Antihypertensive effect of indapamide given in conjunction with captopril in severe hypertension

Summary

The efficacy of captopril alone or in combination with indapamide was evaluated in 17 patients with severe hypertension (diastolic > 120 mmHg) previously treated with triple antihypertensive therapy, i.e. diuretic, beta-blocker and a vasodilator. After a wash-out period of 1 week, captopril was given initially as 75?mg/day for 2 weeks; at the end of this period, the dosage was doubled to 150?mg/day and continued at this level for a further 2 weeks. Indapamide (2.5?mg/day) was then added to the regimen and administered for 1 month. The results showed that captopril alone lowered, but did not normalize the blood pressure. The mean diastolic pressure was reduced to 117 and 103.8 mmHg after dosages of captopril of 75?mg and 150?mg, respectively. On the addition of indapamide, the blood pressure was normalized to 93.82 mmHg mean diastolic pressure. Systolic readings were similarly reduced. Two patients developed skin rashes while on captopril alone: no other treatment-related side-effects were reported once indapamide therapy had commenced.     

The efficacy and tolerance of indapamide in essential hypertension: a multi-centre study in 981 patients

A multi-centre open trial involving 150 cardiologists throughout France was undertaken to assess the efficacy and tolerance of indapamide in the treatment of essential hypertension. An identical protocol was used by all of the cardiologists. A total of 981 patients (mean age 58 years) was included in the trial after an observation period of 1 month during which blood pressure was recorded regularly. Patients were included if they had permanent essential hypertension with a diastolic pressure of 95 mmHg or more. Mean systolic and diastolic blood pressures at the end of the initial observation period were 179/103 mmHg. The treatment period lasted for 4 months during which the patients received 1 tablet of indapamide (2.5 mg) each morning. Blood pressure was measured after 6 and 16 weeks of treatment, and clinical and biological acceptability was also assessed. After 6 weeks of treatment, mean systolic and diastolic blood pressure levels decreased to 158/90 mmHg: after 16 weeks these mean figures were 150/86 mmHg. Blood pressure levels became normal with indapamide treatment alone in 80% of patients. A slight decrease in serum potassium levels was noted in the first 6 weeks of treatment and then became stable. Clinical acceptability was considered good or excellent in 89% of cases and few non-specific side-effects were reported.     

The efficacy and tolerance of indapamide in essential hypertension: a multi-centre study in 981 patients

Summary

A multi-centre open trial involving 150 cardiologists throughout France was undertaken to assess the efficacy and tolerance of indapamide in the treatment of essential hypertension. An identical protocol was used by all of the cardiologists. A total of 981 patients (mean age 58 years) was included in the trial after an observation period of 1 month during which blood pressure was recorded regularly. Patients were included if they had permanent essential hypertension with a diastolic pressure of 95 mmHg or more. Mean systolic and diastolic blood pressures at the end of the initial observation period were 179/103 mmHg. The treatment period lasted for 4 months during which the patients received 1 tablet of indapamide (2.5?mg) each morning. Blood pressure was measured after 6 and 16 weeks of treatment, and clinical and biological acceptability was also assessed. After 6 weeks of treatment, mean systolic and diastolic blood pressure levels decreased to 158/90 mmHg: after 16 weeks these mean figures were 150/86 mmHg. Blood pressure levels became normal with indapamide treatment alone in 80% of patients. A slight decrease in serum potassium levels was noted in the first 6 weeks of treatment and then became stable. Clinical acceptability was considered good or excellent in 89% of cases and few non-specific side-effects were reported.     

