Comparative efficacy and safety of aliskiren, an oral direct renin inhibitor, and ramipril in hypertension: a 6-month, randomized, double-blind trial

OBJECTIVES: This double-blind study compared long-term efficacy, safety and tolerability of the oral direct renin inhibitor aliskiren and the angiotensin-converting enzyme inhibitor ramipril alone and combined with hydrochlorothiazide in patients with hypertension. METHODS: After a 2-4-week placebo run-in, 842 patients [mean sitting diastolic blood pressure (msDBP) 95-109 mmHg] were randomized to aliskiren 150 mg (n = 420) or ramipril 5 mg (n = 422). Dose titration (to aliskiren 300 mg/ramipril 10 mg) and subsequent hydrochlorothiazide addition (12.5 mg, titrated to 25 mg if required) were permitted at weeks 6, 12, 18 and 21 for inadequate blood pressure control. Patients completing the 26-week active-controlled treatment period were re-randomized to their existing regimen or placebo for a 4-week double-blind withdrawal phase. RESULTS: Six hundred and eighty-seven patients (81.6%) completed the active treatment period. At week 26, aliskiren-based therapy produced greater mean reductions in mean sitting systolic blood pressure (17.9 versus 15.2 mmHg, P = 0.0036) and msDBP (13.2 versus 12.0 mmHg, P = 0.025), and higher rates of systolic blood pressure control (< 140 mmHg; 72.5 versus 64.1%, P = 0.0075) compared with ramipril-based therapy. During withdrawal, blood pressure increased more rapidly after stopping ramipril than aliskiren-based therapy; median blood pressure reached 140/90 mmHg after 1 and 4 weeks, respectively. Blood pressure reductions were maintained with continued active treatment. Aliskiren therapy was well tolerated. Overall adverse event rates were similar with aliskiren (61.3%) and ramipril (60.4%); cough was more frequent with ramipril (9.5%) than aliskiren (4.1%). CONCLUSIONS: Aliskiren-based therapy was well tolerated and produced sustained blood pressure reductions in patients with hypertension over 6 months, greater than those with ramipril-based therapy.     

Antihypertensive efficacy,safety, and tolerability of the oral direct renin inhibitor aliskiren in patients with hypertension: a pooled analysis

The antihypertensive efficacy and safety of the direct renin inhibitor aliskiren were assessed in a pooled analysis of data from seven randomized, multicenter studies. Data were available for 7,045 patients (mean age 52.5 to 59.8 years, 50.2 to 72.5% men) with mild-to-moderate hypertension (mean sitting diastolic blood pressure [msDBP] 95 to 109 mm Hg) over treatment durations of 6 to 8 weeks. In placebo-controlled trials, aliskiren reduced mean sitting systolic blood pressure/msDBP from baseline by 8.6 to 12.1/7.2 to 10.3 mm Hg (75 mg), 8.7 to 13.0/7.8 to 10.3 mm Hg (150 mg), 14.1 to 15.8/10.3 to 12.3 mm Hg (300 mg), and 15.7 to 15.8/11.5 to 12.5 mm Hg (600 mg), compared with 2.9 to 10.0/3.3 to 8.6 mm Hg for placebo. Aliskiren demonstrated comparable efficacy in men and women, in patients aged <65 years or ≥65 years, and lowered blood pressure (BP) effectively in all racial subgroups. Combination of aliskiren 150 mg or 300 mg with ramipril, amlodipine, or hydrochlorothiazide provided significant additional BP reductions compared with the respective monotherapies. The overall incidence of adverse events with aliskiren monotherapy was similar to placebo (39.8% vs. 40.2%, respectively). The incidence of diarrhea with aliskiren was higher than placebo due to a significantly higher rate with aliskiren 600 mg (P < .0001 vs. placebo). In conclusion, aliskiren 150 mg or 300 mg provides highly effective and consistent BP lowering with placebo-like tolerability in patients with mild-to-moderate hypertension.     

