Effects of losartan and candesartan monotherapy and losartan/hydrochlorothiazide combination therapy in patients with mild to moderate hypertension

Manolis, Athanasios; Grossman, Ehud; Jelaković, Bojan; Jacovides, Andrew; Bernhardi, David C; Cabrera, Walter; Watanabe, Luis A; Barragan, Jaime; Matadamas, N.; Mendiola, Alfred; Woo, Kam S.; Zhu, Jiaan; Mejia, Agnes D.; Bunt, Ton; Dumortier, Thomas; Smith, Ronald D.

doi:10.1016/s0149-2918(00)83062-3

Cited by 87 publications

(53 citation statements)

References 28 publications

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“…[13][14][15][16][17][18][19][20][21][22][23][24][25] A total of 4066 patients were included in the analysis, and the design and patient characteristics of randomized clinical trials included in the meta-analysis are shown in Table 1. The majority of the trials had a randomized, doubleblind, parallel group design.…”

Section: Resultsmentioning

confidence: 99%

Comparison of the efficacy of candesartan and losartan: a meta-analysis of trials in the treatment of hypertension

2009

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Informed by the findings from prospective observational studies and randomized outcome trials, guidelines for the management of hypertension acknowledge that the benefit of treatment can be attributed largely to blood pressure (BP) reduction. Therefore, quantification of differential BP lowering of different agents within classes of anti-hypertensives is of practical importance. The objective of this analysis was to compare the efficacy of candesartan and losartan with respect to reduction in systolic and diastolic BP (SBP and DBP). A systematic literature search of databases from 1980 to 1 October 2008 identified 13 studies in which candesartan and losartan were compared in randomized trials in hypertensive patients. Data from 4066 patients were included in the analysis using a random effect model. Mean changes in SBP and DBP were compared for each drug alone and after stratification for dose and for combination with hydrochlorothiazide (HCTZ). On the basis of all the data, the weighted mean difference favoured candesartan-3.22 mm Hg (95% confidence interval (CI) 2.16, 4.29) for SBP and 2.21 mm Hg (95% CI 1.34, 3.07) for DBP. These findings were consistent when analyses according to dose and combination with HCTZ were carried out. Thus, it can be concluded that at currently recommended doses, candesartan is more effective than losartan in lowering BP.

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Section: Resultsmentioning

confidence: 99%

Comparison of the efficacy of candesartan and losartan: a meta-analysis of trials in the treatment of hypertension

2009

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“…Furthermore, several angiotensin receptor blockers (ARBs) and diuretics hydrochlorothiazide and furosemide were similarly tested for their inhibitory effects on OAT2-mediated transport of uric acid, since these drugs have been reported to alter SUA levels. [6][7][8]27,28) Losartan (10 mM), telmisartan (10 mM), hydrochlorothiazide (100 mM) and furosemide (100 mM) significantly reduced OAT2-mediated uptake of uric acid ( Fig. 6b) to 85, 58, 65 and 18% of the control, respectively.…”

Section: Effects Of Drugs On Uric Acid Transport By Oat2mentioning

confidence: 97%

Renal Secretion of Uric Acid by Organic Anion Transporter 2 (OAT2/SLC22A7) in Human

Sato

Mamada

Anzai

et al. 2010

Biological & Pharmaceutical Bulletin

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The physiological function of organic anion transporter OAT2 (SLC22A7) remains unclear, but since OAT2 transports purine derivatives, it may be involved in renal handling of uric acid, the final metabolite of purine derivatives. In the present study, we studied uric acid transport in stably OAT2-expressing HEK293 cells (HEK293/OAT2). OAT2 mediated uptake, but not efflux, of [ ]uric acid uptake was inhibited by several mono-or dicarboxylic acids, but it was not trans-stimulated by any of the compounds tested. The pattern of inhibition of OAT2-mediated uric acid transport by various drugs was different from that of OAT1-or OAT3-mediated transport. Furthermore, OAT2-mediated transport of uric acid was inhibited by an antiuricosuric drug, pyrazinecarboxylic acid. These results revealed distinct characteristics of uric acid transport via OAT2 compared with other uric acid transporters, suggesting that OAT2 plays a role in renal uric acid uptake from blood as a first step of tubular secretion. OAT2 may therefore be a potential target for regulating serum uric acid level.

