title: The efficacy of a clinic-based behavioral nutrition intervention emphasizing a DASH-type diet for adolescents with elevated blood pressure. Efficacy and safety of valsartan compared to enalapril in hypertensive children: a 12-week, randomized, double-blind, parallel-group study Randomized, double-blind, controlled study of losartan in children with proteinuria. Dark chocolate for children's blood pressure: randomised trial A randomized, open-label, dose-response study of losartan in hypertensive children. Antihypertensive and renoprotective efficacy and safety of losartan. A long-term study in children with renal disorders. Safety, Efficacy, and Pharmacokinetics of Telmisartan in Pediatric Patients With Hypertension A randomized prospective crossover trial of amlodipine in pediatric hypertension Propranolol versus chlorthalidone--a prospective therapeutic trial in children with chronic hypertension. Randomised trial of effects of calcium antagonists compared with diuretics and β-blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study Carotid artery intimal-medial thickness and left ventricular hypertrophy in children with elevated blood pressure. A crossover comparison of extended release felodipine with prolonged action nifedipine in hypertension. Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients with Hypertension-2 study Effect of Microalbuminuria Lowering on Regression of Left Ventricular Hypertrophy in Children and Adolescents with Essential Hypertension Efficacy and Safety of the Angiotensin Receptor Blocker Valsartan in Children With Hypertension Aged 1 to 5 Years The efficacy and safety of the novel aldosterone antagonist eplerenone in children with hypertension: a randomized, double-blind, dose-response study. Efficacy, safety, and pharmacokinetics of candesartan cilexetil in hypertensive children aged 6 to 17 years. The efficacy and safety of valsartan in obese and non-obese pediatric hypertensive patients. Clinical trial of extended-release felodipine in pediatric essential hypertension Antiproteinuric effects of enalapril and losartan: a pilot study [Evaluation of the efficacy and tolerance of three antihypertensive agents used as single-drug therapy, nifedipine, prazosin and acebutolol in severe, idiopathic hypertension in adolescents]. A randomized, placebo-controlled trial of amlodipine in children with hypertension. Combined low-dose medication and primary intervention over a 30-month period for sustained high blood pressure in childhood. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). The use of clonidine monotherapy in adolescent hypertension. Better renoprotective effect of angiotensin II antagonist compared to dihydropyridine calcium channel blocker in childhood. Effect of allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension: a randomized trial. Efficacy and safety of extended release metoprolol succinate in hypertensive children 6 to 16 years of age: a clinical trial experience. Efficacy, safety and pharmacokinetics of candesartan cilexetil in hypertensive children from 1 to less than 6 years of age Antihypertensive effect and elimination kinetics of captopril in hypertensive children with renal disease. Effectiveness and safety of valsartan in children aged 6 to 16 years with hypertension. A double-blind, dose-response study of losartan in hypertensive children. A double-blind, placebo-controlled, dose-response study of the effectiveness and safety of enalapril for children with hypertension. A double-blind, placebo-controlled, dose-response study of the effectiveness and safety of lisinopril for children with hypertension. Is the Extrapolated Adult Dose of Fosinopril Safe and Effective in Treating Hypertensive Children? Strict blood-pressure control and progression of renal failure in children.
abstract: OBJECTIVE To examine the efficacy of a 3-month clinic-based behavioral nutrition intervention emphasizing a diet high in fruits , vegetables , and low fat dairy ( DASH intervention ) versus routine outpatient hospital-based nutrition care ( RC ) on diet and blood pressure ( BP ) in adolescents with elevated BP . STUDY DESIGN Fifty-seven adolescents with a clinical diagnosis of prehypertension or hypertension ( systolic BP or diastolic BP , 90(th ) to 99(th ) percentile ) were r and omly assigned to  DASH or  RC  .  SBP , DBP , 3-day diet recall , weight , and height were assessed at pretreatment , post-treatment , and 3 months later ( follow-up ) . RESULTS In completer analysis , DASH versus RC had a greater decrease in SBP z scores from baseline to post-treatment ( P < 0.01 ) and a trend for a greater decrease in SBP z scores from baseline through follow-up ( P = .07 ) . DBP z scores changed similarly for conditions from baseline through follow-up . Relative to RC , DASH had a greater increase in intake of fruits ( P < .001 ) , potassium and magnesium ( P < .01 ) , and a greater decrease in total fat ( P < .05 ) from baseline to post-treatment . From baseline through follow-up , DASH versus RC had a greater increase in low fat dairy ( P < .001 ) . CONCLUSIONS The DASH intervention proved more effective than RC in improving SBP and diet quality in adolescents with elevated BP Objective This study compares efficacy and safety of valsartan with enalapril in hypertensive children aged 6–17 years . Method This was a 12-week , r and omized , double-blind , parallel-group , active-controlled