Valsartan/hydrochlorothiazide: a review of its pharmacology,therapeutic efficacy and place in the management of hypertension

The combination of valsartan [an angiotensin II type 1 (AT(1)) receptor blocker] and hydrochlorothiazide (a thiazide diuretic), administered once daily, has been evaluated in the treatment of patients with hypertension in clinical trials ranging in duration from 8 weeks to 3 years. These studies showed that combination treatment with valsartan 80 or 160mg and hydrochlorothiazide 12.5 or 25mg induced significant reductions from baseline in systolic blood pressure (SBP) and diastolic BP (DBP) in patients with mild to severe hypertension. Clinical trials have demonstrated that the combination of valsartan 80 or 160mg with hydrochlorothiazide 12.5 or 25mg is significantly more effective than either drug alone. Furthermore, valsartan plus hydrochlorothiazide was effective at reducing BP in patients unresponsive to monotherapy with either agent alone. Effective BP control with valsartan plus hydrochlorothiazide was maintained in long-term studies, with reductions observed after 3 months of treatment being similar to those seen after 1, 2 or 3 years. Fixed-dose valsartan/hydrochlorothiazide showed similar BP reductions to amlodipine and to valsartan plus benazepril. Valsartan/hydrochlorothiazide also provided effective 24-hour ambulatory SBP/DBP control. Headache, dizziness and fatigue were the most common adverse events occurring in clinical trials; the incidence of these events in valsartan plus hydrochlorothiazide recipients was not significantly different to that in placebo recipients. Hypokalaemia occurred in 4.5% of valsartan plus hydrochlorothiazide recipients; valsartan attenuated the hydrochlorothiazide-associated decrease in serum potassium concentrations. CONCLUSIONS: the combination of valsartan and hydrochlorothiazide is an effective treatment for patients with hypertension. Clinical trials have demonstrated that the combination is more effective than either drug alone, and is effective in patients not responding to monotherapy with either agent. Furthermore, the adverse event profile of valsartan/hydrochlorothiazide is similar to that of placebo. Unless there are compelling or specific indications for other drugs, current data support the use of valsartan/hydrochlorothiazide when patients are unresponsive to monotherapy with either agent. Results from clinical trials evaluating the effects of valsartan/hydrochlorothiazide on cardiovascular morbidity and mortality will help to further define the role of the combination in the management of hypertension.     

Randomized, double-blind, crossover comparison of amlodipine and valsartan in african-americans with hypertension using 24-hour ambulatory blood pressure monitoring

STUDY OBJECTIVE: To compare the efficacy of amlodipine and valsartan in African-American patients with hypertension using ambulatory blood pressure monitoring (ABPM). DESIGN: Prospective, randomized, double-blind, crossover comparison study. SETTING: University-affiliated cardiac center clinic. PATIENTS: Twenty African-Americans (12 men, 8 women), with a history of uncomplicated hypertension (blood pressure > 140/90 mm Hg). INTERVENTION: Patients were randomized to receive amlodipine 5 or 10 mg/day or valsartan 80 or 160 mg/day for 8-10 weeks, depending on response. Dosages were titrated to achieve a blood pressure of 140/90 mm Hg or below. For patients whose blood pressures were not controlled, hydrochlorothiazide 12.5 mg/day was added to their regimens. Patients then underwent 24-hour ABPM. After an intervening washout period during which baseline blood pressure was reestablished, patients received the other treatment. MEASUREMENTS AND MAIN RESULTS: Mean +/- SD baseline blood pressure before the two ABPM periods were 155 +/- 12/100 +/- 8 mm Hg and 156 +/- 11/101 +/- 9 mm Hg, respectively. Fifteen (75%) patients achieved goal blood pressure with amlodipine and 14 (70%) with valsartan (p=0.62). Final daily dosages were as follows: amlodipine 5 mg in nine patients, 10 mg in five patients, and 10 mg plus hydrochlorothiazide in six patients; valsartan 80 mg in nine patients, 160 mg in four patients, and 160 mg plus hydrochlorothiazide in seven patients. Ambulatory blood pressure monitoring was not completed in three patients due to adverse effects: headache and dizziness (one patient each, amlodipine and valsartan) and hyperkalemia (one patient, valsartan). Four patients (20%) in each treatment group had drug-related adverse effects. Results of ABPM including averages for 24-hour, daytime, nighttime, first 4 hours, and last 8 hours, and trough:peak ratios were not significantly different between the amlodipine- and valsartan-based treatments. CONCLUSION: Based on both clinic blood pressure measurements and ABPM data, amlodipine and valsartan produced similar reductions in blood pressure in African-American patients with uncomplicated hypertension.     

