缬沙坦与依那普利、氨氯地平治疗高血压疗效比较

目的　与依那普利及氨氯地平相比较评价缬沙坦治疗原发性高血压病的疗效及安全性。方法　采用随机双盲试验 ,将 2 3 5例轻、中度高血压病患者随机分为缬沙坦组 (n =82 )、依那普利组 (n =76)和氨氯地平组 (n =77)。分别服用缬沙坦 80mg/d、依那普利 10mg/d或氨氯地平 5mg/d ,共 8周。用药 4周后对舒张压≥ 90mmHg者 ,以上剂量加倍。 结果　 8周末缬沙坦、依那普利和氨氯地平均能有效降压 ,有效率分别为 63 .4%、65 .8%、64 .9% ;组间差异无统计学意义。三者降压幅度无显著性差异 (P >0 .0 5 )。依那普利组干咳发生率达 14 .5 % (11/ 76) ,缬沙坦组干咳发生率为 1.2 % (1/82 ) ,二者相比差异有显著性 (P <0 .0 1) ,氨氯地平组出现面部潮红 3 .9% (3 / 77) ,踝肿 2 .6% (2 / 77) ,与前两组相比有显著性差异 (P <0 .0 1)。结论　缬沙坦治疗轻、中度高血压病疗效确切 ,可逆转患者心肌重塑 ,耐受性好     

厄贝沙坦与苯磺酸氨氯地平治疗轻中度原发性高血压的疗效比较

目的:比较厄贝沙坦(安博维)与苯磺酸氨氯地平(络活喜)治疗轻中度原发性高血压的降压疗效.方法:将2008年1月至2009年12月于明确诊断为轻中度原发性高血压患者100例随机分为安博维组和络活喜组各50例,分别应用安博维和络活喜治疗,比较两组治疗8周时的降压疗效.结果:治疗2周、4周、6周和8周时安博维组和络活喜组的降压有效(率)分别为35例(70%)、38例(76%)、41例(82%)、43例(86%)和36例(72%)、39例(78%)、40例(80%)、42例(84%),两组各疗程均无显著性差异.结论:厄贝沙坦(安博维)与苯磺酸氨氯地平(络活喜)治疗轻中度原发性高血压均可获良好疗效,且无明显不良反应.     

Effective and safe reduction of blood pressure with the combination of amlodipine 5 mg and valsartan 160 mg in hypertensive patients not controlled by calcium channel blocker monotherapy

INTRODUCTION: The addition of an angiotensin II receptor blocker to calcium channel blocker-based antihypertensive therapy may be associated with enhanced efficacy and reduced risk of adverse events. METHODS: This 8-week, open-label, single-arm trial evaluated the efficacy and tolerability of the combination of amlodipine and valsartan in patients not responding adequately to treatment with amlodipine or felodipine alone. Patients aged >/=18 years with moderate essential hypertension (defined as mean sitting systolic blood pressure [MSSBP] >/=160 and <180 mmHg) were treated for 4 weeks with once-daily amlodipine 5 mg or felodipine 5 mg. At week 4, patients not adequately responding were treated for an additional 4 weeks with once-daily amlodipine 5 mg plus valsartan 160 mg. Of 214 patients treated for 4 weeks with amlodipine 5 mg or felodipine 5 mg, 181 failed to achieve MSSBP <140 mmHg. These non-responders were treated for an additional 4 weeks with amlodipine 5 mg and valsartan 160 mg. RESULTS: A clinically and statistically significant additional reduction in MSSBP of 13.1 mmHg (95% confidence interval [CI]: 11.4, 14.7; P<0.0001) and a mean sitting diastolic blood pressure of 5.3 mmHg (95% CI: 4.3, 6.3; P<0.0001) were observed. Of patients treated with amlodipine 5 mg and valsartan 160 mg, 51.1% achieved target blood pressure levels (<140/90 mmHg) after 4 weeks. Adverse event rates were low in both treatment phases, and most were mild or moderate in severity. CONCLUSION: The combination of amlodipine/valsartan was effective and well tolerated.     