The efficacy of indapamide in hypertensive patients failing to respond to a beta-blocker alone

A double-blind, placebo-controlled, cross-over study was carried out to evaluate the efficacy and safety of 2.5 mg indapamide in 24 hypertensive patients failing to respond to oxprenolol alone. An additional 6 patients were assessed by ambulatory blood pressure recordings over a 15-hour period with a Remler M2,000 semi-automatic sphygmomanometer. On average, indapamide reduced supine blood pressure by 18.5/10 mmHg and standing blood pressure by 19.6/8.9 mmHg. The ambulatory recordings carried out in 6 patients detected a fall in diastolic pressure not observed using clinic readings in these 6 patients, suggesting that this is a more sensitive method of detecting antihypertensive effect. These responses were not associated with significant changes in heart rate or body weight and there was no significant postural fall in blood pressure. No serious side-effects were reported. Changes in serum potassium, chloride and urate similar to those seen with diuretics were observed. These results suggest that indapamide is a useful and safe adjunct to beta-adrenoceptor blocking therapy for uncontrolled hypertension.     

Cadralazine, a new vasodilator, in addition to a beta-blocker for long-term treatment of hypertension

51 hypertensive outpatients, whose diastolic blood pressure exceeded 100 mmHg after a 2-week period on atenolol alone (100 mg once daily) participated in this long-term study. They received, in addition to atenolol, the vasodilator cadralazine (ISF 2469; 10 to 30 mg once daily) for a standard period of 24 weeks, according to an open design. Cadralazine caused a progressive and important decrease in both systolic and diastolic blood pressure, from 173/111 mmHg (end of atenolol alone) to 154/99 mmHg (12th week, p less than 0.01/p less than 0.01; mean dose, 24.5 mg/day). At this time a diuretic was added as a third-step drug in 15/51 initial patients (29%), and final blood pressure in all patients was 150/96 mmHg (p less than 0.01/p less than 0.01), with positive results in 88% of the cases. During cadralazine treatment, heart rate was always significantly lower than before atenolol alone; the most common side effects, many of which were already present during treatment with atenolol alone, included headache, asthenia, dizziness, palpitation and flushing, and tended to disappear spontaneously as therapy progressed. Routine laboratory tests did not show important changes; sodium excretion was not reduced. In conclusion, the therapeutic efficacy of cadralazine, its low or absent salt and water retention effects, its good tolerability, and the high compliance obtained with once daily administration allowed the use of this vasodilator as a second-step drug for long-term treatment of hypertension.     

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.     

Evaluation of long-term efficacy and acceptability of indapamide SR in elderly hypertensive patients

OBJECTIVE: To assess the long-term antihypertensive efficacy and acceptability of indapamide SR 1.5 mg in elderly hypertensive patients (> or = 65 years). STUDY DESIGN: Open, 12-month, follow-up study of 444 patients, treated with indapamide SR, who were responders and/or achieved target BP levels following a 3-month, randomised, controlled, double-blind short-term comparison of indapamide SR versus hydrochlorothiazide 25 mg and amlodipine 5 mg. RESULTS: The long-term decrease in systolic blood pressure (SBP)/diastolic blood pressure (DBP) after 12 months follow-up with indapamide SR was -24.0/-13.1 mmHg from baseline (M0). The percentage of patients that achieved target BP levels (DBP < 95 mmHg, SBP < or = 160 mmHg) was 80.1% [84.3% for isolated systolic hypertension (ISH) subgroup], and the response rate (BP < 140/90 mmHg or decrease in supine diastolic BP > or = 10 mmHg or in supine systolic BP > or = 20 mmHg) 81.5%. Blood pressure (BP) remained stable throughout the 12 months follow-up period (M3-M15), whatever the previous treatment received during the 3-month, doubleblind period (M0-M3). Clinical and biological acceptability was good. A low occurrence of withdrawals (7.2%), was reported. CONCLUSION: Over the course of the long-term, 12-month follow-up study, indapamide SR was shown to be an effective and well tolerated antihypertensive therapy, even after a switch from amlodipine or hydrochlorothiazide, in patients aged 65 years-80 years with systolo-diastolic hypertension (SDH) or ISH.     

Control of essential hypertension with captopril, an angiotensin converting enzyme inhibitor.

