缬沙坦/氨氯地平复方片剂对单药控制不良的轻中度高血压患者的疗效观察

目的 评价缬沙坦(80 mg)/氨氯地平(5 mg)复方片剂(复方片剂)治疗经氨氯地平5 mg或缬沙坦80 mg控制不良的轻、中度原发性高血压患者疗效和安全性.方法 采用多中心、双盲、双模拟、随机、活性药物对照、平行试验方法进行两项临床研究.在两项研究中对经1～4周洗脱期的轻、中度原发性高血压患者[坐位舒张压≥95 mm Hg(1 mm Hg=0.133 kPa)且<110 mm Hg]分别采用单药氨氯地平5 mg或缬沙坦80 mg治疗4周,在单药导入结束后,坐位舒张压仍然≥90mm Hg且<110 mm Hg的患者随机进入复方片剂组或继续原有的单药治疗,共8周.其间,在治疗4周和试验结束时评估药物的安全性及有效性.结果 治疗结束时,复方片剂组平均坐位收缩压/平均坐位舒张压下降幅度较氨氯地平单药治疗组多4.4mm Hg/3 mm Hg(P<0.0001);较缬沙坦80 mg组多6.4 mm Hg/4.2 mm Hg(P<0.0001).两项研究中复方片剂组的血压控制率(血压<140/90 mmHg)分别为71.0%及71.2%,显著优于氨氯地平或缬沙坦单药治疗组,不良事件发生率与单药治疗组相当.结论 复方片剂组的血压控制率显著优于其两种成分(氨氯地平5 mg或缬沙坦80 mg)单药的治疗,且具有良好的安全性和耐受性.     

Efficacy of the combination of amlodipine and valsartan in patients with hypertension uncontrolled with previous monotherapy: the Exforge in Failure after Single Therapy (EX-FAST) study

In this randomized, double-blind, multicenter study, patients whose blood pressure (BP) was uncontrolled by monotherapy were switched directly to amlodipine/valsartan 5/160 mg (n=443) or 10/160 mg (n=451). After 16 weeks, BP control (levels <140/90 mm Hg or <130/80 mm Hg for diabetics) was achieved in 72.7% (95% confidence interval [CI], 68.6-76.9) of patients receiving amlodipine/valsartan 5/160 mg and in 74.8% (95% CI, 70.8-78.9) receiving amlodipine/valsartan 10/160 mg. Incremental reductions from baseline in mean sitting systolic and diastolic BP were significantly greater with the higher dose (20.0+/-0.7 vs 17.5+/-0.7 mm Hg; P=.0003 and 11.6+/-0.4 vs 10.4+/-0.4 mm Hg; P=.0046). Incremental BP reductions were also achieved with both regimens irrespective of previous monotherapy, hypertension severity, diabetic status, body mass index, and age. Peripheral edema was the most frequent adverse event. These results provide support for the BP-lowering benefits of complementary antihypertensive therapy with amlodipine and valsartan in patients with hypertension uncontrolled by previous monotherapy.     

Comparison of valsartan and amlodipine on ambulatory and morning blood pressure in hypertensive patients

BACKGROUND: Cardiovascular events occur most frequently in the morning. We aimed to study the effects of monotherapy with the long-acting angiotensin II receptor blocker valsartan compared with the long-acting calcium antagonist amlodipine on ambulatory and morning blood pressure (BP). METHODS: We performed ambulatory BP monitoring before and after once-daily dose of valsartan (valsartan group, n = 38) and amlodipine (amlodipine group, n = 38) therapy in 76 hypertensive patients. To achieve the target BP of < or =140/90 mm Hg, valsartan was titrated from 40 mg/day to 160 mg/day (mean dose 124 mg/day) and amlodipine was titrated from 2.5 mg/day to 10 mg/day (mean dose 6.4 mg/day). RESULTS: Both drugs significantly reduced clinic and 24-h systolic BP (SBP) and diastolic BP (DBP) (P <.002). However, the antihypertensive effect of amlodipine was superior to that of valsartan in clinical SBP (-26 mm Hg v -13 mm Hg, P =.001) and 24-h SBP (-14 mm Hg v -7 mm Hg, P =.008). In addition, morning SBP was significantly reduced by amlodipine from 156 to 142 mm Hg (P <.001) but not by valsartan. Both agents reduced lowest night SBP to a similar extent (amlodipine 121 to 112 mm Hg, P <.001; valsartan 123 to 114 mm Hg, P <.002). Reduction in morning SBP surge (morning SBP minus lowest night SBP) was significantly greater in patients treated with amlodipine compared with those treated with valsartan (-6.1 mm Hg v +4.5 mm Hg, P <.02). CONCLUSIONS: Amlodipine monotherapy was more effective than valsartan monotherapy in controlling 24-h ambulatory BP and morning BP in hypertensive patients.     

