尼群地平单用与联合依那普利对原发性高血压治疗作用比较

目的观察单用尼群地平和联合依那普利治疗原发性高血压的临床疗效和安全性。方法将120例轻中度高血压患者随机分为对照组（尼群地平）和治疗组（尼群地平＋依那普利）,疗程12周,检测两组治疗前后血压、心率、心电图和血、尿实验室检查的变化及药物的不良反应。结果对照组和治疗组总有效率分别为71.6%和95%（P〈0.05）,联合用药不良反应与单独用药相比较无明显增加。结论尼群地平和依那普利治疗原发性高血压较单独用尼群地平更有效地控制血压,具有良好的安全性。     

复方尼群洛尔片治疗原发性高血压的随机双盲平行对照多中心临床试验

目的 评价复方尼群洛尔片(钙拮抗剂,抗高血压药)治疗轻中度原发性高血压的疗效和安全性.方法 用随机双盲平行对照多中心临床试验方法 ,共入选437例原发性高血压患者,随机分成试验组和对照组(3∶1),分别服用复方尼群洛尔片(每片含尼群地平5 mg和阿替洛尔10 mg)每日2片或阿替洛尔片(每片25 mg)每月1片,疗程8周.结果 治疗8周后,试验组血压下降幅度大于对照组,2组DBP分别下降(15.0±6.6)、(11.7±5.8)mmHg(P＜0.01),2组SBP分别下降(18.8±10.4)、(15.8±10.1)mmHg(0.01＜P＜0.05);降压总有效率,试验组大于对照组,分别为88.9%和71.6%(P＜0.01).试验组和对照组不良反应发生率分别为30.3%和22.6%(P＞0.05),大多轻微,可自行缓解,实验室检查无明显异常.结论 复方尼群洛尔片治疗轻、中度原发性高血压疗效确切、耐受性好.     

两种联合用药方法治疗轻、中度原发性高血压的疗效比较

目的:比较国产厄贝沙坦与非洛地平或雷米普利合用对轻、中度原发性高血压的降压疗效。方法:60例轻、中度高血压患者随机分两组,经2周安慰剂导入期后,治疗期共8周,其中前4周为单药期,单服厄贝沙坦150 mg, qd;4周后试验组(n=27)联合服用非洛地平5 mg,qd,对照组(n=33)联合服用雷米普利5 mg,qd,均为4周。观察治疗前及治疗后4周和8周24 h动态血压监测,并测治疗前后坐位血压。结果:试验组与对照组治疗4周后坐位血压总有效率分别从48．1％和33．3％增加到88．9％和69．7％;试验组单用4周后无效病例14例,合用非洛地平4周后,显效10例(71．4％),有效2例(14．3％),无效2例(14．3％);对照组无效病例22例合用雷米普利4周后,显效11例(50．0％),有效2例(9．1％),无效9例(40．9％),经Ridit分析,两组降压疗效无显著差异(P>0．05)。动态血压单用4周无效病例,继续合用非洛地平或雷米普利4周后,试验组有效8例(66．7％),无效4例(33．3％);对照组有效4例(36．4％),无效7例(63．6％),经X2检验,2组疗效有显著差异(P<0．05)。试验组平滑指数SBP为(0．68±0．70), DBP为(0．56±0．78);对照组平滑指数SBP为(0．64±0．72),DBP为(0．70±0．69),两组比较无显著差异(P> 0．05)。结论:厄贝沙坦与非洛地平或雷米普利联合用药均有叠加降压作用,当单用厄贝沙坦无效时,前者组合比后者疗效更优,用动态血压的方法分析更加敏感。     

A randomized double-blind study of bisoprolol versus atenolol in mild to moderate essential hypertension

