Evaluation of antihypertensive therapy with the combination of olmesartan medoxomil and hydrochlorothiazide

Chrysant, Steven G.; Weber, Michael A.; Wang, Antonia C.; Hinman, Donald J.

doi:10.1016/j.amjhyper.2003.11.003

Cited by 135 publications

(117 citation statements)

References 38 publications

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“…Our present results show that HCTZ monotherapy induced a greater antihypertensive effect than did LOS monotherapy in DS rats and that combination therapy with both drugs also elicited a greater reduction in blood pressure compared with LOS alone, consistent with previous observations. 31 However, the combination therapy did not result in a decrease in blood pressure greater than that induced by HCTZ monotherapy. One possible explanation for this lack of an additional hypotensive effect is that the dose of HCTZ administered resulted in a near maximal reduction in blood pressure in DS rats, so that the addition of LOS had no further effect.…”

Section: Discussionmentioning

confidence: 90%

“…Another possibility is that this dose of HCTZ did not activate the systemic renin-angiotensin-aldosterone system (RAAS) in the presence of severe salt loading. 31 Loop diuretics such as furosemide, at excessive doses, induce a contraction of intravascular volume, the hemodynamic signal for RAAS activation, as well as a reduction in the production of compensatory natriuretic peptides. Low doses of thiazide diuretics such as HCTZ have been effectively and safely used for the treatment of hypertension.…”

Section: Discussionmentioning

confidence: 99%

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Mechanism underlying the efficacy of combination therapy with losartan and hydrochlorothiazide in rats with salt-sensitive hypertension

et al. 2011

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Although thiazide diuretics are commonly used to supplement angiotensin receptor blockers for treatment of hypertension, the mechanism underlying the therapeutic effects of this drug combination remains unclear. We investigated the antihypertensive and cardioprotective effects of combination therapy with losartan (LOS) and hydrochlorothiazide (HCTZ), in comparison with those of either drug alone, in Dahl salt-sensitive hypertensive rats. Rats fed a high-salt diet from 6 weeks of age were treated with LOS, HCTZ, both drugs (COMB) and vehicle from 6 to 11 weeks. The salt-induced increase in systolic blood pressure was attenuated moderately by LOS and to a greater extent by HCTZ and COMB. Left ventricular (LV) hypertrophy and fibrosis, diastolic dysfunction, as well as angiotensin-converting enzyme and angiotensin II type 1A (AT 1A ) receptor gene expression were attenuated similarly by LOS and HCTZ and more so by COMB. LOS downregulated expression of the AT 1A receptor gene, without affecting that of the AT 2 receptor gene, in the aorta. In contrast, neither HCTZ nor COMB affected aortic expression of the AT 1A receptor gene, but both markedly upregulated that of the AT 2 receptor gene. The salt-induced decrease in the plasma concentration of nitric oxide metabolites was attenuated substantially by LOS and abolished by both HCTZ and COMB. In conclusion, the combination of LOS and HCTZ attenuated hypertension, as well as LV remodeling and diastolic dysfunction, more effectively than did LOS or HCTZ alone in rats with salt-sensitive hypertension. Modulation of the cardiac and vascular renin-angiotensin system may have contributed to these beneficial effects of the drug combination.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Mechanism underlying the efficacy of combination therapy with losartan and hydrochlorothiazide in rats with salt-sensitive hypertension

et al. 2011

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“…All combinations with the angiotensin receptor blockers were developed initially with HCTZ at a dose of 12.5 mg; these combinations typically show additive effects on blood pressure lowering regardless of which angiotensin receptor blocker was evaluated. 6,[19][20][21][22][23][24] Incremental BP-lowering effects have been observed with larger doses of hydrochlorothiazide, that is, 25 mg, in combination with the angiotensin receptor blockers, 6,19 which led to the development of the fixed-dose combination formulations used in our trial. In an earlier study by Benz and coworkers, 19 valsartan-HCTZ at a dose of 160/25 mg lowered the BP by 22/15 mm Hg compared with 18/ 14 mm Hg for valsartan-HCTZ at a dose of 160/ 12.5 mg. Trenkwalder et al 25 also showed that patients not controlled on valsartan-HCTZ 160/ 12.5 mg had an additional 8.4/8.3 mm Hg reduction in BP when the diuretic dose was increased to 25 mg.…”

Section: Principal Findingsmentioning

confidence: 99%

Impact of angiotensin receptor blockade in combination with hydrochlorothiazide 25 mg in 2121 patients with stage 1–2 hypertension

2009

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The antihypertensive effects of telmisartan 80 mg versus valsartan 160 mg, both combined with hydrochlorothiazide (HCTZ) 25 mg, were assessed in a pooled analysis from two large trials with identical study designs in patients with stage 1-2 hypertension. The trials were double-blind with a 4:4:1 randomization scheme to compare once-daily telmisartan 80 mg and HCTZ 25 mg versus once-daily valsartan 160 mg and HCTZ 25 mg versus once-daily placebo on reductions in clinic blood pressure (BP). The primary end point was changes from baseline in BP at the end of 8 weeks. In total, 2121 patients were randomized (telmisartan-HCTZ, 942, valsartan-HCTZ, 952, and placebo, 227) and had baseline seated BPs of 154/102 and 155/102 mm Hg in the two studies, respectively. Changes from baseline in BP after administration of telmisartan-HCTZ (À24.5/ À18.0 mm Hg) were significantly greater than for both placebo (À4.1/À6.5 mm Hg) and valsartan-HCTZ (À22.3/ À16.8 mm Hg) (versus placebo, Po0.0001 for systolic and diastolic BP; versus valsartan-HCTZ, P ¼ 0.0004 for systolic BP and P ¼ 0.0019 for diastolic BP). Adverse event rates were higher in the placebo group than in the active treatment groups (placebo, 41%, telmisartan-HCTZ, 30%, and valsartan-HCTZ, 30%, Po0.05). These data confirm that telmisartan-HCTZ at doses of 80/25 mg lowered systolic and diastolic BP to a greater extent than valsartan-HCTZ at doses of 160/25 mg in stage 1-2 hypertension. The magnitude of the BP-lowering effect provides support for the use of angiotensin receptor blockers with higher doses of a thiazide diuretic (25 mg) to improve hypertension control.

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“…The antihypertensive efficacy of olmesartan medoxomil alone and in combination with HCTZ was studied by Chrysant et al 9 in a factorial design study in 502 hypertensive patients with MSDBP X100 and p115 mm Hg. In this study, olmesartan medoxomil 10, 20 or 40 mg/day alone and in combination with HCTZ 12.5 and 25.0 mg/day were used.…”

Section: Combination Treatmentmentioning

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: 98%

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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Evaluation of antihypertensive therapy with the combination of olmesartan medoxomil and hydrochlorothiazide

Abstract: Olmesartan medoxomil/HCTZ combination therapy produced BP reductions of up to 26.8/21.9 mm Hg and was well tolerated.

Cited by 135 publications

References 38 publications

Mechanism underlying the efficacy of combination therapy with losartan and hydrochlorothiazide in rats with salt-sensitive hypertension

Mechanism underlying the efficacy of combination therapy with losartan and hydrochlorothiazide in rats with salt-sensitive hypertension

Impact of angiotensin receptor blockade in combination with hydrochlorothiazide 25 mg in 2121 patients with stage 1–2 hypertension

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

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