Losartan and prevention of atrial fibrillation recurrence in hypertensive patients

The aim of the study was to evaluate the effect of losartan as compared with amlodipine, both associated with amiodarone, in preventing the recurrence of atrial fibrillation (AF) in hypertensive patients with a history of recent paroxysmal atrial fibrillation. Two hundred and fifty mild hypertensive (SBP > 140 mm Hg and/or DBP > 90 < 100 mm Hg) outpatients in sinus rhythm but with at least two ECG-documented episodes of symptomatic atrial fibrillation in the previous 6 months and in treatment with amiodarone were randomized to losartan or amlodipine and were followed up for 1 year. Clinic blood pressure (BP) and a 24-hour ECG was evaluated every month; the patients were asked to report any episode of symptomatic atrial fibrillation and to perform an ECG as early as possible. Two hundred and thirteen patients completed the study, 107 in the losartan group and 106 in the amlodipine group. After 12 months the SBP/DBP mean values were significantly reduced by both losartan (from 151.4/95.6 to 135.5/83.7 mm Hg, P < 0.001 versus baseline) and amlodipine (from 152.3/96.5 to 135.2/83.4 mm Hg, P < 0.001 versus baseline), with no difference between the two treatments. At least one ECG-documented episode of atrial fibrillation was reported in 13% of the patients treated with losartan and in 39% of the patients treated with amlodipine. The use of losartan in combination with amiodarone seems more effective than amlodipine/amiodarone combination in preventing new episodes of atrial fibrillation in hypertensive patients with recurrent atrial fibrillation. This might be related to possible favorable impact of angiotensin II receptor blockers (ARB) on the atrial electrical and structural remodeling in this type of patients.     

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。     

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.     

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.     

胺碘酮与普罗帕酮治疗阵发性心房颤动的疗效研究

目的对比研究静脉推注胺碘酮与普罗帕酮转复阵发性心房颤动的效果。方法122例房颤持续时间<48h的患者随机分为两组,胺碘酮组62例:胺碘酮5mg/kg10min内静脉推注;普罗帕酮组60例:普罗帕酮70mg静脉推注,5～10min注完。观察30min若未转复可重复应用。结果转复率:胺碘酮组69·4%(43/62),普罗帕酮组60%(36/60),两组转复率比较差异无统计学意义(P>0·05)。结论胺碘酮和普罗帕酮对阵发性房颤均有较高的转复率。     

伊布利特在控制转复阵发性房颤中的作用研究

目的比较伊布利特与胺碘酮和普罗帕酮在转复阵发房颤中的疗效及安全性。方法选择阵发性房颤患者90例,随机分成依布利特组(A组)、胺碘酮组(B组)、普罗帕酮组(C组),每组30例。于入院10min内,三组分别经静脉注射依布利特1 mg、胺碘酮150 mg、普罗帕酮70 mg。观察10 min后若仍未转复为窦性心律,重复首次剂量。观察开始给药后1、2、4、24 h内房颤的转复率、转复时间、心室率、QT和QRS间期变化及用药后不良反应的发生情况。结果 A组在各时间点房颤的转复率(83.33%)均显著高于其他组。A组转复时间(24.3±10.7)min明显短于其他组。A组不反应发生率(3.33%)明显低于C组,但与B组比较差异无统计学意义。各组用药后心率均显著降低,A组给药后QT间期较B组和C组显著延长,B组QT间期在用药各时段无明显变化。C组给药后的QRS间期较A组和B组明显延长,A组和B组的QRS间期用药后无明显变化。结论伊布利特对房颤转复的效果优于胺碘酮和普罗帕酮,伊布利特对心室率和QT间期的影响大于胺碘酮和普罗帕酮,但对QRS间期无明显影响。伊布利特是一种转复房颤快速、有效的药物。     

Synergistic effects of atenolol and amlodipine for lowering and stabilizing blood pressure in 2K1C renovascular hypertensive rats