Summary We have compared the efficacy and pharmacokinetics of bisoprolol, a new cardioselective beta-adrenoceptor antagonist, with atenolol in a randomized double-blind crossover study in 12 patients (mean age 53.5 y) with mild to moderate essential hypertension. After a two week placebo wash-out period without any antihypertensive therapy, the patients were given bisoprolol 10 mg daily or atenolol 50 mg daily, increasing to 20 mg or 100 mg respectively if the sitting diastolic blood pressure did not fall below 90 mm Hg after two weeks of therapy. Crossover occurred after six weeks of active therapy followed by two weeks of placebo wash-out.After 6 weeks of therapy both drugs significantly reduced sitting and standing diastolic blood pressures (bisoprolol by 15% and 16% respectively, atenolo by 11% in both cases). However, while sitting and standing systolic pressures were significantly reduced by bisoprolol (13% and 16% respectively), only standing systolic pressures were significantly reduced by atenolol (11%), and this reduction was significantly less than with bisoprolol (p<0.05). Both drugs similarly reduced mean sitting and standing heart rates.There were no significant differences between the single-dose and steady-state kinetics of either bisoprolol or atenolol. The mean plasma elimination half-life (t_1/2) increased from 12.9 to 13.2 h during steady state on bisoprolol and from 7.2 to 11.5 h on atenolol. The apparent volume of distribution (V_z) was greater for bisoprolol than for atenolol after single dosing (235 1 vs 146 1) and at steady state (216 1 vs 137 1), but clearances were similar for both drugs. The maximum plasma concentration (C_max) of bisoprolol increased from 45 g·l^–1 to 72 g·l^–1 during steady state and the C_max of atenolol increased from 321 g·l^–1 to 410 g·l^–1 Adverse effects occurred in only one patient (lethargy while taking atenolol).These results suggest that bisoprolol has similar efficacy, safety, and pharmacokinetics to atenolol in patients with mild to moderate essential hypertension.     

Comparison of once daily felodipine 10 mg ER and hydrochlorothiazide 25 mg in the treatment of mild to moderate hypertension

Summary The efficacy of extended release felodipine 10 mg (ER) o.d., a new dihydropyridine calcium antagonist, and 25 mg hydrochlorothiazide (HCTZ) o.d. have been compared in a randomized, double-blind, crossover trial in 28 mildly to moderately hypertensive subjects (supine diastolic blood pressure, BP, 95 mm Hg and 110 mm Hg on three separate occasions).Both drugs significantly reduced systolic and diastolic BP in the sitting position felodipine from 157.1/93.8 mm Hg at baseline to 133/78.9 mm Hg 2.5 h after medication and to 138/82.7 mm Hg after 2 weeks of treatment, and HCTZ from 156/95.6 mm Hg to 147/88.4 mm Hg 2.5 h after medication and to 149/89.5 mm Hg also after 2 weeks.A decrease of the same magnitude in standing systolic and diastolic BP was observed after both treatment regimens with the exception of diastolic BP 2.5 h after dosing with HCTZ, which was not significantly lower. At all times (2.5 h and 2 weeks), the reduction in systolic and diastolic BP was greater after felodipine compared to HCTZ. Heart rate was significantly increased after felodipine in both the sitting and standing positions, and both 2.5 h following medication and after 2 weeks of treatment. The difference between the regimens was significant only 2.5 h after dosing. Overall, felodipine 10 mg ER o.d. was superior to 25 mg HCTZ o.d. in lowering BP.Presented in part at the Vth Scientific Meeting of the American Society of Hypertension, 17–20 May 1990, New York     

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.     

尼群地平与氨酰心安单用及合用治疗高血压病的降压效果和对左心功能影响的比较

高血压病Ⅰ、Ⅱ期９０例分为三组，对尼群地平２０ｍｇ、氨酰心安５０ｍｇ单用及合用而剂量减半的降压效果和左心功能影响进行了比较。结果表明两药合用副作用减少，降压效果不变，对左室收缩和舒张功能改善更加全面。     