Effects of valsartan versus olmesartan addition to amlodipine/hydrochlorothiazide combination in treating stage 2 hypertensive patients

Objective: The objective of this study was to assess the effects of valsartan or olmesartan addition to dual therapy with amlodipine + hydrochlorothiazide (HCTZ) in the treatment of stage 2 hypertension.

Research design and methods: 180 patients with diastolic blood pressure (DBP) ≥ 99 and < 110 mm Hg were treated with amlodipine 5 mg + HCTZ 12.5 mg combination. After 4 weeks, 149 patients whose blood pressure (BP) was not controlled, were randomized to the combination of valsartan 160 mg + amlodipine 5 mg + HCTZ 12.5 mg or olmesartan 20 mg + amlodipine 5 mg + HCTZ 12.5 mg for 4 weeks.

Main outcome measures: At the end of each period, clinical and ambulatory BP measurements were recorded.

Results: Both triple combinations produced greater ambulatory and clinical SBP/DBP reduction than dual therapy. However, mean reduction from baseline in the valsartan + amlodipine + HCTZ-treated patients was significantly greater than in the olmesartan + amlodipine + HCTZ-treated patients. Compared with dual therapy, the add-on effect of valsartan was significantly greater than that of olmesartan, the difference being more evident for nighttime SBP/DBP values (-3.3 (95% CI 0.44 – 3.51)/3.0 (95% CI 0.59 – 3.34) mm Hg, p < 0.01).

Conclusions: The addition of valsartan to amlodipine + HCTZ produced greater BP reduction than the addition of olmesartan.     

Comparative effect of canrenone or hydrochlorothiazide addition to valsartan/amlodipine combination on urinary albumin excretion in well-controlled type 2 diabetic hypertensive patients with microalbuminuria

Objective: To compare the effect of adding canrenone or hydrochlorothiazide (HCTZ) to valsartan/amlodipine combination on urinary albumin excretion (UAE) in microalbuminuric type 2 diabetic hypertensives.

Research design and methods: After a 2-week placebo period and after 4 weeks of valsartan 160 mg plus amlodipine 5 mg combination, 120 patients whose blood pressure (BP) was not controlled (> 130/80 mmHg) were randomized to canrenone 25 mg or HCTZ 12.5 mg in addition to the previous therapy for 24 weeks. After the first 6 weeks of triple therapy, canrenone or HCTZ doses were doubled in the patients whose BP was yet uncontrolled. At the end of each period (placebo, dual combination and triple combination therapy), clinic and ambulatory BP measurements were recorded and 24 h UAE was evaluated.

Results: Both triple combinations produced greater clinical and ambulatory BP reduction than dual therapy, with no difference between the two groups. UAE was reduced by both regimens, but the decrease associated with canrenone add-on therapy was more pronounced. At week 24, UAE decreased by 45.3% in the canrenone group and by 20.3% in the HCTZ group (p < 0.01).

Conclusions: These findings indicate that, despite similar BP-lowering effect, the addition of canrenone to valsartan/amlodipine combination was more effective in reducing UAE than HCTZ addition.     

Long-term tolerability and efficacy of the combination of amlodipine/valsartan in hypertensive patients: a 54-week,open-label extension study*

ABSTRACT

Objective: To evaluate the long-term tolerability and efficacy of the amlodipine/valsartan 5/320?mg once daily (o.d.) combination in hypertensive patients.