study . After a single-blind placebo run-in period ( 4–28 days ) , patients with mean sitting systolic blood pressure ( BP ) ( MSSBP ) at least 95th percentile for age , gender , and height were r and omized to receive half the assigned dose for first week , and force-titrated to full dose for 11 weeks ( ≥18 to < 35 kg – valsartan : 80 mg , enalapril : 10 mg ; ≥35 to < 80 kg – valsartan : 160 mg , enalapril : 20 mg ; ≥80 to ⩽160 kg – valsartan : 320 mg , enalapril : 40 mg ) . The primary efficacy variable was changed from baseline in MSSBP to show noninferiority of valsartan to enalapril . Other efficacy variables were changed from baseline in MSDBP , SBP control rate , and 24-h ambulatory BP parameters . Results Of 300 r and omized patients , 281 ( 94 % ) completed the study . At week 12 , MSSBP reductions were similar for valsartan and enalapril ( primary endpoint of noninferiority , P < 0.0001 ) . Least square mean BP reductions from baseline of −15.4/−9.4 mmHg were observed for valsartan compared with −14.1/−8.5 mmHg for enalapril . A similar proportion of patients achieved SBP control  ( valsartan : 67 % ; enalapril : 70 % ) . In the subset of patients who underwent ambulatory BP assessment s , valsartan provided greater reductions  than enalapril  in mean 24-h SBP  ( valsartan : −9.8 mmHg , enalapril : −7.2 mmHg : P = 0.03 ) . The overall incidence of AEs was similar ( valsartan 60 % , enalapril 58 % ) with headache , cough , and nasopharyngitis reported most frequently . Conclusions Valsartan and enalapril provided comparable BP reductions and effective BP control and were well tolerated in hypertensive children aged 6–17 years BACKGROUND AND OBJECTIVES No large , r and omized , double-blind trials in children with proteinuria treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have previously been reported . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS This 12-week , double-blind , multinational study investigated the effects of losartan 0.7 to 1.4 mg/kg per day compared with placebo ( normotensive stratum ) or amlodipine 0.1 to 0.2 mg/kg per day up to 5 mg/d ( hypertensive stratum ) on proteinuria ( morning-void urinary protein-creatinine ratio , baseline > or = 0.3 g/g ) in 306 children up to 17 years of age . 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 < or = 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 Background Higher adult blood pressure , even without hypertension , predicts cardiovascular outcomes , and is predicted by childhood blood pressure . Regular dark chocolate intake lowers blood pressure in adults , but effects in children are unknown . Aim To examine the feasibility of school-based provision of dark chocolate and its short-term efficacy in reducing mean group blood pressure . Methods 194 children ( aged 10–12 years ) were r and omised by class to  intervention ( 7 g dark chocolate daily for 7 weeks , n=124 ) or control ( n=70 ) groups ; 98 % and 93 % provided baseline and follow-up measurements , respectively . Results Intervention and control students had similar systolic ( mean difference 1.7 mm Hg , 95 % CI −0.6 to 4.1 ) and diastolic ( −1.2 mm Hg , 95 % CI −3.6 to 1.3 ) blood pressure , anthropometry and well-being at outcome . Conclusion Results show that providing dark chocolate is feasible and acceptable in the school setting . For a definitive trial , the authors recommend a larger sample , endovascular function measures , and consideration of higher antioxidant ‘ dose ’ by virtue of duration and /or content 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 , r and omized , open-label , dose-ranging study , with a 2-year extension . Patients were r and omized 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 r and omization ) 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 r and omized , 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 BP-lowering 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 clinical ly 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 BACKGROUND Hypertension is a major risk factor for progressive renal failure . We assessed the long term efficacy and safety of losartan in lowering blood pressure ( BP ) and in preserving renal function in hypertensive children with chronic renal disorders . METHODS Losartan was used in 45 consecutive hypertensive children with chronic renal parenchymal disorders and mean glomerular filtration rate ( GFR ) 99.4 mL/min/1.73 m(2 ) . Of the children , 21 had hypertension alone ( H ) and 24 had both hypertension and proteinuria ( H+P ) . Assessment was done at baseline and at preselected time points : visit I , < 0.25 years ; visit II , > /=0.25 and < 0.5 year;visit III , 0.5 to 1.0 year ; and visit IV > 1 year . Both BP control and GFR were the principal outcome measures , and proteinuria was a secondary outcome measure . RESULTS The mean age was 12.85 years and follow-up was 2.42 years ( visit IV ) . Compared with baseline the systolic , diastolic , and mean arterial BP ( MABP ) fell by 9 to 12 mm Hg ( all P < .01 ) in visit I. Diastolic BP and MABP remained significantly lower in all visits ( P < .05 to .001 ) , whereas systolic BP was not statistically lower in visit II . In visit IV the proportion of normotensive children increased significantly compared with baseline ( P < .03 for systolic BP , P < .0004 for diastolic BP ) . In the H+P subgroup , optimal reduction in proteinuria