Combination angiotensin-receptor blocker (ARB)/calcium channel blocker with HCTZ vs the maximal recommended dose of an ARB with HCTZ in patients with stage 2 hypertension: the exforge as compared to losartan treatment in stage 2 systolic hypertension (EXALT) study

This study compared the efficacy and safety of combination angiotensin-receptor blocker (ARB)/calcium-channel blocker (CCB) with hydrochlorothiazide (valsartan/amlodipine/HCTZ 160/5/2mg) vs maximal available combination doses of an ARB with HCTZ (losartan/HCTZ 100/25 mg) in the management of stage 2 hypertension. After 1 to 2 weeks of antihypertensive drug washout, patients with a mean sitting systolic blood pressure (MSSBP) of ≥ 160 mm Hg and <200 mm Hg were randomized to valsartan/amlodipine 160/5 mg (n = 241) or losartan 100 mg (n = 247). At week 3, HCTZ 25 mg was added to both treatments. The primary end point, reduction in MSSBP from baseline to week 6, was significantly greater in the valsartan/amlodipine group than in the losartan group (least-squares [LS] mean change, -31.8 mm Hg vs -26.4 mm Hg; P<.001). Additional reductions occurred after titrating to 320/10/25 mg at week 6 in the valsartan/amlodipine group and switching from losartan/HCTZ to valsartan/amlodipine/HCTZ (week 6, 160/5/25 mg; week 9, 320/10/25 mg) in the losartan group. Achievement of blood pressure <140/90 mm Hg also favored the valsartan/amlodipine group. Dizziness was the only adverse event reported in >5% of patients (5.4% valsartan/amlodipine group, 3.6% losartan group). Moderate doses of an ARB/CCB combination with HCTZ reduced blood pressure more effectively than the maximal dose of an ARB with HCTZ.     

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.     

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.     

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.     

A noninferiority comparison of valsartan/hydrochlorothiazide combination versus amlodipine in black hypertensives

The objective of the study was to demonstrate that reduction in mean 24-hour diastolic blood pressure with 160 mg valsartan and 12.5 mg hydrochlorothiazide was not inferior to 10 mg amlodipine in hypertensive blacks. A total of 482 blacks with stage 1 and stage 2 hypertension (mean seated blood pressure 140 to 180/90 to 110 mm Hg) were enrolled in a double-blind, randomized, prospective study. After a placebo run-in period, patients were randomized to 160 mg valsartan or 5 mg amlodipine for 2 weeks, then force-titrated to 160 mg valsartan and 12.5 mg hydrochlorothiazide or 10 mg amlodipine for an additional 10 weeks. Blood pressure was assessed by 24-hour ambulatory blood pressure monitoring. Other assessments included quality of life, peripheral edema, and safety. Noninferiority of valsartan/hydrochlorothiazide to amlodipine was demonstrated by comparable reductions in mean 24-hour diastolic blood pressure with both treatments (-10.2+/-8.6 mm Hg versus -9.1+/-8.3 mm Hg, respectively; P<0.001 for noninferiority), as well as in mean 24-hour systolic blood pressure (-15.9+/-12.1 mm Hg versus -14.5+/-12.2 mm Hg; P<0.001 for noninferiority). The proportion of patients reporting adverse events and the incidence of most events were similar in both treatment groups, although more patients treated with amlodipine reported peripheral edema (5.8% versus 1.7%; P=0.03) and joint swelling (2.9% versus 0%; P=0.008) compared with valsartan/hydrochlorothiazide. We conclude that a starting dose of valsartan/hydrochlorothiazide (160/12.5 mg) is as effective as high-dose amlodipine (10 mg) in reducing blood pressure in blacks with stage 1 and stage 2 hypertension, and valsartan/hydrochlorothiazide is better tolerated.     

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.     

