 patients with a sitting diastolic blood pressure (DBP) of 90 to 120 mm Hg. After a four-week single-blind placebo-washout phase, ten patients received lisinopril, ten received HCTZ, and four received the combination in increasing doses in a double-blind fashion for the next 12 weeks. The target blood pressure was less than 90 mm Hg DBP and a decrease of at least 10 mm Hg. For the next 12 weeks, the responders continued to receive the same medications; however, the nonresponders from the two groups received the combination, increasing the number of patients receiving both to 13. The DBP was controlled in eight of the ten patients with lisinopril, three of the ten patients with HCTZ, and 11 of 13 (four original and nine nonresponders) with the combination. For the next 28 weeks, 17 patients agreed to continue into a single-blind phase, during which blood pressure was controlled in six of the seven patients who were treated with lisinopril alone and nine of ten who received the combination. The heart rate rose significantly in the HCTZ-treated patients during the short-term treatment and decreased significantly in those treated with lisinopril during the long-term phase. Side effects were more frequent in patients receiving the combination but were always mild and subsided spontaneously. Lisinopril appeared to be more effective than HCTZ as a step-1 drug, and the combination was superior to either agent alone.     

A Randomized,Controlled Trial Comparing Diltiazem,Hydrochlorothiazide, and Their Combination in the Therapy of Essential Hypertension

Study Objectives . To compare the efficacy of combination therapy with sustained-release diltiazem and hydrochlorothiazide (DTZ SR-HCTZ) with that of monotherapy with DTZ SR, HCTZ, or placebo in the treatment of essential hypertension; and to determine whether the addition of a diuretic to diltiazem at apparent optimum doses of each agent significantly enhances their antihypertensive effects. Design . Multicenter, randomized, double-blind, placebo-controlled, parallel-group trial with a 6-week treatment phase. Setting . Private and university-based clinics. Patients and Participants . Subjects of either sex, ranging in age from 18–70 years, with a diagnosis of stable essential hypertension made from two consecutive weekly mean supine diastolic blood pressure (DBP) readings of 95 mm Hg or above to 110 mm Hg or less that varied 7 mm Hg or less after 4–6 weeks in the baseline phase. Of the patients enrolled, 298 met the inclusion criteria. Interventions . Combination therapy with DTZ SR-HCTZ 120 mg-12.5 mg, or monotherapy with DTZ SR 120 mg or HCTZ 12.5 mg, or placebo was administered twice daily. Measurements and Main Results . Combination therapy with DTZ SR-HCTZ lowered both supine DBP and SBP significantly (p<0.005) more than either single agent. The combination also lowered DBP and SBP significantly more than either monotherapy. During a 12-hour in-clinic monitoring period spanning a dosing interval, both the combination and DTZ SR therapies maintained efficacy, whereas the antihypertensive effects of HCTZ dissipated after 8 hours. Treatment-related adverse events for the combination and HCTZ were similar but slightly greater than those for DTZ SR and placebo. Conclusions . The addition of a diuretic to sustained-release diltiazem produced an enhanced antihypertensive effect compared with monotherapy with either individual agent.     

国产坎地沙坦酯与厄贝沙坦治疗原发性轻中度高血压疗效比较

目的探讨国产坎地沙坦酯对原发性轻中度高血压患者的疗效和安全性。方法60例原发性轻中度高血压患者,随机分为坎地沙坦酯和厄贝沙坦组,每组30例,采用双盲双模拟平行对照研究。经过2周的安慰剂清洗期后两组患者分别接受坎地沙坦酯片一日8mg或厄贝沙坦片一日150mg。2周后如果达到预期降压效果,则继续原剂量服药至4周末。如降压效果不理想,加量(坎地沙坦酯一日12mg或厄贝沙坦一日225mg)继续服药2周。观察所有入选患者4周内的血压、不良反应和生化指标变化。结果治疗结束时坎地沙坦酯组收缩压下降15.1%,舒张压下降12.2%;厄贝沙坦组收缩压下降12.6%,舒张压下降9.2%。两组相比无显著差异。两组均未见严重不良反应。结论国产坎地沙坦酯为治疗原发性轻中度高血压安全且有效的药物。     