复方缬沙坦治疗轻中度原发性高血压患者的疗效观察

目的评价复方缬沙坦（缬沙坦80mg／氢氯噻嗪12．5mg复方制剂）治疗经单用缬沙坦80mg控制不良的轻、中度原发性高血压患者疗效和安全性。方法采用多中心、双盲、双模拟、随机、活性药物对照、平行试验方法。对经2周洗脱期的轻、中度原发性高血压患者[坐位舒张压≥95mmHg（1mmHg=0．133kPa）且〈110mmHg]采用单药缬沙坦80mg／d治疗4周,在单药导入结束后,坐位舒张压仍〉190mmHg的864例患者按1：1随机、双盲分为复方缬沙坦组或缬沙坦80mg／d组,继续治疗8周。在治疗4周和结束时评估药物安全性及有效性。结果在轻、中度原发性高血压患者中复方缬沙坦每日1次比单用缬沙坦80mg／d血压进一步下降、达标率提高。治疗结束时平均坐位收缩压多降低3．5mmHg,平均坐位舒张压多下降2．2mmHg,血压控制〈140／90mmHg的患者在复方缬沙坦组和单用缬沙坦80mg／d组分别为53．9％及40．9％。结论轻、中度原发性高血压患者采用复方缬沙坦治疗组降压有效率及达标率均优于每日1次服用缬沙坦80mg／d组。复方缬沙坦适用于缬沙坦单药控制不良的轻、中度原发性高血压患者。     

Combination therapy of amlodipine/benazepril versus monotherapy of amlodipine in a practice-based setting

BACKGROUND: Community-based studies are conducted to determine the degree to which therapeutic interventions will succeed in real world settings. This large practice-based clinical trial assessed the efficacy and tolerability of fixed-dose combination therapy with amlodipine/benazepril, compared with amlodipine monotherapy, in patients with mild-to-moderate hypertension. METHODS: Hypertensive patients currently taking amlodipine were selected based on one of two criteria: inadequate blood pressure (BP) control on amlodipine (diastolic BP [DBP] > or = 90 mm Hg; group 1), or inability to tolerate amlodipine (DBP < or = 90 mm Hg, but with edema; group 2). Eligible patients were switched from 5 or 10 mg of amlodipine to 5/10 mg or 5/20 mg of amlodipine/benazepril for 4 weeks. In group 1 (n = 6410), primary efficacy outcome was change in mean sitting DBP. A secondary efficacy outcome was change in mean sitting systolic BP (SBP). In group 2 (n = 1502), primary efficacy outcome was the percentage of patients whose edema improved during therapy with amlodipine/benazepril when compared with amlodipine monotherapy. RESULTS: In group 1, mean sitting DBP declined from 96.5 mm Hg at baseline to 84.9 mm Hg at week 4, a mean reduction of 11.5 mm Hg (95% confidence interval [CI] -11.8 to -11.3 mm Hg; P < .001). From baseline to week 4, mean sitting SBP declined from 152.9 mm Hg to 137.3 mm Hg, a mean reduction of 15.6 mm Hg (95% CI -16.0 to -15.2 mm Hg; P < .001). In group 2, 85% (95% CI 83%-87%) experienced some improvement in edema compared with baseline levels. CONCLUSIONS: Fixed-dose combination antihypertensive agent amlodipine/benazepril was safe and effective for patients who experienced either inadequate BP control or edema with amlodipine monotherapy.     

24-Hour ambulatory blood pressure control with triple-therapy amlodipine, valsartan and hydrochlorothiazide in patients with moderate to severe hypertension

