Sustained release verapamil in hypertension. Results from a noninvasive ambulatory blood pressure monitoring and a clinical study

Summary The antihypertensive effect of a new sustained-release matrix formulation of verapamil 200 mg was investigated in a dose-response study in patients with mild to moderate essential hypertension. Noninvasive ambulatory blood pressure measurements were recorded over 24 h in 6 patients with diastolic blood pressure 100 mmHg. The patients received sustained-release verapamil 200 mg once daily and twice daily in a randomized order. Each medication period lasted 2 weeks. Verapamil 200 mg twice daily had a better antihypertensive effect than the same dose once daily. After a 6-week placebo period 27 patients with a diastolic blood pressure 100 mmHg were included in a double-blind clinical trial. The patients received sustained release verapamil 200 mg once daily and twice daily in a randomized crossover manner. Each medication period lasted 6 weeks, with an intervening 6-week placebo period. A diastolic blood pressure of 95 mmHg was achieved in 6 patients with the once-daily regimen and in 14 with the twice-daily regimen. The mean fall in diastolic blood pressure was 4 and 9 mmHg, respectively (p<0.05). We conclude that sustained-release verapamil 200 mg once daily gives a satisfactory blood pressure response only in a minority of patients, while 200 mg twice daily has a significantly better antihypertensive effect. Both doses were well tolerated.     

Antihypertensive properties of tiapamil (RO 11-1781)--a new calcium antagonist--in patients with mild and moderate essential hypertension

An open, non-comparative study, with a new calcium antagonist-tiapamil, was undertaken in 22 patients with mild and moderate essential hypertension (stage I-II WHO). After a two-week placebo period, patients were treated with tiapamil, 300-600 mg twice daily during a period of six weeks (Dose-finding period). Thereafter patients were continued on tiapamil during a 54 week period (Long-term follow-up). In some patients it was necessary to add the diuretic hydrochlorothiazide to obtain adequate control of the arterial hypertension. Monotherapy with tiapamil normalized supine diastolic blood pressure after the first six weeks in 17 of the 21 evaluable patients, and reduced it by greater than or equal to 10 mmHg (1.3 kPa) from baseline without normalization in two patients. In the two remaining cases the decrease was less than 10 mmHg. The optimal dose administered at six weeks in those patients who responded to treatment (normalization or decrease by greater than or equal to 10 mmHg.) was 600 mg/day in 32% of the cases, 750-900 mg/day in 47% and more than 900 mg/day in 21%. After completion of the dose-finding part, 19 patients continued treatment for a further 54 weeks. In 16 out of 19 patients hydrochlorothiazide was added to enhance the antihypertensive effect. All three patients who received tiapamil monotherapy throughout the trial, had normalized supine diastolic blood pressure on completing the study. In the 16 patients with the combination therapy, the addition of hydrochlorothiazide led in two patients to no further decrease in supine diastolic blood pressure, to an additional decrease by less than 10 mmHg in ten patients and by greater than or equal to 10 mmHg in four in comparison with the values obtained before starting combination therapy. At the end of the study 11 of these 16 patients had normalized supine diastolic blood pressure. The mean daily dose was 900 +/- 45 mg of tiapamil and 39 +/- 4 mg of hydrochlorothiazide. Both monotherapy and the combination regimen were well tolerated, and no effects attributable to drug interactions were observed. It may be concluded that tiapamil in oral doses of 300-600 mg twice daily is an effective antihypertensive agent with an excellent tolerance when administered for a period of 54 weeks.     