厄贝沙坦及氨氯地平对原发性高血压患者颈-股动脉脉搏传导速度及血清基质金属蛋白酶-9水平的影响

目的探讨厄贝沙坦及氨氯地平对原发性高血压患者颈一股动脉脉搏传导速度（CFPWV）及血清基质金属蛋白酶-9（MMP-9）水平的影响。方法38例轻中度原发性高血压患者为高血压组,根据治疗方法分为厄贝沙坦治疗组、氨氯地平治疗组,每组19例。另选择同期来我院健康体检的38例健康个体为对照组。厄贝沙坦治疗组给予厄贝沙坦口服治疗,氨氯地平治疗组给予氨氯地平口服治疗。各组患者均在治疗前后测量收缩压（SBP）、舒张压（DBP）;应用法国脉搏传导速度测定仪进行CFPWV测定,以评估大动脉弹性。清晨空腹采集静脉血,离心后采集血清,ELISA法检测血清中MMP9水平。结果高血压组患者CFPWV、MMP-9水平明显高于对照组（P〈0．01）;高血压组患者SBP、DBP均明显高于对照组（P〈0．01）。厄贝沙坦治疗组、氨氯地平治疗组患者治疗后CFPWV、MMP-9、SBP、DBP水平均较治疗前明显降低（P〈001）。2组治疗后CFPWV、MMP-9、SBP、DBP水平无显著差异。结论轻中度原发性高血压患者存在动脉结构与功能损害。厄贝沙坦和氨氯地平能有效降低和控制血压,两种药物之间无显著差异。     

Clinic blood pressure responses to two amlodipine salt formulations, adipate and besylate, in adult Korean patients with mild to moderate hypertension: a multicenter, randomized, double-blind, parallel-group, 8-week comparison

BACKGROUND: The commercially available formulation of amlodipine is conjugated with besylate salt to increase water solubility. Recently, a new amlodipine salt formulation has been developed in which the free base of amlodipine is conjugated with a chemically different salt, adipate. OBJECTIVE: The goal of this study was to compare the antihypertensive effect and tolerability of amlodipine adipate with those of amlodipine besylate in patients with mild to moderate hypertension. METHODS: This was a multicenter, randomized, doubleblind, parallel-group study in which patients received 8 weeks of treatment with either amlodipine adipate or amlodipine besylate. The primary efficacy variable was noninferiority of the difference in mean changes from baseline in trough diastolic blood pressure (DBP) after 8 weeks of treatment. Secondary efficacy variables included mean changes in DBP, systolic blood pressure (SBP), and response rate (defined as the proportion of patients whose DBP was <90 mm Hg or whose DBP had decreased from baseline by > or =10 mm Hg). The incidence of adverse events (AEs) was also assessed. RESULTS: Two hundred eleven patients were randomly assigned to receive amlodipine adipate (n = 106) or amlodipine besylate (n = 105). Study patients were primarily female (54.5%), with a mean (SD) age of 52.2 (9.6) years and a mean body weight of 67.1 (10.2) kg; there were no between-group differences in demographic profiles. After 4 weeks of randomized treatment, 58 (27.5%) patients (29 [27.4%] amlodipine adipate, 29 [27.6%] amlodipine besylate) had not achieved a mean DBP <90 mm Hg, and their dose was doubled. Mean DBP changes at 8 weeks were -15.2 (7.3) mm Hg in the amlodipine adipate group and -14.2 (7.4) mm Hg in the amlodipine besylate group (P = NS). Because the 95% CI for the difference in mean DBP changes between groups (-0.53 to 2.55) was within the prespecified lower limit (-4 mm Hg), amlodipine adipate was considered noninferior to amlodipine besylate. Mean SBP changes were -24.9 (12.1) mm Hg in the amlodipine adipate group and -22.0 (14.7) mm Hg in the amlodipine besylate group (P = NS). The response rates were 92.0% for amlodipine adipate and 95.4% for amlodipine besylate (P = NS). The overall incidence of clinical AEs was 20.8% in the amlodipine adipate group and 25.7% in the amlodipine besylate group (P = NS). Drug-related clinical AEs occurred in 5.7% and 12.4% of patients in the respective treatment groups (P = NS). Serum uric acid levels decreased significantly from base-line in both groups (P < 0.001). CONCLUSIONS: Eight weeks of treatment with amlodipine adipate produced significant reductions from baseline in blood pressure in these patients with mild to moderate hypertension. The efficacy of amlodipine adipate was not inferior to that of amlodipine besylate. Tolerability was comparable between the 2 treatment groups.     