Methods: This was a 54-week, multicenter, open-label extension study in patients with mild-to-moderate essential hypertension selected after successfully completing a core study during which they received either placebo, amlodipine, valsartan or combination therapy. Eligible patients (mean sitting diastolic blood pressure [MSDBP] ≤?95?mmHg and mean sitting systolic blood pressure [MSSBP] ≤?150?mmHg; n?=?403) were started with amlodipine/valsartan 2.5/160?mg o.d. Following the initial 2-week treatment period, patients were force titrated to amlodipine/valsartan 5/320?mg o.d. for the remainder of the trial. Only the first 150 patients who successfully completed 28 weeks of the extension study were eligible to continue further treatment for 12 months. Efficacy variables were change from core study baseline in MSDBP and MSSBP at study (extension) endpoint. Safety assessments consisted of monitoring and recording all adverse events and serious adverse events.

Results: Reductions in MSDBP and MSSBP were achieved at each extension visit. At endpoint, the reductions in MSDBP and MSSBP were 17.0 and 24.2?mmHg. Summary statistics by subgroup indicate that the combination of amlodipine/valsartan 5/320?mg was effective regardless of age, gender, or stage of hypertension. Peripheral edema occurred in 1.2% of the patients. No case of edema was classified as serious or severe, and no patient was discontinued due to edema. No deaths or clinically significant laboratory findings were observed during this extension study.

Conclusions: Long-term treatment with the amlodipine/valsartan 5/320?mg combination was well-tolerated. Clinically significant and persistent reductions in blood pressure were achieved. Limitations included an open-label design and inclusion of only those patients at or near goal blood pressure after the preceding core trial.     

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.     

Smooth blood pressure control obtained with extended-release felodipine in elderly patients with hypertension: evaluation by 24-hour ambulatory blood pressure monitoring

OBJECTIVE: To assess, by smoothness index (SI), distribution of the antihypertensive effect of extended-release (ER) felodipine over 24 hours in elderly patients with hypertension. METHODS: After a 4-week washout phase, 35 elderly patients (mean age 69 +/- 4 years) with mild-to-moderate hypertension received 2 weeks' treatment with ER felodipine 5mg once daily. The dosage of ER felodipine was doubled to 10 mg/day and given for a further 2 weeks in non-responders (sitting clinic blood pressure > 140/90mm Hg). The study had an open-label design with no placebo control. After each period, clinic and ambulatory blood pressures were measured. Trough-to-peak (T/P) ratio was computed by dividing the blood pressure (BP) change at trough (22 to 24 hours after drug intake) by the change at peak (2 adjacent hours with a maximal BP reduction between the second and eighth hour after drug intake). SI was calculated as the ratio between the average of the 24, hourly, treatment-induced BP changes and its standard deviation. RESULTS: After the initial 2-week treatment period, clinic and 24-hour ambulatory BP values were higher in non-responders (145 +/- 11/87 +/- 8 and 135 +/- 17/80 +/- 6mm Hg, respectively) than in responders (133 +/- 6/81 +/- 3 and 130 +/- 9/77 +/- 7mm Hg). In non-responders, clinic and 24-hour BP values were lowered after a further 2 weeks of treatment with ER felodipine 10 mg/day (128 +/- 11/78 +/- 6 and 128 +/- 12/75 +/- 5mm Hg). SI was high in responders (0.8 +/- 0.8/0.7 +/- 0.7 for systolic/diastolic BP) and low in non-responders (0.5 +/- 0.6/0.3 +/- 0.6) during the first 2-week treatment period. It increased in non-responders after an additional 2 weeks of treatment with ER felodipine 10 mg/day (1.0 +/- 0.8/0.7 +/- 0.6). Median T/P ratios were 0.73 and 0.61 (systolic BP and diastolic BP) in responders and 0.41 and 0.61 in non-responders after 2 weeks of treatment. At variance with SI, T/P ratios did not increase in non-responders after doubling the dosage of ER felodipine (0.34 and 0.18). ER felodipine did not increase 24-hour heart rate. A total of nine adverse events were recorded in six patients (17%), but no patients withdrew from the study. CONCLUSION: ER felodipine 5 to 10 mg/day smoothly and safely reduces 24-hour ambulatory BP in elderly patients with hypertension.     