ranging from 66 % to 71 % occurred in visits II to IV ( all P < .01 ) . Mean GFR declined at a rate of 9.3 mL/min/1.73 m(2 ) /year before starting losartan , and 1.4 mL/min/1.73 m(2 ) /year subsequently ( P = NS ) . On long term follow-up , GFR fell by 15.9 mL/min/1.73 m(2 ) in the H subgroup and by 5.5 mL/min/1.73 m(2 ) in the H+P subgroup ( P = NS ) . There was no correlation between BP measures and GFR or between the magnitude of BP lowering and proteinuria . Adverse effects ( one serious ) led to discontinuation of losartan in five children ( 11 % ) . CONCLUSIONS Losartan therapy was associated with prolonged and sustained antihypertensive and renoprotective benefits in children with a variety of chronic renal parenchymal disorders . Such benefit may be more pronounced in children with combined hypertension and proteinuria . The agent was well tolerated in the majority of the children Objective . To assess the safety , pharmacokinetics ( PKs ) , and blood pressure (BP)-lowering efficacy of telmisartan in pediatric ( 6 to < 18 years ) patients with hypertension . Study design . Patients with diagnosed hypertension were r and omized to 4 weeks of treatment with placebo , or with 1 of 2 nominal telmisartan dose levels ( 1 mg/kg/d or 2 mg/kg/d ) . The primary end point was change in seated systolic BP ( SBP ) from baseline to study end . Results . A total of 77 patients were r and omized and received at least 1 dose of study medication ( placebo , n = 16 ; low-dose telmisartan , n = 30 ; high-dose telmisartan , n = 31 ) . Adjusted mean changes ( st and ard errors ) in SBP from baseline to study end were −6 ( 2.4 ) , −14 ( 1.7 ) , and −9.7 ( 1.7 ) mm Hg , respectively , in the placebo , high-dose telmisartan , and low-dose telmisartan groups . Conclusions . Telmisartan may be an appropriate therapy for treatment of pediatric hypertension , although more extensive studies are required in patients younger than age 12 Abstract Amlodipine has potential advantages in children since it can be dissolved into a liquid preparation and has a long elimination half-life , allowing for once-daily administration . The objective of this study was to compare the efficacy and compliance of amlodipine with that of st and ard long-acting calcium channel blockers ( felodipine or nifedipine ) in hypertensive children . A r and omized , prospect i ve , crossover study of 11 hypertensive children ( 9–17 years of age , 10 renal transplant patients ) was performed with electronic monitoring of compliance . Each treatment arm was 30 days . No significant differences were observed in mean systolic ( SBP ) and diastolic blood pressures ( DBP ) between amlodipine and the other calcium channel blockers . Using 24-h blood pressure monitoring there were no significant differences over each drug treatment period in both mean day-time and night-time SBP and DBP . Patient compliance was similar in both the amlodipine and the nifedipine/felodipine treatment periods . These data suggest that amlodipine is as effective in pediatric nephrology patients as nifedipine and felodipine . Amlodipine may be optimally suited for treatment of young children because at present it is the only calcium channel blocker which can be administered once daily as a liquid preparation A prospect i ve study of propranolol versus chlorthalidone has been performed in eleven patients with renal hypertension and one with essential hypertension . The patients were treated for 4 to 6 weeks consecutively . Both drugs proved to be effective in lowering elevated systolic and diastolic blood pressure . The mean blood pressure decreased by 22.3 mm Hg in propranolol-treated patients and by 15 mm Hg in chlorthalidone-treated patients . One patient developed an asthmatic attack provoked by propranolol . Four of twelve patients receiving chlorthalidone developed hypokalemia and required potassium supply . Both drugs can be recommended as drugs of first choice in children with hypertension BACKGROUND Calcium antagonists are a first-line treatment for hypertension . The effectiveness of diltiazem , a non-dihydropyridine calcium antagonist , in reducing cardiovascular morbidity or mortality is unclear . We compared the effects of diltiazem with that of diuretics , beta-blockers , or both on cardiovascular morbidity and mortality  in hypertensive patients . METHODS In a prospect i ve , r and omised , open , blinded endpoint study , we enrolled 10,881 patients , aged 50 - 74 years , at health centres in Norway and Sweden , who had diastolic blood pressure of 100 mm Hg or more . We r and omly assigned patients diltiazem , or diuretics , beta-blockers , or both . The combined primary endpoint was fatal and non-fatal stroke , myocardial infa rct ion , and other cardiovascular death . Analysis was done by intention to treat . FINDINGS Systolic and diastolic blood pressure were lowered effectively in the diltiazem and diuretic and beta-blocker groups ( reduction 20.3/18.7 vs 23.3/18.7 mm Hg ; difference in systolic reduction p<0.001 ) . A primary endpoint occurred in 403 patients in the diltiazem group and in 400 in the diuretic and beta-blocker group ( 16.6 vs 16.2 events per 1000 patient-years ; relative risk 1.00 [ 95 % CI 0.87 - 1.15 ] , p=0.97 ) . Fatal and non-fatal stroke occurred in 159 patients in the diltiazem group and in 196 in the diuretic and beta-blocker group ( 6.4 vs 7.9 events per 1000 patient-years ; 0.80 [ 