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.     

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.     

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 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.     

Antihypertensive efficacy of night-time graded-release diltiazem versus morning amlodipine in African Americans

BACKGROUND: The effect of a once daily night-time (10 pm) graded-release diltiazem (GRD) on early morning blood pressure (BP), heart rate (HR), and rate-pressure product (RPP) were compared with the effect of morning (8 am) amlodipine in 262 African American individuals with hypertension. METHODS: The multicenter, randomized, double-blind, parallel-group, dose-to-effect trial evaluated changes from baseline in BP, HR, and RPP (HR x systolic BP) by ambulatory BP monitoring during the first 4 h after awakening (diastolic BP = primary), between 6 am and 12 noon, and over a 24-h period. Patients were randomized to night-time GRD 360 mg (n = 132) or morning amlodipine 5 mg (n = 130) for 6 weeks, and were titrated to GRD 540 mg or amlodipine 10 mg after 6 weeks if clinic systolic BP/diastolic BP (SBP/DBP) was > or = 130/85 mm Hg. RESULTS: Compared with amlodipine, GRD showed significantly greater DBP reductions of 3.5 mm Hg (P < .0049) and 3.2 mm Hg (P < .0019) during the first 4 h after awakening and between 6 am and 12 noon respectively, as well as comparable reduction for the 24-h mean DBP. The SBP reductions during the morning periods were comparable, but the reduction in the 24-h mean SBP was 3.4 mm Hg greater (P < .0022) for amlodipine. Mean reductions in HR and RPP were significantly greater (P < or = .0008) for GRD during all intervals; amlodipine increased whereas diltiazem reduced HR with mean differences of 6.7 to 9.3 beats/min. Both treatments were well tolerated. CONCLUSIONS: Night-time GRD was more effective than morning amlodipine in reducing early morning DBP, HR, and RPP, as well as 24-h HR and RPP in African American individuals with hypertension. Amlodipine was more effective in reducing SBP over the 24-h period.     

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.     

Efficacy and safety of fixed-dose losartan/hydrochlorothiazide/amlodipine combination versus losartan/hydrochlorothiazide combination in Japanese patients with essential hypertension

Abstract

Japanese patients with uncontrolled essential hypertension received single-blind losartan 50?mg/hydrochlorothiazide 12.5?mg (L50/H12.5) for 8 weeks. Patients whose blood pressure (BP) remained uncontrolled were randomized double-blind to fixed-dose losartan 50?mg/hydrochlorothiazide 12.5?mg/amlodipine 5?mg (L50/H12.5/A5) or L50/H12.5 for 8 weeks followed by open-label L50/H12.5/A5 for 44 weeks. Adverse events were assessed. After 8 weeks, diastolic and systolic BP were reduced significantly more with L50/H12.5/A5 versus L50/H12.5 (both p?<?0.001). Mean changes in diastolic and systolic BP were sustained for 44 weeks. L50/H12.5/A5 was well-tolerated and improved BP significantly versus L50/H12.5 in Japanese patients with uncontrolled essential hypertension.

Trial registration: ClinicalTrials.gov identifier: NCT01299376.     

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.     

Antihypertensive efficacy and safety of olmesartan medoxomil compared with amlodipine for mild-to-moderate hypertension