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“…Losartan has been shown to increase urinary uric acid (UA) excretion and decrease SUA level (3). In contrast, other ARBs such as candesartan and valsartan do not have uricosuric activity (4,5). Thus, it seems that the ability of each ARB to decrease SUA cannot be predicted until the uricosuric activities of all ARBs are examined.…”

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confidence: 99%

Concentration-Dependent Inhibitory Effect of Irbesartan on Renal Uric Acid Transporters

et al. 2010

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Hyperuricemia has been associated with hypertension. Approximately 25% of patients with hypertension have hyperuricemia (1), and approximately 30% of patients with hyperuricemia or gout have hypertension (2). Therefore the effects of antihypertensive drugs on serum uric acid (SUA) level, especially angiotensin II-receptor blockers (ARBs), have been scrutinized in recent years. Losartan has been shown to increase urinary uric acid (UA) excretion and decrease SUA level (3). In contrast, other ARBs such as candesartan and valsartan do not have uricosuric activity (4, 5). Thus, it seems that the ability of each ARB to decrease SUA cannot be predicted until the uricosuric activities of all ARBs are examined. In the present study, we focused on another widely-used ARB, irbesartan. One report showed a tendency for irbesartan to decrease SUA level in hypertensive patients with hyperuricemia (6). Therefore we examined the effect of irbesartan on UA transporters involved in regulating SUA level. The UA transporter URAT1 is involved in lumen-to-cytosol reabsorption of UA along the proximal tubule (7). A sugar transport facilitator family member protein GLUT9 (URATv1) functions as an efflux transporter of UA from tubular cells (8) at the basolateral membrane. Mutation of URAT1 or URATv1 is associated with idiopathic renal hypouricemia (7, 9), indicating URAT1 and URATv1 play a dominant role in UA reabsorption and controlling SUA levels. We used Xenopus oocytes expressing URAT1 or URATv1 to examine the cis-inhibitory effects of irbesartan at various concentrations.Cloned human URAT1 and URATv1 were expressed in Xenopus oocytes as described previously (7,8). In brief, defolliculated oocytes were injected with 50 ng of cRNA that was transcribed in vitro using T7 RNA polymerase in the presence of cap analog. After incubation of oocytes in Barth's buffer at 18°C for 2 -3 days, uptake studies were performed in ND 96 buffer (96 mM NaCl, 2 mM KCl, 1.8 mM CaCl 2 , 1 mM MgCl 2 , 5 mM HEPES, pH 7.4) containing 20 μM [ 14 C]UA and ARBs at the indicated concentrations; after 1 h incubation, oocytes were lysed and dried at room temperature. Then the amount of the [ 14 C]UA uptake was measured in a scintillation counter and the uptake rate was determined. For determination of the kinetic parameters, the concentrations of urate were varied from 10 to 1500 μM. Kinetic parameters were obtained by using the Eadie-Hofstee equation. The experiments were performed using 8 -10 oocytes per experiment and repeated three times. All the data are given as the mean ± S.E.M. Student's t-test was used to determine significant differences. A value of P < 0.05 was considered to be significant. Concentration-Dependent Inhibitory Effect of Irbesartan on Renal Uric Acid TransportersMakiko Nakamura Medicine, Tokyo 181-8611, Japan Received March 3, 2010; Accepted July 14, 2010 Abstract. Hyperuricemia is currently recognized as a risk factor for cardiovascular diseases. It has been reported that the angiotensin II-receptor blocker (ARB) losartan decreases...

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Effects of losartan and candesartan monotherapy and losartan/hydrochlorothiazide combination therapy in patients with mild to moderate hypertension

Cited by 87 publications

References 28 publications

Comparison of the efficacy of candesartan and losartan: a meta-analysis of trials in the treatment of hypertension

Comparison of the efficacy of candesartan and losartan: a meta-analysis of trials in the treatment of hypertension

Renal Secretion of Uric Acid by Organic Anion Transporter 2 (OAT2/SLC22A7) in Human

Concentration-Dependent Inhibitory Effect of Irbesartan on Renal Uric Acid Transporters

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