0.65 - 0.99 ] , p=0.04 ) and fatal and non-fatal myocardial infa rct ion in 183 and 157 patients ( 7.4 vs 6.3 events per 1000 patient-years ; 1.16 [ 0.94 - 1.44 ] , p=0.17 ) . INTERPRETATION Diltiazem was as effective as treatment based on diuretics , beta-blockers , or both in preventing the combined primary endpoint of all stroke , myocardial infa rct ion , and other cardiovascular death OBJECTIVES To determine the association between carotid artery intimal-medial thickness ( cIMT ) and left ventricular mass index ( LVMI ) in children with elevated blood pressure . METHODS Study subjects ( n = 32 ; mean age : 13.9 + /- 2.7 years ) were untreated new referrals to a pediatric hypertension clinic with confirmed elevated blood pressure . LVM was calculated from 2-dimensionally guided m-mode echocardiographic measurements of the left ventricle . LVMI was calculated as LVM (g)/height (m)2.7 , and left ventricular hypertrophy ( LVH ) was defined as LVMI > 95th percentile . Carotid artery duplex ultrasound was performed by protocol by experienced vascular sonographers who were unaware of the echocardiography results . The thickest IMT complex of the far wall of the distal common carotid artery was measured in longitudinal B-mode section using a high-resolution linear array of 8 MHz . RESULTS The prevalence of LVH and increased cIMT was 41 % and 28 % , respectively . Subjects with increased cIMT had higher LVMI ( 46.8 g/m2.7 vs 31.4 g/m2.7 ) than those with normal cIMT . The LVH prevalence was 89 % ( 8 of 9 ) among subjects with increased cIMT as compared with 22 % ( 5 of 23 ) in subjects with normal cIMT . cIMT was positively correlated with body mass index ( r = 0.43 ) , interventricular septal thickness ( r = 0.58 ) , posterior wall thickness ( r = 0.54 ) , and LVMI ( r = 0.54 ) . cIMT and LVMI were positively associated after accounting for age , gender , and body mass index . CONCLUSIONS These findings raise the possibility that carotid duplex ultrasound , by indicating the presence of early arterial wall changes , may be useful for predicting other cardiovascular sequelae in hypertensive children In a crossover design , control of blood pressure by extended release felodipine was compared with control by prolonged action nifedipine in 21 children with renal hypertension .  Compliance with once daily felodipine was higher than with nifedipine , at 95.6 ( SEM 2.7)% v 78.9 (6.0)% ( p = 0.02 ) . Mean diastolic blood pressure was lower during the day with felodipine than with nifedipine , at 77.6 ( 2.4 ) v 84.4 ( 2.8 ) mm Hg ( p = 0.05 ) . Similarly , blood pressure load ( the percentage of the day during which the child had blood pressure exceeding the upper limits of normal for age ) was lower for felodipine than for nifedipine : 43.5 (5.5)% v 61.3 (6.3)% . There was an opposite trend during the night , though this did not reach statistical significance . These data suggest that once a day felodipine is effective in children with hypertension . This may be because of improved compliance BACKGROUND The efficacy of new antihypertensive drugs has been question ed . We compared the effects of conventional and newer antihypertensive drugs on cardiovascular mortality and morbidity in elderly patients . METHODS We did a prospect i ve , r and omised trial in 6614 patients aged 70 - 84 years with hypertension ( blood pressure > or = 180 mm Hg systolic , > or = 105 mm Hg diastolic , or both ) . Patients were r and omly assigned conventional antihypertensive drugs ( atenolol 50 mg , metoprolol 100 mg , pindolol 5 mg , or hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily ) or newer drugs ( enalapril 10 mg or lisinopril 10 mg , or felodipine 2.5 mg or isradipine 2 - 5 mg daily ) . We assessed fatal stroke , fatal myocardial infa rct ion , and other fatal cardiovascular disease . Analysis was by intention to treat . FINDINGS Blood pressure was decreased similarly in all treatment groups . The primary combined endpoint of fatal stroke , fatal myocardial infa rct ion , and other fatal cardiovascular disease occurred in 221 of 2213 patients in the conventional drugs group ( 19.8 events per 1000 patient-years ) and in 438 of 4401 in the newer drugs group ( 19.8 per 1000 ; relative risk 0.99 [ 95 % CI 0.84 - 1.16 ] , p=0.89 ) . The combined endpoint of fatal and non-fatal stroke , fatal and non-fatal myocardial infa rct ion , and other cardiovascular mortality occurred in 460 patients taking conventional drugs and in 887 taking newer drugs ( 0.96 [ 0.86 - 1.08 ] , p=0.49 ) . INTERPRETATION Old and new antihypertensive drugs were similar in prevention of cardiovascular mortality or major events . Decrease in blood pressure was of major importance for the prevention of cardiovascular events Microalbuminuria ( MA ) is associated with increased cardiovascular risk in adult hypertensive patients , but no study has specifically examined the effects of MA lowering on regression of left ventricular hypertrophy ( LVH ) among pediatric patients with hypertension . Fifty-five patients with essential hypertension , 11–19 years old , were prospect ively studied . All patients received concomitant therapy of hydrochlorothiazide and angiotensin-converting enzyme inhibitor . Five patients also required angiotensin receptor blocker to achieve the blood pressure goal . Baseline and 12-month follow-up measures of left ventricular mass index ( LVMI ) , determined by