缬沙坦和氨氯地平联合应用对高血压病患者血小板活化及纤溶活性的影响

目的　探讨缬沙坦和氨氯地平联合应用对高血压病 (EH)患者血小板活化状态和纤溶活性的影响。方法　 69例EH患者随机分为缬沙坦组 ( 2 3例 )、氨氯地平组 ( 2 3例 )、缬沙坦 +氨氯地平组 ( 2 3例 )。疗程 12周。治疗前后测定血浆中血小板α 颗粒膜蛋白 (GMP 140 )、组织型纤溶酶原激活剂 (t PA)及其抑制物 (PAI 1)水平。结果　三组EH患者治疗后GMP 140含量、PAI 1活性均明显降低 (P <0 0 1) ,t PA活性显著升高 (P <0 0 1)。联合治疗组降低GMP 140和升高t PA的幅度高于缬沙坦组和氨氯地平组 (P <0 0 5 )。血浆GMP 140、PAI 1降低幅度和t PA升高幅度与血压变化无显著相关 (P >0 0 5 )。结论　缬沙坦、氨氯地平均能有效抑制血小板活化、改善纤溶活性 ,两药联合应用有一定相加作用     

Trough-to-peak ratio,smoothness index,and circadian blood pressure profile after treatment with once-daily fixed combination of losartan 100 and hydrochlorothiazide 25 in essential hypertension

The once-daily fixed combination of losartan 100 mg/hydrochlorothiazide 25 mg was evaluated for safety and efficacy in a multicenter open study by using 24-h ambulatory blood pressure monitoring in untreated patients with moderate-to-severe essential hypertension or patients with uncontrolled hypertension despite treatment with monotherapy or low-dose combination. After a 2-week washout period, 41 patients (22 men, 19 women) aged 34-74 years, showing a mean daytime blood pressure > 135/85 mm Hg, were treated with losartan 100 mg/hydrochlorothiazide 25 for 8 weeks. Ambulatory blood pressure was monitored at the end of the washout period and during the last week of treatment. A significant reduction in the average values of clinic blood pressure (from 169.9 +/- 13.5 mm Hg to 139.5 +/- 15.6 mm Hg, p < 0.001 for systolic blood pressure [SBP]; and from 102.2 +/- 7.1 mm Hg to 85.1 +/- 9.5 mm Hg, p < 0.001 for diastolic blood pressure [DBP]) was observed after treatment in the whole group of 41 patients. Likewise, average values of both 24-h SBP and 24-h DBP were significantly reduced (from 145.7 +/- 13.1 mm Hg to 128.3 +/- 14.6 mm Hg, p < 0.001 for 24-h SBP; and from 90.3 +/- 7.3 mm Hg to 79.2 +/- 8.6 mm Hg, p < 0.001 for 24-h DBP). The average lowering at peak was 20.2 +/- 11.8 mm Hg for 24-h SBP and 12.1 +/- 7.4 mm Hg for 24-h DBP, whereas the lowering at trough was 17.8 +/- 12.0 mm Hg and 10.4 +/- 8.1 mm Hg, respectively. The trough-to-peak ratio (T/P) was 0.88 for SBP and 0.86 for DBP, and the smoothness index was 7.36 for SBP and 6.37 for DBP. The response rate was 87.8% (blood pressure lowering > 5 mm Hg of either 24-h SBP or 24-h DBP average values). Among responders, T/P ratio was 0.89 for SBP and 0.87 for DBP, and the smoothness index was 8.09 for SBP and 7.15 for DBP. No side effects or changes in metabolic parameters were observed. The fixed combination of losartan 100 mg/hydrochlorothiazide 25 was very effective and well tolerated.     