Safety and efficacy of the oral direct renin inhibitor aliskiren in elderly patients with hypertension

OBJECTIVES: To evaluate the efficacy, safety and tolerability of aliskiren in elderly patients (> or =65 years old) with essential hypertension. METHODS: In this double-blind, multicenter study, 355 elderly patients with hypertension [office mean sitting systolic blood pressure (msSBP) > or =145-<180 mmHg and mean 24-h ambulatory systolic BP (ASBP) > or =135 mmHg] were randomized to once-daily treatment for 8 weeks with aliskiren 75 mg (n = 91), 150 mg (n = 84), 300 mg (n = 94) or the comparator lisinopril 10 mg (n = 86). The primary efficacy variable was change in mean 24-h ASBP. RESULTS: At endpoint, aliskiren 75 mg, 150 mg, 300 mg and lisinopril 10 mg lowered mean 24-h ASBP (least-squares mean+/-SEM) by 8.4+/-0.8, 7.1+/-0.8, 8.7+/-0.8 and 10.2+/-0.9 mmHg, and mean 24-h ambulatory diastolic BP by 4.5+/-0.5, 3.6+/-0.5, 3.9+/-0.5 and 6.3+/-0.5 mmHg, respectively, with no significant difference between aliskiren doses. The trough-to-peak ratio for ASBP reduction with aliskiren 75 mg, 150 mg, 300 mg and lisinopril 10 mg was 0.77, 0.64, 0.79 and 0.87, respectively. All treatments lowered office msSBP and mean sitting diastolic BP (msDBP) compared with baseline. A significantly greater proportion of patients receiving aliskiren 300 mg achieved BP control (msSBP/msDBP <140/90 mmHg) compared with those receiving aliskiren 75 mg (36.2% vs 24.2%, p = 0.033). There was no evidence of dose-related increases in the rate of adverse events with aliskiren treatment. CONCLUSIONS: Aliskiren, a novel direct renin inhibitor, provides effective 24-h BP lowering with no evidence of dose-related increases in the incidence of adverse events in elderly patients with hypertension.     

A comparison of the tolerability of the direct renin inhibitor aliskiren and lisinopril in patients with severe hypertension

Patients with severe hypertension (>180/110 mm Hg) require large blood pressure (BP) reductions to reach recommended treatment goals (<140/90 mm Hg) and usually require combination therapy to do so. This 8-week, multicenter, randomized, double-blind, parallel-group study compared the tolerability and antihypertensive efficacy of the novel direct renin inhibitor aliskiren with the angiotensin converting enzyme inhibitor lisinopril in patients with severe hypertension (mean sitting diastolic blood pressure (msDBP)>or=105 mm Hg and <120 mm Hg). In all, 183 patients were randomized (2:1) to aliskiren 150 mg (n=125) or lisinopril 20 mg (n=58) with dose titration (to aliskiren 300 mg or lisinopril 40 mg) and subsequent addition of hydrochlorothiazide (HCTZ) if additional BP control was required. Aliskiren-based treatment (ALI) was similar to lisinopril-based treatment (LIS) with respect to the proportion of patients reporting an adverse event (AE; ALI 32.8%; LIS 29.3%) or discontinuing treatment due to AEs (ALI 3.2%; LIS 3.4%). The most frequently reported AEs in both groups were headache, nasopharyngitis and dizziness. At end point, ALI showed similar mean reductions from baseline to LIS in msDBP (ALI -18.5 mm Hg vs LIS -20.1 mm Hg; mean treatment difference 1.7 mm Hg (95% confidence interval (CI) -1.0, 4.4)) and mean sitting systolic blood pressure (ALI -20.0 mm Hg vs LIS -22.3 mm Hg; mean treatment difference 2.8 mm Hg (95% CI -1.7, 7.4)). Responder rates (msDBP<90 mm Hg and/or reduction from baseline>or=10 mm Hg) were 81.5% with ALI and 87.9% with LIS. Approximately half of patients required the addition of HCTZ to achieve BP control (ALI 53.6%; LIS 44.8%). In conclusion, ALI alone, or in combination with HCTZ, exhibits similar tolerability and antihypertensive efficacy to LIS alone, or in combination with HCTZ, in patients with severe hypertension.     

