Doxazosin in combination with atenolol in essential hypertension: a double-blind placebo-controlled multicentre trial

Doxazosin (mean dose 11 mg) given once daily in combination with 100 mg atenolol (n = 44) was compared with placebo and atenolol (n = 43) in a double-blind, multicenter study in patients with mild to moderate essential hypertension. In the atenolol/doxazosin-treated group, standing blood pressure significantly decreased by 17.0/12.3 mm Hg compared to 6.2/6.7 mm Hg in the atenolol/placebo group whereas supine blood pressure decreased by 13.2/9.8 mm Hg and 9.2/6.0 mm Hg, respectively in the two groups. Serum lipids did not change significantly in either group. The majority of side-effects reported were mild and transient. This study confirms that doxazosin may be safely combined with a beta-blocker. Doxazosin proved to be well tolerated and effective in patients with blood pressure refractory to atenolol alone.     

Nicardipine versus nifedipine: multicentre controlled trial in essential hypertension

Ninety-five hypertensive outpatients of both sexes, aged 23 to 65 years with diastolic blood pressures above 105 but below 120 mmHg (greater than 14.0 but less than 16.0 kPa), after one week on a placebo were randomly assigned either to nicardipine plus a placebo (40 mg/day - 48 patients) or nifedipine sustained-release plus a placebo (20 mg/day - 47 patients) for an additional six weeks. The study groups were homogeneous and comparable. After the run-in period the average blood pressure was 181 +/- 17/116 +/- 9 mmHg (24.1 +/- 2.3/15.5 +/- 1.2 kPa) in the nicardipine and 177 +/- 22/116 +/- 9 mmHg (23.6 +/- 2.9/15.5 +/- 1.2 kPa) in the nifedipine group (p greater than 0.10). In the acute oral test (nicardipine 40 mg to all the subjects; blood pressure measured at 30 min intervals during two hours) almost identical hypotensive effects within and between groups were observed (mean arterial pressure decrease of 11%, after 120 min; p less than 0.05). At the end of this trial blood pressure decreased further to 152 +/- 12/94 +/- 11 mgHg (20.3 +/- 1.6/12.5 +/- 1.5 kPa) (mean decrease of 20%; p less than 0.01) on nicardipine and to 145 +/- 12/94 +/- 11 mmHg (19.3 +/- 1.6/12.5 +/- 1.5 kPa) (mean decrease of 20%; p less than 0.01) on nifedipine. There were no significant changes in pulse rate. The observed between-group differences were trivial (p greater than 0.10). The laboratory data did not alter appreciably during this study. Three patients on nicardipine and four on nifedipine reported headache, palpitations and flushing: one patient on nicardipine and two on nifedipine were as a result excluded from the trial. It was concluded that nicardipine and nifedipine sustained-release were comparably effective and well-tolerated drugs suitable as the first-line agents for the management of mild to moderate hypertension.     

Piretanide in the treatment of essential hypertension. A double-blind comparison versus placebo

In a randomized, double-blind parallel group study the 24-hour hypotensive effect of piretanide and its influence on biochemical variables were compared with those of placebo in patients with mild to moderate essential hypertension. Sixty patients entered the study, all of whom met the inclusion criteria (RRdiast between 95 and 120 mmHg). There was no drop-out during the study, so that the results of all 60 patients were statistically analysed. Piretanide produced a significant reduction of both systolic and diastolic blood pressure over 24 hours which was evident at four weeks and was maintained and further enhanced over the ensuing trial period. A mean maximal fall (at 12 weeks) of 10.7% (BPdiast supine) was observed. Placebo tablets did not produce any clinically relevant changes in systolic blood pressure, whereas a slight decrease was seen in diastolic blood pressure. This blood pressure reduction was significantly less in the placebo group than in the piretanide group at the end of the study (weeks 10 and 12). Dose doubling was needed in 13 of the 30 patients in the piretanide group, whereas as many as 20 out of 30 patients needed dose doubling in the placebo group. Pulse rate did not change relevantly during the trial in either group. A slight reduction in body weight was observed in the piretanide group. The mean values of serum potassium and sodium showed a slight decrease but remained within the normal range during the study period. A small increase in serum phosphorus was noted. None of these changes required any specific measures.(ABSTRACT TRUNCATED AT 250 WORDS)     

依那普利治疗原发性高血压37例

原发性高血压患者37例(男24,女13;年龄50±7yr,)用依那普利5mg,bid,po×1wk,逐周递增10mg,最大剂量20mg,bid;卡托普利治疗相同患者17例作对照,剂量为12.5mg,tid,po×1wk,逐周递增12.5mg,最大剂量50mg,tid;2组疗程均为4wk。结果:2药治疗前、后血压下降均有非常显著差异;但2药组间比较无差异。依那普利可降低总外周阻力。     

Enalapril and nifedipine in the treatment of mild to moderate essential hypertension: a 6 month comparison.