Time to achieve blood-pressure goal: influence of dose of valsartan monotherapy and valsartan and hydrochlorothiazide combination therapy

BACKGROUND: Our objective was to assess time to achieve blood-pressure (BP) goal with incremental doses of valsartan alone, and together with hydrochlorothiazide (HCTZ), in patients with uncomplicated hypertension. METHODS: This analysis pooled patient-level data from nine randomized, double-blind, fixed-dose, placebo-controlled trials (N = 4278) of once-daily valsartan 80 mg, 160 mg, and 320 mg, and valsartan/hydrochlorothiazide (HCTZ) 80/12.5 mg, 160/12.5 mg, 160/25 mg, 320/12.5 mg, and 320/25 mg. Kaplan-Meier methods estimated the cumulative proportion of patients achieving BP <140/90 mm Hg over 8 weeks and the median time to BP goal. The HCTZ 12.5-mg and 25-mg doses were pooled for the time-to-goal analysis in patients receiving combinations with valsartan 160 mg or 320 mg. RESULTS: Overall, the median time-to-goal was 8.1 weeks with valsartan 160 mg, 6.1 weeks with valsartan 320 mg, 2.6 weeks with valsartan 160 mg/HCTZ, and 2.1 weeks with valsartan 320 mg/HCTZ. In patients with stage 2 hypertension, the median time-to-goal was 4.3 weeks with valsartan 160 mg/HCTZ and 2.4 weeks with valsartan 320 mg/HCTZ. Goal rates by Week 4 for valsartan/HCTZ exceeded rates by Week 8 with the same doses of valsartan alone. Overall, the proportion that achieved BP goal by Week 8 was 32.6% with valsartan 80 mg, 48.4% with valsartan 160 mg, 54.2% with valsartan 320 mg, 74.6% with valsartan 160 mg/HCTZ, and 84.8% with valsartan 320 mg/HCTZ, versus 24.2% with placebo. With valsartan 320 mg/HCTZ, 75.8% of stage 2 patients and 94% of stage 1 patients reached BP goal by Week 8. Discontinuation rates due to adverse events were generally low across doses. CONCLUSIONS: In both stage 1 and stage 2 hypertension, BP control is achieved more frequently and promptly when patients receive higher doses of valsartan monotherapy or valsartan combination therapy, with a favorable benefit-risk profile.     

Peripheral and central blood pressure responses of combination aliskiren/hydrochlorothiazide and amlodipine monotherapy in African American patients with stage 2 hypertension: the ATLAAST trial

Efficacy of antihypertensive agents on central blood pressure (BP) in African Americans is not well studied. The authors report on an 8-week double-blind, randomized study of African American patients with stage 2 hypertension that compared brachial and central BP responses (substudy of 53 patients) to combination aliskiren/hydrochlorthiazide (HCTZ) and amlodipine monotherapy. Following a 1- to 4-week washout, initial therapy was aliskiren/HCTZ 150/12.5 mg (n=166) or amlodipine 5 mg (n=166) for 1 week, forced-titrated to aliskiren/HCTZ 300/25 mg or amlodipine 10 mg for 7 weeks. Mean seated systolic BP reductions from baseline was similar with both treatments (-28.6 mm Hg with aliskiren/HCTZ vs -28.2 mm Hg with amlodipine). In the substudy, significantly greater reductions in central systolic BP was observed with aliskiren/HCTZ vs amlodipine (-30.1 mm Hg vs -21.2; P=.031), although 24-hour mean ambulatory BP reductions between the two groups were similar. Central pressure is considered an important risk factor in African Americans, and these findings may suggest a new treatment option for these patients.     

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.     

Effects of valsartan or amlodipine alone or in combination on plasma catecholamine levels at rest and during standing in hypertensive patients