AIM: To test the synergistic effects of atenolol and amlodipine on lowering blood pressure (BP) and reducing blood pressure variability (BPV) in 2-kidney, one-clip (2K1C) renovascular hypertensive rats. METHODS: Forty-eight 2K1C renovascular hypertensive rats were randomly divided into 6 groups. They were respectively given 0.8% carboxymethylcellulose sodium (control), atenolol (10.0 mg/kg), amlodipine (1.0 mg/kg), and combined atenolol and amlodipine (low dose: 5.0+0.5 mg/kg; intermediate dose: 10.0+1.0 mg/kg; high dose: 20.0+2.0 mg/kg). The drugs were given via a catheter in a gastric fistula. BP was recorded for 25 h from 1 h before drug administration to 24 h after administration. RESULTS: Compared with BP before medication, all 3 doses of combined atenolol and amlodipine significantly decreased the BP at 24 h after administration, except for the low dose on diastolic BP. Compared with the control group, all 3 doses of combined atenolol and amlodipine significantly reduced the average BP levels for the 24 h period after administration; furthermore, the high and intermediate doses also significantly decreased the BPV levels for the same period. The q values calculated by probability sum analysis for systolic and diastolic BP for the 24 h period after administration were 2.29 and 1.45, respectively, and for systolic and diastolic BPV for the same period they were 1.41 and 1.60, respectively. CONCLUSION: There is significant synergism between atenolol and amlodipine in lowering and stabilizing BP in 2K1C renovascular hypertensive rats.     

Prevention of recurrences in patients with lone atrial fibrillation. The dose-dependent effect of angiotensin II receptor blockers.

BACKGROUND: Atrial fibrillation (AF) leads to the activation of the renin-angiotensin system (RAS), which seems to play an important role in atrial remodelling. It is not known yet whether RAS blockade may prevent recurrences in patients with lone AF. METHODS AND RESULTS: Patients with an episode of persistent AF for >7 days, in the absence of cardiac or extracardiac causes and with normal blood pressure values (lone AF), were recruited. Ninety patients were randomised and scheduled for electrical cardioversion. Three groups of patients were compared: Group I was treated with amiodarone 400 mg daily (30 patients), group II was treated with amiodarone 400 mg daily plus irbesartan 150 mg daily (30 patients) and group III with amiodarone 400 mg daily plus irbesartan 300 mg daily (30 patients). The primary endpoint was the time to a first recurrence of AF. The patients were cardioverted and followed. The Kaplan-Meier analysis of time to first recurrence during the follow-up period showed that patients treated with amiodarone 400 mg plus irbesartan 300 mg had a greater probability of remaining free of AF (77% vs. 52% for amiodarone and 65% for amiodarone+irbesartan 150 mg), hazard ratio for a recurrence in group III: 0.47 (95% CI 0.27-0.82; p=0.001). CONCLUSIONS: The combination of irbesartan plus amiodarone decreased the rate of AF recurrences, with a dose-dependent effect, in lone AF patients.     

Trough:peak ratio and smoothness index in the evaluation of 24-h blood pressure control in hypertension: a comparative study between valsartan/hydrochlorothiazide combination and amlodipine

OBJECTIVE: The aim of this study was to measure the time-effect profiles of a once-daily administered valsartan/hydrochlorothiazide combination and amlodipine on blood pressure using various indices derived from 24-h ambulatory blood pressure (BP) monitoring. METHODS: Of the 310 randomized outpatients with uncomplicated mild-to-moderate primary hypertension, 259 (133 on valsartan/hydrochlorothiazide, 126 on amlodipine) were eligible for analysis. After a 2-week placebo wash-out period, the patients were randomly allocated to treatment with either valsartan 80 mg once daily (o.d.) or amlodipine 5 mg o.d. for 4 weeks; in the case of an unsatisfactory blood pressure response, the treatments could be respectively changed to the fixed combination of valsartan 80 mg plus hydrochlorothiazide 12.5 mg o.d. or amlodipine 10 mg o.d. for a further 8 weeks. The trough:peak ratio (global and individualized approaches) and smoothness index (i.e., the ratio between the average of the 24-hourly BP changes after treatment and the corresponding standard deviation) were calculated from 24-h ambulatory blood pressure recordings made after the placebo period and after 4 weeks and 12 weeks of active treatment. RESULTS: Both regimens effectively lowered systolic and diastolic ambulatory pressures after 4 weeks and 12 weeks (all P<0.001) but, among the responders, the valsartan/hydrochlorothiazide combination had a greater antihypertensive effect during the night-time hours after 12 weeks (P=0.03/0.02). In the responders, the placebo-adjusted, mean trough:peak ratios were 0.76/0.74 in the valsartan/hydrochlorothiazide group (n = 111) and 0.66/0.62 in the amlodipine group (n = 101). The corresponding global trough:peak ratios were 0.61/0.57 for the valsartan/hydrochlorothiazide combination and 0.56/0.56 for amlodipine. However, the between-group differences in individual or global trough:peak ratios were not significant. The smoothness index was slightly, but insignificantly, greater for valsartan/hydrochlorothiazide than for amlodipine in the responders and the groups as a whole. CONCLUSION: Valsartan/hydrochlorothiazide and amlodipine were equally effective in reducing ambulatory BP, but the valsartan/hydrochlorothiazide combination led to more homogeneous BP control during the inter-dosing interval. Trough:peak ratio and smoothness index did not reflect this finding accurately.     