Additive hypotensive effect of angiotensin-converting enzyme inhibition and angiotensin-receptor antagonism in essential hypertension

The study was designed to assess the antihypertensive effect of combined angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 receptor (AT1) antagonism in patients with essential hypertension. Twenty patients with uncontrolled ambulatory diastolic blood pressure (BP) after 6 weeks of ACE inhibitor monotherapy (benazepril, 20 mg, o.d.) were randomized to receive double-blind valsartan, 80 mg, o.d. (AT1 antagonist) or matching placebo for 5 weeks while continuing to receive background benazepril. Then patients crossed over to the alternative regimen for a second 5-week period. The 24-h ambulatory BP was monitored on the final day of the benazepril monotherapy period and on the final day of each double-blind treatment period. Valsartan added to benazepril produced a significant antihypertensive effect with a benefit over placebo of 6.5 +/- 12.6/4.5 +/- 8.0 mm Hg (systolic/diastolic) for average awake ambulatory BP (p < 0.05), 7.1 +/- 9.4/5.6 +/- 6.5 mm Hg for asleep BP (p < 0.01), and 6.8 +/- 9.7/4.9 +/- 6.8 mm Hg for average 24-h ambulatory BP (p < 0.01). Pulse rate was unaffected. Plasma active renin was higher on the benazepril-valsartan combination compared with benazepril-placebo (p < 0.05). There was no change in routine biochemical variables when valsartan was added to benazepril. Six patients reported mild dizziness or fatigue (three also with placebo). These data suggest that in hypertensive patients uncontrolled with an ACE inhibitor, the addition of an AT1 antagonist provides a powerful and safe antihypertensive drug combination.     

Efficacy and tolerability of candesartan cilexetil/hydrochlorothiazide and amlodipine in patients with poorly controlled mild-to-moderate essential hypertension.

The antihypertensive efficacy and tolerability of combination therapy with candesartan cilexetil, 16 mg plus hydrochlorothiazide (CC/HCTZ), 12.5 mg was compared with that of amlodipine, in a multicentre, double-blind, randomised, parallel-group study in patients with mild-to-moderate essential hypertension inadequately controlled by monotherapy. After a two week run-in period on existing therapy, patients with a sitting diastolic blood pressure (DBP) of 90-110 mmHg and a sitting systolic blood pressure (SBP) 相似文献   

缬沙坦氨氯地平对老年高危高血压患者的疗效及相关影响

目的研究缬沙坦氨氯地平复方制剂对老年高危高血压患者的降压疗效以及对血管内皮功能、氧化应激水平的影响。方法选取在我院就诊的84例老年高危高血压患者,随机分为缬沙坦氨氯地平组(A组,42例,服用缬沙坦氨氯地平复方制剂80/5mg,每日1次)、氨氯地平组(B组,42例,服用氨氯地平单药5mg,每日1次),观察16周,试验结束后比较各组的坐位静息血压水平、血压达标率、血清一氧化氮(NO)、内皮素-1(ET-1)、丙二醛(MDA)含量及超氧化物歧化酶(SOD)的活性。结果治疗结束时,A、B 2组的血压降幅差异有统计学意义(P<0.05),A组的血压达标率与血清NO水平高于B组(P<0.05),ET-1水平低于B组(P<0.05)。A组的血清MDA水平低于B组(P<0.05),SOD活性水平高于B组(P<0.05)。结论对于老年高危高血压患者,应用缬沙坦氨氯地平复方制剂治疗血压达标率更高,能更好地减轻体内的氧化应激水平、保护血管内皮功能。     