Oral clonidine for rapid control of accelerated hypertension

Thirty emergency-room patients, 15 men and 15 women, from 27 to 64 years old with diastolic blood pressures (DBP) greater than 115 mm Hg, were admitted to an open-label, oral loading trial of clonidine. At this time, their supine mean arterial pressures (MAP) averaged 150 +/- 2 mm Hg. An initial clonidine dose of 0.1 to 0.2 mg was to be followed every hour by another 0.1 mg until the DBP had been lowered to a level allowing treatment to be continued on an ambulatory basis or until a total of 0.5 mg had been given. A satisfactory response--defined as a reduction of the supine DBP to 105 mm Hg or lower if the baseline was between 115 and 135 mm Hg, or reduction of a baseline DBP greater than 135 mm Hg by at least 30 mm Hg--was achieved in all but one of the patients in an average of 118 minutes; the mean dose required was 0.26 mg. The mean reduction from the baseline MAP was 23.1 +/- 0.9%. Drug-related adverse experiences comprised drowsiness and dry mouth in 13 patients. Thereafter, 28 of the patients were chronically treated with clonidine for an average of 73 days. In 24 patients treated for at least 80 days, the daily clonidine dose averaged 0.375 mg. All the patients required concurrent diuretic therapy. A satisfactory response (as defined above) to this maintenance treatment was shown by 85% of the patients, and full blood-pressure control (supine DBP less than 95 mm Hg) was attained in 78%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of the effect of candesartan cilexetil on the steady-state pharmacokinetics of tacrolimus in renal transplant patients

BACKGROUND: Candesartan cilexetil is a possible treatment for hypertension in renal allograft recipients. Tacrolimus is widely used as an immunosuppressant following renal transplantation. The aim of this study was to evaluate the effect of multiple doses of candesartan cilexetil on the steady-state pharmacokinetics of tacrolimus. METHODS: Twelve patients received oral doses of tacrolimus twice daily for 12 days from study day -2 until day 10, single oral doses of candesartan cilexetil placebo on study days -2 to -1, single oral doses of 2 mg candesartan cilexetil once daily on study days 1 to 3, oral doses of 4 mg candesartan cilexetil once daily on study days 4 to 6, and oral doses of 16 mg candesartan cilexetil once daily on study days 7 to 9. Serial blood samples were collected on days -1, 6 and 9 and were analysed for tacrolimus using microparticle enzyme immunoassay. RESULTS: Mean C(max,ss) and AUC(tau,ss) values for tacrolimus on day 6 (4 mg candesartan) and day 9 (16 mg candesartan cilexetil) were similar to those on day -1 (tacrolimus alone). Renal function did not change under treatment with candesartan cilexetil compared with baseline. The co-administration of multiple oral doses of cardesartan cilexetil with oral doses of tacrolimus was well tolerated. CONCLUSIONS: Concomitant administration of multiple doses of candesartan cilexetil does not alter the steady-state pharmacokinetics of tacrolimus.     

Evaluation of the antihypertensive efficacy and tolerability of moexipril,a new ACE inhibitor,compared to hydrochlorothiazide in elderly patients

Objective: To compare the antihypertensive efficacy of moexipril, a new angiotensin-converting enzyme (ACE) inhibitor, to treatment with hydrochlorothiazide (HCTZ). Patients: Two hundred and one non-hospitalized male and female patients between 65 and 80 years of age with essential hypertension. Methods: This was a multicentre, placebo-controlled, double-blind study with a parallel group design. Subjects with a sitting diastolic blood pressure (DBP) ≥ 95 mmHg were randomized to monotherapy with placebo, moexipril 7.5 mg o.d., moexipril 15 mg o.d. or HCTZ 25 mg o.d. for 8 weeks. Results: Throughout the study period treatment with moexipril and HCTZ resulted in significant reductions of DBP compared with placebo, but there were no significant differences between the active treatment groups. At end point the adjusted mean reductions were 10.5, 8.7 and 10.1 mmHg in the HCTZ, moexipril 7.5 mg and moexipril 15 mg groups, respectively, compared to 3.9 mmHg in the placebo group. Treatment with moexipril was associated with two cases of first dose hypotension and two cases of moderate and reversible increases in serum creatinine levels. Otherwise, both dosages of moexipril were well tolerated and the overall percentages of patients who had adverse experiences were smaller than in the placebo group. Conclusion: Moexipril is well tolerated and is at least as effective as HCTZ in elderly patients with essential hypertension. Received: 26 January 1995/Accepted in revised form: 11 September 1995     

The efficacy and safety of amlodipine in the treatment of mild and moderate essential hypertension in general practice

The antihypertensive efficacy and safety of amlodipine was evaluated in an open, multicenter general practice study. Hypertensive patients with sitting diastolic blood pressure in the range 95-115 mm Hg entered an initial 2-week baseline period during which they received placebo in a single-blind fashion. The dose of any concomitant antihypertensive treatment was kept constant for 4 weeks prior to baseline evaluations and throughout the study. Patients with an average sitting diastolic blood pressure > or = 95 mm Hg and < or = 115 mm Hg at two consecutive visits during the baseline period continued to the 8-week dose adjustment phase of the study. Patients were started on 5 mg of amlodipine once daily adjusted after 4 weeks to 10 mg once daily to achieve a target sitting diastolic blood pressure < or = 90 mm Hg. Amlodipine treatment produced significant falls in blood pressure (-23.7/-17.3 mm Hg; p < 0.05) with no effect on heart rate. Amlodipine was well tolerated, with most adverse events being mild or moderate. Investigators' global evaluation of toleration was excellent or good in 92% of patients. Subgroup analysis showed amlodipine to be equally efficacious and well tolerated in elderly or young patients, and in patients taking amlodipine as monotherapy or combination therapy.     