echocardiography and urine microalbumin/creatinine ratio ( MA/Cr ) , were collected . MA was defined as MA/Cr > 30 μg/mg . LVH was defined as LVMI > 38.6 g/m2.7 . The primary end points were reductions in MA and LVMI of 25 % or more . Weight ( r = 0.83 ) , body surface area ( r = 0.85 ) , body mass index ( BMI ) ( r = 0.86 ) , systolic blood pressure ( SBP ) ( r = 0.57 ) , diastolic blood pressure ( DBF ) ( r = 0.49 ) , mean arterial pressure ( r = 0.53 ) and MA ( r= 0.87 ) were all univariate correlates of LVMI . In a multiple regression analysis , MA , BMI and SBP were significant correlates of LVMI . MA alone explained 76 % of the variance of LVMI , whereas BMI and SBP explained only 1.6 and 0.4 % of the variance , respectively . MA was the most significant correlate of follow-up LVMI after BMI and SBP were included in the overall multiple regression models . Thus , MA is a strong predictor of LVH in hypertensive children and adolescents . MA lowering halts the progression of LVH or induces its regression The efficacy and safety of valsartan were studied in 90 children ( mean age : 3.2 years ; 60 % male ; 30 % black ) with systolic blood pressure ( SBP ) ≥95th percentile . Nineteen percent received valsartan  in addition to previous antihypertensive therapy . Subjects were r and omly assigned to low- , medium- , or high-dose valsartan for 2 weeks ( phase 1 ) and then reassigned r and omly to placebo or to remain on the same valsartan dose for 2 additional weeks ( phase 2 ) . After this , subjects were enrolled into a 52-week , open-label phase during which valsartan was dosed to achieve SBP < 95th percentile . Statistically significant reductions in SBP and diastolic blood pressure of ≈8.5 mm Hg and 5.7 mm Hg , respectively , were observed at the end of phase 1 in all of the valsartan dose groups . SBP and diastolic blood pressure were also significantly lower during phase 2 in valsartan recipients compared with placebo recipients . SBP < 95th percentile was achieved in 77.3 % of subjects during the open-label phase . Adverse events were minor and occurred at similar frequencies in each of the 3 dose groups in phase 1 and at equal frequencies in the valsartan and placebo arms in phase 2 . Serious adverse events and drug-related adverse events occurred infrequently during both the double-blind ( 2.2 % and 5.6 % , respectively ) and open-label ( 14.8 % and 6.8 % , respectively ) portions of the  study . Valsartan treatment had no demonstrable negative effects on growth and development . In this study , the first trial of an antihypertensive agent conducted in children < 6 years of  age  , valsartan  effectively lowered SBP and diastolic blood pressure compared with placebo OBJECTIVES To determine the efficacy and safety of eplerenone therapy in children with hypertension . STUDY DESIGN A total of 304 children age 4 - 16 years with systolic blood pressure ( SBP ) > or=95th percentile were r and omized to low-dose ( 25 mg daily ) , middle-dose ( 25 mg twice daily ) , or high-dose ( 50 mg twice daily ) eplerenone ( phase A ) , then rer and omized to active therapy or placebo for another 4 weeks ( phase B ) . The primary endpoint was change in SBP in phase B. RESULTS During phase A , mean SBP decreased from baseline by 8 mm Hg , and diastolic blood pressure ( DBP ) decreased by up to 3.8 mm Hg ; no dose-response relationship was demonstrated . Mean differences in SBP from placebo during phase B were -2.61 for the low-dose group , + 2.32 for the middle-dose group , and -2.76 mm Hg for the high-dose group ; only the reduction in the high-dose group was statistically significant ( P = .048 ) . No significant effects on DBP of eplerenone therapy relative to placebo were detected . Eplerenone was well tolerated , with a rate of adverse events comparable to that of placebo . CONCLUSIONS Short-term treatment with eplerenone reduced blood pressure in children with hypertension and had acceptable tolerability This 4-week r and omized , double blind , placebo-controlled study ( N=240 ) , 1-year open label trial ( N=233 ) , and single-dose pharmacokinetic study ( N=22 ) evaluated c and esartan cilexetil ( 3 doses ) in hypertensive children aged 6 to 17 years . Seventy-one percent were 12 years of age or older , 71 % were male , and 47 % were black .  Systolic (SBP)/diastolic ( DBP ) blood pressure declined 8.6/4.8 - 11.2/8.0 mm Hg with c and esartan and 3.7/1.8 mm Hg with placebo ( P<.01 compared to placebo for SBP and for the mid and high doses for DBP ; placebo-corrected 4.9/3.0 - 7.5/6.2 mm Hg ) . The slopes for dose were not , however , different from zero ( P>.05 ) . The response rate ( SBP and DBP < 95th percentile ) after 1 year was 53 % . The pharmacokinetic profiles in 6- to 12- and 12- to 17-year-olds were similar and were comparable to adults . Eight c and esartan patients discontinued treatment because of an adverse event .  