To compare the effects of valsartan and amlodipine alone or in combination on plasma norepinephrine (NE) at rest and standing for 10 minutes in patients with hypertension, 47 patients with a sitting diastolic blood pressure (BP) (DBP)>95 mm Hg and<110 mm Hg were randomized in a double-blind fashion to either valsartan or amlodipine. During the first 4 weeks of treatment, patients received a low dose of either valsartan (80 mg) or amlodipine (5 mg). The patients were force-titrated to the high dose of either drug (160 or 10 mg) for 4 weeks. After 8 weeks of therapy, those who still had a DBP>90 mm Hg (nonresponders) received combination therapy with the other drug, whereas patients with a DBP<90 mm Hg (responders) continued on monotherapy. Decreases in ambulatory BP and clinic systolic BP and DBP were significant (P<.05) after 8 weeks' therapy with no difference between the 2 groups. Amlodipine but not valsartan as monotherapy consistently increased NE levels at rest and enhanced NE levels during standing. Valsartan decreased basal NE in responders. Combination therapy with valsartan and amlodipine did not attenuate the rise in NE levels induced by amlodipine. This study indicates that therapy with amlodipine increases peripheral sympathetic basal tone and reactivity to standing in patients with hypertension, whereas valsartan does not. Combined therapy with amlodipine/valsartan did not attenuate the sympathetic activation induced by amlodipine. The hypotensive action of valsartan may be mediated in part by an inhibition of the sympathetic baroreflex in patients with hypertension.     

24-Hour ambulatory blood pressure response to combination valsartan/hydrochlorothiazide and amlodipine/hydrochlorothiazide in stage 2 hypertension by ethnicity: the EVALUATE study

Several studies reported racial/ethnic differences in blood pressure (BP) response to antihypertensive monotherapy. In a 10-week study of stage 2 hypertension, 320/25 mg valsartan/hydrochlorothiazide (HCTZ) reduced ambulatory BP (ABP) significantly more effectively than 10/25 mg amlodipine/HCTZ. Results (post hoc analysis) are described in Caucasians (n=256), African Americans (n=79), and Hispanics (n=86). Compared with clinic-measured BP (no significant treatment-group differences in ethnic subgroups), least-squares mean reductions from baseline to week 10 in mean ambulatory systolic BP (MASBP) and mean ambulatory diastolic BP (MADBP) favored valsartan/HCTZ over amlodipine/HCTZ in Caucasians (-21.9/-12.7 mm Hg vs -17.6/-9.5 mm Hg; P=.0004/P<.0001). No treatment-group differences in MASBP/MADBP were observed in African Americans (-17.3/-10.6 vs -17.9/-9.5; P=.76/P=.40) or Hispanics (-17.9/-9.7 vs -14.2/-7.2; P=.20/P=.17). Based on ABP monitoring, valsartan/HCTZ is more effective than amlodipine/HCTZ in lowering ABP in Caucasians. In African Americans and Hispanics, both regimens are similarly effective.     

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.     

Comparison of aliskiren/hydrochlorothiazide combination therapy with hydrochlorothiazide monotherapy in older patients with stage 2 systolic hypertension: results of the ACTION study

Patients with stage 2 systolic hypertension require sizable blood pressure (BP) reductions to achieve recommended targets. This randomized double-blind study compared a single-pill combination of the direct renin inhibitor aliskiren and hydrochlorothiazide (aliskiren/HCTZ) with HCTZ monotherapy in older patients (older than 55 years) with systolic BP ≥160 mm Hg and <200 mm Hg. After a 1- to 4-week washout, 451 patients were randomized to once-daily aliskiren/HCTZ 150/12.5 mg or HCTZ 12.5 mg for 1 week, and then double the doses for 7 weeks. Overall baseline BP was 168.8/91.4 mm Hg. At week 4 (primary) end point, aliskiren/HCTZ provided significantly greater BP reductions from baseline than HCTZ monotherapy (29.6/9.3 mm Hg vs 22.3/6.8 mm Hg) and resulted in a greater proportion of patients achieving BP goal of <140/90 mm Hg (51.1% vs 33.3%). Aliskiren/HCTZ therapy provides substantial BP reductions and may thus be a useful treatment option for older patients 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.     