Dose-response relation of the angiotensin converting enzyme inhibitor ramipril in mild to moderate essential hypertension

The effects of various dosage levels of ramipril on blood pressure were examined in a double-blind multicenter clinical trial. Patients with mild to moderate essential hypertension were first entered into a single-blind washout placebo phase of 4 weeks duration. The patients were then randomized to 1 of 3 treatment groups and received either 1.25, 2.5 or 5 mg of ramipril orally once a day for 6 weeks. After 6 weeks of treatment, the diastolic blood pressure had been decreased by 16.0 mm Hg (53 patients), 16.5 mm Hg (54 patients) and 19.9 mm Hg (53 patients) for the 1.25, 2.5 and 5 mg groups, respectively. Systolic blood pressure had decreased by an average of 22.5 mm Hg independent of the dose administered. Diastolic blood pressure was decreased to less than or equal to 90 mm Hg in 64%, 63% and 77% of the patients in the 3 groups, respectively. The differences in these percentages among the groups were not statistically significant. The tolerability of the drug was good; discontinuation of treatment was necessary for 1 patient in the 1.25 mg group and medication was lowered for 2 patients because of adverse reactions. There were no clinically significant changes of any laboratory variables, except for an increase in uric acid serum levels.     

Efficacy, tolerance and hormonal effects of a new oral angiotensin converting enzyme inhibitor, ramipril (HOE 498), in mild to moderate primary hypertension

The immediate (0 to 24 hours) and long-term (4 weeks) hypotensive effects of a new long-acting angiotensin converting enzyme inhibitor, ramipril (HOE 498), as well as adverse effects and tolerance, were evaluated in 34 patients with primary hypertension. Further, effects on serum and urinary aldosterone and circulating angiotensin II concentrations were measured. After short- and long-term administration of 5 or 10 mg of ramipril, the mean blood pressure was significantly lowered compared with placebo. The mean maximum decrease in blood pressure was noted 4 to 8 hours after administration of ramipril once daily. Sustained blood pressure reduction was achieved after 4 weeks of treatment. Serum concentrations of aldosterone and plasma levels of circulating angiotensin II were reduced for up to 12 hours after drug intake, and tended to return to pretreatment levels at 24 hours. Serum angiotensin converting enzyme activity was markedly suppressed for more than 24 hours after a single dose of 5 or 10 mg ramipril. No subjective or objective adverse effects were noted, and the tolerance to the drug was very good.     

Blood pressure lowering in essential hypertension with an oral renin inhibitor, aliskiren

Inhibition of the first and rate-limiting step of the renin-angiotensin system has long been an elusive therapeutic goal. Aliskiren, the first known representative of a new class of completely nonpeptide, orally active, renin inhibitors, has been shown to inhibit the production of angiotensin I and II in healthy volunteers and to reduce blood pressure (BP) in sodium-depleted marmosets. The aim of this randomized, double-blind, active comparator trial study was to assess the BP-lowering efficacy and safety of aliskiren. Two hundred twenty-six patients, 21 to 70 years of age, with mild to moderate hypertension, were randomly assigned to receive 37.5 mg, 75 mg, 150 mg, or 300 mg aliskiren or 100 mg losartan daily for 4 weeks. Dose-dependent reductions in daytime ambulatory systolic pressure (mean change, mm Hg [SD of change]; -0.4 [11.7], -5.3 [11.3], -8.0 [11.0], and -11.0 [11.0], P=0.0002) and in plasma renin activity (median change % [interquartile range]; -55 [-64, -11], -60 [-82, -46], -77 [-86, -72], and -83 [-92, -71], P=0.0008) were observed with 37.5, 75, 150, and 300 mg aliskiren. The change in daytime systolic pressure with 100 mg losartan (-10.9 [13.8]) was not significantly different from the changes seen with 75, 150, and 300 mg aliskiren. Aliskiren was well tolerated at all doses studied. This study demonstrates that aliskiren, through inhibition of renin, is an effective and safe orally active BP-lowering agent. Whether renin inhibition results in protection from heart attack, stroke, and nephropathy, similar to angiotensin-converting enzyme inhibition and angiotensin receptor blockade, needs to be researched.     