1 Captopril, an orally active angiotensin converting enzyme inhibitor, was compared with hydrochlorothiazide (HCT) in the treatment of mild and moderate essential hypertension. 2 Twenty outpatients received no antihypertensive therapy for 2 weeks, after which they were given placebo for 8 weeks. Since their diastolic blood pressure remained above 100 mm Hg, they were then randomized to receive either captopril (twelve patients) or HCT (eight patients) for a 4-week titration period. If the supine diastolic blood pressure (SDBP) was normalized, (less than or equal to 90 mm Hg) by the end of titration period, the established regimen was continued for an 8-week maintenance period; if not, the alternate drug was added in increasing doses for up to 4 weeks and the combined therapy was maintained for the remaining 4 weeks. 3 After the first 4 weeks of therapy, both groups showed a statistically significant decrease in both systolic and diastolic blood pressure. Normalization of SDBP occurred in 75% of patients treated with captopril alone, and the addition of HCT produced normalization in the remainder. HCT alone resulted in normalization of SDBP in 50% of patients and the blood pressure of the remaining patients was normalized after the addition of captopril. 4 Captopril given orally, either alone or in conjunction with HCT, is an effective agent for the control of mild and moderate essential hypertension. 5 In our series the main side effects encountered were vertigo and dizziness, transient eosinophilia, a rise of BUN and or/a rise of SGPT or SGOT.     

Antihypertensive effects of verapamil, captopril and their combination at rest and during dynamic exercise.

In order to investigate the antihypertensive effects of verapamil (CAS 52-53-9) and captopril (CAS 62571-86-2), administered alone or in combination therapy, the blood pressure and heart rate effects of these two drugs at rest and during dynamic exercise were evaluated in a double blind study in 30 moderate or severe essential hypertensive patients. After a 30-day placebo wash-out period, 15 patients (age 60.6 +/- 8.0 years, mean +/- SD) were allocated to verapamil sustained-release treatment (120 mg b.i.d. for the first month of therapy and 240 mg b.i.d. for the second one) and 15 patients (age 58.4 +/- 10.0 years) to captopril treatment (25 mg b.i.d. and 50 mg b.i.d. for the first and second month of therapy, respectively). At low dosage both verapamil and captopril significantly (p less than 0.001) and markedly reduced blood pressure values. Goal diastolic blood pressure of 90 mmHg was achieved in 40% and 20% of patients in the verapamil group and in the captopril group, respectively, at high dosage. In contrast to captopril, verapamil induced a significant and dose-dependent heart rate reduction and markedly attenuated the pressor and tachycardiac responses to dynamic exercise. The combination of verapamil 240 mg b.i.d. plus captopril 50 mg b.i.d. was then administered to patients, whose blood pressure was not satisfactorily controlled by monotherapy. This regimen allowed a better blood pressure control both at rest and during exercise than on monotherapy and induced a complete blood pressure normalization in 62% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Blood pressure reduction with olmesartan in mild-to-moderate essential hypertension: a planned interim analysis of an open label sub-study in German patients

OBJECTIVE: To present the baseline characteristics and open-label treatment phase results for German patients in OLMEBEST, a European, multinational, partially randomized, partially double-blind study in patients with mild-to-moderate essential hypertension. RESEARCH DESIGN AND METHODS: After a 2-week placebo run-in, patients received olmesartan 20 mg for 8 weeks. Controlled patients (mean sitting diastolic blood pressure [sDBP] < 90 mmHg) continued on olmesartan 20 mg/day for a further 4 weeks. Non-controlled patients (sDBP > 90 mmHg) were randomized to olmesartan 40 mg/day or olmesartan 20 mg/day plus 12.5 mg hydrochlorothiazide for 4 weeks. Of 823 patients included, 558 continued olmesartan 20 mg treatment and 228 patients were randomized to olmesartan 40 mg/day or combination therapy. Efficacy variables included the change from baseline in mean sitting DBP and systolic blood pressure [sSBP] at Week 8 (and Week 12 for controlled patients), and the proportion of controlled patients and responders (mean sDBP < 90 mmHg or improvement of > 10 mmHg from baseline at Week 8). RESULTS: After 8 weeks of olmesartan medoxomil 20 mg, mean reduction from baseline in sDBP was 11.8 mmHg and in sSBP was 17.1 mmHg. In controlled patients continuing open-label olmesartan medoxomil 20 mg, mean reduction from baseline at 12 weeks in sDBP was 14.9 mmHg and in sSBP was 20.1 mmHg. At Week 8, the response rate was 76% and the control rate was 70%. Olmesartan medoxomil 20 mg/day was well tolerated; 30.9% of patients experienced an adverse event, and the majority of these events were judged by the investigators to be mild. CONCLUSION: Olmesartan medoxomil monotherapy at the recommended dosage of 20 mg once daily is effective and well tolerated in patients with mild-to-moderate hypertension.     