Aliskiren alone or in combination with hydrochlorothiazide in patients with the lower ranges of stage 2 hypertension: The ACQUIRE randomized double-blind study

Patients with stage 2 hypertension (systolic blood pressure [SBP] ≥160mm Hg and/or diastolic blood pressure [DBP] ≥100mm Hg) are at high cardiovascular risk and require intensive blood pressure (BP)-lowering therapy. This randomized double-blind study is the first prospective trial specifically designed to evaluate the direct renin inhibitor aliskiren in patients with a mean sitting SBP ≥160 mm Hg and <180mm Hg (the lower ranges of stage 2 systolic hypertension). After a 2- to 4-week washout period, 688 patients were randomized to once-daily aliskiren/hydrochlorothiazide (HCT) 150/12.5mg or aliskiren 150mg for 1 week and then double the doses for 11 weeks. Baseline BP was 167.1/95.0mm Hg. At week 12, both aliskiren/HCT and aliskiren provided substantial BP reductions from baseline (30.0/12.6 mm Hg and 20.3/8.2 mm Hg, respectively). Aliskiren/HCT lowered BP significantly more than aliskiren (least-squares mean between-treatment differences [95% confidence interval] were -9.7 [-12.0 to -7.4] for SBP and -4.5 [-5.8 to -3.2] for DBP; both P<.0001). Similar BP reductions were seen in the subgroups of patients with isolated systolic hypertension and obesity. Aliskiren, with or without HCT, provides clinically significant BP reductions and may therefore be an effective treatment option in patients with stage 2 hypertension.     

The effects of amlodipine compared to losartan in patients with mild to moderately severe hypertension

The calcium channel blocker amlodipine and angiotensin II receptor blocker losartan, with or without hydrochlorothiazide (HCTZ), were compared for the treatment of mild to moderate hypertension in a multicenter, double-blind, parallel-group clinical trial. Following a 2-week placebo run-in, 440 adults (45-80 years old) were randomized to receive either amlodipine 5 mg once daily or losartan 50 mg once daily. Patients who failed to meet the sitting diastolic blood pressure (BP) reduction goal of 相似文献   

Aliskiren-based dual- and triple-combination therapies in high-risk US minority patients with Stage 2 hypertension

Previously, we reported the efficacy of aliskiren/amlodipine in US minority adults with stage 2 hypertension, with additional blood pressure (BP) lowering from the addition of hydrochlorothiazide (HCTZ). A subgroup analysis in patients with hypertension and comorbidities of diabetes, cardiometabolic syndrome, or obesity, and in black participants is reported. This 8-week, multicenter, double-blind study included 412 self-identified minority patients with mean sitting systolic BP (msSBP) ≥160 mm Hg and <200 mm Hg). Patients were randomized to receive either combination aliskiren/amlodipine 150/5 mg or amlodipine 5 mg. Doses were forced-titrated to a maximum of aliskiren/amlodipine/HCTZ 300/10/25 mg or aliskiren/amlodipine 300/10 mg, respectively. There were 256 black (62%), 118 diabetic (29%), 284 cardiometabolic syndrome (69%), and 249 obese (60%) randomized patients. Baseline msSBP was ～167 mm Hg across all subgroups. Least-square mean reductions in msSBP, the primary efficacy outcome, from baseline to week 8 across all subgroups, ranged from 35 to 37 mm Hg with aliskiren/amlodipine/HCTZ and 28 to 30 mm Hg with aliskiren/amlodipine (P < .01 for all between-treatment comparisons). Both regimens were well tolerated. Among high-risk patients, such as diabetics or those with cardiometabolic syndrome, combination aliskiren/amlodipine is effective in lowering BP; the addition of HCTZ provided incremental BP-lowering efficacy while maintaining tolerability. However, because our subgroups were not mutually exclusive, the generalization of our findings to the population seen in clinical practice is limited.     

Efficacy and safety of sacubitril/valsartan compared with olmesartan in Asian patients with essential hypertension: A randomized,double‐blind, 8‐week study