不同降压药物联合治疗对老年高血压患者血压变异性的影响

摘要： 目的 比较缬沙坦联合氨氯地平或氢氯噻嗪对老年高血压患者血压变异性的治疗作用。方法 80 例老年高血压患者随机分为 2 组, 分别给予缬沙坦联合氨氯地平 （氨氯地平组） 或缬沙坦联合氢氯噻嗪 （氢氯噻嗪组） 降压治疗, 监测 2 组 24 h 动态血压, 观察治疗前、 治疗第 6 周和第 12 周, 2 组血压及血压变异性的变化。同时观察 2 组 6 周末血压达标率。记录治疗过程中的不良反应情况。结果 2 组治疗 6 周和 12 周的 24 h 平均收缩压 （SBP）、白昼 SBP、 夜间 SBP、 晨峰 SBP、 24 h 收缩压变异性 （SBPV） 均较治疗前降低 （P < 0.05）。24 h SBP、 白昼 SBP、 夜间 SBP、 24 h SBPV 及白昼 SBPV 分组因素与时间因素存在交互作用 （P < 0.05）。治疗第 6 周和第 12 周, 氨氯地平组 24 h SBP、 白昼 SBP、 夜间 SBP 及白昼 SBPV 较氢氯噻嗪组降低 （P < 0.05）, 治疗第 12 周, 氨氯地平组 24 h SBPV 低于氢氯噻嗪组 （P < 0.01）。2 组血压达标率和不良反应发生率差异均无统计学意义。结论 缬沙坦联合氨氯地平或氢氯噻嗪均能有效控制老年高血压患者血压变异性, 而缬沙坦联合氨氯地平在降低血压和血压变异性方面作用更强。     

缬沙坦/氢氯噻嗪复方制剂和缬沙坦降压疗效的比较

目的:对比缬沙坦/氢氯噻嗪(缬沙坦80mg/氢氯噻嗪12.5mg)复方制剂与缬沙坦(缬沙坦80mg)治疗轻、中度原发性高血压的谷峰比值(TPR)和平滑指数(SI),评价缬沙坦/氢氯噻嗪的降压疗效。方法:选择轻、中度原发性高血压病患者[SBP≥140mmHg且<160mmHg(1mmHg=0.133kPa),DBP≥95mmHg并且<110mmHg]84例,随机分为缬沙坦/氢氯噻嗪和缬沙坦组,共服药8周,观察服药前后血压及生化指标的变化。结果:治疗8周后,缬沙坦/氢氯噻嗪组和缬沙坦组降压有效率分别为84.2、52.5,达标率分别为73.9、42.9,两组间差异有统计学意义(P<0.001)。缬沙坦/氢氯噻嗪组TPR为SBP76.7、DBP71.2,均>50;SI为SBP1.14±0.39、DBP1.09±0.27,均>1。缬沙坦组的TPR为SBP77.6、DBP71.3,均>50;SI为SBP1.24±0.39、DBP1.19±0.27,均>1。两组的TPR和SI差别无统计学意义(P>0.05)。结论:缬沙坦80mg/氢氯噻嗪12.5mg复方制剂治疗轻中度原发性高血压患者疗效优于单用缬沙坦80mg,TPR和SI...     

Amlodipine/Valsartan/Hydrochlorothiazide

Amlodipine/valsartan/hydrochlorothiazide (HCTZ) is a fixed-dose combination of the well established antihypertensive agents amlodipine (a calcium channel antagonist), valsartan (an angiotensin II receptor antagonist), and HCTZ (a thiazide diuretic). In patients with moderate or severe hypertension, triple combination therapy with amlodipine + valsartan + HCTZ produced significantly greater reductions from baseline in mean sitting systolic and diastolic BP (msSBP and msDBP) than either valsartan + HCTZ, amlodipine + HCTZ, or amlodipine + valsartan in a large, 8-week, randomized, double-blind, multinational, phase III trial. Furthermore, the proportion of patients achieving overall BP control at endpoint was significantly greater with the triple combination regimen than with any of the dual regimens, with significantly more triple combination recipients achieving msSBP and msDBP control at each assessment throughout the trial. Subgroup analyses of this study suggested that amlodipine + valsartan + HCTZ was generally more effective in reducing BP and providing overall BP control than the dual combination therapies, irrespective of age, race, gender, ethnicity, or hypertension severity. Several smaller studies provide data that support the efficacy of amlodipine + valsartan + HCTZ in patients whose BP is inadequately controlled with amlodipine + valsartan, amlodipine + HCTZ, or valsartan + HCTZ dual combination therapy. Treatment with amlodipine + valsartan + HCTZ for up to 8 weeks was generally well tolerated in the large, phase III trial, with most adverse events being transient and of mild to moderate severity.     