Regression of left ventricular hypertrophy on long-term treatment with captopril of severe hypertensives refractory to standard triple treatment

Ten patients (mean age 53 years; range 37-65 years) with hypertension refractory to standard triple treatment were selected for measurement of blood pressure and echocardiographic evaluation of the left ventricular dimensions before and after 3, 6 and 12 months of captopril therapy. In each patient the dose of captopril was titrated to a maximum of 150 mg t.d.s. (range 25 to 150 mg t.d.s.) with a therapeutic goal of less than or equal to 90 mm Hg diastolic blood pressure. Most patients had added diuretic therapy. Four patients were unable to complete the study, two because of insufficient response to captopril therapy, and two because of side-effects (skin rash and cough). A significant fall in blood pressure was seen after three months of treatment and a reduced blood pressure was still maintained after 12 months. Over the same period, the average number of drugs was reduced from 3.6 to 2.1 per patient. A gradual reduction of septal and posterior wall thickness were noted, from 12.8 and 11.5 mm to 10.0 and 8.5 mm, respectively, after 12 months. Calculated left ventricular muscle mass was insignificantly reduced from 281 to 243 g after 12 months. The present study suggests that in hypertension resistant to conventional multiple therapy, captopril can reduce the blood pressure, and, in the long run it can also induce reversal of left ventricular wall thickening without causing deterioration of left ventricular function.     

ANGIOTENSIN-CONVERTING ENZYME INHIBITION AS FIRST-LINE TREATMENT FOR HYPERTENSION

1. Perindopril (4 mg) was compared with atenolol (50 mg), captopril (25 mg b. d.) or a diuretic (hydrochlorothiazide 50 mg and amiloride 5 mg) in three studies involving a total of 503 hypertensive patients with a diastolic blood pressure (DBP) of 95–125 mmHg.
2. A 4 week single-blind placebo period preceded 12 weeks of active treatment. Dose titration was at weeks 4 and 8 if supine DBP >90 mmHg. The dose was doubled and if necessary a diuretic was added in the atenolol or captopril comparisons, and atenolol was added in the diuretic study.
3. The fall in supine blood pressure (BP) was 27/17 mmHg with perindopril and 21/16 mmHg for atenolol. Monotherapy controlled 55% of patients on perindopril and 48% on atenolol, increasing to 78% and 58% with the addition of hydrochlorothiazide, respectively. Captopril caused a BP fall of 19/12 mmHg compared with 27/18 mmHg for perindopril, with 49% of both groups being controlled on monotherapy.
4. Diuretic addition produced a greater antihypertensive effect with perindopril (75%) compared with 57% for captopril in achieving control. Perindopril caused a comparable fall in supine BP to the diuretic combination 27/19 mmHg and 31/18 mmHg, but the fall in erect systolic BP was significantly greater for the diuretic. At 3 months, 85% of the diuretic group and 78% of the perindopril group achieved the target BP.
5. A multicentre trial of 856 patients treated with perindopril (690 patients treated for 1 year or more) has shown that BP control is maintained in the long term with a low incidence of side-effects (7.9%) causing withdrawal from treatment. These studies demonstrate that perindopril compares favourably with standard first-line therapy for mild to moderate hypertension.     