氨氯地平-缬沙坦复合片的药物经济学研究

目的比较氨氯地平-缬沙坦复合片与氨氯地平、缬沙坦自由联合用药在治疗国人高血压中的药物经济学特性。方法通过文献研究的途径,采用成本最小分析法。其中成本按照Pharmacy & Medical Impact Model的思想进行计算。结果氨氯地平-缬沙坦复合片与缬沙坦、氨氯地平自由联合用药相比,每人每年总共可以节约431元。随着使用氨氯地平-缬沙坦复合片人数比例的增加,节约的费用会逐步增加,最多可达1145万元,占总费用的0.67%。结论氨氯地平-缬沙坦复合片的成本低于自由联合应用,具有较好的成本效果和成本效益。     

Efficacy and safety of a single-pill combination of amlodipine/valsartan in Asian hypertensive patients inadequately controlled with amlodipine monotherapy

Abstract

Objective:

The antihypertensive efficacy of amlodipine/valsartan combination has not been evaluated in Asian patients as previous large-scale studies enrolled very few patients. This multicentre, randomised, double-blind study assessed the efficacy and safety of a single-pill combination of amlodipine/valsartan versus amlodipine in Asian hypertensive patients.     

Synergism of amlodipine and candesartan on blood pressure reduction and organ protection in hypertensive rats

This study was designed to investigate the possible synergism of amlodipine and candesartan on the reduction of blood pressure (BP) in hypertensive rats. The end organ protection was also observed. In acute experiment, spontaneously hypertensive rats (SHRs) were treated with intragastric administration of amlodipine (0.5, 1, 2, 3 mg/kg), candesartan (1, 2, 3, 4, 6, 8 mg/kg), and 14 different combinations to find the possible ratio of synergistic interaction. In two kidneys, one clip (2K1C) rats, the effects of amlodipine (1 mg/kg), canderastan (2 mg/kg) and their combination on BP reduction were also observed. In chronic study, SHRs were treated with amlodipine (1 mg/kg), candesartan (2 mg/kg), and their combination for 5 months. Organ damage evaluation was performed after BP recording. The probability sum test (q test) was used to evaluate the synergistic action. There is a synergistic interaction between amlodipine and candesartan on BP reduction. The optimal dose ratio is 1:2. The synergistic effect was also confirmed by 2K1C hypertensive rats. In chronic study, this combination (1:2) possessed an obvious synergism on the reduction of BP and BP variability (BPV) and protection on end organs. Multiple regression analysis showed that heart and aortic hypertrophy indexes and glomerular damage parameters were positively related to BP and BPV. In conclusion, combination of amlodipine and candesartan exhibited a potent antihypertensive effect and possessed an obvious synergism on BP reduction and organ protection in hypertension. The optimal proportion was 1:2. BP and BPV reduction may both importantly contribute to end organ protection.     

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.     