Felodipine extended release in mild to moderate hypertension

A multi-centre study was carried out to examine the antihypertensive effect and adverse event profile of felodipine in an extended-release (ER) formulation given once daily as monotherapy. Doses of 5 mg, 10 mg or 20 mg felodipine ER were compared with placebo in 183 patients with mild or moderate hypertension. All antihypertensive medication was discontinued on entering a 4-week placebo run-in period. If, at the end of the run-in period, supine diastolic blood pressure was in the range greater than 95 less than 120 mmHg, patients were randomly allocated to double-blind treatment with felodipine, 5 mg, 10 mg or 20 mg, or placebo, to be taken once daily for 4 weeks. Supine and standing blood pressure, heart rate and body weight were measured every 2 weeks during the trial. Assessments were made 24 hours after intake of the study drug. Adverse events were recorded at each review. Over the 4-week treatment period, a dose-related decrease in supine diastolic blood pressure was observed, this reduction occurring already during the first 2 weeks of active treatment. In the placebo group and the felodipine 5 mg, 10 mg and 20 mg groups, supine blood pressure (systolic/diastolic) decreased by 7/6 mmHg, 9/8 mmHg, 12/10 mmHg and 14/11 mmHg, respectively. Supine diastolic blood pressure reduction in the felodipine 10 mg group and both systolic and diastolic blood pressure reductions in the 20 mg group were significantly greater than with placebo. Standing diastolic blood pressure reduction was significantly greater in all three dose groups on felodipine compared with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)     

不同剂型美托洛尔治疗轻度高血压患者疗效分析

【摘要】目的比较不同剂型的美托洛尔对轻度高血压的临床疗效和安全性分析。方法64例原发性轻度高血压患者,采取随机单盲法分为常规组及缓释组。常规组（32例）：酒石酸美托洛尔片12．5mg,2次／d,可增至25mg,2次／d;缓释组（32例）：琥珀酸美托洛尔缓释片23．75mg,1次／d,可增加至47．5mg／d。入组前及治疗6周后测量诊室血压,记录24h动态血压及24h动态心电图,监测肝肾功能、血糖、血脂,记录药物不良反应。结果6周后两组诊室血压达标率均较高（78．1％VS87．5％）,但差异无统计学意义（P〉0．05）;动态血压显示两组收缩压及舒张压较治疗前均有显著降低（P〈0．05）,但两组间差异无统计学意义（P〉0．05）;缓释组晨峰血压增高发生率较对照组显著降低（P〈0．05）;两组平均心率差异无统计学意义。缓释组全部窦性心搏RR间期（简称NN间期）的标准差（standard diviation of NN intervals,SDNN）,相邻正常窦性心搏RR间期之差的平方根值（root mean squarevaluesofthestandarddeviationbetweenadjaeentnormalnumberofintervals,RMSSD）,相邻RR间期〉50ms的百分比（percentagebetween R-R and theperiod〉50ms,PNN50）较常规组显著增加（P〈0．05）;两组实验前后肝肾功能及血脂、血糖差异无统计学意义（P〉0．05）,无明显药物不良反应。结论对轻度原发性高血压,美托洛尔有较高的单药达标率,琥珀酸美托洛尔缓释片较酒石酸美托洛尔片可显著降低晨峰血压．提高心率变异性。     

Is initial dose titration of amlodipine worthwhile in patients with mild to moderate hypertension?

Amlodipine, a dihydropyrimidine calcium antagonist, is effective in the treatment of patients with mild to moderate hypertension at doses of 5-10 mg daily. The aim of the study reported here was to determine whether an early increase in dosage of amlodipine provided an advantage in terms of antihypertensive effect. This was a single-blind, randomised study in 115 patients with mild to moderate hypertension (diastolic blood pressure 95-114 mmHg) conducted at 10 centres with two parallel groups. Group I received amlodipine 5 mg once daily for the entire 10-week treatment period, while group II received amlodipine 5 mg once daily for two weeks, with the option to increase the dose to 10 mg once daily were the diastolic blood pressure to exceed 90 mmHg. The dose was increased in 40% of group II patients (20/50). Diastolic and systolic blood pressure decreased steadily until the end of the sixth week of treatment in both groups, with no statistically significant difference between the groups. The response rate (diastolic blood pressure < or = 90 mmHg) at the end of treatment was 84% in both groups. Because there is no advantage in an early increase in dosage of amlodipine in terms of antihypertensive effect, a dose increase should not be considered until after six weeks of treatment at 5 mg once daily.     

Control of blood pressure in hypertensive patients with felodipine extended release or nifedipine retard.