Effects of a fixed-dose ACE inhibitor-diuretic combination on ambulatory blood pressure and arterial properties in isolated systolic hypertension

The ideal therapy for patients with isolated systolic hypertension remains unclear; diuretics, calcium channel blockers, and angiotensin-converting enzyme (ACE) inhibitors are all used in clinical practice. The aim of this study was to determine whether a fixed-dose ACE inhibitor/diuretic combination would reduce ambulatory blood pressures (BP) and arterial stiffness in isolated systolic hypertension more than antihypertensive monotherapy. In this randomized, double-blind study, 8 weeks of fosinopril/hydrochlorothiazide combination (10/12.5 mg titrated up to 20/12.5 mg) was compared with the calcium channel blocker (amlodipine, 5 mg titrated up to 10 mg) and diuretic (indapamide, 2.5 mg) monotherapy in 28 patients with isolated systolic hypertension. Each patient received all 3 therapies. Assessments included 24-hour ambulatory BP, clinic BP, and applanation tonometry-derived augmentation index. At 8 weeks, the fall in average 24-hour systolic BP and night time systolic BP were significantly greater in the fosinopril-hydrochlorothiazide group, compared to amlodipine and indapamide. The decrease in augmentation index and central aortic systolic BP was also greater in the fosinopril-hydrochlorothiazide group, compared to either amlodipine or indapamide. There was no difference between therapies in decrease in clinic systolic or diastolic BP, or diastolic ABP (average 24-h, diurnal, or nocturnal). Compared with either calcium channel blocker or diuretic therapy, a fixed-dose ACE inhibitor-diuretic combination induces greater reductions in systolic ABP, particularly at night, favorable effects that may be related to a decrease in the intensity of or delay in arterial wave reflections. ACE inhibitor-diuretic combination therapy is a useful approach to cardiovascular risk reduction in isolated systolic hypertension.     

Efficacy and safety of aranidipine enteric-coated tablets compared with amlodipine in Chinese patients with mild to moderate essential hypertension: a multicenter, randomized, double-blind, parallel-controlled clinical trial

This is a multicenter, randomized, double-blind, parallel-controlled study, conducted in Chinese patients with mild to moderate essential hypertension. After a 2-week washout period, 236 eligible patients were randomly to receive aranidipine 5-10 mg/d (n = 118) or amlodipine 5-10 mg/d (n = 118) for 10 weeks. The blood pressure and heart rate were evaluated in outpatient clinics, and ambulatory blood pressure monitoring was performed in 24 patients in each group. The blood pressure was significantly decreased in both groups. Compared with amlodipine, the patients who received aranidipine had less response in blood pressure (P < 0.01). The trough/peak ratios of diastolic blood pressure in aranidipine and amlodipine groups were 0.57 ± 0.20 and 0.68 ± 0.19, respectively (P = 0.119). Adverse events occurred at 11.86% and 7.63% in the aranidipine and amlodipine groups, respectively (P = 0.348). Headache was observed at an incidence of >3.0% in both groups, and the serum glucose and lipid profile had no significant change in the amlodipine group. In conclusion, once-daily administration of aranidipine (5-10 mg) effectively controlled blood pressure, and the short-term treatment might result in it being less effective than amlodipine. It had a stable action over 24-hour period, and the mechanism of that is not yet clear. Aranidipine had a good safety similar to that of amlodipine.     

Olmesartan medoxomil/amlodipine/hydrochlorothiazide: fixed-dose combination in hypertension