This study assessed the efficacy and safety of angiotensin receptor neprilysin inhibitor sacubitril/valsartan vs olmesartan in Asian patients with mild‐to‐moderate hypertension. Patients (N = 1438; mean age, 57.7 years) with mild‐to‐moderate hypertension were randomized to receive once daily administration of sacubitril/valsartan 200 mg (n = 479), sacubitril/valsartan 400 mg (n = 473), or olmesartan 20 mg (n = 486) for 8 weeks. The primary endpoint was reduction in mean sitting systolic blood pressure (msSBP) from baseline with sacubitril/valsartan 200 mg vs olmesartan 20 mg at Week 8. Secondary endpoints included msSBP reduction with sacubitril/valsartan 400 mg, and reductions in clinic and ambulatory BP and pulse pressure (PP) vs olmesartan. In addition, changes in msBP from baseline in the Chinese subpopulation, elderly (≥65 years), and in patients with isolated systolic hypertension (ISH) were assessed. Sacubitril/valsartan 200 mg provided a significantly greater reduction in msSBP than olmesartan 20 mg at Week 8 (between‐treatment difference: −2.33 mm Hg [95% confidence interval (CI) −4.00 to −0.66 mm Hg], P < 0.05 for non‐inferiority and superiority). Greater reductions in msSBP were also observed with sacubitril/valsartan 400 mg vs olmesartan 20 mg (−3.52 [−5.19 to −1.84 mm Hg], P < 0.001 for superiority). Similarly, greater reductions in msBP were observed in the Chinese subpopulation, in elderly patients, and those with ISH. In addition, both doses of sacubitril/valsartan provided significantly greater reductions from baseline in nighttime mean ambulatory BP vs olmesartan. Treatment with sacubitril/valsartan 200 or 400 mg once daily is effective and provided superior BP reduction than olmesartan 20 mg in Asian patients with mild‐to‐moderate hypertension and is generally safe and well tolerated.     

Single-pill combination of telmisartan/amlodipine in patients with severe hypertension: results from the TEAMSTA severe HTN study

This 8-week, randomized, double-blind, controlled study compared efficacy and tolerability of telmisartan/amlodipine (T/A) single-pill combination (SPC) vs the respective monotherapies in 858 patients with severe hypertension (systolic/diastolic blood pressure [SBP/DBP] ≥180/95 mm Hg). At 8 weeks, T/A provided significantly greater reductions from baseline in seated trough cuff SBP/DBP (-47.5 mm Hg/-18.7 mm Hg) vs T (P<.0001) or A (P=.0002) monotherapy; superior reductions were also evident at 1, 2, 4, and 6 weeks. Blood pressure (BP) goal and response rates were consistently higher with T/A vs T or A. T/A was well tolerated, with less frequent treatment-related adverse events vs A (12.6% vs 16.4%) and a numerically lower incidence of peripheral edema and treatment discontinuation. In conclusion, treatment of patients with substantially elevated BP with T/A SPCs resulted in high and significantly greater BP reductions and higher BP goal and response rates than the respective monotherapies. T/A SPCs were well tolerated.     

Comparison of the effects of aliskiren/valsartan in combination versus valsartan alone in patients with Stage 2 hypertension

The extent to which the combination of a renin inhibitor with an angiotensin receptor blocker (ARB) lowers clinic and ambulatory blood pressure (BP) versus an ARB alone in stage 2 hypertension is not well known. Hence, we performed an 8-week, randomized, double-blind study in 451 patients with stage 2 hypertension to compare the efficacy of the combination of aliskiren/valsartan 300/320 mg versus valsartan 320 mg. The primary endpoint was change in seated systolic BP from baseline to week 8 analyzed on the intent-to-treat (ITT) population using the last-observation-carried-forward (LOCF) approach; patients completing the entire treatment period (per-protocol completers) were similarly analyzed. For the predefined primary analysis, systolic BP reductions for aliskiren/valsartan (n = 230) and valsartan (n = 217) were ?22.1 and ?20.5 mm Hg, respectively (P = .295). In per-protocol completers, aliskiren/valsartan (n = 201) lowered BP significantly greater than valsartan (n = 196); ?23.7 mm Hg versus ?20.3 mm Hg, respectively (P = .028). Although limited by a small sample size (n = 76) using ambulatory BP monitoring, aliskiren/valsartan lowered the 24-hour BP significantly more than valsartan alone (?14.6/?9.0 mm Hg versus ?5.9/?4.2 mm Hg; P < .01). Safety and tolerability were similar for the two treatment groups. These data demonstrate the importance of multiple modalities to assess BP changes in clinical trials of antihypertensive therapies, particularly in stage 2 hypertension.