To determine the effectiveness and safety of once-daily combination therapy with amlodipine, valsartan and hydrochlorothiazide for reducing ambulatory blood pressure (ABP) in patients with moderate to severe hypertension, a multicenter, double-blind study was performed (N=2271) that included ABP monitoring in a 283-patient subset. After a single-blind, placebo run-in period, patients were randomized to receive amlodipine/valsartan/hydrochlorothiazide (10/320/25?mg), valsartan/hydrochlorothiazide (320/25?mg), amlodipine/valsartan (10/320?mg) or amlodipine/hydrochlorothiazide (10/25?mg) each morning for 8 weeks. Efficacy assessments included change from baseline in 24-h, daytime and night time mean ambulatory systolic BP (SBP) and diastolic BP (DBP). Statistically significant and clinically relevant reductions from baseline in all these parameters occurred in all treatment groups (P<0.0001, all comparisons versus baseline). At week 8, least squares mean reductions from baseline in 24-h, daytime and night time mean ambulatory SBP/DBP were 30.3/19.7, 31.2/20.5 and 28.0/17.8?mm?Hg, respectively, with amlodipine/valsartan/hydrochlorothiazide; corresponding reductions with dual therapies ranged from 18.8-24.1/11.7-15.5, 19.0-25.1/12.0-16.0 and 18.3-22.6/11.1-14.3?mm?Hg (P≤0.01, all comparisons of triple versus dual therapy). Treatment with amlodipine/valsartan/hydrochlorothiazide maintained full 24-h effectiveness, including during the morning hours; all hourly mean ambulatory SBP and mean ambulatory DBP measurements were ≤130/85?mm?Hg at end point. Amlodipine/valsartan/hydrochlorothiazide combination therapy was well tolerated. Once-daily treatment with amlodipine/valsartan/hydrochlorothiazide (10/320/25?mg) reduces ABP to a significantly greater extent than component-based dual therapy and maintains its effectiveness over the entire 24-h dosing period.     

Effect of valsartan addition to amlodipine on ankle oedema and subcutaneous tissue pressure in hypertensive patients

The aim of this study was to assess the effect of valsartan addition to amlodipine on ankle foot volume (AFV) and pretibial subcutaneous tissue pressure (PSTP), two objective measures of ankle oedema. After a 4-week placebo period, 80 grade 1-2 hypertensive patients (diastolic blood pressure (DBP)>90 mm Hg and <110 systolic blood pressure (SBP)>140 mm Hg) were randomized to amlodipine 10 mg or valsartan 160 mg or amlodipine 10 mg plus valsartan 160 mg for 6 weeks according to an open-label, blinded end point, crossover design. At the end of the placebo period and of each treatment period, blood pressure, AFV and PSTP were evaluated. AFV was measured using the principle of water displacement. PSTP was assessed connecting the subcutaneous pretibial interstitial environment with a water manometer. Both amlodipine and valsartan monotherapy significantly reduced SBP (-16.9 and -14.5 mm Hg, respectively, P<0.01 vs baseline), and DBP (-12.9 and -10.2 mm Hg, respectively, P<0.01 vs baseline) but the reduction was greater with the combination (-22.9 mm Hg for SBP, P<0.01 vs monotherapy; -16.8 mm Hg for DBP, P<0.01 vs monotherapy). Amlodipine monotherapy significantly increased both AFV (+23%, P<0.01 vs baseline) and PSTP (+75.5%, P<0.001 vs baseline) whereas valsartan monotherapy did not influence them. As compared to amlodipine alone, the combination produced a less marked increase in AFV (+6.8%, P<0.01 vs amlodipine) and PSTP (+23.2%, P<0.001 vs amlodipine). Ankle oedema was clinically evident in 24 patients with amlodipine and in six patients with the combination. These results suggest that angiotensin receptor blockers partially counteract the microcirculatory changes responsible for calcium channel blockers induced oedema formation.     

Efficacy and safety of amlodipine/valsartan compared with amlodipine monotherapy in patients with stage 2 hypertension: a randomized,double-blind,multicenter study: the EX-EFFeCTS Study

Achieving blood pressure (BP) targets in stage 2 hypertension usually requires two or more drugs, which should be selected from different classes. This study compared the efficacy and tolerability of amlodipine/valsartan with amlodipine in patients with stage 2 hypertension. In this multicenter, randomized, double-blind, 8-week study, 646 patients with stage 2 hypertension (mean sitting systolic blood pressure [MSSBP] ≥160 mm Hg) received amlodipine/valsartan 5/160 mg or amlodipine 5 mg for 2 weeks, prior to being force-titrated to amlodipine/valsartan 10/160 mg or amlodipine 10 mg, respectively, for a further 6 weeks. Hydrochlorothiazide could be added at Week 4 if MSSBP was ≥130 mm Hg. At endpoint Week 4, reductions in MSSBP were significantly greater in patients receiving amlodipine/valsartan than in those receiving amlodipine (30.1 mm Hg vs. 23.5 mm Hg; P < .0001). Likewise, MSSBP reductions in patients with baseline MSSBP ≥180 mm Hg were also greater for amlodipine/valsartan at Week 4 (40.1 mm Hg vs. 31.7 mm Hg for amlodipine; P = .0018). Differences favoring amlodipine/valsartan were also seen for BP control. Amlodipine/valsartan was generally well tolerated. These findings support the rationale for combining agents with complementary mechanisms of action, such as amlodipine and valsartan, in the management of stage 2 hypertension.     