Antihypertensive Effect and Tolerability of Perindopril in Indian Hypertensive and Type 2 Diabetic Patients: 1-Year Randomised, Double-Blind, Parallel Study vs Atenolol

OBJECTIVE: This study compared the antihypertensive effect and acceptability of a perindopril-based group with that of an atenolol-based group in Indian hypertensive type 2 (non-insulin-dependent) diabetic patients. DESIGN AND SETTING: 100 ambulant patients aged between 35 and 69 years were recruited into this monocentric, randomised, double-blind study in two parallel groups for 1 year after a 1-month washout period on placebo. The setting was a tertiary care institution. PATIENTS: All patients had stable, essential hypertension between 95mm Hg and 115mm Hg, type 2 diabetes with glycosylated haemoglobin (HbA(1C)) <12%, and albuminuria between 300mg and 3.5g/24 hours. There were 50 patients per treatment group and two patient population groups were studied, intention-to-treat (ITT) and per-protocol (PP). The former constituted all patients, whilst the latter included those without major protocol deviation and who completed the 12-month study. INTERVENTIONS: The study drugs were perindopril 4 to 8mg once daily or atenolol 50 to 100mg once daily. In each group therapeutic adjustment was planned by doubling the dose and then by the addition of hydrochlorothiazide 25mg daily. Nifedipine 30 to 60mg daily was subsequently added if the desired drop in blood pressure was not obtained. The ITT group was analysed by Student's t-test, and a 2-way analysis of variance was performed for the PP population. MAIN OUTCOME MEASURES: A comparison of the control of hypertension, biochemical abnormalities, blood sugar and adverse effects was performed in the atenolol group versus the perindopril group. RESULTS: On single-dose therapy after 1 month 17 patients (60%) had normal blood pressure [diastolic blood pressure (DBP) 相似文献   

Candesartan cilexetil: an update of its use in essential hypertension

Candesartan cilexetil is converted to the angiotensin II receptor antagonist candesartan during absorption from the gastrointestinal tract. The selective and competitive binding of candesartan to the angiotensin II type 1 (AT(1)) receptor prevents binding of angiotensin II, a key mediator in the renin-angiotensin system. Significant reductions in systolic BP and diastolic BP are achieved with a once-daily dosage of candesartan cilexetil 2 to 32 mg/day in patients with mild to moderate hypertension. In randomised studies, candesartan cilexetil 8 to 16 mg/day was at least as effective as therapeutic dosages of losartan or other angiotensin II receptor antagonists. At a dosage of up to 32 mg/day candesartan cilexetil demonstrated greater antihypertensive efficacy than losartan 50 or 100 mg/day. In comparative trials, candesartan cilexetil demonstrated similar or greater antihypertensive efficacy compared with enalapril or hydrochlorothiazide and equivalent efficacy compared with amlodipine. The efficacy of candesartan cilexetil is not affected by age, and the drug provided significant BP reductions in Black patients and in those with severe hypertension. Long-term clinical studies to assess the effects of treatment with candesartan cilexetil on cardiovascular morbidity and mortality are ongoing. Regression of left ventricular hypertrophy has been seen with candesartan cilexetil treatment in patients with hypertension. Furthermore, the drug has favourable effects on renal function in patients with hypertension with or without coexisting diabetes mellitus. Renal vascular resistance and albumin excretion were reduced following treatment with candesartan cilexetil. Glucose homeostasis and lipid metabolism were not affected by treatment in patients with type 2 diabetes mellitus. Candesartan cilexetil is well tolerated and is not associated with cough, a common adverse effect of angiotensin converting enzyme inhibitor treatment. A pooled analysis of clinical trials found that the tolerability profile of candesartan cilexetil is not significantly different from that of placebo. Adverse events are not dose-related and are generally of mild to moderate severity. Conclusions: Candesartan cilexetil is an effective antihypertensive agent with a tolerability profile similar to that of placebo. Comparative data indicate that candesartan cilexetil has antihypertensive efficacy equivalent to that of other major classes of antihypertensive agents and has a long duration of action. Therefore, candesartan cilexetil is a useful therapeutic option in the management of patients with hypertension.     