1. In a double-blind, randomised, parallel group study, 128 patients with sitting diastolic blood pressure between 95 and 125 mm Hg (Phase V) after 2-4 weeks run-in on placebo, received enalapril 10-40 mg once daily (65 patients) or nifedipine retard 10-40 mg twice daily (63 patients), utilising a double dummy technique. Dual target blood pressures were less than 150 mm Hg systolic and less than 90 mm Hg sitting diastolic. Inadequate responders had hydrochlorothiazide 12.5-50 mg once daily added. 2. The 3 h post-dose sitting blood pressures were lowered by 18/14 mm Hg (enalapril) and 20/14 mm Hg (nifedipine), but nifedipine gave greater standing reductions (16/13 mm Hg enalapril, 22/17 mm Hg nifedipine). The dual target blood pressures were achieved by 45% of those taking enalapril monotherapy and 43% of those taking nifedipine monotherapy. At the end of the hydrochlorothiazide phase the dual target pressures were achieved by 63% of the enalapril group and 56% of the nifedipine group. 3. Overall, 17 patients reported adverse events during the placebo run-in. During the active treatment-periods, 42 patients in the enalapril group experienced adverse events, as did 49 of those on nifedipine. Orthostatic effects were confined to those taking enalapril, whereas flushing/erythema, oedema and palpitations were more common in the nifedipine group. 4. Five patients in the enalapril and 14 in the nifedipine groups were withdrawn because of adverse events. One of those withdrawn on enalapril had angioneurotic oedema.(ABSTRACT TRUNCATED AT 250 WORDS)     

地拉普利与卡托普利治疗原发性高血压的比较

目的：探索地拉普利治疗原发性高血压病的疗效。方法：原发性高血压病人３０例（男性１６例，女性１４例：年龄６２±ｓ１１ａ）采用地拉普利１５～６０ｍｇ，ｐｏ，ｂｉｄ，共４ｗｋ为地拉普利组。另设对照组３０例（男性１７例，女性１３例；年龄６５±９ａ）采用卡托普利１２．５～２５ｍｇ，ｐｏ，ｂｉｄ或ｔｉｄ共４ｗｋ为卡托普利组。结果：地拉普利组剂量３０～６０ｍｇ／ｄ，总有效率８７％，增加剂量未见疗效增加；卡托普利组总有效率９０％，组间经Ｒｉｄｉｔ分析法检验：Ｐ＞０．０５。２组副作用均轻微。结论：地拉普利治疗原发性高血压的疗效好，且安全。     

Enalapril in essential hypertension: a comparative study with propranolol. Enalapril in Hypertension Study Group (UK).

We report the first comparative study on enalapril maleate, a new angiotensin converting enzyme inhibitor, in patients with uncomplicated mild to moderate essential hypertension. Fifty-four patients were randomly assigned to treatment with enalapril or propranolol for 16 weeks following a placebo run-in-phase. The study was double-blind. Enalapril and propranolol both reduced blood pressure, though the changes were significantly treated with enalapril were normotensive at the end of the study. Enalapril treatment was associated with a significant reduction in weight. Both drugs raised plasma potassium and urea. No haematological abnormalities occurred with enalapril and there were no reports of rash, taste disturbance or proteinuria. At the end of the trial the mean daily dose of enalapril was 20 mg and that of propranolol was 180 mg.     

Clinical evaluation of labetalol alone and combined with chlorthalidone in essential hypertension: A double-blind multicentre controlled study

Summary In a multicentre, double-blind, crossover, placebo-controlled study, the antihypertensive effect of labetalol 100 mg and chlorthalidone 10 mg, given alone or in combination, has been assessed in 32 hypertensive patients. The combination had a greater effect in reducing blood pressure than did its separate components. This was particularly evident after exercise. Heart rate increased during chlorthalidone therapy, decreased during labetalol therapy, and a summation effect was observed during treatment with the combination. In most cases additivity was observed, as no interaction between the single components was observed, except for heart rate after exercise, and for diastolic blood pressure in the upright position. No interaction was observed either in the biochemical indices or in the clinical side-effects.     