Comparison of aliskiren/hydrochlorothiazide combination therapy and amlodipine monotherapy in patients with stage 2 systolic hypertension and type 2 diabetes mellitus

Patients with stage 2 hypertension and diabetes are at high cardiovascular risk and require large blood pressure (BP) reductions to reach treatment goals. This randomized double-blind study compared aliskiren/hydrochlorothiazide (HCTZ) combination therapy with amlodipine monotherapy in 860 patients with mean sitting systolic BP (msSBP) ≥160 mm Hg to <200 mm Hg and type 2 diabetes. Patients received either once-daily aliskiren/HCTZ 150/12.5 mg or amlodipine 5 mg for 1 week then force-titrated to double the doses for 7 weeks. Baseline BP was 167.7/91.4 mm Hg. At week 8 end point, aliskiren/HCTZ provided significantly greater reductions in msSBP than amlodipine (28.8 mm Hg vs 26.2 mm Hg; P<.05). Mean sitting diastolic BP reductions were similar with aliskiren/HCTZ (9.9 mm Hg) and amlodipine (9.0 mm Hg). Achievement of BP control (<130/80 mm Hg) was significantly greater with aliskiren/HCTZ (23.2%) than amlodipine (13.8%; P<.0001). Aliskiren/HCTZ provides substantial msSBP reductions and greater BP control rates than amlodipine, and offers an attractive treatment option for patients with hypertension and diabetes mellitus.     

贝那普利/氨氯地平复方制剂与贝那普利单药治疗轻中度高血压的多中心随机双盲平行对照研究

目的 评价贝那普利/氨氯地平复方片剂与贝那普利片单药治疗轻、中度高血压患者的有效性和安全性.方法 本研究为多中心、随机、双盲、平行对照研究.356例原发性高血压患者经2周洗脱期后,再给予4周贝那普利片10 mg单药治疗,220例平均坐位舒张压(SeDBP)仍≥90 mm Hg(1 mm Hg=0.133 kPa)的患者随机分为贝那普利(10 mg)/氨氯地平(5 mg)固定剂量复方片剂组(复方制剂组,1片/d,n=113)和贝那普利片单药组(单药治疗组,20 mg/d,n=107),治疗4周末两组诊室SeDBP≥90 mmHg者剂量加倍.SeDBP＜90 mm Hg者续服原剂量,共随机双盲治疗8周.以总有效率和SeDBP下降差值作为主要疗效指标.其中74例患者(复方片剂组38例,单药组36例)完成了24 h动态血压监测,并作为降压疗效的评价指标.结果 随机、双盲治疗8周末,复方片剂组SeDBP下降值为(11.7±6.8)mm Hg、达目的 血压占65.7%、总有效率为88.5%;单药治疗组SeDBP下降值为(7.7±6.9)mm Hg、达目的 血压占35.5%、总有效率为65.5%.两组组间比较差异均有统计学意义(P＜0.001).24 h动态血压监测结果,复方制剂组和单药组的舒张压/收缩压(DBP/SBP)的谷/峰比率(T/P)分别为83.1%/76.0%和85.8%/79.5%(P＜0.05).复方制剂组与单药治疗组的不良反应发生率分别为16.8%和35.5%(P＜0.01).结论 贝那普利/氨氯地平复方制剂治疗原发性高血压患者的降压疗效明显优于贝那普利单药治疗,且有良好的耐受性.