Effects of enalapril in insulin-dependent diabetic subjects with mild to moderate uncomplicated hypertension

The antihypertensive efficacy of enalapril and its effects on the metabolism and kidney function were investigated in 11 insulin-dependent diabetic subjects with uncomplicated mild to moderate hypertension. During a short-term single-blind controlled trial, one daily dose of 20 or 40 mg enalapril significantly reduced both systolic and diastolic blood pressure. In the supine position, mean systolic blood pressure declined from 169 +/- 6 to 142 +/- 6 mmHg (P less than .01) and mean diastolic blood pressure from 101 +/- 1.5 to 85 +/- 2 mmHg (P less than .001). No changes in heart rate or postural hypotension were observed. During 1 yr of treatment, the antihypertensive efficacy of enalapril did not decline, and no clinical side effects were observed. Inhibition by enalapril of angiotensin-converting enzyme did not modify daily insulin requirements, glycemic control, uricemia, or lipid metabolism; kalemia and the markers of diabetic nephropathy were not significantly altered. These results suggest that enalapril once daily should be used as the first step in the treatment of diabetic patients with mild to moderate hypertension.     

Use of nebivolol in patients with mild and moderate hypertension

AIM: To evaluate the effectiveness and safety of the beta-adrenoblocker nebivolol in patients with mild and moderate essential hypertension. MATERIAL AND METHODS: The trial enrolled 20 patients. 11 of them had mild and 9 moderate arterial hypertension (mean age 47.1 +/- 9.52 years, hypertension history 6.98 +/- 2.75 years). 2-5 days after discontinuation of hypotensive drugs the examination was made including blood count, ECG, echocardiography, 24-h AP monitoring. It was repeated on days 56-60 of nebivolol therapy. Arterial pressure and heart rate were measured at the start of the treatment and 1, 3, 5 and 8 weeks later. RESULTS: Nebivolol treatment significantly reduced systolic arterial pressure in 30% and diastolic arterial pressure in 50% patients, heart rate decreased on the treatment day 7-10. On the treatment day 56-60 systolic and diastolic pressure lowered significantly in 53.3% and 66.7% patients, respectively. The analysis of changes in echocardiographic evidence found no significant shifts in volume and linear parameters. Nebivolol was well tolerated by 85% patients. Side effects included head ache, cardialgia, dizziness, weakness and nausea. CONCLUSION: Nebivolol (nebilet) is an effective hypotensive drug with mild side effects. Further studies on nebivolol effects on myocardial mass are needed.     

Diltiazem for treatment of essential hypertension: a double-blind controlled study with reserpine

In a double-blind, parallel, 12-week trial, antihypertensive effects of diltiazem and reserpine were compared in 107 patients with essential hypertension. Diltiazem reduced blood pressure from 176/100 mmHg to 154/86 mmHg after 12 weeks, and reserpine reduced blood pressure from 171/96 mmHg to 155/85 mmHg. The difference between diltiazem and reserpine was not statistically significant. However, among a subset of patients given 180 mg/day of diltiazem, a significantly better antihypertensive effect was achieved than among a subset given 0.3 mg of reserpine. The incidence of side effects and complications in the diltiazem group was about one half that in the reserpine group (12.3% and 27.1%, respectively). Side effects of diltiazem were mild, and the drug was extremely well tolerated. These results show that diltiazem is an effective antihypertensive drug for the treatment of mild to moderate essential hypertension.     

A comparison of initial treatment with losartan/HCTZ versus losartan monotherapy in chinese patients with mild to moderate essential hypertension

The antihypertensive efficacy and tolerability of losartan/hydrochlorothiazide (HCTZ) and losartan monotherapy as initial treatment were compared in a double-blind trial in Chinese patients with mild to moderate essential hypertension. Patients were randomised to initial treatment with either losartan/HCTZ (50 mg/12.5 mg) or losartan alone (50 mg). The doses were doubled after four weeks if diastolic blood pressure (SiDBP)was >90 mmHg. Both losartan/HCTZ and losartan alone significantly reduced SiDBP and SiSBP from baseline at the first measurement at 4 weeks (-10.1/-15.3 and -6.1/-6.9 mmHg, respectively; p<0.001) and at 8 weeks (-13.1/-18.5 and -8.7/-10.9 mmHg; p<0.001). The reductions with losartan/HCTZ were significantly greater than with losartan alone at weeks 4 and 8 (p<0.001). Both regimens were similarly well tolerated. In conclusion, initial therapy with losartan/HCTZ is effective and well tolerated in the treatment of Chinese patients with mild to moderate essential hypertension and produces a greater reduction in blood pressure than losartan alone.     