Effect on blood pressure control of switching from valsartan monotherapy to losartan/hydrochlorothiazide in Asian patients with hypertension: results of a multicentre open-label trial

ABSTRACT

Study design: An open-label, multicentre study was conducted to evaluate the antihypertensive efficacy of a 4-week course of losartan 50?mg plus hydrochlorothiazide 12.5?mg in Asian patients with essential hypertension whose blood pressure had previously been treated with but not controlled by valsartan 80?mg.

Methods: A total of 237 eligible patients with mean trough sitting diastolic blood pressure (SiDBP) 95–115?mmHg and a mean trough sitting systolic blood pressure (SiSBP) < 190?mmHg entered the baseline period of treatment with valsartan 80?mg/day for 4 weeks. Those (n = 165) whose SiDBP remained > 90?mmHg and who were not excluded for other reasons were then switched to a single-tablet formulation of losartan 50?mg/hydrochlorothiazide 12.5?mg combination once daily for a further 4 weeks.

Results: Mean SiDBP (study primary endpoint) at the end of combination therapy was reduced to 86.9 mmHg from 95.2 mmHg. SiSBP (study secondary endpoint) was reduced to 132.6 mmHg from 140.7 mmHg. Mean reductions after switching from valsartan 80?mg to losartan 50?mg/hydrochlorothiazide 12.5?mg were thus 8.3 and 8.1 mmHg for SiDBP and SiSBP, respectively (?p ≤ 0.001 for both outcomes). The goal of SiDBP ≤ 90 mmHg was attained in 72% of the patients previously not controlled to the same level by valsartan 80?mg/day. Combination therapy with losartan 50?mg/hydrochlorothiazide 12.5?mg was generally well tolerated. Mean compliance with the losartan 50?mg/hydrochlorothiazide 12.5?mg combination was > 99%.

Conclusion: These results demonstrate that in Asian patients who do not reach the goal of mean trough SiDBP ≤ 90?mmHg with valsartan monotherapy at 80?mg once-daily, switching to a single-tablet combination of losartan 50?mg/hydrochlorothiazide 12.5?mg once-daily is well tolerated, provides effective control of blood pressure and is an excellent choice to achieve blood pressure reduction goals.     

Effects of a new long-acting beta-blocker bopindolol (LT 31-200) on blood pressure,plasma catecholamines,renin and cholesterol in patients with arterial hypertension

Summary Bopindolol (LT 31-200), a new, long-acting, non-selective beta-blocker, was given as monotherapy to 13 patients, 12 with essential hypertension and 1 with renovascular hypertension. After a placebo period of 4–6 weeks, bopindolol was given once daily, starting with 1 mg and subsequently increasing at two-weekly intervals to 2 and 4 mg once daily until a diastolic blood pressure⩽90 mmHg was achieved. The effective dose was continued for 12 weeks. In 10 patients plasma levels of renin, noradrenaline, adrenaline and cholesterol were measured during placebo and after 3 months of therapy. Blood pressure and heart rate were lowered significantly during bopindolol treatment. The mean effective dose was 2.2 mg per day. In 10/13 patients a diastolic blood pressure⩽90 mmHg was achieved. Side effects were minimal. Changes in plasma noradrenaline and adrenaline were small and not significant, but renin and cholesterol were significantly reduced. Thus, LT 31-200 is an effective and well tolerated beta-blocker when given in a once daily dosage.     

Antihypertensive and metabolic effects of long-term treatment with amosulalol in non-insulin dependent diabetics.

In this open study, 41 hypertensive patients with non-insulin dependent diabetes mellitus were treated with the combined alpha- and beta-adrenoceptor blocker amosulalol hydrochloride for 24 weeks, either alone or added to existing antihypertensive therapy. The effects on blood pressure, glucose and lipid metabolism were examined. Daily administration of 20 to 60 mg amosulalol caused a significant reduction in both systolic and diastolic blood pressure within 2 weeks. This effect was stable, lasting for the entire trial period. The mean systolic and diastolic blood pressure decreased from 174 +/- 13/92 +/- 9 mmHg at the beginning to 148 +/- 16/80 +/- 11 mmHg at the end of the trial. Heart rate was not affected. Plasma glucose and haemoglobin Alc levels showed a tendency to decrease without any statistical significance. Total and HDL-cholesterol and triglyceride levels also remained unchanged. Although 3 patients had complained of dizziness, all were easily manageable. The results indicate that amosulalol is effective in the treatment of hypertension in non-insulin dependent diabetics and does not affect glucose and lipid metabolism.     