Abstract：

Objective To evaluate the efficacy and tolerability of the fixed combination of amlodipine 5 mg/benazepril 10 mg once-daily therapy, compared with benazepril, 10 mg, monotherapy in patients with mild and moderate hypertension, and to evaluate the 24 h antihypertensive efficacy and the duration of action by ambulatory blood pressure monitoring Methods In a multicenter, randomized,double-blind, parallel controlled trial, 356 cases of hypertensive patients after 2 weeks wash-out, and then given 4 weeks of benazepril 10 mg monotherapy, 220 patients with mean seated diastolic blood pressure (SeDBP)remained ≥90 mm Hg(1 mm Hg = 0. 133 kPa)were randomly divided into benazepril 10 mg/amlodipine 5 mg(BZ10/AML5)fixed-dose combination therapy group(once a day, n = 113), and benazepril monotherapy group(daily 20 mg, n = 107). In the two groups the patients with SeDBP≥90 mm Hg were doubled the dosage of the initial regimen at the end of 4-week treatment for additional 4 weeks , and the patients with SeDBP ＜ 90 mm Hg remained the initial regimen for additional 4 weeks. The primary endpoint was to evaluate the improvement of SeDBP at the end of 8-week treatment. There were 74 patients(the combination therapy group n = 38, monotherapy therapy group n = 36)completed the 24 h ambulatory blood pressure monitoring which was included in the final efficacy analysis. Results The randomized, doubleblind treatment for 8 weeks, the mean value of SeDBP reduction, the reaching target blood pressure rate and total successful response rate to the treatment(a SeDBP ＜ 90 mm Hg or a decrease of 10 mm Hg or more from baseline)were(11.7 ± 6.8)mm Hg, 65.7% and 88.5% in the combination therapy group,respectively, and were(7.7 ±6. 9)mm Hg, 35.5% and 65.5% in the monotherapy group, respectively.There were statistically significant difference between the combination therapy and the monotherapy groups in all the 3 indexs(P ＜ 0. 001). The fixed combination significantly reduced systolic blood pressure(SBP)and diastolic blood pressure(DBP)values throughout the 24 h. The trough to peak ratios of DBP/SBP in the fixed compound of benazepril/amlodipine(10 mg/5 mg)and benazepril(20 mg)alone were 83. 1%/76. 0% and 85.8%/79. 5%, respectively. Adverse events rates were 16. 8% in the combination therapy group and 35.5% in the monotherapy group(P ＜ 0. 001). Conclusions The combination therapy with benazepril/amlodipine was superior to benazepril monotherapy and was well tolerated in patients with essential hypertension and allowing a satisfactory BP control for 24 hours.     

Amlodipine added to quinapril vs quinapril alone for the treatment of hypertension in diabetes: the Amlodipine in Diabetes (ANDI) trial

This randomized, comparative, parallel-group trial investigated strategies of blood pressure (BP)-lowering in patients with diabetes and hypertension. Patients not reaching goal BP (<130/80 mm Hg) after 4-week open-label treatment with quinapril 20 mg/d (n=374) received 40 mg/d quinapril (n=167) or 20 mg/d quinapril plus amlodipine besylate (5 mg/d; n=162) for 6 weeks. Patients receiving combination therapy vs monotherapy had significantly greater reductions in mean +/- SE sitting systolic BP (9.9+/-1.0 mm Hg vs 4.3+/-1.1 mm Hg; P<.001) and diastolic BP (6.5+/-0.6 mm Hg vs 2.7+/-0.6 mm Hg; P<.001). No significant differences between groups were observed in percentage of patients achieving goal BP (10.1% with combination therapy vs 8.2% with monotherapy). A clinically neutral effect was observed on high-sensitivity C-reactive protein in both groups. Treatments were well tolerated; fewer than 3% of patients in any group discontinued due to treatment-emergent or treatment-related adverse events. In diabetic hypertensive patients, 20 mg/d quinapril plus 5 mg/d amlodipine besylate was a more effective BP-lowering strategy than monotherapy with 40 mg/d quinapril.     

Clinically additive effect between doxazosin and amlodipine in the treatment of essential hypertension

The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure has reported that combinations of low doses of antihypertensive agents from different classes may provide additional antihypertensive efficacy and minimize the likelihood of dose-dependent adverse effects. Doxazosin and amlodipine, alone and in combination, were compared for efficacy in reducing blood pressure (BP) in 75 patients with predominantly moderate (Stage 2) hypertension. This was a double-blind, randomized, crossover study. After a 2-week washout period, patients in group A (n = 37) received amlodipine 10 mg and patients in group B (n = 38) received doxazosin 4 mg for 6 weeks. All patients then received reduced-dose combination therapy (amlodipine 5 mg and doxazosin 2 mg) for 6 weeks. Subsequently, patients received 6 weeks of monotherapy with the alternate medication (group A received doxazosin 4 mg and group B received amlodipine 10 mg). During both monotherapy periods, doxazosin and amlodipine significantly reduced systolic and diastolic BP (P < .001 v baseline). BP further decreased with combination therapy (P < .01 v monotherapy). The percentage of patients with Stage 2 hypertension who achieved a target BP of < 140/< 90 mm Hg increased from 78% with monotherapy to 94% with combination therapy. Fewer adverse effects were observed during combination therapy. It is concluded that there is an additional fall in blood pressure when reduced doses of doxazosin and amlodipine are used in combination for the treatment of hypertension, suggesting that doxazosin should be considered as an effective add-on treatment to calcium-channel blockers.     