1. This multicentre hospital study compared the antihypertensive efficacy and the tolerability of once daily felodipine extended release (ER) with twice daily nifedipine retard (R) in hypertensive patients inadequately controlled on metoprolol monotherapy. 2. One hundred patients, aged 20-70 years, whose seated diastolic blood pressure was 100-115 mmHg after 4 to 6 weeks of metoprolol (200 mg day-1) monotherapy, were randomised, double-blind, to receive felodipine ER 10 mg once daily or nifedipine R 20 mg twice daily for 8 weeks. The dosage of felodipine or nifedipine was doubled if seated diastolic blood pressure exceeded 95 mmHg, 2 or 4 weeks after randomisation. Metoprolol 200 mg once daily was taken throughout the trial. 3. Fifty-one patients received felodipine ER and 49 nifedipine R; 46 and 45 respectively completed the 8 week trial. About half of patients on each treatment needed the higher dose. The baseline characteristics of the felodipine and nifedipine groups were generally well balanced. 4. Seated diastolic blood pressure was reduced by 17 mmHg for felodipine (24 h post-dose) and by 9 mmHg for nifedipine (12 h post-dose), a difference between treatments of 8 mmHg (95% confidence interval 5 to 12 mmHg, P less than 0.0001). The attained blood pressures at the end of the study (felodipine 90 +/- 10, mmHg, mean +/- s.d.; nifedipine 95 +/- 10) were also significantly different (95% confidence interval for the 5 mmHg difference, -9 to -1 mmHg, P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

A multi-centre comparative study between ramipril and enalapril in patients with mild to moderate essential hypertension

A multi-centre, randomized, double-blind, parallel group study was undertaken in order to assess efficacy and tolerability of ramipril as compared to enalapril in mild to moderate hypertension. A 4-week placebo run-in period was followed by 4 weeks of treatment with active medication (5 mg ramipril or 10 mg enalapril in a single morning dose). In patients not responding to this dosage regimen at the end of a 4-week treatment period, the dose was doubled. After 8 weeks of active medication, 3 mg daily of the diuretic piretanide was added to the treatment of patients not responding to the doubled dose. A total of 202 patients was admitted in the placebo phase from which 174 patients who had evaluable data at the end of the study were included in the efficacy analysis. Based on the definition of a 'responder' as a patient who achieved a supine diastolic blood pressure of 90 mmHg or less, 40% of those on 5 mg ramipril achieved this level within 4 weeks; in the enalapril group, the corresponding figure was 36.6%. By the end of 12 weeks of active treatment, a total of 55% of the ramipril group had responded to a daily dose of 5 to 10 mg ramipril. An additional 18% responded when 3 mg piretanide was added to the regimen. In the enalapril group, 59% responded to 10 to 20 mg enalapril. A further 17% responded to addition of piretanide to 20 mg enalapril. A total of 19 patients developed 29 adverse drug events while receiving ramipril, alone and in combination with piretanide. In the enalapril group, 24 patients developed 36 adverse events during enalapril monotherapy and combination treatment. It is concluded that ramipril and enalapril in a ratio of 1:2 have comparable antihypertensive efficacy in mild to moderate hypertension but the number of adverse reactions was slightly higher with enalapril in this study.     

卡维地洛和美托洛尔治疗原发性轻中度高血压疗效比较

目的评价卡维地洛和美托洛尔治疗原发性轻中度高血压的疗效及安全性。方法68例原发性轻中度高血压患者随机分为卡维地洛组（n=33）和美托洛尔组（n=35），分别接受卡维地洛（一日2次，每次6．25～25mg）和美托洛尔（一日2次，每次12．5～50mg）治疗，为期12周。观察治疗前后24小时、日间、夜间平均血压及谷／峰比值、不良反应和实验室检查指标的变化。结果治疗后两组24小时、日间、夜间平均收缩压和舒张压均有明显下降（P〈0．05），且均有较好的谷／峰比。两组总有效率无显著差异（P〉0．05）。两组均未见严重不良反应。结论卡维地洛和美托洛尔均能平稳、有效、安全地治疗原发性轻中度高血压。相对于美托洛尔，卡维地洛对心率及糖酯代谢的影响较小。     