C and esartan is an effective , well-tolerated antihypertensive agent for children aged 6 to 17 years and has a pharmacokinetic profile that is similar to that in adults This post hoc analysis assessed the efficacy and tolerability of valsartan for the treatment of hypertension in obese vs non-obese children and adolescents . After a 1-week antihypertensive washout period , 142 obese and 119 non-obese hypertensive children and adolescents aged 6 to 16 years were r and omized to 2 weeks of once-daily treatment with valsartan 10 to 20 mg , 40 to 80 mg , or 80 to 160 mg , followed by re-r and omization to either valsartan or placebo for an additional 2 weeks . Patients could continue to receive valsartan during an optional 52-week , open-label extension . Valsartan result ed in statistically significant ( P<.05 ) and clinical ly relevant reductions in mean sitting blood pressure ( BP ) , ranging from approximately 7/4 mm Hg ( valsartan 10 - 20 mg ) to 13/9 mm Hg ( valsartan 80 - 160 mg ) in both obese and non-obese patients . BP control was achieved in 44 % of obese and 56 % of non-obese patients . Following re-r and omization , non-obese patients experienced an increase in BP during placebo treatment , albeit levels remained below baseline , whereas BP reductions were maintained in valsartan recipients ( P<.05 ) . The most frequent adverse events during the open-label phase were headache and fever .  Valsartan provides similar antihypertensive efficacy in obese and non-obese hypertensive children and adolescents , with good tolerability in both patient population Abstract .Essential hypertension in pediatric patients may require pharmacological treatment . There is a need for efficacious , safe , and well-tolerated antihypertensive agents with a once-a-day dosing regimen in children and adolescents . The aim of the trial was to evaluate the dose-response and tolerability of the dihydropyridine calcium channel blocker , felodipine extended-release tablets ( felodipine ER ) , given once daily to pediatric patients with essential hypertension . A r and omized double-blind , parallel-group , multi-center clinical study comparing felodipine ER ( 2.5 , 5 , or 10 mg once daily ) and placebo was performed on pediatric patients with a baseline systolic ( SBP ) or diastolic blood pressure ( DBP ) above the 95th percentile for age , sex , and height . Of 133 r and omized patients , 128 ( 96.2 % ) completed the 3 weeks of double-blind treatment . The study population included 50 % children 6–12 years of age or Tanner stage ≤3 , 39 % black , and 40 % female patients . All doses of felodipine ER and placebo  decreased both SBP and DBP . The 5-mg dose of felodipine ER result ed in a significant decline in trough sitting , st and ing , and supine DBP ( placebo-adjusted , −4.6 , −5.06 , and −5.05 mmHg , respectively , P<0.05 ) compared with placebo . However , there was no significant decline in SBP . The 2.5- and 10-mg doses showed no significant differences compared with placebo in lowering BP . The effect of felodipine ER was comparable in patient subgroups by age , race , and gender . The drug was well tolerated . The study failed to show a dose response of felodipine ER in pediatric patients with essential hypertension . This finding might be explained in part by the limitations of study design . The spectrum of side effects in pediatric patients was comparable with that in adults , except for a lower incidence of peripheral edema . Further studies are needed to clarify the role of felodipine ER in the management of children and adolescents with essential hypertension In this r and omized double-blind crossover trial we compared the antiproteinuric effects of enalapril and losartan in six children with proteinuria and underlying renal injury . The primary endpoint was reduction in proteinuria during therapy . The study had two 8-week on-drug arms , with a 4-week washout period between . Baseline proteinuria was similar , enalapril 87 mg/m2 per hour and losartan 77 mg/m2 per hour . The mean reduction in proteinuria with enalapril was 48 % ( 37%–57 % ) with a st and ard error of the mean of 3 % ; with losartan it was 31 % ( 14%–52 % ) with a st and ard error of the mean of 7 % . Although there was a significant reduction in proteinuria with the use of both drugs , the difference in reduction of proteinuria , 48 % versus 31 % , was not considered clinical ly significant . Potassium remained below 4.5 mmol/l in all patients . No patient 's creatinine rose more than the st and ard deviation of our assay . Blood pressure ( BP ) control was acceptable in four of the six patients ; two patients had persistently elevated or increased BP on each drug . Side effects were minimal ; none requiring withdrawal , one requiring dose reduction . Studies have shown that angiotensin converting enzyme inhibitors can reduce proteinuria in children with renal disorders . No studies to date have examined the reduction of proteinuria achieved by angiotensin receptor blockers . Our study , although small , suggests that angiotensin receptor blockers may reduce proteinuria as effectively , and as safely , as angiotensin converting enzyme inhibitors The antihypertensive efficacy of single-drug therapy with nifedipine ( N ) , prazosin ( P ) , or acebutolol ( A ) and the influence of these agents on coronary risk factors including hypoglycemia , hyperuricemia , and hyperlipidemia , were studied in adolescents with hypertension . Ninety patients ( 73 girls and 17 boys ) aged 14 to 18 years with idiopathic hypertension ( IH ) were r and omized into three groups . Each group received N , P , or A as single-drug therapy for six months . Systolic and diastolic blood pressures fell in all three groups , from 152/90 mmHg to 127/70 mmHg * with N , from 150/90 mmHg to 121/70 mmHg * with P , and from 148/92 mmHg to 122/74 mmHg * mmHg with A. In 17 % of cases , N failed to reduce blood pressures below the 90th