The antihypertensive efficacy of the angiotensin II receptor blocker olmesartan medoxomil has been shown to compare favourably with that of other antihypertensive agents. This randomized, double-blind study compared the antihypertensive efficacy of the starting dose of olmesartan medoxomil with that of the calcium channel blocker amlodipine besylate (amlodipine) in subjects with mild-to-moderate hypertension. Following a 4-week, single-blind, placebo run-in period, 440 subjects aged >/=18 years were randomized to the starting dose of olmesartan medoxomil (20 mg/day), amlodipine (5 mg/day), or placebo for 8 weeks. Subjects were evaluated by 24-h ambulatory blood pressure monitoring (ABPM) and by seated cuff blood pressure (BP) measurements at trough. The primary end point was the change from baseline in mean 24-h diastolic blood pressure (DBP) by ABPM at Week 8. Secondary end points included change from baseline in mean 24-h ambulatory systolic blood pressure (SBP) at 8 weeks, change from baseline in mean seated trough cuff DBP and SBP measurements, and response and control rates for DBP <90 and <85 mmHg. Control rates for SBP <140 and <130 mmHg were also calculated. Olmesartan medoxomil and amlodipine produced significantly greater reductions in ambulatory and seated DBP and SBP compared with placebo. Mean reductions in ambulatory and seated BP were similar between the two active agents; however, in the olmesartan medoxomil group, significantly more patients achieved the SBP goal of <130 mmHg and the DBP goal of <85 mmHg. Both drugs were well tolerated at the recommended starting dose. Although amlodipine was associated with a higher incidence of oedema, this did not reach statistical significance. Olmesartan medoxomil is an effective antihypertensive agent, with BP-lowering efficacy at the starting dose similar to that of amlodipine, and is associated with more patients achieving the rigorous BP goals of SBP <130 mmHg and DBP <85 mmHg.     

A comparison of the efficacy and safety of irbesartan/HCTZ combination therapy with irbesartan and HCTZ monotherapy in the treatment of moderate hypertension

This prospective, double-blind, parallel-group study randomized patients with moderate hypertension (seated systolic blood pressure (SeSBP) 160-179 mm Hg when seated diastolic blood pressure (SeDBP) <110 mm Hg; or SeDBP 100-109 mm Hg when SeSBP <180 mm Hg) 3:1:1 to treatment with irbesartan 300 mg/hydrochlorothiazide (HCTZ) 25 mg combination therapy (n=328), irbesartan 300 mg monotherapy (n=106) or HCTZ monotherapy 25 mg (n=104). Treatment was initiated at half dose, with forced titration to full dose after two weeks followed by ten further weeks' treatment. The primary efficacy variable was the mean reduction in SeSBP from baseline to week 8. Baseline characteristics were similar between groups, with mean baseline blood pressure approximately 162/98 mm Hg; the mean age was 55 years. At week 8 there was a reduction in SeSBP of 27.1 mm Hg with irbesartan/HCTZ, compared with 22.1 mm Hg with irbesartan monotherapy (P=0.0016) and 15.7 mm Hg with HCTZ (P<0.0001). Both the rate of decline and the total degree of decline achieved were greatest with irbesartan/HCTZ and least with HCTZ. A significantly greater percentage of patients reached a treatment goal of SeSBP <140 mm Hg and SeDBP <90 mm Hg by week 8 with irbesartan/HCTZ (53.4%), compared with irbesartan (40.6%; P=0.0254) and HCTZ (20.2%; P<0.0001) alone. Treatment was well tolerated in all three-treatment groups with a slight increase in adverse events in the combination therapy group. In conclusion, irbesartan/HCTZ (300/25 mg) is well tolerated and achieves rapid and sustained reductions in both systolic blood pressure and diastolic blood pressure in patients with moderate hypertension.     

Comparative effects of amlodipine monotherapy and combination therapy with betaxolol on cardiac autonomic nervous activity and health-related quality of life in patients with poorly controlled hypertension.

BACKGROUND: The aim of the study was to evaluate whether the combined treatment of calcium channel blocker, amlodipine and beta-blocker, betaxolol, favorably affects cardiac autonomic nervous activity (CANA) and health-related quality of life (HRQL). METHODS AND RESULTS: A total of 65 patients with a poor blood pressure (BP) control with a low dose amlodipine therapy were randomly assigned to the amlodipine dose-up group (n=21) and betaxolol adding group (n=44). Before and after a 6-month treatment, BP, heart rate variability (HRV), HRQL and blood chemistries were evaluated. Low frequency (LF) spectra/high frequency (HF) spectra and HF/total power spectra (TP) were calculated as indexes of CANA, and HRQL was assessed by the questionnaire sheets. BP was well controlled in all patients of the present study. In the betaxolol adding group, LF/HF decreased (2.1+/-1.9 to 1.3+/-0.9, p<0.05) and HF/TP reciprocally increased (0.41+/-0.17 to 0.52+/-0.18, p<0.05), whereas the amlodipine dose-up group showed no significant changes in the HRV. HRQL was significantly improved in the betaxolol adding group, whereas it remained unchanged in the amlodipine dose-up group. Blood chemistries remained unchanged except for the slightly increased plasma brain natriuretic peptide concentrations in the betaxolol adding group (36+/-47 to 62+/-62 pg/ml, p<0.05). CONCLUSIONS: Combined treatment of amlodipine and betaxolol appears to be more useful than amlodipine dose-up therapy, because combined treatment improves CANA and HRQL.     