依普罗沙坦与氯沙坦在轻中度原发性高血压病人中的降压疗效比较

目的:以氯沙坦为对照,观察依普罗沙坦治疗轻、中度原发性高血压(EH)病人的疗效与安全性。方法:采用前瞻性、随机、双盲、阳性药对照研究。符合方案的50例轻、中度EH病人经筛选期(2 wk)、安慰剂导入期(2 wk)后,随机分为依普罗沙坦组(n=24)与氯沙坦组(n=26)。在治疗期,2组病人分别每日1次口服依普罗沙坦600 mg或氯沙坦50 mg。若4 wk血压不达标,即坐位舒张压(DBP)≥90 mmHg (1 mmHg=0．133 3 kPa),加氢氯噻嗪12．5 mg,每日1次口服至8 wk。观察治疗前、治疗后4 wk与8 wk血压、心率以及治疗前后血、尿常规,血生化及心电图改变。结果:在治疗后8 wk,依普罗沙坦组的收缩压(SBP)与DBP分别下降了(12±s 10)mmHg与(12±5)mmHg,氯沙坦组的降压幅度分别为(14±9)mmHg与(10±6)mmHg,治疗前后比较有非常显著差异(P<0．01);但2组间血压下降的幅度无显著差异(P>0．05)。依普罗沙坦组与氯沙坦组的降压总有效率分别为100％和8l％,2组疗效无显著差异(P>0．05)。依普罗沙坦组加用氢氯噻嗪病例为9例(38％),而氯沙坦组为6例(23％),p> 0．05。2组心率及血液生化检查结果,治疗前后变化均无显著意义(P>0．05),均无严重不良反应发生。结论:依普罗沙坦与氯沙坦均能有效降低轻、中度EH病人的血压,疗效相似,都具有良好的安全性。     

厄贝沙坦治疗轻、中度高血压病

目的 :评价国产厄贝沙坦对轻、中度原发性高血压的降压疗效及安全性。方法 :为双盲对照试验。轻、中度原发性高血压病人 40例 (男性 3 2例女性 8例 ,年龄 49a±s 1 0a)随机分为厄贝沙坦组和缬沙坦组各 2 0例 ,分别给予厄贝沙坦 1 5 0mg ,po,qd或缬沙坦 80mg ,po,qd ;2wk后按血压决定维持原剂量或厄贝沙坦增加到 3 0 0mg ,po,qd或缬沙坦增加为 1 60mg,po,qd;总疗程 4wk。结果 :厄贝沙坦治疗 4wk末的总有效率为 75 % ,收缩压下降 (2 .7± 1 .8)kPa,舒张压下降 (1 .5± 0 .8)kPa均P <0 .0 1 ;不良反应的发生率为 5 %。结论 :国产厄贝沙坦治疗轻、中度原发性高血压的短期疗效明显 ,每日服药 1次 ,疗效持久、稳定     

A dose-response study of atenolol in mild to moderate hypertension in general practice.

A double-blind, crossover, multicentre study of 98 previously untreated patients with mild to moderate essential hypertension was carried out in general practice to assess the effect of 50 mg, 100 mg, and 200 mg atenolol, given once daily, compared with that of placebo over a period of 4 weeks each. At the end of the double-blind phase, all patients took 100 mg atenolol daily for a further 8 weeks. All three doses of atenolol produced statistically significant falls in systolic and diastolic pressure and pulse rate (p less than 0.001). The lowest pressures were achieved with 100 mg daily; a difference of 22/15 mmHg at the end of the double-bling phase, and a difference of 25/16 mmHg at the final observation. Body weight, blood urea, blood uric acid, and serum electrolytes remained within normal limits throughout the study. The incidence of side-effects with 50 mg and 100 mg atenolol was not significantly different from that caused by placebo, but the incidence of tiredness at the 200 mg dose level was greater than that caused by placebo and by the lower doses. The incidence of possible side-effects elicited by a questionnaire was low, the greatest number being volunteered by patients taking placebo. It is concluded that the optimal dose of atenolol for treating patients with mild to moderate hypertension in general practice is 100 mg daily.     