Amlodipine/Valsartan: fixed-dose combination in hypertension

Amlodipine, a dihydropyridine calcium channel blocker, and valsartan, an angiotensin II receptor blocker, are established antihypertensive agents. Fixed-dose combinations of amlodipine/valsartan are available in several European countries and in the US. Individual dose titration with amlodipine and valsartan is generally recommended before changing to the fixed-dose combination. Amlodipine/valsartan, at approved dosage regimens, achieved significantly greater reductions in mean sitting diastolic and systolic blood pressure (BP) than amlodipine or valsartan monotherapy, or placebo in two randomized, double-blind, factorial trials in patients with mild to moderate hypertension. Approximately 80-90% of patients receiving approved dosages of amlodipine/valsartan achieved a response, defined as a mean sitting diastolic BP <90 mmHg or a >or= 10 mmHg reduction from baseline. Subgroup analyses of data from the two trials showed that the antihypertensive efficacy of amlodipine/valsartan in the elderly, Black patients and those with stage 2 hypertension was consistent with that observed in the overall study population. Marked reductions in BP were also observed in patients whose BP was previously uncontrolled on monotherapy (with various antihypertensives) who were switched (without washout) to amlodipine/valsartan in a phase IIIb-IV study. Amlodipine/valsartan was generally well tolerated in clinical trials. In particular, the incidence of peripheral oedema was significantly lower in patients receiving amlodipine/valsartan than in those treated with amlodipine monotherapy.     

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     

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.     

Pharmacokinetic and antihypertensive profile of amlodipine and felodipine-ER in younger versus older patients with hypertension

To evaluate the impact of age on the pharmacokinetics and blood pressure (BP) responses of a dihydropyridine (DHP) with large versus small first-pass metabolism in hypertensive subjects, younger (n = 28) and older (n = 35) patients with hypertension were randomized to placebo, felodipine-ER 5 mg/d, or amlodipine 5 mg/d. In the young subjects, the first dose of either DHP did not decrease BP and chronic dosing decreased BP by approximately 10 mm Hg, which had disappeared by 24 hours. In the older group, felodipine-ER decreased systolic BP by approximately 10 mm Hg after the first dose and by approximately 20 mm Hg after chronic dosing, which had disappeared after 24 hours. The first dose of amlodipine caused a gradual fall in BP and chronic dosing by approximately 20 mm Hg and still by approximately 10 mm Hg at 120 hours. Older subjects showed approximately 30% higher area under the concentration–time curves and plasma concentrations of felodipine and amlodipine, but (apparent) elimination half-lives did not differ between younger and older subjects. The chronic antihypertensive responses correlated well with both plasma levels and pretreatment BP. Age has only a modest impact on the pharmacokinetics of amlodipine and felodipine-ER but markedly affects the BP response to the first dose of either DHP and the duration of action after chronic dosing of amlodipine.     

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.     

Clinical effectiveness of low-dose chlorthalidone (6.25 mg) + atenolol combination in stage I hypertensive patients: a multicenter,randomized, controlled study

ABSTRACT

Objective: To compare the efficacy and safety of low-dose chlorthalidone + atenolol combination with atenolol and atenolol + amlodipine combination in stage I hypertensive patients uncontrolled on active run-in monotherapy.

Methods: Newly diagnosed stage I hypertensive patients were randomized to active run-in monotherapy either with atenolol 25?mg (98/300) or chlorthalidone 6.25?mg (100/300) or amlodipine 2.5?mg (102/300). A total of 282/300 patients (atenolol 92, chlorthalidone 91, amlodipine 99) completed the active run-in phase successfully. Patients uncontrolled on active run-in monotherapy (atenolol 33, chlorthalidone 45, amlodipine 47) received the study treatment, namely atenolol 50?mg alone, chlorthalidone 6.25?mg + atenolol 25?mg and atenolol 25?mg + amlodipine 2.5?mg, respectively. Efficacy of the therapy was evaluated by BP measurement at weeks 12 and 20 post-therapy.

Results: Post-active run-in monotherapies, the study treatment groups showed a significant fall in mean SBP and DBP from baseline (p?<?0.05). The mean fall in SBP and DBP was comparable for study treatments (atenolol 50?mg, atenolol 25?mg + chlorthalidone 6.25?mg and atenolol 25?mg + amlodipine 2.5?mg) (p = 0.337 for SBP and p = 0.054 for DBP) at week 12 and (p = 0.744 for SBP and p = 0.855 for DBP) at week 20; also, the percentage of responders was comparable for the three study treatment groups (p = 0.799) indicating that the low-dose chlorthalidone + atenolol combination is non-inferior to the high-dose atenolol alone and atenolol + amlodipine combination. No serious laboratory/clinical adverse events were reported in this study.

Conclusion: Chlorthalidone 6.25?mg in combination with atenolol 25?mg is effective and safe in stage I (JNC 7) essential hypertensive patients. This low dose of chlorthalidone could reduce dose-related concerns over metabolic adverse effects and may lead to wider usage of this proven antihypertensive agent in combination therapy.