A new dimension in hypertension management with the amlodipine/perindopril combination

Recent guidelines are consistent in acknowledging that most hypertensive patients need at least two drugs for optimal blood pressure (BP) control. Trial data are available to support the use of a renin-angiotensin system (RAS) blocker (ie, an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker), plus a diuretic, a RAS blocker plus a calcium channel blocker (CCB), and a CCB plus a diuretic. The ACCOMPLISH trial demonstrated somewhat convincingly that an ACE inhibitor/CCB is superior to the same ACE inhibitor plus a thiazide. In the ASCOT trial, amlodipine/perindopril was superior to beta-blocker/thiazide in its effects on all major cardiovascular outcomes and new-onset diabetes. Further substudies of ASCOT provided plausible explanations for the benefits of amlodipine/perindopril strategy. In the CAFE substudy, amlodipine/perindopril was significantly more effective in the reduction of central BP as compared to atenolol/bendroflumethiazide, despite similar brachial BP reduction. More recently, analysis of long-term BP variability provided a further explanation for the reduction of cardiovascular events with amlodipine/perindopril in ASCOT. Thus, the combination of perindopril and amlodipine seems an ideal logical evidence-based pair of antihypertensive agents to select.     

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.     

Pathogenesis of hypertension in African Americans

Hypertension is a compelling disease process that disproportionately affects African Americans. It is the single largest risk factor for cardiovascular disease in African Americans. The end organ manifestations of hypertension are striking and include higher rates of stroke, significantly increased renal disease including end-stage renal disease requiring dialysis, higher risk of left ventricular hypertrophy, and an associated higher risk of heart failure. The cause of these more aggressive end organ phenomena is likely multifactorial and includes a mix of genetic and environmental influences. Intriguing polymorphisms of the epithelial sodium channel are consistent with patterns of hypertension seen in African Americans. Obesity, especially in African-American women, may be closely related to hypertension as a result of sympathetic nervous system stimulation.     

Long-term efficacy and safety of triple-combination therapy with olmesartan medoxomil and amlodipine besylate and hydrochlorothiazide for hypertension

J Clin Hypertens (Greenwich). 2012;14:149–157. ©2012 Wiley Periodicals, Inc. Most patients with hypertension require combination therapy in order to achieve blood pressure (BP) goals. This 40‐week open‐label extension of the 12‐week double‐blind Tri ple Therapy With Olmesartan Medoxomil, Amlodipine, and Hydrochlorothiazide in Hyperten si ve Patient s Study (TRINITY) evaluated the efficacy and safety of triple‐combination treatments with olmesartan medoxomil, amlodipine besylate, and hydrochlorothiazide (OM/AML/HCTZ) in 2112 participants with moderate to severe hypertension. Following 2 weeks of initial treatment with OM 40/AML 5/HCTZ 12.5 mg, participants not achieving BP goal were titrated to OM 40/AML 5/HCTZ 25 mg or OM 40/AML 10/HCTZ 12.5 mg on a randomized basis. At week 16, participants who did not achieve BP goal were further titrated to OM 40/AML 10/HCTZ 25 mg. At the end of the study, 44.5% to 79.8% of participants reached BP goal and the mean BP decreased from 168.6/100.7 mm Hg (baseline BP at randomization) to 125.0 to 136.8 mm Hg/77.8 to 82.5 mm Hg, depending on treatment. Long‐term treatment with OM/AML/HCTZ was well tolerated and effective with no new safety concerns.     

