A double-blind, dose-response study of losartan in hypertensive children

Shahinfar, Shahnaz; Cano, Francisco; Soffer, Beth A.; Ahmed, Tuli; Santoro, Emanuela; Zhang, Zhongxin; Gleim, Gilbert W.; Miller, Kenneth M.; Vogt, Beth A.; Blumer, Jeffrey L.; Briazgounov, Igor

doi:10.1016/j.amjhyper.2004.09.009

Cited by 102 publications

(70 citation statements)

References 20 publications

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“…are similar to results from a previous trial in older children, in which average dosages of approximately $0.75 mg/kg per day provided a consistent antihypertensive effect (9). No linear dose response for BP was observed at 3 weeks between the low-dose versus the medium-dose or highdose regimens.…”

Section: Discussionsupporting

confidence: 78%

“…The majority of clinical AEs were reflective of the routine illnesses experienced in young children or related to the underlying cause of their hypertension, especially recurrent urinary tract infections. The safety profile is consistent with studies of losartan in older children with hypertension (9) and CKD (12). The safety profile was similar in the young cohort to that of the overall population, except that the six AESIs observed over the entire treatment period occurred in this subgroup.…”

Section: Discussionsupporting

confidence: 70%

“…Nonetheless, it is unlikely that placebo would produce a persistent antihypertensive effect throughout the 12-week base phase in these children, who predominantly had a primary renal cause of their hypertension. Considering the statistically significant antihypertensive efficacy of losartan in older children (9), coupled with the BP-lowering effects observed in children aged 1-6 years with valsartan (4), it is reasonable to conclude that despite the lack of a dose response, losartan lowers BP in children aged,6 years.…”

Section: Discussionmentioning

confidence: 99%

“…In children aged 1 month to 16 years, the pharmacokinetic parameters of losartan and its active metabolite E-3174 were similar across all age groups after oral administration, and treatment was well tolerated (8). A randomized, double-blind study showed that once-daily losartan reduced BP in a dosedependent manner and was well tolerated in hypertensive children aged 6-16 years (9). This randomized clinical study explored the dose-response relationship and the safety and tolerability of losartan in hypertensive children aged 6 months to 6 years.…”

Section: Introductionmentioning

confidence: 99%

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A Randomized, Open-Label, Dose-Response Study of Losartan in Hypertensive Children

Webb

Wells

Shahinfar

et al. 2014

Clinical Journal of the American Society of Nephrology

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Background and objectives Once-daily losartan reduces BP in a dose-dependent manner and is well tolerated in hypertensive children aged 6-16 years. This study assessed the dose-response relationship, safety, and tolerability of losartan in hypertensive children aged 6 months to 6 years.Design, setting, participants, & measurements This was a 12-week, randomized, open-label, dose-ranging study, with a 2-year extension. Patients were randomized to losartan at the following dosages: 0.1 mg/kg per day (low), 0.3 mg/kg per day (medium), or 0.7 mg/kg per day (high). Losartan was titrated to the next dose level (to a 1.4 mg/kg per day maximum dosage, not exceeding 100 mg/d, which was not one of the three original doses offered at randomization) at weeks 3, 6, and 9 for patients who did not attain their goal BP and were not taking the highest dose. Dose response was evaluated by analyzing the slope of change in sitting systolic BP (SBP; primary end point) and diastolic BP (DBP; secondary end point) after 3 weeks compared with baseline. Adverse events (AEs) were recorded throughout.Results Of the 101 patients randomized, 99 were included in the analysis (low dose, n=32; medium dose, n=34; and high dose, n=33). Mean sitting BP decreased from baseline in the low-, medium-, and high-dose groups by 7.3, 7.6, and 6.7 mmHg, respectively, for SBP and 8.2, 5.1, and 6.7 mmHg, respectively, for DBP after 3 weeks. No dose-response relationship was established by the slope analysis on SBP (P=0.75) or DBP (P=0.64). The BPlowering effect was observed throughout the 2-year extension. The incidence of AEs was low and comparable between groups.Conclusions Hypertensive children aged 6 months to 6 years treated with losartan 0.1-0.7 mg/kg per day had clinically significant decreases from baseline in SBP and DBP, yet no dose-response relationship was evident. Losartan, at a dosage up to 1.4 mg/kg per day, was well tolerated.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Randomized, Open-Label, Dose-Response Study of Losartan in Hypertensive Children

Webb

Wells

Shahinfar

et al. 2014

Clinical Journal of the American Society of Nephrology

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“…Losartan dosing was calculated on the basis of data from pediatric pharmacokinetic and dose-response studies (20). The daily starting dose was approximately 0.7 mg/kg.…”

Section: Study Medicationsmentioning

confidence: 99%

Randomized, Double-Blind, Controlled Study of Losartan in Children with Proteinuria