硝苯地平缓释剂联合利尿剂治疗173例老年高血压患者安全性与有效性临床观察

目的探讨硝苯地平缓释剂联合不同利尿剂(氢氯噻嗪和吲达帕胺)的治疗方案对老年高血压患者的降压安全性及有效性,以寻找适合我国老年高血压患者的降压方案。方法将173例老年高血压患者随机分为3组,Nif组服硝苯地平缓释片10 mg/次,2次?d-1;Nif+HCTZ组在服用硝苯地平基础上加服氢氯噻嗪,剂量为12.5 mg/次,1次?d-1,Nif+ID组在服用硝苯地平基础上加服吲达帕胺,剂量为2.5 mg/次,1次?d-1,疗程8周,考察用药期间血压的变化,进而评价3种用药方案的有效率及安全性。结果 Nif组平均坐位血压从(172.4±12.3)/(101.4±8.6)mmHg降为(150.9±11.6)/(86.4±7.1)mmHg;Nif+HCTZ组平均坐位血压从(176.7±13.6)/(100.8±7.65)mmHg降为(139.7±12.7)/(81.3±8.2)mmHg;Nif+ID组平均坐位血压从(175.4±11.8)/(105.2±9.03)mmHg降为(142.5±10.8)/(81.6±8.6)mmHg。2种联合用药方案有效率与Nif组降压有效率相比,差异有统计学意义(P<0.01),对血钾和肾功能影响差异无统计学意义。主要不良反应为颜面潮红和踝部水肿,Nif+HCTZ组及Nif+ID组比Nif组老年患者不良反应明显减少。结论硝苯地平缓释剂联合利尿剂氢氯噻嗪或吲达帕胺,降压有效率高于单用硝苯地平缓释剂,对老年高血压患者代谢无影响,是老年高血压的有效治疗方案。     

Haemodynamic changes in peripheral arterial circulation during antihypertensive treatment with captopril, methyldopa and indapamide

Structural changes in resistance vessels of the lower limbs have been detected in early stages of arterial hypertension. In these patients it might be important to reduce blood pressure by drugs which do not impair peripheral blood flow. Twenty-four patients with arterial hypertension, without target organ damage were randomly given a placebo, 50 mg captopril, 500 mg methyldopa or 2.5 mg indapamide and their blood pressure, arterial blood flow and peripheral resistance were measured at baseline and at the peak action of the antihypertensive treatment. Significant decreases in blood pressure and peripheral resistance have been induced by a single oral dose of captopril and methyldopa: a concomitant significant increase in peripheral blood flow to the lower limbs was also observed during methyldopa treatment. No acute effect was observed on the placebo or on indapamide: the latter induced a decrease in blood pressure and in peripheral resistance along with an increase in arterial blood flow during long-term treatment after four weeks of therapy. Our observations seem to support the usefulness in hypertensive patients with concomitant lesions in the peripheral arterial tree of antihypertensive agents such as methyldopa and indapamide which increase blood flow and reduce peripheral resistance while lowering high blood pressure.     

Perindopril/indapamide 2/0.625 mg/day: a review of its place in the management of hypertension