A comparison of amlodipine with enalapril in the treatment of moderate/severe hypertension.

1. The safety and efficacy of amlodipine vs enalapril as monotherapy was evaluated in patients with moderate/severe hypertension (supine DBP 105-125 mm Hg, SBP 140-220 mm Hg). 2. After 2 weeks placebo treatment 31 patients were randomised by the technique of minimisation in an observer-blind study to receive once daily treatment with either amlodipine (15 patients) 5-10 mg, or enalapril (16 patients) 5-20 mg for 8 weeks. The study design concluded with 2 weeks placebo treatment. In addition to clinic measurements, home blood pressure monitoring (Copal UA-251) was performed during the study. 3. Clinic supine systolic blood pressure was reduced from 177 to 152 mm Hg (amlodipine) and 183 to 169 mm Hg (enalapril) (95% CI for the intergroup difference -22.1, 0.3, P = 0.06) after 8 weeks treatment. 4. Clinic supine diastolic blood pressure was reduced from 110 to 93 mm Hg (amlodipine) and 109-102 mm Hg (enalapril) (95% CI for the intergroup difference -17.7, -2.7, P < 0.01) after 8 weeks treatment. 5. Home blood pressure recordings confirmed these reductions in blood pressure. Although the reduction in blood pressure was greater for the amlodipine treated group, the differences between treatments were not statistically significant. 6. Both drugs were reasonably well tolerated. The adverse events occurring most frequently in the amlodipine group were headache (5), peripheral oedema (3), upper respiratory infection (3) and anxiety (2). The adverse events occurring most frequently in the enalapril treated patients were headache (6), dizziness (3) and upper respiratory infection (2).     

Serotonergic blockade compared with beta-adrenergic blockade in systemic hypertension: a double-blind comparison of ketanserin with propranolol

The safety and efficacy of ketanserin, a competitive serotonin blocking agent, and propranolol were compared in 33 patients with mild to moderate hypertension (sitting diastolic blood pressure [DBP] 95-115 mm Hg) using a placebo run-in, randomized, double-blind parallel study design. All patients received placebo for 4 weeks, then were randomized to receive increasing doses of either ketanserin (20, 40 mg twice daily) or propranolol (40, 80 mg twice daily) to achieve a goal sitting DBP less than 90 mm Hg. Patients not achieving the goal blood pressure with either drug as monotherapy, received the other drug in combination. At the end of the active monotherapy phase (week 10 of the study), propranolol demonstrated a greater decrease in DBP from baseline, as compared to ketanserin (-7.9 +/- 10.9 mm Hg with propranolol, P less than 0.05; -1.0 +/- 7.2 mm Hg with ketanserin, P = NS). Four out of 16 patients achieved goal response on propranolol, compared to 3/17 for ketanserin. With combination treatment, 9/18 patients reached the goal response; the addition of propranolol to ketanserin in non-responders resulted in further reduction of sitting DBP of -10.3 +/- 6.3 compared to monotherapy (P less than 0.001), while the addition of ketanserin to non-responders produced no significant response in sitting DBP. Propranolol showed a consistent effect in slowing heart rate. Ketanserin displayed less frequent side effects than propranolol. Propranolol used twice daily appears to be more effective than twice daily ketanserin use in patients with mild to moderate hypertension.     

Ketanserin combined with a beta-blocker or diuretic in essential hypertension. A multicentre study

Summary The antihypertensive effect of ketanserin 40 mg b.d. in combination with a beta-adrenergic blocking agent or a diuretic was assessed in an open study in 35 patients with essential hypertension, who had not responded to treatment with beta-blockers, diuretics or their combination.The ketanserin/beta-blocker combination decreased mean sitting systolic/diastolic blood pressure (SBP/DBP) from 169/107 mm Hg to 156/91 mm Hg at the end of the 12-week active treatment period. The decrease in systolic blood pressure was significant only at Week 8, while the decrease in diastolic blood pressure was highly significant at all times. A significant reduction in heart rate by 10 beats·min^–1 was observed with the ketanserin + -blocker combination.The ketanserin/diuretic combination led to a significant reduction in mean SBP/DBP from 164/106 mm Hg to 146/92 mm Hg after 12 weeks, with no significant change in heart rate. Body weight slightly increased in both groups.There were significantly fewer adverse reactions with the ketanserin/diuretic combination than with the ketanserin/beta-blocker combination.The results indicate a potentially useful therapeutic role for ketanserin in combination with beta-blockers or diuretics.