Effect of add-on direct renin inhibitor aliskiren in patients with non-diabetes related chronic kidney disease

ABSTRACT: BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) plays an important role in the progression of chronic kidney disease (CKD). Although dual RAAS inhibition results in worse renal outcomes than monotherapy in high risk type 2 diabetes patients, the effect of dual RAAS inhibition in patients with non-DM CKD is unclear. The aim of this study was to evaluate the potential renoprotective effect of add-on direct renin inhibitor in non-DM CKD patients. METHODS: We retrospectively enrolled 189 non-DM CKD patients who had been taking angiotensin II receptor blockers (ARBs) for more than six months. Patients were divided into an add-on aliskiren group and an ARB monotherapy group. The primary outcomes were a decline in glomerular filtration rate (GFR) and a reduction in urinary protein-to-creatinine ratio at six months. RESULTS: The baseline characteristics of the two groups were similar. Aliskiren 150 mg daily reduced the urinary protein-to-creatinine ratio by 26% (95% confidence interval, 15 to 37%; p < 0.001). The decline in GFR was smaller in the add-on aliskiren group ([MINUS SIGN]2.1 vs. -4.0 ml/min, p = 0.038). Add-on aliskiren had a neutral effect on serum potassium in the non-DM CKD patients. In subgroup analysis, the proteinuria-reducing effect of aliskiren was more prominent in patients with a GFR less than 60 ml/min, and in patients with a urinary protein-to-creatinine ratio greater than 1.8. The effect of aliskiren in retarding the decline in GFR was more prominent in patients with hypertensive nephropathy than in those with glomerulonephritis. CONCLUSION: Add-on direct renin inhibitor aliskiren (150 mg daily) safely reduced proteinuria and attenuated the decline in GFR in the non-DM CKD patients who were receiving ARBs.     

Safety and tolerability of the direct renin inhibitor aliskiren: a pooled analysis of clinical experience in more than 12,000 patients with hypertension

While the safety of renin-angiotensin system (RAS)-blocking drugs such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers is well known, less is known about the new direct renin inhibitor aliskiren. The authors pooled data from 12 randomized controlled trials of aliskiren in patients with hypertension and analyzed the incidence and types of adverse events (AEs) and laboratory abnormalities. Studies were characterized as short-term (≤2 months) placebo-controlled or long-term (>2 months) active-controlled. Relative risks for AEs of particular interest for RAS blockers were calculated. In short-term studies, AEs occurred in similar proportions of aliskiren 150 mg and 300 mg (33.6% and 31.6%, respectively) and placebo treatment groups (36.8%). In long-term studies, a lower proportion of patients treated with aliskiren 150 mg and 300 mg had AEs (33.7% and 43.2%, respectively) than those treated with ACE inhibitors (60.1%), angiotensin receptor blockers (53.9%), and thiazide diuretics (48.9%). Events of special interest, including angioedema, hyperkalemia, and diarrhea occurred in similar proportions of patients taking aliskiren, placebo, and comparator agents. In studies of up to 36 weeks, patients treated with aliskiren were significantly less likely to develop cough than those treated with ACE inhibitors. At the registered doses of 150 mg and 300 mg daily, aliskiren has safety and tolerability profiles similar to placebo, other RAS blockers, and diuretics. Cough rates are lower with aliskiren compared with ACE inhibitors.     

奥美沙坦酯与氯沙坦钾治疗中国轻、中度原发性高血压患者8周的疗效与安全性比较

目的 通过与氯沙坦钾比较评价奥美沙坦酯治疗轻、中度原发性高血压患者的疗效和安全性。方法采用随机、双盲、双模拟、阳性对照、平行分组、多中心临床试验方法。共入选287例轻、中度原发性高血压患者,按照1：1的比例随机分组,分别接受奥美沙坦酯20mg或氯沙坦钾50mg,每天1次口服治疗。在用药4周后对患者进行血压评价,如果患者舒张压（DBP）仍≥90mmHg（1mmHg=0．133kPa）,则试验药物剂量加倍,直至8周试验结束;治疗4周后DBP〈90mmHg的患者则维持原剂量继续治疗至第8周。结果（1）治疗4周后,奥美沙坦酯组坐位DBP谷值平均下降11．72mmHg,氯沙坦钾组平均下降9．23mmHg,两组间比较P=0．004。（2）治疗8周后,奥美沙坦酯组坐位DBP谷值平均下降12．94mmHg,氯沙坦钾组平均下降11．01mmHg,两组间比较P=0．035。（3）治疗4周后,奥美沙坦酯组有效数为81例（65．3％）,氯沙坦钾组有效数为68例（52．7％）,两组间比较P=0．028;治疗8周后,两组有效病例数和有效率相当,P〉0．05。（4）治疗8周后,24h动态血压监测显示,奥美沙坦酯组DBP和SBP的个体和总体谷／峰比值均高于氯沙坦钾组,奥美沙坦酯在24h内的作用持续时间比氯沙坦钾组长。（5）奥美沙坦酯组和氯沙坦钾组发生的与试验药物有关的不良事件的发生率分别为10．5％和13．9％,P〉0．05。结论奥美沙坦酯每日口服20～40mg能够有效、安全地治疗高血压。与氯沙坦钾每日口服50-100mg相比,奥美沙坦酯的降压效果优于氯沙坦钾。     