Metoprolol monotherapy in the treatment of mild hypertension

Metoprolol tartrate (MT) as monotherapy was administered orally in 17 patients with mild hypertension. All other drugs were discontinued 2 weeks prior to MT therapy. The present study group consisted of 10 men and 7 women within the age range of 42 to 71 years (mean ± S.D. = 55.8 ± 8). MT was administered at an initial dose of 50 mg twice daily. Subsequently, the dose of MT was titrated on a biweekly basis for a period of 12 weeks until the diastolic blood pressure was < 90 mmHg or a maximum daily dose of 300 mg was administered. The blood-pressure-lowering effect of MT was found to be clinically satisfactory and statistically significant (P < 0.05). Mild fatigue and swelling of the extremities were seen in two patients each. Mild headache, transient diarrhea, and mild cloudiness of mind were seen in one patient. From this study it is concluded that MT is a safe and effective first-step antihypertensive agent. The long-term effect of MT as a monotherapy in the treatment of mild hypertension needs further clinical evaluation.     

Efficacy and tolerability of tiapamil in patients with mild to moderate essential hypertension

Although early experience with tiapamil, a new calcium antagonist structurally related to verapamil, showed good antihypertensive efficacy and minimal adverse effects, recent studies have shown conflicting results. This single-blind dose-titration study was designed to determine the therapeutic efficacy, duration of action, and safety profile of tiapamil in patients with essential hypertension. After a 2-week washout period, patients received placebo for 4 weeks. Patients with a sitting diastolic blood pressure (SDBP) of 95-114 mm Hg received tiapamil 300 mg twice daily with dose increments of 150 mg twice daily every 2 weeks to a maximum of 1,200 mg/day. Once blood pressure (BP) control was achieved or patients were receiving 600 mg twice daily, they were followed up for an additional 2 weeks. Twenty of the initial 31 patients completed the trial, and 17 patients were receiving the highest dose of tiapamil. Nine patients dropped out because of adverse effects. No significant decreases in BP and heart rate (HR) were either noted by the clinic or apparent by 24-h ambulatory BP readings. Random assays of drug supplies showed that patients received the required dosage. The incidence of adverse effects rose with increasing doses of tiapamil: 27.6% of patients at 300 mg twice daily, 48% at 450 mg twice daily, and 81.8% at 600 mg twice daily. Dizziness, headache, and palpitations were the most frequent adverse effects. These results show that tiapamil given at a daily dose of 600-1,200 mg exhibits very little effect in lowering BP in patients with mild to moderate essential hypertension. Moreover, the incidence of adverse effects is much higher than reported in earlier studies.     

Comparison of two slow-release formulations of metoprolol with conventional metoprolol and atenolol in hypertensive patients

We have compared the beta-adrenoceptor blocking and antihypertensive effects of chronic once daily treatment with conventional metoprolol 200 mg, two 'long-acting' formulations of metoprolol 200 mg and atenolol 100 mg in a cross-over study in 12 hypertensive patients concurrently receiving diuretic therapy. The peak effects of all compounds were similar, with significant reductions in exercise heart rate and blood pressure. Twenty-four hours after dosing only atenolol treatment was consistently associated with a reduction in both exercise heart rate (P less than 0.001) and blood pressure (P less than 0.02) when compared with placebo. Once daily treatment of hypertension with metoprolol, even in 'long-acting' formulations, cannot be recommended because of waning antihypertensive effect which would be missed at routine clinic attendance. Metoprolol should be prescribed twice daily in hypertension. So-called long-acting formulations do not always confer benefits over conventional dose forms.     

Once daily enalapril in general practice patients with mild to moderate essential hypertension

Thirty-nine general practice patients with mild to moderate essential hypertension were treated with enalapril 10 to 40 mg once daily alone or in combination with hydrochlorothiazide 12.5 to 25 mg once daily for 20 weeks. Eighty-one percent of patients responded with a satisfactory reduction in supine diastolic blood pressure, and 58% became normotensive. No serious adverse clinical or laboratory effects were noted. Enalapril alone or in combination with low dose diuretic administered once daily was an effective alternative regimen for mild to moderate hypertension.     

Control of hypertension in elderly patients with felodipine and metoprolol: a double-blind, placebo-controlled clinical trial.