Results of a phase III, 8-week, multicenter, prospective, randomized, double-blind, parallel-group clinical trial to assess the effects of amlodipine camsylate versus amlodipine besylate in Korean adults with mild to moderate hypertension

BACKGROUND: Amlodipine besylate has been used in Korea for the treatment of hypertension for >17 years, with well-established efficacy and tolerability. Amlodipine camsylate is a newer formulation developed for generic use. It has been assessed in terms of physical stability and pharmacokinetic and pharmacodynamic properties and been found to be effective in lowering blood pressure in preclinical and Phase I and II trials. However, to date, no studies have compared the clinical effectiveness of amlodipine camsylate and amlodipine besylate in treating hypertension. OBJECTIVE: This study was designed to determine the effectiveness and tolerability of amlodipine camsylate compared with amlodipine besylate in Korean patients with mild to moderate hypertension. METHODS: This Phase III, 8-week, prospective, randomized, double-blind, parallel-group study was conducted in 13 cardiology centers across the Republic of Korea. Male and female Korean patients aged 18 to 75 years having uncomplicated, mild to moderate, essential hypertension (sitting diastolic blood pressure [SiDBP] 90-<110 mm Hg) and receiving no antihypertensives in the 2 weeks before randomization were eligible. Patients were randomly assigned to receive oral treatment with amlodipine camsylate or amlodipine besylate. For the first 4 weeks, patients received amlodipine 5 mg QD (morning). After 4 weeks, if either blood pressure was > or =140/ > or =90 mm Hg or SiDBP had not decreased by > or =10 mm Hg from baseline, the dose of amlodipine was increased to 10 mg QD for 4 weeks. Trough blood pressure and heart rate were measured in duplicate with the patient in the sitting position at each clinic visit (baseline [week 0] and weeks 4 and 8 of treatment); mean values were calculated and recorded. At weeks 4 and 8, tolerability was assessed using history taking and laboratory analysis, and compliance was assessed using pill counts. The primary end point was change from baseline in SiDBP at week 8. Secondary end points were change from baseline in sitting systolic blood pressure (SiSBP) at week 8 in the total population and in the subgroup of patients who had previously received antihypertensive treatment versus those who had not. RESULTS: A total of 189 patients were enrolled (mean age, 53 years; 105 women, 84 men; mean body weight, 65.8 kg). One patient in the amlodipine camsylate group dropped out of the study at week 0 of treatment (this patient did not use any study medication) and was excluded from the modified intent-to-treat (ITT) analysis. Thus, 188 patients were treated and included in the ITT analysis (94 patients per treatment group; ITT analysis); 161 patients were included in the perprotocol (PP) analysis (n = 80 for amlodipine camsylate, n = 81 for amlodipine besylate) (14 patients in the amlodipine camsylate group and 13 patients in the amlodipine besylate group were excluded from the PP analysis due to consistent withdrawal or protocol violation). Mean (SD) SiSBP and SiDBP were significantly decreased from baseline in both groups (amlodipine camsylate, from 146.7 [12.3]/96.6 [5.4] to 127.9 [14.8]/83.4 [7.7] mm Hg [both, P < 0.001]; amlodipine besylate, from 146.8 [12.8]/96.7 [5.1] to 128.0 [10.1]/83.8 [7.5] mm Hg [both, P < 0.001]). The differences in SiSBP/SiDBP between the 2 groups at week 8 were not significant. The SiDBP response rates in the subgroups that had and had not been previously treated with antihypertensives were statistically similar (56/69 [81.2%] and 83/92 [90.2%], respectively). The prevalences of clinical adverse events (AEs) were not significantly different between the 2 treatment groups (amlodipine camsylate, 27.3 %; amlodipine besylate, 28.7%). The most common AEs were dizziness and dyspnea (both in 3/94 [3.2%] and 1/94 [1.1%] patients who received amlodipine camsylate and amlodipine besylate, respectively). CONCLUSION: The effectiveness and tolerability of amlodipine camsylate were not significantly different from those of amlodipine besylate in these Korean adults with mild to moderate hypertension.     

Treatment of hypertension in patients > or =65 years of age: experience with amlodipine