缬沙坦治疗轻、中度高血压病的疗效和安全性

目的 :评价缬沙坦 （Valsartan,VAL ）治疗轻、中度高血压病的疗效和安全性。方法 :采用随机、单盲和平行对照方法 ,经 1周药物冲洗期及 2周安慰剂导入期后 ,10 2例轻、中度高血压患者进入 8周治疗期 ,每日 1次服用 VAL80 m g（5 2例 ）或依那普利 （Enalapril,ENA ） 5 m g（5 0例 ） ,2周后如坐位舒张压 （Si DBP）≥ 90 mm Hg（1m m Hg=0 .133k Pa）则剂量加倍 ,4周后如仍无效则每日加服双氢克尿噻 2 5 mg。于服安慰剂期末及治疗 2、4、6、8周末测诊室血压 ,心率 （HR）并记录症状、体征 ;于服安慰剂末及治疗 8周末行 2 4 h动态血压监测 （ABPM）各 1次。结果 :两组药物均能明显降低血压 （P<0 .0 1） ;VAL组有效率 92 % ,ENA组有效率 88% ,组间比较无显著性差异 （P >0 .0 5 ）。 8周末 VAL组 Si SBP/ Si DBP下降 （2 1± 9） / （16± 5 ） mm Hg,ENA组下降 （2 0± 9） / （13± 7） mm Hg。 2、4、6、8周末血压下降值 ,组间比较无显著性差异 （P>0 .0 5 ）。 VAL组和 ENA组分别有 4 4 %和 6 0 %患者加用利尿剂。VAL降压谷峰值比率 6 9% ,ENA为 4 9%。咳嗽发生率 VAL组 （4% ）明显低于 ENA组 （18% ） ,差异有显著性 （P<0 .0 5 ）。结论 :VAL （80～ 16 0 m g/ d）对轻、中度高血压病疗效确切、安全、耐受性好 ,干咳的不良反应明显低于     

Comparative double-blind study of ramipril and captopril in mild to moderate essential hypertension

The angiotensin converting enzyme inhibitors ramipril and captopril were administered in doses of 10 mg once daily and 50 mg twice daily, respectively, to patients with mild to moderate essential hypertension. After a 4-week single-blind placebo washout period, patients were treated for 12 weeks with 1 of the drugs under double-blind conditions. Patients who did not respond after 6 weeks of treatment were given 50 mg hydrochlorothiazide concomitantly. The ramipril group showed greater decreases in blood pressure compared with baseline values: 20.1/14.9 mm Hg (ramipril) compared with 16.5/13.5 mm Hg (captopril). A further 6 weeks of treatment lowered the blood pressure even more: 22.5/20.0 mm Hg (ramipril) compared with 20.5/18.6 mm Hg (captopril). Concomitant hydrochlorothiazide given to nonresponders reduced the blood pressure levels in 24 of 40 patients in the ramipril group and in 20 of 36 patients in the captopril group. At the end of the study the overall response to treatment with ramipril alone and ramipril plus hydrochlorothiazide was 77.1%. The overall response rate in the captopril group was 82.7%. No clinically relevant adverse reaction occurred in any patient. Ramipril given once daily was as effective as captopril given twice daily in lowering blood pressure. Both drugs proved to be safe during treatment for 12 weeks.     

