Two multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy and tolerability of amlodipine and valsartan in combination and as monotherapy in adult patients with mild to moderate essential hypertension

Philipp, Thomas; Smith, Timothy R.; Glazer, Robert; Wernsing, Margaret; Yen, Joseph; Jin, James; Schneider, Helmut; Pospiech, R

doi:10.1016/j.clinthera.2007.03.018

Cited by 234 publications

(199 citation statements)

References 31 publications

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“…In contrast, ARBs are the best-tolerated class of antihypertensive drugs and not only reduce BP without inducing a reflex increase in sympathetic nervous activity (and resulting tachycardia or palpitations) 35 but also, probably through inducing venous vasodilation, diminish the CCB-induced increase in hydrostatic pressure 36 and thereby reduce the frequency of edema. 8,37 This favorable safety profile of the CCB-ARB combination was clearly confirmed in our study where very few adverse events occurred even in subjects treated with the higher doses of both drugs. In particular, only one event of hypotension was reported as an adverse effect.…”

Section: Discussionsupporting

confidence: 78%

Efficacy of olmesartan/amlodipine combination therapy in reducing ambulatory blood pressure in moderate-to-severe hypertensive patients not controlled by amlodipine alone

Bilo

Koch²,

Hoshide

et al. 2014

Hypertens Res

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This previously unpublished, preplanned analysis investigated the efficacy of the olmesartan/amlodipine combination at different doses on 24-h blood pressure (BP) control, as well as assessed trough estimation of trough-to-peak ratio (TPR) and smoothness index (SI). Ambulatory BP monitoring was performed in patients with moderate-to-severe hypertension whose BP was inadequately controlled after 8 weeks' treatment with amlodipine 5 mg. Patients were randomized to continue with amlodipine 5 mg or to receive olmesartan/amlodipine 10/5, 20/5 or 40/5 mg for 8 weeks (Period II). Patients not achieving BP control were uptitrated to a more powerful regimen for another 8 weeks (Period III). During Period II, each olmesartan/ amlodipine combination reduced 24-h systolic and diastolic BP (SBP/DBP), as well as morning and early morning SBP/DBP, significantly more than amlodipine 5 mg (Po0.001 for all). TPRs were higher in each olmesartan/amlodipine group than with amlodipine 5 mg, and SI values showed dose-related increases; olmesartan/amlodipine 40/5 mg produced a significantly higher SI for SBP and DBP (1.55 and 1.33, respectively) than amlodipine 5 mg (0.96 and 0.77, respectively, Po0.0001 for each). During Period III, uptitrated patients showed further BP reductions, which were largest in those on olmesartan/amlodipine 40/10 mg. SI values increased in uptitrated patients and were highest with olmesartan/amlodipine 40/10 mg (SBP 1.62/DBP 1.41). The olmesartan/amlodipine combination effectively reduces BP over 24 h, including the morning hours, in a dose-related manner. Compared with amlodipine alone, the olmesartan/amlodipine combination has a better 24-h coverage (TPR) and a dose-related improvement in BP lowering homogeneity (SI).

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Section: Discussionsupporting

confidence: 78%

Efficacy of olmesartan/amlodipine combination therapy in reducing ambulatory blood pressure in moderate-to-severe hypertensive patients not controlled by amlodipine alone

Bilo

Koch²,

Hoshide

et al. 2014

Hypertens Res

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“…16 Obviously, the size of additional BP-lowering effect Table 4 Number (%) of patients with most frequently reported (X0.2% in either group) adverse events that were suspected to be related to administration of study drug (safety population, double-blind phase) achieved by doubling valsartan dose was smaller compared with what was observed when hydrochlorothiazide or amlodipine were added to valsartan. [17][18][19] However, the aim of our study was not to undermine the usefulness of combination therapy in achieving BP control, but rather to show that, in a number of subjects, using the same ARB as a high-dose monotherapy may be sufficient to achieve the therapeutic target. Although the BP changes observed in ValTop are in line with the dose-response curve described in other studies, 14,15 ValTop provides a deeper insight into the characteristics of response to increasing dosages of valsartan.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness and safety of high-dose valsartan monotherapy in hypertension treatment: the ValTop study