厄贝沙坦治疗轻、中度高血压病

目的 :评价厄贝沙坦治疗轻、中度高血压病的临床疗效和安全性。方法 :选取轻、中度高血压病病人 ,采用双盲双模拟、随机对照法 ,比较厄贝沙坦与氯沙坦的降压效果。经 2wk安慰剂导入期后 ,服厄贝沙坦 (5 8例 ) 75mg ,qd或氯沙坦 (5 9例 ) 5 0mg ,qd ,于wk 4末坐位舒张压≥ 12kPa者则剂量加倍 ,继续服用 4wk。厄贝沙坦组 17例病人与氯沙坦组 14例病人 ,分别于治疗前及治疗wk 8末行 2 4h动态血压监测。结果 :8wk治疗末 ,有效率厄贝沙坦组 83%、氯沙坦组 78% ,2组比较差异无显著意义 (P >0 .0 5 )。厄贝沙坦的谷 /峰值收缩压为 81% ,舒张压为 70 % ,氯沙坦分别为 75 % ,71%。 2组最常见的不良反应是头晕。结论 :对轻、中度高血压病 ,厄贝沙坦是一种有效、安全且耐受性好的降压药     

A comparison of bisoprolol and atenolol in the treatment of mild to moderate hypertension.

1. Fourteen patients (mean age 56.0, range 37-61 years; eight females) with mild essential hypertension (DBP greater than 90 mm Hg on placebo) completed a randomised, double-blind placebo controlled crossover study comparing the hypotensive effects of bisoprolol (10-20 mg) and atenolol (50-100 mg) each taken once daily. 2. Bisoprolol had a significantly greater antihypertensive effect than atenolol, reducing sitting blood pressures by 15.9 mm Hg (diastolic) and 21.9 mm Hg (systolic) compared with placebo. Corresponding figures for atenolol were 10.7 and 5.7 mm Hg respectively. Bisoprolol reduced standing blood pressures by 15.9 mm Hg (diastolic) and 22.8 mm Hg (systolic) compared with 7.3 and 8.6 mm Hg respectively for atenolol. 3. Examination of the pharmacokinetic data showed that bisoprolol had a median elimination half-life of 11.2 h during chronic dosing, compared with 6.4 h for atenolol. For bisoprolol, the median clearance fell from 264 ml min-1 after a single dose to 212 ml min-1 during chronic dosing, although clinically significant accumulation would not be expected during chronic administration. 4. Overall, the results suggest that bisoprolol may be a more effective antihypertensive agent than atenolol but larger studies are necessary to confirm these findings.     

Once daily amlodipine in the treatment of mild to moderate hypertension.

1. The antihypertensive efficacy of once-daily amlodipine was studied in a group of 30 patients with mild to moderate hypertension in a double-blind, placebo controlled parallel group study. The dose range of amlodipine was 2.5-10 mg daily titrated at 2 weekly intervals for a total treatment period of 8 weeks. 2. Amlodipine produced a significant reduction in blood pressure compared with placebo, the mean difference between baseline and 8 weeks (corrected for placebo effect) being 16/12 mm Hg supine, 14/4 mm Hg standing. 3. Blood pressure returned to baseline values during a terminal 4 week washout period on placebo. 4. There were no significant effects on heart rate. 5. Two patients experienced slight ankle oedema while receiving amlodipine 10 mg daily but the active drug was otherwise well tolerated. 6. Plasma concentration of amlodipine, sampled 24 h after the preceding dose, increased as the dose titration sequence was followed, averaging 2.5 ng ml-1 on 2.5 mg, 4.9 ng ml-1 on 5 mg and 10.5 ng ml-1 on 10 mg.     

Comparison of atenolol 50 mg and 100 mg as initial treatment in uncomplicated mild to moderate hypertension

Summary After screening a local population in the northern part of The Netherlands for hypertension, 59 patients with a diastolic pressure (DP) between 95 and 130 mmHg were randomized and treated either with 50 mg atenolol (n=29) or 100 mg atenolol (n=30) for 1 month. There was no significant difference between the two treatments, neither in the fall in systolic and diastolic pressures nor in the number of complaints reported. It is concluded that in the initial treatment of uncomplicated mild to moderate hypertension, 100 mg atenolol has no advantage over a 50 mg dose.     