centiles . Heart rate was not influenced by N or P but decreased from 84 to 75 bpm with A. Although none of the drugs modified serum uric acid levels , fractional uric acid secretion rose with P and A ( from 4.1 % to 6 % with P ; and from 4.4 % to 6 % with A ) . The lipid profile remained unchanged under N and P , whereas a decrease in serum LDL-cholesterol from 99.6 to 88.8 % mg * was seen with A. Fasting serum glucose levels increased from 86.4 to 92.7 mg % * in the group given A. N , P , and A are suitable for single-drug therapy of IH in adolescents ; the most appropriate drug should be selected on the basis of medical history OBJECTIVES Evaluation of the efficacy and safety of amlodipine in hypertensive children . STUDY DESIGN A r and omized , double blinded , placebo-controlled , parallel-group , dose-ranging study was conducted at 49 centers in North and South America . The primary end point was the effect of amlodipine on systolic blood pressure ( BP ) ; secondary end points included the effect of amlodipine on diastolic BP , the effect of amlodipine as a function of dose and body size , and evaluation of safety . RESULTS We enrolled 268 hypertensive children ( mean age , 12.1 + /- 3.3 years ) ; 84 ( 31.3 % ) had primary hypertension , and 177 ( 66 % ) were boys .  Amlodipine produced significantly greater reductions in systolic BP than placebo ; these were -6.9 mm Hg for 2.5 mg daily ( P=.045 vs placebo ) and -8.7 mm Hg for 5 mg daily ( P=.005 vs placebo ) . The underlying cause of hypertension had no effect on the response to amlodipine . There was a significant dose-response effect of amlodipine on both systolic and diastolic BP beginning at doses > or = 0.06 mg/kg per day . Systolic BP < or = 95(th ) percentile was achieved in 34.6 % of subjects with systolic hypertension . Amlodipine was well tolerated , with just 6 children withdrawn from treatment because of drug-related adverse events . CONCLUSIONS Amlodipine effectively lowers systolic BP in a dose-dependent manner in hypertensive children who require drug treatment Studies of the pathobiologic consequences of high blood pressure in childhood , as well as those following blood pressure levels into young adulthood , indicate that early intervention in the natural history of essential hypertension is warranted . In an exploratory study of the concept , 95 children out of 1604 ( aged 8 to 18 years ) , who persistently scored higher than the 90th percentile for blood pressure over a 4-month period , considering the race , sex , and height of the children , were studied . Five series of replicate measurements with 30 total observations were obtained . Children with evidence of secondary hypertension were excluded . The study children were r and omly divided into treatment ( n = 48 ) and high-comparison ( n = 47 ) groups . Treatment consisted of low-dose combined drug therapy ( propranolol and chlorthalidone ) with an educational program directed towards hypertension and dietary and exercise modification . Monthly follow-up was continued for 30 months . Significant systolic ( -3.59 mm Hg ) and diastolic ( -1.73 mm Hg ) changes were noted up to 30 months ( p less than 0.05 ) with minimal side effects . Furthermore , analyses suggested that the blood pressure change , at least in the first month , was mostly attributable to drug therapy . Moreover , the mechanism of blood pressure change appeared to be race-specific , with whites having pulse rate changes and blacks having significant weight changes , which were associated with blood pressure change . This trial shows further research is warranted to determine optimum approaches for early treatment of essential hypertension to prevent future hypertensive disease CONTEXT Antihypertensive therapy is well established to reduce hypertension-related morbidity and mortality , but the optimal first-step therapy is unknown . OBJECTIVE To determine whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of coronary heart disease ( CHD ) or other cardiovascular disease ( CVD ) events vs treatment with a diuretic . DESIGN The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) , a r and omized , double-blind , active-controlled clinical trial conducted from February 1994 through March 2002 . SETTING AND PARTICIPANTS A total of 33 357 participants aged 55 years or older with hypertension and at least 1 other CHD risk factor from 623 North American centers . INTERVENTIONS Participants were r and omly assigned to receive chlorthalidone , 12.5 to 25 mg/d ( n = 15 255 ) ; amlodipine , 2.5 to 10 mg/d ( n = 9048 ) ; or lisinopril , 10 to 40 mg/d ( n = 9054 ) for planned follow-up of approximately 4 to 8 years . MAIN OUTCOME MEASURES The primary outcome was combined fatal CHD or nonfatal myocardial infa rct ion , analyzed by intent-to-treat . Secondary outcomes were all-cause mortality , stroke , combined CHD ( primary outcome , coronary revascularization , or angina with hospitalization ) , and combined CVD ( combined CHD , stroke , treated angina without hospitalization , heart failure [ HF ] , and peripheral arterial disease ) . RESULTS Mean follow-up was 4.9 years . The primary outcome occurred in 2956 participants , with no difference between treatments . Compared with chlorthalidone ( 6-year rate , 11.5 % ) , the relative risks ( RRs ) were 0.98 ( 95 % CI , 0.90 - 1.07 ) for amlodipine ( 6-year rate , 11.3 % ) and 0.99 ( 95 % CI , 0.91 - 