BACKGROUND: Hypertension is a common finding in patients > or =65 years of age that contributes to cardiovascular morbidity and mortality, but many patients are untreated or their hypertension inadequately controlled. Recent randomized controlled studies have demonstrated the benefits of treating hypertension in the elderly. OBJECTIVE: This study was undertaken to assess the efficacy and tolerability of amlodipine, a long-acting calcium channel blocker, in elderly (> or =65 years of age) patients with mild to moderate hypertension (diastolic blood pressure 95 to 114 mm Hg). METHODS: This was an open-label, multicenter, 10-week, general-practice study involving patients >18 years of age. Patients with malignant or secondary hypertension or unstable angina were excluded, as were those who had experienced an acute myocardial infarction or stroke in the preceding 3 months or had been treated with an alpha-blocker in the preceding 6 months. Patients were assigned to 1 of 4 treatment schedules: amlodipine monotherapy or combination therapy and amlodipine given once daily in the morning or in the evening. Approximately 50% of patients would receive a morning dose, and approximately 80% would receive amlodipine as monotherapy. The paired t test was used to assess the significance of differences from baseline values, with significance set at P < 0.05. RESULTS: A total of 5135 patients received amlodipine and were included in the tolerability analysis. Of these, 3511 of 3628 patients (96.8%) <65 years and 1471 of 1507 patients (97.6%) > or =65 years (including 336 of 349 [96.3%] > or =75 years) were included in the efficacy analysis. Significant reductions (P < 0.05) in blood pressure were noted in all groups after 4 and 8 weeks of treatment. The equivalence of efficacy in all age groups was seen in terms of reduction in blood pressure (reduction of 21/15 mm Hg in patients <65 years of age, 25/16 mm Hg in those > or =65 years of age, and 26/17 mm Hg in those > or =75 years of age) compared with baseline. Therapy was successful in 2878 patients (82.0%) <65 years of age, in 1238 patients (84.2%) > or =65 years of age, and in 284 patients (84.5%) > or =75 years of age. The incidence of adverse events was similar in all age groups (18.0%, <65 years; 22.3%, > or =65 years; and 24.1%, > or =75 years), with no statistically significant differences between groups. Tolerability was rated as good or excellent in all patients, with no significant differences between groups. CONCLUSIONS: Once-daily amlodipine was effective in the treatment of mild to moderate hypertension in this patient population and demonstrated a low frequency of adverse events, a high degree of tolerability, and improved well-being. Morning rather than evening dosing appeared to confer a slight advantage.     

Atenolol and chlorthalidone therapy for hypertension: a double-blind comparison

In a randomized, double-blind, parallel-group study of 31 patients with mild to moderate hypertension, we compared a placebo regimen with a regimen of atenolol and chlorthalidone (Tenoretic). The study, which lasted seven weeks, began with a single-blind two-week placebo lead-in period, followed by a four-week double-blind treatment phase, and concluded with a one-week single-blind placebo washout period. Of 24 patients included in the analysis of efficacy, seven received one Tenoretic 50 tablet per day (atenolol, 50 mg; chlorthalidone, 25 mg), nine received one Tenoretic 100 tablet per day (atenolol, 100 mg; chlorthalidone, 25 mg), and eight received placebo. Supine systolic/diastolic blood pressure (mean +/- SD) decreased from 154 +/- 15.2/102 +/- 4.6 mm Hg during the baseline period to 128 +/- 8.5/85 +/- 4.0 mm Hg during treatment in the group receiving Tenoretic 100, from 153 +/- 12.6/104 +/- 5.4 mm Hg to 137 +/- 4.5/91 +/- 4.4 mm Hg in the group receiving Tenoretic 50, and from 150 +/- 11.9/101 +/- 1.6 mm Hg to 145 +/- 11.6/93 +/- 5.1 mm Hg in the group receiving placebo. Reductions in systolic and diastolic blood pressures in the active treatment groups were significantly greater than the pressure reductions in the group receiving placebo (P less than .05 to .1). The combination of atenolol and chlorthalidone was well tolerated, and in no case was treatment discontinued because of side effects. This study showed that one tablet per day of either Tenoretic 50 or Tenoretic 100 is effective and well tolerated in the treatment of mild to moderate hypertension.     

雷公藤多苷联合氯沙坦或氨氯地平治疗肾移植后蛋白尿

背景:蛋白尿和蛋白尿多少是影响移植肾功能存活的独立危险因素,雷公藤多苷或氯沙坦均有降尿蛋白作用.目的:观察雷公藤多苷联合氯沙坦或氨氯地平对治疗肾移植后蛋白尿的临床效果.方法:选择佛山市第一人民医院随访的肾移植后伴轻、中度高血压及蛋白尿患者40例,随机数字表法分为2组,雷公藤多苷+氯沙坦组口服雷公藤多苷0.5 mg/(kg·d),氯沙坦50 mg/d;雷公藤多苷+氨氯地平组口服雷公藤多苷0.5 mg/(kg·d),氨氯地平5 mg/d,要求血压控制在130/80 mm Hg(1 mm Hg=0.133 kPa)以下,观察治疗6个月,检测血压、肝肾功能、血尿常规,药物浓度,24 h尿蛋白,药物不良反应.结果与结论:40例患者均进入结果分析,患者用药后收缩压、舒张压均显著下降(P < 0.05),治疗6个月后,收缩压、舒张压均降至正常水平(P < 0.01).两组血压下降值、平均动脉压及治疗总有效率差异无显著性意义(P > 0.05).两组患者治疗前后血尿素氮、肌酐和血尿酸差异无显著性意义(P > 0.05).尿蛋白均减少,但差异亦无显著性意义(P > 0.05);环孢素用量较前减少(P < 0.05).提示雷公藤多苷联合氯沙坦或氨氯地平用于肾移植后伴轻、中度高血压伴蛋白尿患者,能平稳降压,减少环孢素用量,减少蛋白尿,保护移植肾肾功能.     