1. Forty-nine patients aged 65-80 years, whose Phase V diastolic blood pressure (dBP) was above 95 mmHg after 4 weeks open treatment with metoprolol 50 mg twice daily were randomized to receive, double-blind, the calcium antagonist felodipine (n = 32) 2.5 mg twice daily or placebo (n = 17) in addition to metoprolol for 2 weeks. If the dBP remained greater than 95 mmHg, the dose of felodipine or placebo was doubled for a further 2 weeks; if the dBP was still greater than 95 mmHg, the dose of felodipine was doubled again to 10 mg twice daily or the corresponding placebo dose given. The duration of the double-blind period was 6 weeks, all patients receiving metoprolol 50 mg twice daily throughout. 2. At the end of the double-blind period, the seated dBP was reduced from 103 +/- 5 (mean +/- s.d.) to 88 +/- 7 mmHg (P less than 0.001) by felodipine and from 105 +/- 100 +/- 11 mmHg (NS) by placebo. The differences between these reductions (P less than 0.01) and between the final dBPs (P less than 0.001) were significant. Eighty-nine per cent of patients receiving felodipine and 33% of those receiving placebo (P less than 0.001) had controlled (dBP less than or equal to 95 mmHg) BPs. Half (14/27 completing) of the patients receiving felodipine required 2.5 mg throughout; 9/27 needed 5 mg and 4/27 10 mg twice daily. Adverse events occurred with equal frequency in the two groups, but the profile was different.(ABSTRACT TRUNCATED AT 250 WORDS)     

A multi-centre,placebo controlled comparative study between 200 mg and 400 mg celiprolol in patients with mild to moderate essential hypertension

Summary

A two-centre, double-blind, placebo controlled, randomized 3-way crossover study was undertaken to assess the efficacy, tolerability and safety of celiprolol in mild to moderate essential hypertension. A 4-week single-blind placebo run-in/ screening period, during which no antihypertensive medication was given, was followed by 3 consecutive 4-week treatment periods with placebo or celiprolol (200?mg or 400?mg daily). At the end of the 4-week placebo run-in/screening period, 26 hospital out-patients with a seated mean blood pressure (systolic/ diastolic) of 161.4/101.7 mmHg and a mean pulse rate of 75 beats/min entered the double-blind crossover phase of the study. Results showed that there was no significant difference in seated mean systolic or diastolic blood pressure between 200?mg celiprolol daily (149.2/92.3 mmHg) and 400?mg celiprolol daily (149.1/ 92.5 mmHg). However, mean seated systolic and diastolic blood pressures were significantly (p<0.05) lower on celiprolol than on placebo (157.1/98.2 mmHg). Neither dose of celiprolol had a significant effect on seated pulse rate. No patient was withdrawn due to an adverse event and no laboratory assessment outside the normal range was reported to be of any clinical significance. It is concluded that oral celiprolol, 200?mg or 400?mg daily, is effective and well tolerated for controlling mild to moderate essential hypertension. Since both doses had very similar effects on blood pressure there is no advantage in this group of patients for the 400?mg daily dose of celiprolol.     

Long-term antihypertensive efficacy of ketanserin plus chlorthalidone

The long-term antihypertensive efficacy of a combination of ketanserin (20 mg), an S2 antagonist with alpha 1 blocking activity, and chlorthalidone (25 mg), given o.d., was evaluated in fifteen patients with primary hypertension of mild to moderate degree, aged 45-65 years, up to a 12-month observation period. Systolic (SBP) and diastolic (DBP) blood pressure, and heart rate (HR) were measured by an automatic recorder (Sentron Bard Biomedical) twice at rest after 5 min in a supine position and after 2 and 5 min in an upright position, 24 h after the last antihypertensive dose. Thirteen patients completed the study whilst two were lost to the follow-up. A significant reduction was observed in both SBP and DBP at rest. In particular, SBP was reduced from 167 +/- 17 mmHg to 152 +/- 21 mmHg (p less than 0.01) after 1 month of therapy and was kept constant at this level throughout the observation period. DBP was also reduced from the first control [99 +/- 7 vs. 90 +/- 9 mmHg (p less than 0.01)] without any increase during the follow-up. HR was unchanged throughout the study. Four patients had dizziness and orthostatic hypotension after the first dose of the drug combination but were able to continue the study without further adverse reactions. These data support the conclusion that long-term treatment with the combination of a small dose of ketanserin and chlorthalidone is able to reduce systolic and diastolic blood pressure, without remarkable untoward side-effects.     