The antihypertensive agents olmesartan medoxomil, amlodipine and hydrochlorothiazide (HCTZ) are now available as a fixed-dose combination tablet (olmesartan medoxomil/amlodipine/HCTZ). In a 12-week, randomized, double-blind, multicentre trial (TRINITY) in adults with moderate to severe hypertension, olmesartan medoxomil?+?amlodipine?+?HCTZ triple combination therapy produced significantly greater least squares mean reductions from baseline in seated diastolic blood pressure (BP) [primary endpoint] and seated systolic BP than olmesartan medoxomil/amlodipine, olmesartan medoxomil/HCTZ or amlodipine?+?HCTZ. Furthermore, significantly more patients achieved BP goals and targets with the triple combination regimen than with any of the dual combination regimens at week 12, with olmesartan medoxomil?+?amlodipine?+?HCTZ also demonstrating benefit over the dual regimens in terms of ambulatory BP control. According to subgroup analyses of the TRINITY trial, olmesartan medoxomil?+?amlodipine?+?HCTZ was more effective in reducing BP and achieving BP goals than each of the dual therapies, irrespective of hypertension severity, age, sex, race or diabetes mellitus status. Data from a number of smaller clinical studies indicated that olmesartan medoxomil?+?amlodipine?+?HCTZ triple combination therapy provides antihypertensive efficacy in patients whose BP is not adequately controlled with olmesartan medoxomil?+?amlodipine. Olmesartan medoxomil?+?amlodipine?+?HCTZ was generally well tolerated in the TRINITY study, with adverse events usually being mild or moderate in severity.     

Comparison of quinapril and atenolol as single drugs or in combination with hydrochlorothiazide in moderate to severe hypertensives, using automated ambulatory monitoring.

1. Forty patients with moderate to severe hypertension and daytime ambulatory diastolic blood pressure > or = 90 mm Hg were randomized double-blind to once-daily treatment with either quinapril up to 20 mg (n = 20) or atenolol up to 100 mg (n = 20) as single drugs or in combination with hydrochlorothiazide 25 mg over a period of 12 weeks. 2. Conventional and ambulatory blood pressure, heart rate, side effects and metabolic changes were compared at the end of the run-in period on placebo, after 4 weeks on monotherapy and at the end of the 12-week period of active treatment. 3. Quinapril and atenolol reduced conventional blood pressure equally with substantial additional effect seen on combination therapy. The two regimens induced a significant decrease in ambulatory BP. However, the atenolol treated ambulatory hypertensive group experienced significantly greater decreases in diastolic blood pressure during 24 h, awake and sleep periods than did the quinapril group. 4. Adverse reactions were mild with both drugs except for severe Raynaud phenomenon in one patient in the atenolol group. Triglyceride levels were significantly increased with atenolol alone and in combination with hydrochlorothiazide. 5. Thus, within the limits of the dose ranges tested, quinapril and atenolol as single drugs or in combination with hydrochlorothiazide reduce significantly conventional and ambulatory blood pressure in moderate to severe hypertensives, but atenolol is more effective in reducing ambulatory diastolic blood pressure.     

Effects of valsartan or ramipril addition to amlodipine/hydrochlorothiazide combination on left ventricular mass in diabetic hypertensive patients with left ventricular hypertrophy

Objective: The objective of this study was to compare valsartan or ramipril addition to amlodipine + hydrochlorothiazide (HCTZ) on blood pressure (BP) and left ventricular hypertrophy (LVH) in hypertensive diabetic patients with LVH.

Research design and methods: 293 patients were treated with amlodipine 10 mg + HCTZ 12.5 combination and then randomized to receive valsartan 160 mg or ramipril 5 mg, in addition to the previous therapy, for 1 year.

Main outcome measures: Clinic BP was measured every month; echocardiographic assessments were performed at the end of the placebo period, both before the randomization and after 1-year of triple combination therapy.

Results: Both triple regimens similarly reduced SBP/DBP values (-13.5/10.9 mm Hg in the valsartan group and -13.4/10.4 mm Hg in the ramipril group). Triple combination including valsartan better reduced LVMI (-20.1%, p < 0.001), interventricular septal thickness (IVST) (-20.3%, p < 0.001) and left ventricular posterior wall thickness (PWT) (-16.3%, p < 0.001), compared with triple combination including ramipril (-14%, p < 0.01; -16.2%, p < 0.001 and -9%, p < 0.01, respectively); the difference between treatments being statistically significant (p < 0.05). Triple combination with valsartan gave a greater increase of E/A ratio (p < 0.05 between groups).

Conclusions: Valsartan addition to dual therapy with amlodipine + HCTZ was more effective than ramipril addition in reducing LVH.