Initial angiotensin-converting enzyme inhibitor/calcium channel blocker combination therapy achieves superior blood pressure control compared with calcium channel blocker monotherapy in patients with stage 2 hypertension

BACKGROUND: The Seventh Report of the Joint National Committee (JNC 7) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommends initial combination therapy for patients whose blood pressure (BP) is >20/10 mm Hg above goal. This study evaluated the efficacy and safety of initial combination therapy versus that of monotherapy in patients with stage 2 hypertension, who by definition meet the JNC 7 recommendation for initial combination antihypertensive therapy. METHODS: This multicenter, double-blind, 12-week study randomized 364 patients with stage 2 hypertension to fixed-dose combination therapy with amlodipine besylate/benazepril HCl (5/20 mg/d titrated to 10/20 mg/d) or amlodipine besylate monotherapy (5 mg/d titrated to 10 mg/d). RESULTS: Significantly more patients randomized to combination therapy (74.2%) compared with those randomized to monotherapy (53.9%; P <.0001) achieved the primary end point (reductions in systolic BP > or =25 mm Hg, if baseline systolic BP was <180 mm Hg, or > or =32 mm Hg, if baseline systolic BP was > or =180 mm Hg). Significantly more patients randomized to combination therapy compared with monotherapy attained BP goals of <140/90 mm Hg (61.0% v 43.3%; P =.0007) and < or =130/85 mm Hg (35.7% v 19.1%; P =.0004). Among patients with baseline systolic BP > or =180 mm Hg, combination therapy resulted in significantly greater reductions in systolic BP compared with monotherapy (-42.3 v -30.4 mm Hg; P =.001). More than 90% of patients in each group were titrated to the higher dose. Both treatments were well tolerated. CONCLUSIONS: Combination therapy was well tolerated and resulted in significantly greater BP reductions and attainment of BP goals compared with monotherapy in patients with stage 2 hypertension. This evidence supports the recommendation of combination therapy as first-line treatment in stage 2 hypertension.     

Improving Blood Pressure Control: Increase the Dose of Diuretic or Switch to a Fixed‐Dose Angiotensin Receptor Blocker/Diuretic? The Valsartan Hydrochlorothiazide Diuretic for Initial Control and Titration to Achieve Optimal Therapeutic Effect (Val‐DICTATE) Trial

To assess the strategy of increasing the dose of a diuretic compared with using an angiotensin receptor blocker in combination with a diuretic, the authors performed a multicenter, randomized, parallel group trial in hypertensive patients (baseline blood pressure [BP], 153/97 mm Hg) whose BP remained uncontrolled on initial low-dose diuretic monotherapy (hydrochlorothiazide [HCTZ] 12.5 mg Hg). Patients with stage 1 and 2 hypertension were randomized to treatment with valsartan/HCTZ (160/12.5 mg) or to doubling of the HCTZ dose (25 mg). The primary end point was the percentage of patients whose clinic BP values were <140/90 mm Hg following 4 weeks of double-blind therapy. A significantly higher proportion (P<.001) of hypertensive patients met BP control levels in the valsartan/HCTZ (160/12.5 mg) group compared with the HCTZ 25 mg group (37% vs 16%). Changes from baseline in BP were significantly greater (P<.001) for both systolic BP and diastolic BP in the combination therapy arm compared with the diuretic monotherapy arm (-12. 4/-7.5 mm Hg in valsartan/HCTZ 160/12.5 mg group vs -5.6/-2.1 mm Hg in HCTZ 25 mg group). Tolerability and adverse events were similar in the 2 treatment groups. This study suggests that in the management of hypertension, utilizing an angiotensin receptor blocker/diuretic combination was more effective in lowering BP and achieving BP goals when compared with increasing the dose of the diuretic.     

Comparison of the effects on 24-h ambulatory blood pressure of valsartan and amlodipine, alone or in combination with a low-dose diuretic, in elderly patients with isolated systolic hypertension (Val-syst Study)