综合干预对轻中度高血压患者血压和心率的影响

目的寻找轻中度高血压患者新的有效护理干预方法。方法469例轻中度高血压患者随机分为3组,观察组171例、对照组Ⅰ149例和对照组Ⅱ149例;观察组采用磁珠耳穴贴压加有氧运动和饮食疗法;对照组Ⅰ采用有氧运动加饮食疗法;对照组Ⅱ采用药物治疗;观察3组患者的血压、心率变化及不良反应。结果观察组护理干预前后血压和心率比较有极显著性差异（P〈0．01）;对照组Ⅰ护理干预前后血压比较差异有显著性（P〈0．05）,心率比较差异无显著性（P〉0．05）;对照组Ⅱ护理干预前后收缩压和心率比较差异无显著性（P〉0．05）;观察组无不良反应。结论磁珠耳穴贴压加有氧运动和饮食疗法是轻、中度高血压患者的有效护理干预方法,且成本低,无不良反应。     

A comparison of the efficacy and tolerability of enalapril and sustained-release diltiazem in mild to moderate essential hypertension

The subjects of this multicenter study were 159 patients aged 21 to 76 years with mild to moderate uncomplicated essential hypertension. The patients were randomly assigned to receive up to 40 mg of enalapril daily or 360 mg of sustained-release diltiazem daily for a titration period of eight weeks and then maintenance doses for four weeks. The treatment goal was a supine diastolic blood pressure of less than 90 mmHg or a fall of at least 10 mmHg from baseline. During titration, 62% of the enalapril-treated patients and 51% of the diltiazem-treated patients reached the treatment goal after two weeks, 82% and 74% after four weeks, 87% and 84% after six weeks, and 92% and 87% after eight weeks. During the maintenance period, 85% of the enalapril-treated and 87% of the diltiazem-treated patients maintained the goal blood pressure. Treatment side effects were reported by 21% of the enalapril-treated patients and 29% of the diltiazem-treated patients; treatment was discontinued in two patients from each group because of side effects. It is concluded that both drugs were generally well tolerated and effective in the treatment of adult mild to moderate essential hypertension.     

Combined action of enalapril or timolol with hydrochlorothiazide plus amiloride in hypertension

59 mild to moderate hypertensives were treated for four weeks with 50 mg hydrochlorothiazide plus 5 mg of amiloride, then concomitantly with these diuretics with either enalapril (10-20 mg) or timolol (10-20 mg) in two parallel treatment groups for an additional 12 weeks in an open study. Addition of these drugs lowered the blood pressure by 25 +/- 3/16 +/- 2 mm Hg and 15 +/- 3/14 +/- 1 mm Hg, respectively. The difference of the reduction of the systolic blood pressure between enalapril and timolol group at the end of the combined treatment was statistically significant (p less than 0.01). The mean serum potassium was elevated by 0.3 mmol/l after addition of enalapril to the diuretic treatment, but none of the patients developed hyperkalaemia. No adverse effects on other routine laboratory values were observed. Both drug combinations can be considered efficient, well tolerated and safe in the treatment of mild to moderate hypertension.     

Comparison of efficacy and tolerability of amlodipine orotate versus amlodipine besylate in adult patients with mild to moderate hypertension: a multicenter, randomized, double-blind, placebo-controlled, parallel-group, 8-week follow-up, noninferiority trial