塞利洛尔和阿替洛尔治疗轻中度高血压的随机双盲试验

目的:观察塞利洛尔治疗原发性高血压的短期和长期疗效.方法:原发性高血压60例,按4:1的比例随机分为试验组和对照组,分别服用塞利洛尔片和阿替格尔片,疗程6Wk.结果:试验组和对照组降压的总有效率分别为83.0%和86.7%,无显著差异.血压分别下降2.3/1.7 kPa(17.3/12.8mmHg)和2.4/1.7/kPa(18.2/12.8 mmHg),治疗前后差异非常显著.试验组心率下降程度较小,1例感疲乏,1例出现皮疹,无一例因不良反应而停药.结论:塞利洛尔治疗轻、中度原发性高血压安全有效.     

An open, parallel, comparative evaluation of amlodipine and nitrendipine in the monotherapeutic treatment of mild and moderate essential hypertension

The efficacy and safety of the dihydropyridine calcium antagonists amlodipine and nitrendipine as single-agent therapy of mild to moderate hypertension were compared in an open, parallel-group study. Interim analysis of data from 74 patients (43 male, 31 female) from an expected final total of 96 patients is reported. Amlodipine normalized blood pressure (< or = 90 mm Hg) in 94.7% of patients with a mean final dose of 8.3 mg/day, compared with normalization of blood pressure in 83.3% of patients treated with nitrendipine with a mean final dose of 28.3 mg/day. Only nitrendipine produced a statistically significant increase in heart rate after 2 and 4 weeks of therapy. Nitrendipine-treated patients reported more adverse events (47.2%) than the amlodipine-treated group (26.3%). Two patients from the nitrendipine group discontinued treatment due to treatment-related adverse events and one patient required a dose reduction. In the amlodipine-treated group, all adverse events were mild to moderate and dose reduction was required in one patient. In conclusion, although amlodipine and nitrendipine have comparable antihypertensive efficacy, in this study amlodipine was associated with fewer adverse effects.     

Effective dose range of enalapril in mild to moderate essential hypertension.

The dose-response relationship of enalapril was evaluated in a double-blind, balanced, two-period, incomplete-block study in 91 patients with mild to moderate essential hypertension. Patients were randomly assigned to two of six treatments: placebo, 2.5, 5, 10, 20 and 40 mg/day of enalapril maleate. There were two 3-week treatment periods, each preceded by a 4-week, single-blind placebo washout. Each dose of enalapril produced significant decreases in standing and supine systolic and diastolic blood pressure after 2 and 3 weeks of treatment. There were no significant changes on placebo. There was a significant linear dose response relationship for both mean blood pressure and mean change from baseline in blood pressure (P less than 0.01 for systolic and mean arterial pressure, and P less than 0.05 for diastolic pressure). Enalapril was associated with an increasing dose-response relationship across the 2.5-40 mg/day range. The 2.5 mg/dose is effective in some patients; however, doses greater than or equal to 10 mg/day may be necessary to achieve satisfactory blood pressure control.     

Short-term double-blind comparison of doxazosin and atenolol in patients with mild to moderate hypertension

The antihypertensive effect and safety of doxazosin once-daily was compared with that of atenolol once-daily in 40 patients with mild to moderate hypertension. During the first 4 weeks all patients received placebo therapy. During the subsequent 10 weeks patients were randomized to doxazosin or atenolol treatment. Treatment was initiated with 1 mg doxazosin or 50 mg atenolol once-daily. The dose could be doubled biweekly until a final dose of 16 mg doxazosin or 100 mg atenolol was reached. The average final dose of doxazosin was 6.4 +/- 0.8 mg (SEM) and that of atenolol 66.7 +/- 5.7 mg. During the 10 weeks of active treatment, the systolic and diastolic blood pressure tended to be lower (p less than 0.05) in patients on atenolol, this difference was however not significant for the standing blood pressure. Recumbent and standing heart rate were lower (p less than 0.01) during atenolol. Multiple regression analysis showed that in the doxazosin group the recumbent systolic blood pressure after 10 weeks of treatment was significantly (p less than 0.05) and independently related to age, recumbent systolic blood pressure at randomization, and the changes in recumbent heart rate. In neither group severe adverse reactions were observed. However, two patients on doxazosin dropped out of the study: one because of blurred vision and persistent high blood pressure, and one because of fatigue and palpitations. No patient dropped out of the atenolol group during the study.     