A double-blind comparison of the effects of carvedilol and captopril on serum lipid concentrations in patients with mild to moderate essential hypertension and dyslipidaemia

Summary We have studied 250 patients with mild to moderate essential hypertension (diastolic blood pressure 95 – 114 mmHg) and dyslipidaemia (high-density lipoprotein cholesterol (HDL-C) below 1.03 mmol·l^–1, total cholesterol 5.17–9.05 mmol·l^–1, and triglycerides 2.26–5.64 mmol·l^–1) in a controlled double-blind, multicentre, parallel group trial.The patients took a fat-modified diet. After a 4-week placebo period, patients who continued to fulfil the selection criteria were randomly allocated to treatment with either carvedilol (a vasodilating -blocker) 25–50 mg o.d. (n=116) or captopril (an ACE inhibitor) 25–50 mg o.d. (n=117) for 6 months.In both groups there were favourable effects on the serum lipids. The relative changes (medians) in the carvedilol and captopril group were respectively: increase in HDL-C by 11% and 8%, decrease in total cholesterol by 11% and 10%, in low-density lipoprotein cholesterol by 16% and 12%, and in triglycerides by 13% and 14%. Equivalence of the two treatments was confirmed for the target variable change in HDL-C at a significance level of 5%.Reductions in supine systolic/diastolic blood pressures were comparable in the two groups (carvedilol: 23/19 mmHg, captopril: 20/18 mmHg).The improvement in lipid metabolism in patients treated with carvedilol is probably due to its ₁-blocking properties.     

Enalapril in moderate to severe hypertension: A comparison with atenolol

Patients with moderate to severe essential hypertension (mean untreated supine blood pressure 190/112 mm Hg) received once daily enalapril 20-40 mg or atenolol 50-100 mg, supplemented if required by hydrochlorothiazide 25-100 mg, in a randomized observer-blind trial. Both regimens produced a highly significant reduction in supine and standing blood pressure. There was no significant difference in the antihypertensive effects of enalapril and atenolol when they were used as monotherapy. After hydrochlorothiazide was added to patients not achieving 'target' blood pressure, the fall in systolic pressure was significantly greater in the enalapril group than in the atenolol group, despite similar dosage of hydrochlorothiazide in the two groups. At the end of 6 months' treatment, a supine diastolic blood pressure of 90 mm Hg or below was achieved in 74% of patients on enalapril plus hydrochlorothiazide and 56% of patients on atenolol plus hydrochlorothiazide. This difference was not statistically significant. A small rise in plasma urea and creatinine was observed in the enalapril group and a small rise of urea only in the atenolol group. These changes were statistically significant but of uncertain clinical importance. This study confirms that once daily enalapril and atenolol, both alone and in combination with hydrochlorothiazide, are effective drugs in the management of moderate to severe hypertension.     

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.     

硝苯地平联合卡托普利治疗原发性高血压效果观察

目的 探讨硝苯地平联合卡托普利治疗原发性高血压的临床效果.方法 将2009年1月至2012年12月就诊的原发性高血压患者102例,完全随机分为对照组和治疗组,各51例.对照组给予卡托普利片20 mg/次,3次/d;治疗组给予卡托普利片20 mg/次,3次/d和硝苯地平控释片30 mg/次,1次/d.连续用药8周.比较2组患者血压、心率、血尿素氮、肌酐与β2微球蛋白.结果 治疗组总有效率为88.3％（45/51）,明显高于对照组的72.5％（37/51）,差异有统计学意义（P＜0.05）;对照组治疗后收缩压、舒张压、心率均低于治疗前[分别为（137 ±8）mmHg（1 mmHg =0.133 kPa）比（153±9）mmHg、（92±7）mmHg比（97±6）mmHg、（77 ±6）次/min比（87±6）次/min,均P＜0.05];治疗组治疗后舒张压、收缩压、心率均低于治疗前[分别为（129±7）mmHg比（153±10） mmHg、（89±6）mmHg比（97±6）mmHg、（75±5）次/min比（86±6）次/min,均P＜0.05].治疗组治疗后收缩压和舒张压低于对照组,差异有统计学意义（P＜0.05）.对照组治疗前血尿素氮、肌酐和β2微球蛋白分别为（6.8±0.9）mmol/L、（107±13） mmol/L、（687±81）μg/L;治疗后分别为（6.2±0.9） mmol/L、（104±12） mmol/L、（427 ±55） μg/L;治疗组治疗前尿素氮、肌酐和β2微球蛋白分别为（6.6±0.6）mmol/L、（106±12） mmol/L、（683±76） μg/L;治疗后分别为（6.0 ± 0.7） mmol/L、（102±12） mmol/L、（414 ±53） μg/L.2组患者治疗后血尿素氮和β2微球蛋白较本组治疗前明显下降,差异有统计学意义（P＜0.05）.结论 硝苯地平联合卡托普利治疗原发性高血压具有明显的降压作用,疗效较好,不良反应少.     