OBJECTIVE: The purpose of this study was to compare the efficacy and tolerability of amlodipine orotate with those of amlodipine besylate in Korean patients with mild to moderate hypertension. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group study was designed as a noninferiority study. To be included in the study, previously untreated patients had to have a sitting diastolic blood pressure (SiDBP) of 90 to 109 mm Hg. Previously treated patients had to discontinue their current annhypertensive medications and have a baseline SiDBP between 90 and 109 mm Hg after a 2-week washout period. Patients who met the inclusion criteria were randomly assigned to receive 5 mg amlodipine orotate or 5 mg amlodipine besylate for 8 weeks. The medication dose was doubled (10 mg QD for either amlodipine orotate or amlodipine besylate) 4 weeks after enrollment if SiDBP was >or=90 mm Hg. The primary efficacy analysis was noninferiority of the difference in mean trough SiDBP changes from baseline for amlodipin eorotate as compared with amlodipine besylate after 8 weeks of treatment. For the secondary efficacy analysis, 2 other measures were analyzed after 8 weeks of treatment. The SiDBP response rate was defined as an SiDBP measurement<90 mm Hg at the last clinical follow-up visit or an absolute reduction of >or=10 mm Hg in SiDBP from baseline until the last clinical follow-up visit. In addition, noninferiority of the difference in mean trough sitting systolic blood pressure (SiSBP) changes from baseline was analyzed for amlodipine orotate as compared with amlodipine besylate. The drug compliance rate was estimated by pillcount. RESULTS: Eligible patients (n=109; 43 women and 66 men) were randomly assigned to receive amlodipine orotate (n=53) or amlodipine besylate (n=56). No significant differences were found in sex, age, weight, or current smoking between the groups (all, P=NS). The proportion of patients with previous antihypertensive medications was not different between the groups (47.2% [25/53] in the amlodipine orotate group and 50.0% [28/56] in the amlodipine besylate group; P=NS). No significant differences were found in baseline SiDBP (mean [SD], 100 [6] mm Hg [range, 90-109 mm Hg] in the amlodipine orotate group and 100 [6] mm Hg [range, 90-108 mm Hg] in the amlodipine besylate group; P=NS) or in baseline SiSBP (mean [SD], 149 [14] mm Hg [range, 125-179 mm Hg] in the amlodipine orotate group and 146 [10] mm Hg [range, 123-167 mm Hg] in the amlodipine besylate group; p=NS). The mean (SD) changes in SiDBP were -15.6 (6.3) mm Hg for the amlodipine orotate group and -14.5 (5.5) mm Hg for the amlodipine besylate groups was 1.1 (5.9) mm Hg (95% CI, -0.87 to infinity), and because the lower boundary of the 95% CI was greater than -5 mm Hg, amlodipine orotate was considered noninferior to amlodipine besylate. The response rate was 48 of 51 (94.1%) in the amlodipine orotate group compared with 50 (92.6%) of 54 in the amlodipine besylate group after 8 weeks of treatment (P=NS). The mean (SD) compliance rates were 97.6% (3.6%) in the amlodipine orotate group and 96.5% (4.3%) in the amlodipine besylate group (P=NS). The incidence of drug-related adverse events (AEs) was similar between the groups (1/53 [1.9%]) in the amlodipine orotate group vs 4/55 [7.3%] in the amlodipine besylate group; P=NS). The most common drug-related AE overall was peripheral edema (2/55 [3.6%]), and the most common of all the AEs was upper respiratory tract infection (4/55 [7.3%]) in the amlodipine besylate group. The most common drug-related AE was headache (1/53 [1.9%]) in the amlodipine orotate group and peripheral edema (2/55 [3.6%]) in the amlodipine besylate group. No severe AEs were found in either group. CONCLUSION: The reduction in SiDBP after 8 weeks of amlodipine orotate treatment was noninferior to that of amlodipine besylate in these Korean patients with mild to moderate hypertension. The SiDBP response rate and the reduction in SISBP after 8 weeks of amlodipine orotate treatment were not significantly different from those of amlodipine besylate treatment. Both agents were wel tolerated.     

Aliskiren-based stepped-care treatment algorithm provides effective blood pressure control

Aims: Recent guidelines for the management of hypertension recommend an individualised stepped‐care treatment approach in mild‐to‐moderate hypertensive patients, to achieve blood pressure (BP) goals. This study evaluated the probability of patients achieving BP targets with an aliskiren‐based stepped‐care treatment regimen. Methods: This was a 24‐week, open‐label, non‐comparator study design that included six sequential 4‐week treatment periods in patients with mild‐to‐moderate hypertension. Over the potential 24 weeks of active treatment, incremental therapy included the following add‐on therapies at 4‐week intervals: aliskiren 150–300 mg once daily, hydrochlorothiazide (HCTZ) 12.5–25 mg once daily, and finally amlodipine 5–10 mg once daily, as needed to achieve target BP. Subjects achieving BP targets following any given 4 weeks of therapy were considered study completers, while subjects not achieving their clinical BP target entered into the next step of incremental therapy. The primary efficacy end‐point was the estimated cumulative probability of patients achieving BP target. Results: Of 256 patients treated, 232 (90.6%) completed the study. Baseline mean sitting BP was 155.7/91.7 mmHg. At study end‐point, the estimated cumulative probability of reaching BP target was 86.12%. The stepped‐care treatment regimen was well tolerated at the maximal recommended doses of all the individual complimentary therapies. Conclusion: An aliskiren‐based stepped‐care treatment regimen that subsequently included both HCTZ and amlodipine is effective in achieving BP goals in approximately 90% of patients with mild‐to‐moderate hypertension.     