OBJECTIVE: The aim of this study was to compare the time-effect profiles of a once-daily administration of valsartan and amlodipine, each given alone or in combination with hydrochlorothiazide, in terms of ambulatory blood pressure (BP) and heart rate in elderly patients with isolated systolic hypertension. METHODS: One hundred and sixty-four elderly outpatients with systolic hypertension received valsartan 80 mg (n=79) or amlodipine 5 mg (n=85) once daily for eight weeks, after which the patients with poorly controlled office BP were up-titrated to valsartan 160 mg or amlodipine 10 mg once daily. If their office systolic BP was still >140 mmHg after eight weeks at these doses, 12.5 mg hydrochlorothiazide was added for a further eight weeks. The hourly BP decreases in all of the patients were calculated on the basis of 24-h ambulatory recordings made after the placebo period and at the end of active treatment. The trough/peak ratio and smoothness index were calculated in the responders. RESULTS: Both the valsartan- and amlodipine-based treatments effectively lowered mean 24-h, daytime and night-time systolic ambulatory BP (all p<0.001) without any significant differences between the two regimens. Ambulatory heart rate decreased in the subjects on valsartan and slightly increased in those on amlodipine (the differences in 24-h and daytime heart rate were significant (p=0.008 and 0.002 respectively). Among the 138 responders, the valsartan-based treatment had a greater anti-hypertensive effect during the daytime hours (p=0.02), a difference that was also significant for average 24-h BP (p=0.02). The mean systolic BP trough/peak ratio was 0.56 in the patients on valsartan, and 0.77 in those on amlodipine (NS). The smoothness index was respectively 1.70 and 1.58 (NS). CONCLUSIONS: The present results show that both the valsartan- and amlodipine-based treatments lead to a similar long-term reduction in 24-h systolic BP. However, in treatment responders, valsartan has a greater anti-hypertensive effect during the daytime.     

Efficacy and tolerability of a fixed-dose combination of telmisartan plus hydrochlorothiazide in patients uncontrolled with telmisartan monotherapy.

The antihypertensive effects of a telmisartan 80 mg/hydrochlorothiazide (HCTZ) 12.5 mg fixed-dose combination and telmisartan 80 mg monotherapy were compared in patients with a history of mild-to-moderate essential hypertension and inadequate BP control (DBP > or = 90 mm Hg) following 8 weeks of telmisartan monotherapy. At the end of this period, 491 patients (62.9% men; mean age 55.3 years) whose DBP was > or = 90 mm Hg were double-blind randomised to once-daily telmisartan 80 mg/HCTZ 12.5 mg (n = 246) or telmisartan 80 mg (n = 245). Trough (24 h post-dose) clinic BP was measured after 4 and 8 weeks of double-blind therapy. At the end of double-blind treatment, patients receiving telmisartan 80 mg/HCTZ 12.5 mg had significant additional decrements in clinic SBP/DBP over telmisartan 80 mg of -5.7/-3.1 mm Hg (P < 0.01). Most of the additional effect occurred during the first 4 weeks of treatment. The proportion of patients with normalised BP (SBP < 140 mm Hg and DBP < 90 mm Hg) was significantly greater in the telmisartan 80 mg/HCTZ 12.5 mg group than the telmisartan 80 mg group (41.5%vs 26.1%;P < 0.05). Both treatments were well tolerated. The incidence of adverse events was similar except for diarrhoea, which occurred more frequently in the telmisartan 80 mg/HCTZ 12.5 mg group, and oedema, which occurred more frequently in the telmisartan group. Our results indicate that a telmisartan 80 mg/HCTZ 12.5 mg fixed-dose combination confers significant additional BP reductions compared with continuation of telmisartan monotherapy in non-responders.     

Comparative efficacy and safety of combination aliskiren/amlodipine and amlodipine monotherapy in African Americans with stage 2 hypertension

Initial multiple drug therapy for hypertension achieves greater and quicker reductions and higher blood pressure (BP) control rates than monotherapy. This 8-week, prospective, multicenter, randomized, double-blind study compared the efficacy and safety of the initial combination of aliskiren/amlodipine with amlodipine monotherapy in African Americans with stage 2 hypertension. After a 1- to 4-week washout, patients received aliskiren/amlodipine 150/5 mg or amlodipine 5 mg for 1 week and then were force-titrated to aliskiren/amlodipine 300/10 mg or amlodipine 10 mg for 7 weeks. At week 8, greater reductions in mean sitting systolic BP were obtained with aliskiren/amlodipine (n = 220) than with amlodipine (n = 223) (least squares mean change [standard error of the mean], -34.1 [1.14] mm Hg vs -28.9 [1.12] mm Hg; P<.001). Ambulatory and central BP measures were consistent with clinic BP findings, although these were conducted in a small subset of patients (n = 94 in ambulatory BP monitoring substudy and n = 136 for central BP). More patients achieved goal BP (<140/90 mm Hg) with aliskiren/amlodipine than with amlodipine at week 8 (57.3% vs 48.0%; P = .051). Both treatment groups had similar adverse event rates (35.0% and 32.7%, respectively). The most common adverse events were peripheral edema (7.7% with aliskiren/amlodipine and 9.0% with amlodipine), headache, fatigue, and nausea. The combination of aliskiren/amlodipine reduced peripheral, ambulatory, and central BP more than amlodipine alone with similar tolerability in African Americans with stage 2 hypertension.     