Long-term exposure to telmisartan as monotherapy or combination therapy: efficacy and safety

This multicentre, open-label extension study to four controlled trials involved 888 patients with mild-to-moderate primary hypertension. Patients received telmisartan 40-80 mg once daily with add-on hydrochlorothiazide (HCTZ; 12.5-25 mg) if necessary and/or other antihypertensives to achieve diastolic blood pressure (DBP) control (<90 mmHg). Treatment continued for up to 4 years. At treatment end, 578 (65.1%) patients were on telmisartan monotherapy, 106 (11.9%) were on telmisartan + HCTZ 12.5 mg, 101 (11.4%) were on telmisartan + HCTZ 25 mg, and 103 (11.6%) were on telmisartan + another antihypertensive + HCTZ. Overall, 84.4% (746/884) patients achieved DBP control. The highest proportion of responders was in the telmisartan monotherapy (40 or 80 mg) treatment category (89.0% 1,511/574 patients]). The mean change in systolic blood pressure (SBP)/DBP from the previous trial baseline to last available trough was -21.2/-17.3 mmHg with telmisartan alone, -24.6/-16.7 mmHg with telmisartan + HCTZ, and - 18.7/-14.9 mmHg with telmisartan + another antihypertensive +/- HCTZ. Most adverse events were of mild-to-moderate intensity and unrelated to treatment. The proportions of patients discontinuing the study due to adverse events, by treatment at onset, were 7.3% (65/888) with telmisartan monotherapy, 6.6% (20/304) with telmisartan + HCTZ and 2.9% (3/103) with telmisartan + another antihypertensive +/- HCTZ. There were 15 deaths during the study, but none was considered drug related. Thus, telmisartan alone or in combination with other antihypertensives achieved and maintained clinically relevant reductions in DBP and SBP. This long-term analysis supports the favourable efficacy and safety profile of telmisartan both as monotherapy and in combination with other antihypertensive drugs.     

Comparative efficacy and safety ofnisoldipine extended-release (ER) andamlodipine (CESNA-III study) in African American patients with hypertension

BackgroundThis study evaluates the efficacy of the new dihydropyridine calcium antagonist nisoldipine extended-release (ER) compared to amlodipine on ambulatory and clinic blood pressures (BP) and heart rates in African American patients with hypertension.MethodsThis prospective, double-blind trial randomized 192 patients with office diastolic BP of 95 to 114 mm Hg to receive either nisoldipine (20 to 60 mg once daily) or amlodipine (5 to 10 mg once daily) for 12 weeks in a titration-to-effect design. Using ambulatory monitoring, efficacy was assessed by measuring change from baseline in systolic and diastolic BP and heart rate during three time intervals: 24-h mean period, awake, and sleep. In addition, a subanalysis was performed to evaluate patients whose nocturnal decline in BP was elevated (nondippers) versus those whose BP declined by 10% or more (dippers).ResultsSubstantial and significant mean changes from baseline in 24-h BP were observed for patients treated with nisoldipine ER (−23/−16 ± 3/2 mm Hg) and amlodipine (−20/15 ± 3/2 mm Hg) (between-group comparisons, P = .07 for systolic BP; P = .50 for diastolic BP). Significant and similar reductions also were observed for clinic, awake, and sleep BP. Reductions in BP in the nondippers was substantially greater than in patients with a dipper profile. Neither agent had a significant effect on ambulatory heart rate. Adverse events were mild and infrequent (headache, edema, and dizziness at rates of 4% to 15%), and similar for both agents.ConclusionsNisoldipine ER was as effective as amlodipine in reducing 24-h BP in African-American patients with hypertension, with a similar adverse effect profile. Thus, this new therapy for delivery of a dihydropyridine calcium channel blocker is a useful antihypertensive strategy for African-American 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.