Blood pressure response, but not adverse event incidence, correlates with dose of angiotensin II antagonist

Püchler, Kurt; Laeis, Petra; Stumpe, Klaus O.

doi:10.1097/00004872-200106001-00006

Cited by 47 publications

(43 citation statements)

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“…[34][35][36] Tachycardia caused by reflex activation of the sympathetic nervous system is one of the major adverse effects of CCB therapy. Unlike other dihydropyridine CCBs, however, azelnidipine has been shown to inhibit sympathetic activity.…”

Section: Combined Antihypertensive Therapy With Olmesartan T Ishimitsmentioning

confidence: 99%

Angiotensin-II receptor antagonist combined with calcium channel blocker or diuretic for essential hypertension

et al. 2009

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To achieve the target blood pressure recommended by the latest guidelines, multiple antihypertensive drugs are needed in most patients. In this study, the efficacy of treatment using an angiotensin II receptor antagonist (ARB) combined with a calcium channel blocker (CCB) or a diuretic was compared from multiple perspectives in patients with hypertension. Twenty-nine patients with essential hypertension, who had failed to achieve their target blood pressure (o130/85 mm Hg for patients o65 years old and o140/90 mm Hg for those X65 years) when treated with the ARB olmesartan at 20 mg day À1 , were additionally given 8-16 mg day À1 of the CCB azelnidipine or 1-2 mg day À1 of trichlormethiazide (a thiazide diuretic) in a randomized crossover manner for 4 months each. At the end of each combination therapy period, blood and urine samples were collected and arterial stiffness was evaluated by measuring the cardio-ankle pulse wave velocity. Compared with monotherapy, the blood pressure was reduced similarly by adding azelnidipine (À12/À10 mm Hg) or trichlormethiazide (À14/À9 mm Hg). The heart rate was decreased with the CCB by 4 b.p.m. (Po0.05), whereas it was unchanged with the thiazide. Serum K, lipids and blood glucose were not significantly changed with either combination, whereas serum uric acid was increased with the thiazide (Po0.01) but was unchanged with azelnidipine. Plasma levels of renin, angiotensin II and aldosterone were also increased with the thiazide period, whereas high-sensitivity C-reactive protein and oxidized low-density lipoprotein were decreased with azelnidipine. In addition, the cardio-ankle vascular index, a parameter of arterial stiffness, was decreased with the azelnidipine period but was unchanged with the thiazide period (Po0.01). It is suggested that the combination of olmesartan and azelnidipine has advantages over the combination of olmesartan and a thiazide with respect to avoiding hyperuricemia, sympathetic activation, renin-angiotensin-aldosterone system stimulation, inflammation, oxidative stress, and increased arterial stiffness in patients with moderate hypertension. These properties may provide cardiovascular protection in addition to the hypotensive effect.

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Section: Combined Antihypertensive Therapy With Olmesartan T Ishimitsmentioning

confidence: 99%

Angiotensin-II receptor antagonist combined with calcium channel blocker or diuretic for essential hypertension

et al. 2009

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“…7,9 The most frequently reported AE was headache ( Table 7). The most notable difference between olmesartan medoxomil and placebo was in dizziness (2.3% vs 0.4% of patients), which may be related to the pharmacodynamic effect of the active drug.…”

Section: Clinical Safety and Tolerabilitymentioning

confidence: 99%

The new oral angiotensin II antagonist olmesartan medoxomil: a concise overview

Brunner

2002

J Hum Hypertens

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The new orally active angiotensin II (A II) type-1 receptor antagonist olmesartan medoxomil is a prodrug, which is rapidly converted in vivo to the active metabolite, olmesartan. The pharmacology, antihypertensive efficacy and safety of olmesartan medoxomil and/or the pharmacologically active metabolite, olmesartan, have been evaluated in both non-clinical and clinical models. Orally administered olmesartan medoxomil is rapidly absorbed from the gastrointestinal tract and converted during absorption to olmesartan, which is subsequently excreted without further metabolism. Peak plasma concentrations of olmesartan occur 1-3 h after administration, after which concentrations decrease with an elimination half-life of 10-15 h. The absolute bioavailability of olmesartan from olmesartan medoxomil tablets is 28.6%. In a single-dose crossover study in 16 patients with mild-to-moderate hypertension receiving a sodium-restricted diet, statistically significant lowering

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“…The results of these studies are summarised in Table 3, and will be briefly discussed here. Pü chler et al, 3 analysed the results of 3055 patients from seven US and European studies. In these studies, olmesartan medoxomil was used in daily doses ranging from 2.5 to 80 mg and resulted in significant, dose dependent reduction of BP up to a dose of 40 mg/day with no further BP reduction with the 80 mg dose.…”

Section: Placebo Comparative Studiesmentioning

confidence: 99%

“…In several randomised placebo-controlled studies, olmesartan medoxomil has demonstrated significant antihypertensive effects compared to placebo. 1,2 In other comparative studies, olmesartan medoxomil showed similar blood pressure (BP) lowering efficacy with angiotensin converting enzyme (ACE) inhibitors, calcium channel blockers, b-blockers and diuretics, [3][4][5][6][7][8][9] but superior antihypertensive potency against other ARBs given in equivalent starting doses. [10][11][12][13] In other studies, olmesartan medoxomil given in the highest recommended daily doses, its antihypertensive effect was similar to other ARBs.…”

Section: Introductionmentioning

confidence: 97%

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Treatment of hypertension with olmesartan medoxomil, alone and in combination with a diuretic: an update

2007

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Olmesartan medoxomil is an angiotensin II (Ang II) receptor blocker (ARB) that has been approved by the US Food and Drug Administration (FDA) for the treatment of hypertension. It is a prodrug that is hydrolysed in the gut into its active metabolite, olmesartan (RNH-6270). Olmesartan is highly selective for the Ang II type 1 receptor (AT1) to which it binds completely and insurmountably and has very little affinity for the other receptor subtypes AT2 and AT4. After oral administration, in animals and humans, it achieves a maximal blood drug concentration within a maximal time of approximately 2 h. It is then slowly eliminated in the urine and faeces. His half-life is approximately 13 h, which makes it suitable for once-daily administration. Olmesartan medoxomil given orally in single daily doses of 20-40 mg has demonstrated significant blood pressure (BP) lowering effects in hypertensive patients. A medline search for the preparation of this manuscript was conducted and revealed 128 references, from 2000 to 2007. Of these, only 16 well-designed prospective clinical trials were selected. The remaining were either animal studies, reviews or studies in progress. In well-designed clinical trials, olmesartan medoxomil has demonstrated similar antihypertensive actions to the other antihypertensive drugs, as well as other members of its class given the highest recommended doses. In addition, the BP lowering effect of olmesartan, like the other members of its class, is greatly enhanced in combination with a diuretic. Its safety profile is similar to the other ARBs and no different than placebo.

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Blood pressure response, but not adverse event incidence, correlates with dose of angiotensin II antagonist

Cited by 47 publications

References 0 publications

Angiotensin-II receptor antagonist combined with calcium channel blocker or diuretic for essential hypertension

Angiotensin-II receptor antagonist combined with calcium channel blocker or diuretic for essential hypertension

The new oral angiotensin II antagonist olmesartan medoxomil: a concise overview

Treatment of hypertension with olmesartan medoxomil, alone and in combination with a diuretic: an update

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