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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension

Eplerenone is a highly selective aldosterone blocker, which is under development for the treatment of hypertension and heart failure. To assess its usefulness in older patients with systolic hypertension and widened pulse pressure, we compared the effects of eplerenone with amlodipine, on clinic blood pressure (BP) and pulse pressure and in a subset of the patients, ambulatory BP, vascular compliance, and urinary albumin excretion. The study involved 269 patients > or =50 years of age who were randomly assigned to either eplerenone (50 to 200 mg daily) or amlodipine (2.5 to 10 mg daily) in a double-blind titration to effect design. After 24 weeks of therapy, reductions in clinic systolic BP were similar for both treatments (eplerenone, -20.5+/-1.1 mm Hg; amlodipine, -20.1+/-1.1 mm Hg). Reductions in clinic diastolic BP were modestly larger on amlodipine (-6.9+/-0.7 mm Hg) compared with eplerenone (-4.5+/-0.7 mm Hg) (P=0.014). Pulse pressure was also reduced similarly from baseline by the 2 treatment groups (eplerenone, -15.9 mm Hg versus amlodipine, -13.4 mm Hg, P=0.07). Changes from baseline in pulse wave velocity after 24 weeks of therapy were statistically similar for eplerenone and amlodipine. In patients with microalbuminuria at baseline (>30 mg albumin/g creatinine), eplerenone reduced the urinary albumin/creatinine ratio by 52% compared with a reduction of 10% by amlodipine (P=0.04). Thus, eplerenone was as effective as amlodipine in lowering systolic BP and pulse pressure as well as pulse wave velocity in older patients with widened pulse pressure hypertension. Furthermore, eplerenone reduced microalbuminuria to a greater extent than amlodipine in this older patient group.     

A titrate-to-goal study of switching patients uncontrolled on antihypertensive monotherapy to fixed-dose combinations of amlodipine and olmesartan medoxomil ± hydrochlorothiazide

In the prospective, open-label, titrate-to-goal Blood Pressure Control in All Subgroups With Hypertension (BP-CRUSH) study, 999 patients with hypertension uncontrolled on monotherapy (mean age, 55.6 ± 11.4 years; baseline blood pressure [BP], 153.7 ± 9.2/91.9 ± 8.6 mm Hg) were switched to fixed-dose amlodipine/olmesartan medoxomil (AML/OM) 5/20 mg. Patients were uptitrated every 4 weeks to AML/OM 5/40 mg and 10/40 mg to achieve BP < 120/70 mm Hg. Patients were subsequently uptitrated every 4 weeks to AML/OM+hydrochlorothiazide (HCTZ) 10/40+12.5 mg and 10/40+25 mg to achieve BP <125/75 mm Hg. The primary end point, the cumulative percentage of patients achieving seated systolic BP < 140 mm Hg (< 130 mm Hg for patients with diabetes) by week 12, was 75.8%. The mean (± standard error) BP changes from baseline during the titration periods ranged from -14.2±0.4 mm Hg/-7.7 ± 0.3 mm Hg for AML/OM 5/20 mg to -25.1 ± 0.7 mm Hg/-13.7 ± 0.4 mm Hg for AML/OM+HCTZ 10/40+25 mg. By week 20, the cumulative BP threshold of <140/90 mm Hg was achieved by 90.3% of patients. An ambulatory BP monitoring substudy (n=243) showed that 24-hour efficacy was maintained. Treatment-emergent adverse events (TEAEs), mostly mild to moderate in severity, occurred in 529 patients (53.0%). Drug-related TEAEs occurred in 255 patients (25.5%). This well-tolerated, treat-to-goal algorithm enabled a large proportion of patients with uncontrolled hypertension on monotherapy to safely achieve BP control on single-pill AML/OM combination therapy or triple therapy with the addition of HCTZ. .     

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.     

Comparative efficacy of aliskiren/valsartan vs valsartan in nocturnal dipper and nondipper hypertensive patients: a pooled analysis

This pooled analysis of ambulatory blood pressure (BP) monitoring data from two 8-week randomized controlled trials compared the antihypertensive efficacy and safety of combination aliskiren/valsartan vs valsartan alone in hypertensive patients (nocturnal dippers or nondippers). At study end, patients were taking aliskiren/valsartan 300/320 mg or valsartan 320 mg. In dippers (n=138) and nondippers (n=132), aliskiren/valsartan provided significantly (P<.05) greater reductions from baseline to week 8 than valsartan in 24-hour, daytime, and last-4-hour mean ambulatory systolic BP (maSBP). Treatment differences were more pronounced in nondippers. Nighttime maSBP reductions with aliskiren/valsartan were significantly greater vs valsartan in nondippers (-17.0 mm Hg vs -8.9 mm Hg; P<.05) but not dippers (-7.6 mm Hg vs -4.5 mm Hg; P=.16). In all time periods, combination therapy was generally associated with BP reductions that were greater in nondippers than dippers. Conversion from nondipper to dipper status was 32% vs 22% for aliskiren/valsartan vs valsartan (P=.48). Both treatments were similarly well tolerated. Although the addition of aliskiren to valsartan did not significantly alter dipper status, our data suggest an increased contribution of the renin-angiotensin-aldosterone system to the nondipper status of hypertensive patients.     

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.     

Effects of the angiotensin II receptor blockers telmisartan versus valsartan on the circadian variation of blood pressure: impact on the early morning period

BACKGROUND: Ambulatory blood pressure (BP) monitoring has shown that BP typically declines by 10% to 20% during sleep and increases fairly rapidly in the early morning period. Because the early morning period has been associated with both loss of hypertension control and increased rates of myocardial infarction and stroke, there has been interest in evaluating the effects of antihypertensive therapy at this particular time of the day. The purpose of this study was to assess the effects of a long half-life (telmisartan, 24 h) versus intermediate half-life (valsartan, 6 to 9 h) on early morning BP in two scenarios: after an active dose and after a missed dose of each agent. METHODS: The study was a double-blind, randomized trial that compared telmisartan (40 to 80 mg once daily) versus valsartan (80 to 160 mg once daily) on early morning BP in 490 patients with hypertension. Ambulatory BP recordings were performed at baseline after a placebo period and again after 6 and 8 weeks of double-blind therapy in a randomized cross-over design. The monitoring patients received either an active dose or a placebo dose (to mimic a "missed" dose). The primary study end point was reduction in the BP in the early morning period (last 6 h of the dosing period). RESULTS: After the active dose, telmisartan reduced the BP during the last 6 h of the dosing period by -11/-7.6 +/- 0.8/0.6 mm Hg compared to -8.7/-5.8 +/- 0.8/0.6 mm Hg on valsartan (P = .02 for systolic BP and.01 for diastolic BP). On the day of the missed dose, telmisartan reduced the early morning BP by -9.0/-6.3 +/- 0.7/0.6 mm Hg versus -7.4/-5.1 +/- 0.7/0.4 mm Hg on valsartan (P = .09 for systolic BP and.06 for diastolic BP). On the day of the missed dose, reductions in 24-h average BP for the two antihypertensive agents were -10.3/-6.9 mm Hg for telmisartan versus -8.7/-5.9 mm Hg for valsartan (P = .06 for systolic BP and.056 for diastolic BP). CONCLUSIONS: On a day of active therapy, telmisartan lowered both systolic and diastolic BP to a greater extent than valsartan for the last 6 h of the dosing interval. On a day in which a dose was missed, there was a notable trend for greater BP reduction during the latter part of the dosing interval on telmisartan versus valsartan. These results demonstrate that telmisartan achieved a greater effect than valsartan on BP during the early morning period in patients with hypertension.