The effect of slow-release nicardipine on ambulatory and clinic blood pressure in mild hypertension.

1. The antihypertensive efficacy of a long acting formulation of the calcium channel blocking drug, nicardipine, was assessed using clinic and ambulatory (Remler M2,000) blood pressure measurements. 2. Eleven patients with essential hypertension (mean +/- s.e. mean; 173 +/- 6.6/103 +/- 1.9 mmHg) completed a randomised double-blind, placebo-controlled, cross-over study. The dose of nicardipine used was 60 mg twice daily for 4 weeks. 3. Mean ambulatory blood pressure was reduced from 164 +/- 5.3/97 +/- 2.9 to 151 +/- 5.2/88 +/- 2.4 mmHg (P less than 0.01); this effect was shown to be sustained for 8 h after the morning dose. Mean ambulatory heart rate was not significantly affected by treatment. 4. Clinic lying systolic blood pressure was reduced on treatment from 169 +/- 7.1 to 157 +/- 5.9 mmHg (P less than 0.2) and diastolic blood pressure from 99 +/- 3.6 to 89 +/- 3.9 mmHg (P less than 0.05). 5. One patient was withdrawn because of dizziness and flushing while on nicardipine; vasodilatory side effects such as headache, palpitations and flushing on nicardipine were noted by three patients. 6. We conclude that the long acting formulation of nicardipine studied in a dose of 60 mg twice daily is effective as monotherapy and is relatively well tolerated in mild hypertension. 7. This study highlights the importance of ambulatory blood pressure measurement in detecting significant changes in blood pressure, thereby permitting the study of small numbers of patients.     

Efficacy and tolerability of amlodipine in patients with mild-to-moderate hypertension.

Twenty-one subjects with mild or moderate systemic hypertension were treated for 12 weeks with amlodipine, a new calcium antagonist of the dihydropyridine group. Initial amlodipine dose was 5 mg once daily, but the dose could be increased after four or eight weeks to 10 mg once daily if diastolic blood pressure was not less than or equal to 90 mmHg (12.0 kPa). At the end of the study, a substantial reduction of systolic blood pressure (20 mmHg-2.7 kPa-from baseline) and diastolic blood pressure (14 mmHg-1.9 kPa-from baseline) was observed. Statistically significant changes in systolic and diastolic blood pressure were produced after four weeks of treatment. There were no statistically significant changes in heart rate throughout the study. Six patients with mild and five patients with moderate hypertension became normotensive after amlodipine treatment (64%). Two with mild hypertension finished the trial without change in hypertensive status, and four with initially moderate hypertension changed to mild at the end of the study. Only one patient dropped out due to an adverse reaction, two adverse events were rated severe, but did not require discontinuation. Overall impressions of efficacy were excellent or good in two-thirds of cases and poor in 10%; overall impressions of toleration were excellent or good in 71% of cases and poor in 10%. It is concluded that amlodipine is useful and well tolerated in patients with mild or moderate hypertension.     

Treatment of mild-to-moderate hypertension with calcium channel blockers: a multicentre comparison of once-daily nifedipine GITS with once-daily amlodipine