Treatment of hypertension in the elderly

We have evaluated the effectiveness of antihypertensive therapy for predominant systolic hypertension in 55 patients, aged 61 to 76 years, with untreated systolic blood pressures of at least 160 mm Hg and diastolic blood pressures less than 100 mm Hg. In this retrospective analysis, 41 of the patients had been treated with the centrally acting agent guanabenz (average dose 24 +/- 14 [SD] mg daily) given alone, and 14 had received a combination of guanabenz (17 +/- 10 mg daily) and hydrochlorothiazide (60 +/- 30 mg daily). After six months of therapy, each regimen significantly decreased both systolic and diastolic blood pressures. Moreover, there were no differences between the two treatment regimens in their antihypertensive efficacy, and there was no evidence of orthostatic effects. In both treatment groups, approximately 50% of the patients had excellent therapeutic responses (decrease in supine systolic blood pressure of at least 20 mm Hg). The main side effects of treatment were drowsiness and dry mouth, though these tended to be mild and of short duration. Thus, in predominant systolic hypertension in elderly patients, guanabenz, either alone or in combination with a diuretic, appears to be an effective and well tolerated form of treatment.     

Efficacy and tolerability of a switch to fixed-dose combination therapy with amlodipine besylate/benazepril hydrochloride after monotherapy with amlodipine besylate: Data from the African-American subpopulation of a practice-based, open-label study (the LOGIC study)

Background: The LOGIC (LOtrel: Gauging Improved Control) study assessed the efficacy and tolerability of switching from amlodipine besylate monotherapy to fixed-dose combination therapy with amlodipine besylate/benazepril hydrochloride (HCI) in patients who were experiencing uncontrolled blood pressure (BP) or edema with monotherapy.Objective: This article reports the efficacy and tolerability of amlodipine besylate/benazepril HCI combination therapy in the predefined African-American population of the LOGIC study.Methods: This multicenter (1518 centers across the United States), practice-based, open-label, clinical trial enrolled patients with mild to moderate essential hypertension. Patients in group 1 had uncontrolled BP (sitting diastolic BP [DBP] ≥90 mm Hg and ≤110 mm Hg) during treatment with amlodipine besylate monotherapy 5 or 10 mg/d, and those in group 2 had controlled BP (sitting DBP ⩽90 mm Hg), but also had experienced edema during amlodipine besylate monotherapy. Participants were instructed to discontinue amlodipine besylate and were given amlodipine besylate/benazepril HCl 5/10 mg/d or 5/20 mg/d for 4 weeks. For group 1, the primary efficacy outcome was the change in mean sitting DBP (MSDBP) from baseline to week 4; a secondary efficacy outcome was the change in mean sitting systolic BP (MSSBP) from baseline to week 4. The primary efficacy outcome for group 2 was the percentage of patients whose edema improved with the switch to combination therapy. The secondary efficacy variables in group 2 were the changes in MSDBP and MSSBP from baseline to week 4. Patients in groups 1 and 2 were questioned about any adverse events that may have occurred since the previous visit. At both study visits, medications were reviewed, and the level of edema was assessed.Results: A total of 2055 African-American patients were enrolled in the study. At study end, African-American patients in group 1 (n = 1422 assessable patients) experienced significant reductions in MSSBP (13.9 mm Hg) and MSDBP (10.4 mm Hg) from those achieved during amlodipine besylate monotherapy (both P < 0.001). In group 2 (n = 266 assessable patients), 81% of African-American patients reported improvement in edema, and BP remained well controlled.Conclusions: In this study of an African-American subpopulation of patients with mild to moderate essential hypertension who had uncontrolled BP while receiving amlodipine besylate monotherapy, switching from amlodipine besylate monotherapy to fixed-dose amlodipine besylate/benazepril HCl combination therapy reduced BP to a greater extent than with amlodipine besylate alone, and reduced the incidence of edema in patients who were edematous but who had controlled BP. Fixed-dose combination therapy with amlodipine besylate/benazepril HCI has the potential to improve BP control, leading to improved clinical outcomes and enhanced treatment compliance.