培哚普利与卡托普利治疗原发性高血压各60例的比较

目的 :比较培哚普利与卡托普利对原发性高血压的治疗作用。方法 :中度原发性高血压病人12 0例 ,随机分为 2组。培哚普利组 60例 (男性 4 5例 ,女性 15例 ;年龄 60±s 15a) ,采用培哚普利 4～ 8mg ,po ,qd× 4wk ;卡托普利组 60例 (男性 4 5例 ,女性 15例 ;年龄 60± 14a) ,采用卡托普利 12 .5～ 2 5mg ,po ,tid× 4wk。每组 16例进行了 2 4h动态血压监测。结果 :培哚普利组总有效率为92 % ,卡托普利组总有效率为 78% ,2组差异不显著(P >0 .0 5) ;不良反应发生率 ,培哚普利组 12 % ,卡托普利组 2 8% (P <0 .0 5) ,均轻微。结论 :培哚普利与卡托普利对中度高血压病疗效均较好 ,培哚普利组不良反应较少     

Suppressive effect of captopril on platelet aggregation in essential hypertension

Effects of captopril on platelet aggregation were studied in 12 essential hypertensive subjects. At the same time, the effects of captopril and angiotensin II on platelet aggregation in vitro were examined in 20 volunteers. A 50-mg oral dose of captopril was administered daily to hypertensive subjects for 2 weeks; the dose was then increased to 100 mg daily for the next 2 weeks. Values of platelet aggregation induced by ADP, epinephrine, collagen, and arachidonic acid before captopril treatment were 71.9 +/- 4.5, 77.3 +/- 4.2, 72.4 +/- 4.1, and 70.8 +/- 4.3% (mean +/- SE), respectively. Two weeks after daily administration of 50 mg captopril, these values were 56.7 +/- 4.5, 50.8 +/- 7.6, 64.0 +/- 4.6, and 60.9 +/- 3.9%, respectively, with significant reduction of platelet aggregation (p less than 0.001, p less than 0.01, p less than 0.01, and p less than 0.005, respectively). Daily administration of 100 mg captopril also had a significant suppressive effect on platelet aggregation. Changes of platelet count and serum lipids were not significant. In vitro, captopril and angiotensin II added to platelet-rich plasma had no effect on platelet aggregation. These results show that the suppressive effect of captopril on platelet aggregation is a secondary action in vivo.     

Comparison of once-daily captopril or enalapril in mild essential hypertension

The purpose of this study was to assess the effect of a daily low dose of the angiotensin-converting enzyme (ACE) inhibitors, captopril or enalapril, in mild essential hypertension. Nine men with seated diastolic blood pressure between 95 and 104 mm Hg on placebo participated in the study. After one month of placebo, captopril 25 mg was administered; blood pressure, heart rate, ACE activity and plasma renin activity were measured hourly for 4 hours. Each patient then received captopril 50 mg once daily for 8 weeks and similar measurements were made 24 hours post-dose every 2 weeks. After another month of placebo, the identical protocol was repeated after enalapril 5 mg. Although blood pressure and ACE activity decreased significantly (P less than 0.05) within 2-4 hours of the acute doses of each inhibitor, neither captopril or enalapril produced significant reductions 24 hours after the small daily dose. Thus, neither ACE inhibitor alone was adequate to control blood pressure in mild hypertension when given once daily during 8 weeks of treatment.     

Fluvoxamine versus fluoxetine in major depressive episode: a double-blind randomised comparison

A double-blind, multinational study was conducted to compare the efficacy and safety of fluvoxamine and fluoxetine in outpatients with major depressive episode; 184 patients were randomised to fluvoxamine (100 mg/day) or fluoxetine (20 mg/day) for 6 weeks. Both drugs were effective and there were no statistically significant differences between them in the area under the curve of change from baseline in the Hamilton depression rating scale (HAMD) total score. However, the percentage of HAMD responders (>or= 50% decrease in HAMD total score) at week 2, the clinical global improvement severity of illness score at week 2 and the depression subscale of the irritability, depression and anxiety scale at weeks 1, 2 and 4, all showed significant advantages for fluvoxamine. During the last 2 weeks, fluvoxamine was significantly more effective in improving the HAMD sleep disturbance scale. Both drugs were well tolerated and there were no marked differences in their side effect profiles which were typical of SSRIs. Fluvoxamine and fluoxetine have similar efficacy and safety profiles in the treatment of major depressive episode; the findings of this study indicate that fluvoxamine may have a faster onset of action with respect to resolution of depressive symptoms and result in a better improvement in sleep quality.     