BACKGROUND: Hypertension is one of the most important causes of cardiovascular disease, and treatment of hypertension leads to a significant reduction in cardiovascular mortality and morbidity. Although calcium channel blockers are regarded as an important part of the therapeutic armamentarium against cardiovascular diseases, and are among the most frequently prescribed antihypertensive medications, concern has been aroused about these drugs, particularly the short-acting dihydropyrldine derivatives. However, the value of nifedipine GITS(Adalat-Crono), the long-acting dihydropyrldine, is in need of being re-established. OBJECTIVE: To compare the effectiveness, safety and tolerability of once-daily nifedipine and amlodipine treatment in patients with mild-to-moderate essential hypertension. DESIGN: Randomised multicentre trial with an open comparison of treatments for 12 weeks, with a preceding placebo run-in period of 2 weeks (patients on beta-blockers at the time of enrollment entered a mandatory 2-week wash-out period before being allowed In the placebo run-in period;this wash-out period was one week for patients using any antihypertensive medication other than beta-blockers). SETTING: Nine centres (all university hospitals) in Turkey. PATIENTS: 155 patients with essential hypertension(diastolic blood pressure 95-109 mmHg). INTERVENTIONS: Initial treatment (step 1) consisted of 30 mg nifedipine GlTS (n = 76; (Adalat-Crono tablets), or 5 mg amlodipine (n = 79; Norvasct5-mg tablets), either administered once daily, as a morning dose, or f the blood pressure was not below 140/90 mmHg, or the reduction In diastolic blood pressure was lower than 10 mmHg after a treatment period of 6 weeks, the dose was increased (Step 2) to 60 mg once daily in the nifedipine group, or 10 mg once daily in the amlodipine group. MAIN EFFICACY PARAMETER: Diastolic blood pressure at trough after 12 weeks of active compound therapy adjusted to baseline. RESULTS: After 12 weeks of treatment, the mean diastolic blood pressure was 83.1 and 81.9 mmHg,in the nifedipine and amlodipine groups, respectively (p = 0.436). The mean decrease in systolic blood pressure (28.5 +/- 11.9 and 28.2 +/- 11.2 mmHg in the nifadipine and amlodipine groups, respectively) and the mean decrease in diastolic blood pressure (16.4A +/- 7.0 and 17.5 +/- 6.9 mmHg in the nifedipine and amlodipine groups, respectively), as well as the responder rates (88.1%and 92.1%, in the nifediplne and amlodipine groups, respectively) were comparable at the end of the study. No significant differences between groups were detected In the efficacy parameters assessed in this study. Both drugs were well tolerated. The overall incidence of adverse events was 7.9% in the nifadipine group and 10.1% In the amlodipine group. However, more patients discontinued treatment prematurely in the amlodipine group (13 patients; 19.7%), than in the nifedipine group (four patients; 5.6%). CONCLUSIONS: The results of this study demonstrated that once-daily nifedipine in GITS formation and amlodipine are comparably safe and effective treatment options in patients with mild-to-moderate essential 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.     

Nitric oxide, erectile dysfunction and beta-blocker treatment (MR NOED study): benefit of nebivolol versus metoprolol in hypertensive men

1. Hypertensive men treated with beta-blockers frequently complain of erectile dysfunction. The present study investigated the effects of two beta(1)-adrenoceptor-selective antagonists, namely nebivolol and metoprolol, on erectile function in hypertensive men. 2. Male out-patients (age range 40-55 years) with newly diagnosed or existing stage 1 essential hypertension (mean seated systolic blood pressure 140-159 mmHg; diastolic blood pressure 90-99 mmHg) were enrolled in the study. All patients lived in a stable, heterosexual partnership and had no history of sexual dysfunction. After a 2-week placebo run-in period, patients were randomized double-blind to either Treatment group A (comprising nebivolol 5 mg once daily for 12 weeks, followed by placebo for 2 weeks and then metoprolol succinate 95 mg once daily for 12 weeks) or Treatment group B (comprising metoprolol succinate 95 mg for 12 weeks, placebo for 2 weeks and then nebivolol 5 mg for 12 weeks). An international index of erectile function (IIEF) questionnaire and a diary documented patients' sexual function and activity. 3. Nebivolol and metoprolol lowered blood pressure to a similar extent. Metoprolol, but not nebivolol, significantly decreased the IIEF erectile function subscore by 0.92 in the first 8 weeks after onset of beta-blocker treatment. In contrast with metoprolol, nebivolol improved secondary sexual activity scores and other IIEF subscores. 4. Despite similar antihypertensive efficacy of the cardioselective beta(1)-adrenoceptor antagonists nebivolol and metoprolol, nebivolol may offer additional benefits by avoiding erectile dysfunction in male hypertensive patients on long-term beta-adrenoceptor antagonist therapy.