Comparison of the efficacy and acceptability of nicardipine and propranolol, alone and in combination, in mild to moderate hypertension.

1. We evaluated the relative efficacies and tolerability of various low-dose combinations of nicardipine and propranolol in patients with mild-moderate essential hypertension (DBP Phase V of greater than 90-125 mmHg; WHO Grades I and II) in order to select the best one. 2. Sixty patients completed the double-blind, balanced, randomised three-way cross-over protocol, with each phase lasting 4 weeks, and in which twice daily nicardipine 40 mg or propranolol 80 mg was compared with four twice daily combinations of nicardipine (20 or 30 mg) plus propranolol (40 or 80 mg). 3. At 'peak' effect time (i.e., 2 h post-dosing) all four treatment combinations were significantly more effective than propranolol, with effects ranging from 9-23 mmHg (systolic) and 5-15 mmHg (diastolic). Only the two 30 mg nicardipine combinations with propranolol were more effective than nicardipine monotherapy, further reducing BP by 8-13 mmHg (systolic) and 5-7 mmHg (diastolic); there were no significant differences between them. 4. 'Trough' diastolic pressures were not different between treatments and 'trough' BP control was sub-optimal on all treatments. 5. 70% of patients on nicardipine monotherapy, 33% of those on propranolol monotherapy and 30% of patients during the placebo run-in complained of symptoms. In terms of complaint rates, there was little to choose between the four combinations (27-33%). Serum potassium and creatinine levels were elevated following propranolol monotherapy by 0.19 mmol 1-1 and 6.5 mumol 1-1 respectively (P less than 0.01 for both) and following the nicardipine 30 mg/propranolol 80 mg combination. Nicardipine monotherapy elevated serum T4 levels by an average of 0.57 ng dl-1 (P less than 0.05). 6. The twice daily combination of nicardipine 30 mg plus propranolol 40 mg was therefore the optimum one in terms of its efficacy and tolerability. Further studies need to be performed to test the hypothesis that a higher dose of propranolol might ameliorate troublesome vasodilator side effects. However, none of the treatments studied was ideal for clinical use in the twice daily dosage used in this study.     

Long-term double-blind comparison of doxazosin and atenolol in patients with mild to moderate hypertension

The antihypertensive effect and safety of doxazosin once daily as well as the effect on serum lipids was compared with that of atenolol once daily in 40 patients with mild to moderate hypertension. During the first 4 weeks, all patients received placebo therapy. During the subsequent 46 weeks, patients were randomized to doxazosin or atenolol treatment. Treatment was initiated with 1 mg doxazosin or 50 mg atenolol once daily. The dose could be doubled biweekly for 10 weeks until a final dose of 16 mg doxazosin or 100 mg atenolol was reached. The patients then entered the maintenance phase for 36 weeks. The average final dose of doxazosin was 9.2 +/- 1.3 (SEM) mg and that of atenolol was 76.5 +/- 6.2 mg. During the 46 weeks of active treatment, the recumbent diastolic blood pressure (DBP) tended to be lower (p less than 0.05) in patients receiving atenolol at 10, 12, and 22 weeks of treatment. Recumbent systolic BP (SBP) and standing SBP and DBP were not different, however, between patients receiving doxazosin and those receiving atenolol. Recumbent and standing heart rate (HR) were lower (p less than 0.01) during atenolol. The decrease in serum total triglycerides, total cholesterol, and low-density lipoprotein (LDL)-cholesterol after 46 weeks of doxazosin was different (p less than 0.05) from the changes observed during atenolol therapy. Our data indicate that the antihypertensive action of doxazosin is accompanied by favorable effects on serum lipids.