Once vs twice daily administration of a fixed combination of captopril plus hydrochlorothiazide in essential hypertension: a double-blind crossover study in known responders to a standard combination.

The purpose of this randomized, double-blind, crossover trial was to compare the hypotensive effects of a fixed combination of captopril (C) 50 mg and hydrochlorothiazide (HCTZ) 25 mg (C 50/HCTZ 25) once daily with those of a fixed combination of C 25 mg and HCTZ 12.5 mg (C 25/HCTZ 12.5) twice daily. We studied 199 patients (108 M, 91 F) with mild to moderate essential hypertension whose BP was already controlled by the co-administration of C 25 mg and HCTZ 12.5 mg twice daily. They were randomly assigned to either C 25/HCTZ 12.5 twice daily during the first 6 weeks and C 50/HCTZ 25 once daily during the second 6 weeks or C 50/HCTZ 25 once daily followed by C 25/HCTZ 12.5 twice daily. Both regimens showed comparable efficacy on office diastolic BP (91.6 vs 91.3 mm Hg). Systolic BP was slightly but significantly higher (P = 0.02) with the once daily formulation (141.2 vs 139.1 mm Hg). Fixed combinations once daily and twice daily resulted in identical working ambulatory BP (133.7 +/- 13/83.6 +/- 8 mm Hg vs 132.4 +/- 11/83.3 +/- 7 mm Hg) without affecting heart rate. Adverse events were reported by 16% of patients and cough was the most common occurring in 7%. In conclusion, these results indicate that the fixed combination of C 50/HCTZ 25 given once daily controls office and working BP as well as the fixed combination C 25/HCTZ 12.5 given twice daily in patients with mild to moderate hypertension.     

Glucose tolerance during chronic captopril therapy in patients with essential hypertension

We conducted a prospective evaluation of the effects of chronic captopril therapy on glucose tolerance in 8 nondiabetic, hypertensive patients and 6 hypertensive patients with impaired glucose tolerance, including 3 diabetic patients. Captopril was well tolerated by all patients, and no untoward effects were observed. Chronic captopril therapy produced a significant decrease in blood pressure in all patients. No patients with normal glucose tolerance developed diabetes mellitus. Neither fasting nor post-glucose-load venous plasma glucose deteriorated in any patients during chronic captopril therapy. There were no significant changes in the insulinogenic index (delta IRI/delta BS at 30 min post-glucose load) in patients with either normal or impaired glucose tolerance. These results suggest that, in addition to its antihypertensive effect, chronic captopril therapy does not compromise glucose metabolism in hypertensive patients. Thus, captopril may have a clinical advantage in that it apparently can be given safely to hypertensive patients with either normal or impaired glucose metabolism.     

A double-blind comparison of indoramin and propranolol in the treatment of moderate to severe essential hypertension

Summary

In a double-blind study, patients with moderate to severe essential hypertension were treated randomly with either indoramin or propranolol orally. The dose of both drugs was increased as necessary, to a predetermined level, in order to reduce the diastolic (Phase V) blood pressure to 100 mmHg or less. Patients were followed up for 12 weeks. There were 23 patients on propranolol and 27 on indoramin. The blood pressure in 22 patients on propranolol and 25 patients on indoramin was satisfactorily controlled in both the supine and standing positions. Mean supine blood pressure decreased from 181.3±14.2/116.2±6.8 mmHg to 140.6±7.1/95, 7±3.6 mmHg after 12 weeks of treatment in patients receiving propranolol and from 188.3±18.9/118.4±8.7 mmHg to 144.7±7.3/95.7±2.5 mmHg in those treated with indoramin. There were no significant differences between the effects on supine and standing blood pressures and blood pressure control was maintained throughout the 12-week period in patients receiving indoramin and those receiving propranolol. Propranolol reduced the mean heart rate by approximately 16 beats/min in both the supine and standing positions. The maximum effect was seen 4 weeks after starting treatment and was maintained throughout the study. Sinus bradycardia (heart rate <60/min) occurred in 9 (39%) patients receiving propranolol. Indoramin caused a small but significant reduction in mean heart rate of approximately 4 beatslmin in both the supine and standing positions. The maximum effect was seen after 2 weeks of treatment and was maintained for the rest of the duration of treatment. Eight (34.8%) patients on propranolol and 8 (29.6%) patients on indoramin experienced side-effects. These were mild to moderate in nature in the majority of cases. Fatigue and dizziness from indoramin and fatigue from propranolol were the commonest side-effects reported. Neither drug produced any significant alteration in the haematological and biochemical variables studied.