奥美沙坦酯治疗轻度及中度原发性高血压疗效和安全性的评价

目的:评价奥美沙坦酯治疗轻度及中度原发性高血压的疗效和安全性。方法:80例轻度及中度原发性高血压患者随机接受奥美沙坦酯20 mg或缬沙坦80 mg治疗,每日1次,总疗程8周。结果:奥美沙坦酯组治疗前的收缩压(SBP)/舒张压(DBP)为(155.2±11.4)/(96.1±5.2)mmHg(1 mmHg=0.133 kPa),治疗后的血压为(138.8±10.2)/(86.5±4.8)mmHg,血压下降幅度为(16.4±8.1/9.6±5.1)mmHg。缬沙坦组治疗前的SBP/DBP为(156.1±12.2)/(97.2±5.1)mmHg,治疗后的血压为(139.5±10.4)/(88.0±5.5)mmHg,血压下降幅度为(15.6±7.8/9.1±4.9)mmHg。2组治疗前后血压下降幅度差异均有统计学意义(P<0.01),2组间差异无统计学意义(P>0.05)。奥美沙坦酯组和缬沙坦组降压显效率分别为59.0%和60.5%,总有效率分别为87.2%和86.8%,2组间差异无统计学意义。本实验中奥美沙坦酯组出现不良反应者少。结论:奥美沙坦酯治疗轻度及中度原发性高血压疗效确切,且安全可靠。     

马尼地平治疗轻中度高血压患者的疗效观察

目的评价盐酸马尼地平治疗原发性轻中度高血压患者的降压疗效。方法选择门诊原发性轻中度高血压患者180例,随机分为试验组(90例)和对照组(90例),试验组给予盐酸马尼地平和苯磺酸氨氯地平模拟剂,对照组给予苯磺酸氨氯地平和盐酸马尼地平模拟剂,比较2组患者基线和治疗期末的血压和心率。2组患者中各选择24例在双盲治疗期开始和结束时进行24 h动态血压监测,比较2组24h、昼间、夜间血压平均值和谷峰比值及平滑指数。结果试验组与对照组治疗期末舒张压和收缩压下降值比较,差异无统计学意义(P>0.05);与基线比较,2组治疗期末收缩压和舒张压明显降低(P<0.01)。24 h动态血压监测分析,2组间治疗期末24 h、昼间及夜间收缩压和舒张压下降值差异无统计学意义(P>0).05);与基线比较,试验组和对照组治疗期末收缩压和舒张压明显降低(P<0.05,P<0.01);试验组谷峰比值较对照组明显降低(P<0.05),而平滑指数和不良反应发生率差异无统计学意义(P>0.05)。结论盐酸马尼地平治疗原发性轻中度高血压患者疗效可靠,不良反应较轻。     

比索洛尔/氢氯噻嗪复方片治疗中国轻中度原发性高血压的临床疗效和安全性研究

目的采用24小时动态血压监测观察比索洛尔／氢氯噻嗪复方片(Lodoz)治疗90例中国轻、中度高血压患者的降压效果和安全性。方法选择90例收缩压<180 mm Hg(1 mm Hg= 0．133 kPa),舒张压95-109 mm Hg的轻、中度高血压患者,口服Lodoz(2．5 mg/6．25 mg)共4周或Lodoz(5 mg／6．25 mg)8周,用24小时动态血压监测评价治疗4周、8周后动态血压变化及安全性。结果(1)4周和8周末诊室收缩压/舒张压分别降低(14．89±10．99)／(10．37±7．35)mm Hg和(19．40±10．55)／(13．31±7．77)mm Hg,全天、日间、夜间的24小时动态平均血压均明显降低,差异有统计学意义(P均<0．05)。4周和8周末的总有效率分别为59．3％和69．8％。(2)Lodoz(2．5 mg／6．25 mg)对收缩压和舒张压的谷／峰比值(T／P比值)分别为91．5％和94．4％,降压平滑指数(SI)为9．07／6．48;Lodoz(5 mg／6．25 mg)对收缩压和舒张压的T／P比值为79．9％和80．5％,SI为4．17／4．47。(3)Lodoz可能有使“非勺型”血压转变为“勺型”血压的趋势。(4)不良反应主要有血尿酸升高、头晕、头痛、腹泻、口干、肢端发凉、蚁行感,均为轻度。结论Lodoz能够持续、平稳、有效地降低24小时血压,且安全性良好。     

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.