et al. 2010

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Early combination therapy is increasingly recommended in hypertension management because of increased risk of adverse effects with high-dose monotherapy. However, this risk is not necessarily increased for high doses of angiotensin receptor blockers (ARB). ValTop study compared efficacy and safety of high vs. conventional dose of valsartan in hypertensive patients. ValTop was a controlled, randomized, double-blind trial. Of 6035 screened subjects, 4004 mild-to-moderate hypertensive patients (mean seated diastolic blood pressure (MSDBP) 90-109 mm Hg) started 4-week open-label treatment with valsartan 160 mg. Of them, 3776 were randomized to receive valsartan 160 mg (N¼1900) or 320 mg (N¼1876) o.d. for 4 weeks. In 28-week open-label extension study, all participating patients (N¼642) received valsartan 320 mg. Valsartan 160 mg reduced MSDBP by 10.0 mm Hg in the initial open-label phase. Further BP reductions in the double-blind phase were significantly (Po0.0001) greater in the 320 mg group than in the 160 mg group for MSDBP (1.6 ± 0.18 mm Hg vs. 0.5 ± 0.18 mm Hg) and mean seated systolic BP (3.3 ± 0.31 mm Hg vs. 0.7 ± 0.31 mm Hg). The size of the additional effect of the 320 mg dose on BP was similar in subjects controlled or not by the initial 160 mg dose. Adverse event (AE) rates were similar in both treatment groups, drug-related AEs occurring in o5% of subjects in each phase. High-dose valsartan is safe and effective in uncomplicated mild-to-moderate hypertension independently of the initial response to a moderate dose. High-dose ARB monotherapy may thus be a viable option in hypertension management.

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“…The nifedipine GITS formulation offers, in addition, the advantage of controlled drug release, making it suitable for once‐daily administration, and an observational study suggests that candesartan reduces the risk of cardiovascular disease and heart failure in comparison with another angiotensin receptor blocker (ARB), losartan 16, 18. A placebo arm was included in DISTINCT in accordance with the International Conference on Harmonisation guideline for evaluation of fixed‐dose combination products for the treatment of hypertension and similar to other multifactorial trials of combination antihypertensive therapies 20, 21, 22, 23. DISTINCT demonstrated that initial combination therapy with nifedipine GITS/candesartan cilexetil was more effective in lowering BP and meeting target BP goals (SBP <140 and DBP <90 mm Hg) vs respective monotherapies at the same doses in participants with hypertension.…”

mentioning

confidence: 99%

Nifedipine GITS/Candesartan Combination Therapy Lowers Blood Pressure Across Different Baseline Systolic and Diastolic Blood Pressure Categories: DISTINCT Study Subanalyses

Kjeldsen

Cha

Villa

et al. 2016

The Journal of Clinical Pharma

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DISTINCT was an 8‐week, double‐blind, randomized study to investigate the antihypertensive efficacy and safety of various nifedipine gastrointestinal treatment system (GITS)/candesartan cilexetil (N/C) dose combinations, vs respective monotherapies or placebo, in patients with diastolic blood pressure (DBP) ≥95 to <110 mm Hg. The current prespecified analysis compared BP reduction in participants with mild vs moderate baseline hypertension (ie, systolic [S]BP <160 mm Hg vs ≥160 mm Hg and DBP <100 mm Hg vs ≥100 mm Hg). A total of 1362 patients were analyzed by descriptive statistics. In all patient subgroups investigated, the NC combinations (ie, N: 20, 30, or 60 mg; C: 4, 8, 16, or 32 mg daily) provided greater SBP and DBP lowering and higher rates of BP control (defined as BP <140/90 mm Hg) than respective monotherapies or placebo, with greatest absolute BP reductions observed in the moderately elevated SBP or DBP subgroups. A trend to dose‐response relationship was observed in each subgroup. In each SBP and DBP subgroup, treatment‐related vasodilatory events (flushing, headache, or edema) were less frequent for patients receiving NC combination therapy than N monotherapy. These analyses support the use of calcium antagonist and angiotensin receptor blocker combination therapy in patients with both mild and moderate hypertension, for whom effective BP normalization and good drug tolerance would greatly reduce the risk of cardiovascular events.

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Two multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy and tolerability of amlodipine and valsartan in combination and as monotherapy in adult patients with mild to moderate essential hypertension

Cited by 234 publications

References 31 publications

Efficacy of olmesartan/amlodipine combination therapy in reducing ambulatory blood pressure in moderate-to-severe hypertensive patients not controlled by amlodipine alone

Efficacy of olmesartan/amlodipine combination therapy in reducing ambulatory blood pressure in moderate-to-severe hypertensive patients not controlled by amlodipine alone

Effectiveness and safety of high-dose valsartan monotherapy in hypertension treatment: the ValTop study

Nifedipine GITS/Candesartan Combination Therapy Lowers Blood Pressure Across Different Baseline Systolic and Diastolic Blood Pressure Categories: DISTINCT Study Subanalyses

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