Efficacy of combination therapy with amlodipine besylate/benazepril hydrochloride for lowering systolic blood pressure in stage 2 hypertension

The Systolic Evaluation of Lotrel Efficacy and Comparative Therapies (SELECT) study compared daily treatment with combination amlodipine besylate/benazepril hydrochloride 5/20 mg, amlodipine besylate 5 mg, and benazepril hydrochloride 20 mg in 505 patients aged 55 years of age or older with stage 2 hypertension (systolic blood pressure [BP] > or =160 and < or =200 mm Hg and diastolic BP > or =60 and < or =100 mm Hg). BP and pulse pressure were assessed by conventional office BP measurements and 24-hour ambulatory BP monitoring. In this analysis, combination therapy was associated with significantly greater reductions in mean 24-hour BP, pulse pressure, and mean ambulatory BP during various time intervals compared with either monotherapy in the intent-to-treat population, in those with isolated and predominantly systolic hypertension, and in dippers and nondippers. Adverse event rates were low and similar in all treatment groups. This study demonstrated that combination therapy is superior to monotherapy in older patients with stage 2 systolic hypertension and is well tolerated.     

Amlodipine/benazepril combination therapy for hypertensive patients nonresponsive to benazepril monotherapy

BACKGROUND: Most patients with hypertension require two or more antihypertensive medications to achieve blood pressure (BP) goals. This double-blind study compared the efficacy and safety of high-dose combinations of amlodipine besylate (5 mg and 10 mg) and benazepril hydrochloride (40 mg) to benazepril hydrochloride (40 mg) alone in hypertensive patients not adequately controlled with benazepril hydrochloride (40 mg) monotherapy. METHODS: After a 2-week washout period and a 4-week lead-in period with benazepril 40 mg daily, patients with a mean sitting diastolic BP > or =95 mm Hg (i.e., nonresponders to benazepril 40 mg) were randomly assigned to active treatment with either a combination of amlodipine 5 mg and benazepril 40 mg for 4 weeks followed by a forced titration to amlodipine 10 mg and benazepril 40 mg for an additional 4 weeks, or to benazepril 40 mg alone for 8 weeks. RESULTS: The mean reduction in sitting BP from baseline (on benazepril) to endpoint (after 8 weeks of treatment) was 17/14 mm Hg with amlodipine/benazepril and 5/7 mm Hg with benazepril (P <.0001). The percentage of patients who met the diastolic BP response criteria (<90 mm Hg at endpoint or > or =10 mm Hg decrease from baseline) was 80% in the amlodipine/benazepril group and 45% in the benazepril group (P <.0001). The incidence of adverse events was infrequent and comparable for both treatment groups. CONCLUSION: High-dose amlodipine/benazepril combination therapy (5 mg/40 mg and 10 mg/40 mg) is an effective, safe, and well-tolerated treatment option for hypertensive patients who do not respond adequately to benazepril alone.     

Antihypertensive efficacy of the oral direct renin inhibitor aliskiren as add-on therapy in patients not responding to amlodipine monotherapy

This study investigated the addition of the direct renin inhibitor aliskiren to amlodipine in patients with mild to moderate hypertension that was inadequately controlled with amlodipine alone. Following once-daily treatment with amlodipine 5 mg for 4 weeks, patients whose hypertension responded inadequately to therapy (mean sitting diastolic blood pressure [DBP] 90-109 mm Hg) (n=545) were randomized to 6 weeks of double-blind treatment with amlodipine 5 mg plus aliskiren 150 mg, amlodipine 5 mg, or amlodipine 10 mg. At the study's end, mean systolic blood pressure and DBP reductions with the combination of aliskiren 150 mg and amlodipine 5 mg (11.0/8.5 mm Hg) were significantly greater (P<.0001) than with amlodipine 5 mg (5.0/4.8 mm Hg)--the comparator group--but similar to amlodipine 10 mg (9.6/8.0 mm Hg). All treatments were well tolerated. Edema occurred more frequently with amlodipine 10 mg (11.2%) than with combination therapy (2.1%) or amlodipine 5 mg (3.4%). In conclusion, aliskiren 150 mg plus amlodipine 5 mg shows similar but not better blood pressure-lowering efficacy when compared with amlodipine 10 mg in patients not completely responsive to amlodipine 5 mg; less edema was noted with combination therapy.