Webb¹,

Lam²,

Loeys³

et al. 2010

Clinical Journal of the American Society of Nephrology

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Results: Twelve weeks of treatment with losartan significantly reduced proteinuria compared with amlodipine/placebo: losartan ؊35.8% (95% confidence interval: ؊27.6% to ؊43.1%) versus amlodipine/placebo 1.4% (95% confidence interval: ؊10.3% to 14.5%), P < 0.001. Significance remained after adjustment for differences across treatment groups in change in BP (losartan produced incremental systolic and diastolic BP reductions versus amlodipine of 5.4 and 4.6 mmHg, respectively; and versus placebo of 3.8 and 4.0 mmHg, respectively). Proteinuria reduction was consistently observed in the normotensive (؊34.4% losartan; 2.6% placebo) and hypertensive (؊41.5% losartan; 2.4% amlodipine) strata, and in all prespecified subgroups, including age, gender, race, Tanner stage, weight, prior therapy with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, as well as among the most common etiologies of proteinuria. Adverse event incidence was low and comparable in all groups.Conclusions: Losartan significantly lowered proteinuria and was well tolerated after 12 weeks in children aged 1 to 17 years with proteinuria with or without hypertension, a population that has not previously been rigorously studied.

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Screening for Hypertension in Children and Adolescents

Gartlehner

Schaaf

Orr

et al. 2020

JAMA

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ImportanceChildhood hypertension can result in adverse outcomes during adulthood; identifying and treating primary and secondary childhood hypertension may reduce such risks.ObjectiveTo update the evidence on screening and treatment of hypertension in childhood and adolescence for the US Preventive Services Task Force.Data SourcesPubMed, Cochrane Library, International Pharmaceutical Abstracts, EMBASE, and trial registries through September 3, 2019; bibliographies from retrieved articles, experts, and surveillance of the literature through October 6, 2020.Study SelectionFair- or good-quality English-language studies evaluating diagnostic accuracy of blood pressure screening; cohort studies assessing the association of hypertension in childhood and adolescence with blood pressure or other intermediate outcomes in adulthood; randomized clinical trials (RCTs) or meta-analyses of pharmacological and lifestyle interventions.Data Extraction and SynthesisTwo reviewers independently assessed titles/abstracts and full-text articles, extracted data, and assessed study quality; the evidence was synthesized qualitatively.Main Outcomes and MeasuresSensitivity, specificity, and measures of association between childhood and adulthood blood pressure; reduction of childhood blood pressure; adverse effects of treatments.ResultsForty-two studies from 43 publications were included (N>12 400). No studies evaluated the benefits or harms of screening and the effect of treating childhood hypertension on outcomes in adulthood. One study reported a sensitivity of 0.82 and a specificity of 0.70 for 2 office-based blood pressure measurements. Twenty observational studies suggested a significant association between childhood hypertension and abnormal blood pressure in adulthood (odds ratios, 1.1-4.5; risk ratios, 1.45-3.60; hazard ratios, 2.8-3.2). Thirteen placebo-controlled RCTs and 1 meta-analysis assessed reductions in systolic (SBP) and diastolic blood pressure from pharmacological treatments. Pooled reductions of SBP were −4.38 mm Hg (95% CI, −7.27 to −2.16) for angiotensin-converting enzyme inhibitors and −3.07 mm Hg (95% CI, −4.99 to −1.44) for angiotensin receptor blockers. Candesartan reduced SBP by −6.56 mm Hg (P < .001; n = 240). β-Blockers, calcium channel blockers, and mineralocorticoid receptor antagonists did not achieve significant reductions over 2 to 4 weeks. SBP was significantly reduced by exercise over 8 months (−4.9 mm Hg, P ≤ .05; n = 69), by dietary approaches to stop hypertension over 3 months (−2.2 mm Hg, P < .01; n = 57), and by a combination of drug treatment and lifestyle interventions over 6 months (−7.6 mm Hg; P < .001; n = 95). Low-salt diet did not achieve reductions of blood pressure.Conclusions and RelevanceObservational studies indicate an association between hypertension in childhood and hypertension in adulthood. However, the evidence is inconclusive whether the diagnostic accuracy of blood pressure measurements is adequate for screening asymptomatic children and adolescents in primary care.

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A double-blind, dose-response study of losartan in hypertensive children

Cited by 102 publications

References 20 publications

A Randomized, Open-Label, Dose-Response Study of Losartan in Hypertensive Children

A Randomized, Open-Label, Dose-Response Study of Losartan in Hypertensive Children

Randomized, Double-Blind, Controlled Study of Losartan in Children with Proteinuria

Screening for Hypertension in Children and Adolescents

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