The fixed low-dose combination of the ACE inhibitor perindopril and the non-thiazide diuretic indapamide has been evaluated in the management of patients with mild to moderate hypertension. Combination therapy aims to improve overall therapeutic efficacy while minimising adverse effects. In well-designed multicentre clinical trials, perindopril/indapamide at doses ranging from 2/0.625 to 8/2.5 mg/day was significantly more effective than placebo in achieving adequate blood pressure (BP) control. A similar reduction in supine BP was observed when combined perindopril/indapamide 2/0.625 mg/day was compared with losartan 50 mg/day or atenolol 50 mg/day. Similar reductions in 24-hour ambulatory BP were also seen with perindopril/indapamide 2/0.625 mg/day and irbesartan 150 mg/day. However, response and normalisation rates were significantly higher with combination therapy than with losartan or irbesartan monotherapy. Combined perindopril/indapamide 2/0.625 mg/day therapy effectively reduced BP in elderly patients aged 65 to 85 years to a significantly greater extent than either atenolol 50 mg/day or placebo. Supine BP was also normalised in approximately two-thirds of patients in a small noncomparative trial in patients with hypertension and renal impairment. Low-dose perindopril/indapamide 2/0.625 mg/day was well tolerated in clinical trials; the most common adverse events were headache and cough. Hypokalaemia, associated with the use of diuretics, occurred with a higher incidence with combined perindopril/indapamide 2/0.625 mg/day therapy than with either atenolol 50 mg/day or placebo. Perindopril/indapamide 2/0.625 mg/day has shown efficacy in well designed comparative trials with atenolol, losartan and irbesartan including elderly patients and patients with renal impairment. Studies comparing this dosage of perindopril/ indapamide with other combination therapies would be beneficial in allowing the place of perindopril/indapamide to be more accurately determined. The fixed-low dose combination of perindopril/indapamide provides a promising and well tolerated treatment option in the management of patients with mild to moderate hypertension.     

FAILURE OF ASPIRIN TO MODIFY THE HYPOTENSIVE ACTION OF CAPTOPRIL IN SPONTANEOUSLY HYPERTENSIVE RATS

1. Oral administration of the angiotensin converting enzyme inhibitor, captopril (30 mg/kg per day) to spontaneously hypertensive rats of the Okamoto strain progressively reduced arterial blood pressure by 60 mmHg over 4–5 days. 2. Oral treatment of spontaneously hypertensive rats with aspirin (200 mg/kg per day) for one week did not alter blood pressure, but it greatly reduced the vasodepressor effects of intravenous injections of arachidonic acid (3 mg/kg). 3. The fall in blood pressure of spontaneously hypertensive rats treated concurrently with both aspirin (200 mg/kg per day) and captopril (30 mg/kg per day) was not different to the fall observed in rats treated with captopril alone. 4. The hypotensive action of captopril in spontaneously hypertensive rats does not appear to be due to stimulation of vasodilator prostanoid biosynthesis.     

A pharmacokinetic and pharmacodynamic study of the potential drug interaction between tasosartan and atenolol in patients with stage 1 and 2 essential hypertension

The primary objective of this study was to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of tasosartan and atenolol administered alone and concomitantly under steady-state conditions in 17 patients ages 18 to 65 years diagnosed with stage 1 to 2 essential hypertension. After a 3- to 14-day qualification period, all patients received placebo tasosartan on days--1 through 5 and 25 through 34, atenolol alone (50 mg) on days 1 through 5, atenolol (50 mg) + tasosartan (50 mg) on days 6 through 19, and tasosartan (50 mg) alone on days 20 through 24. A PK and PD evaluation of atenolol alone was performed on study day 5. On study day 19, PK and PD of both tasosartan and atenolol were assessed. PK and PD evaluation for tasosartan alone was assessed on study day 24. The coadministration of atenolol + tasosartan did not affect the pharmacokinetics of tasosartan, its major metabolite (enoltasosartan), or atenolol when compared with tasosartan or atenolol administered separately. For area under the change in diastolic blood pressure curve, the reduction was significantly greater after tasosartan + atenolol compared with that after atenolol alone (336 +/- 85 and 190 +/- 71 mmHg.24 h; p < 0.05 for combination and atenolol alone, respectively; mean +/- SEM). Combination therapy also caused a maximal reduction in diastolic blood pressure that is significantly more than with monotherapy with atenolol (-27 +/- 2 mmHg and -20 +/- 2 mmHg, respectively, p < 0.05). The additive effects of tasosartan and atenolol in decreasing diastolic blood pressure may provide a rationale for combination antihypertensive therapy.