1.08 ) for lisinopril ( 6-year rate , 11.4 % ) . Likewise , all-cause mortality did not differ between groups . Five-year systolic blood pressures were significantly higher in the amlodipine ( 0.8 mm Hg , P = .03 ) and lisinopril ( 2 mm Hg , P<.001 ) groups compared with chlorthalidone , and 5-year diastolic blood pressure was significantly lower with amlodipine ( 0.8 mm Hg , P<.001 ) . For amlodipine vs chlorthalidone , secondary outcomes were similar except for a higher 6-year rate of HF with amlodipine ( 10.2 % vs 7.7 % ; RR , 1.38 ; 95 % CI , 1.25 - 1.52 ) . For lisinopril vs chlorthalidone , lisinopril had higher 6-year rates of combined CVD ( 33.3 % vs 30.9 % ; RR , 1.10 ; 95 % CI , 1.05 - 1.16 ) ; stroke ( 6.3 % vs 5.6 % ; RR , 1.15 ; 95 % CI , 1.02 - 1.30 ) ; and HF ( 8.7 % vs 7.7 % ; RR , 1.19 ; 95 % CI , 1.07 - 1.31 ) . CONCLUSION Thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive . They should be preferred for first-step antihypertensive therapy The effect of a central ly acting agent ( clonidine ) vs a diuretic as a single agent was studied in a group of hypertensive adolescents . Following placebo therapy , adolescents with blood pressure greater than 95th percentile were r and omized to clonidine 0.1 mg or hydrochlorothiazide 25 mg , each given twice daily . Following 12 weeks ' active treatment , those who had not achieved blood pressure goals proceeded to clonidine 0.2 mg or hydrochlorothiazide 50 mg twice daily . Blood pressure and clinical assessment was performed at two-week intervals . Cardiovascular response to mental stress and pre-post stress catecholamines were obtained prior to active therapy and during therapy . Clonidine therapy significantly lowered systolic and diastolic pressure and heart rate ( p less than .01 ) . Hydrochlorothiazide significantly lowered systolic pressure only . Mental stress testing result ed in a lower diastolic pressure and heart rate response ( p less than .01 ) , with lower norepinephrine in the clonidine-treated group . The diuretic group had higher plasma norepinephrine and no significant reduction in stress response . Hypertensive juveniles may be more sensitive to central control of blood pressure and more resistant to diuretics BACKGROUND The dihydropyridine calcium channel blocker amlodipine and the angiotensin II antagonist irbesartan effectively reduce blood pressure in hypertensive children . METHODS Eligible for the open-label , r and omized study were nephropathic children between 6.0 and 18 years of age with plasma creatinine < 177 micromol/L , overt proteinuria , untreated arterial hypertension ( systolic , 5 to 30 mm Hg ; and diastolic , 1 to 15 mm Hg;>95th centile ) and stable immunosuppressive treatment . The initial dose of amlodipine was 5 mg ( body weight , 20 to 40 kg ) and 10 mg ( body weight,>40 kg ) , respectively , that of irbesartan , which was 75 mg ( body weight , 20 to 40 kg ) and 150 mg ( body weight,>40 kg ) , respectively . The dosage was doubled if necessary . RESULTS A total of 26 children aged 6.1 to 17 years were allocated to receive either amlodipine ( N = 13 ) or irbesartan ( N = 13 ) for 16 weeks . Severe edema and headache occurred in two patients on amlodipine who withdrew from the study . No adverse experiences were noted in patients given irbesartan . Amlodipine [ by 12 ( 10 to 14)/7 ( 5 to 10 ) mm Hg ; median and interquartile range , respectively ] and irbesartan [ by 13 ( 9 to 16)/9 ( 7 to 11 ) mm Hg , respectively ] reduced blood pressure ( P < 0.01 ) in a similar fashion . Heart rate , plasma sodium , and creatinine did not change . Irbesartan slightly increased plasma potassium [ by 0.1 ( 0.0 to 0.2 ) mmol/L ; P < 0.05 ] . Plasma albumin and the urinary albumin/creatinine ratio were similar before and with amlodipine . On the contrary , irbesartan increased plasma albumin [ by 4 ( 3 to 5 ) g/L ; P < 0.03 ] and decreased the urinary albumin/creatinine ratio [ by 242 ( 68 to 312 ) mg/mmol ; P < 0.03 ] . CONCLUSION The study demonstrates that in children the effect of angiotensin II antagonists on proteinuria is better than that of dihydropyridine calcium channel blockers CONTEXT Hyperuricemia is a predictor for the development of hypertension and is commonly present in new-onset essential hypertension . Experimentally increasing uric acid levels using a uricase inhibitor causes systemic hypertension in animal models . OBJECTIVE To determine whether lowering uric acid lowers blood pressure ( BP ) in hyperuricemic adolescents with newly diagnosed hypertension . DESIGN , SETTING , AND PATIENTS R and omized , double-blind , placebo-controlled , crossover trial ( September 2004-March 2007 ) involving 30 adolescents ( aged 11 - 17 years ) who had newly diagnosed , never-treated stage 1 essential hypertension and serum uric acid levels > or = 6 mg/dL. Participants were treated at the Pediatric Hypertension Clinic at Texas Children 's Hospital in Houston . Patients were excluded if they had stage 2 hypertension or known renal , cardiovascular , gastrointestinal tract , hepatic , or endocrine disease . INTERVENTION Allopurinol , 200 mg twice daily for 4 weeks , and placebo , twice daily for 4 weeks , with a 2-week washout period between treatments . The order of the treatments was r and omized . MAIN OUTCOME MEASURES Change in casual and ambulatory blood pressure . RESULTS For casual BP , the mean change in systolic BP for allopurinol was -6.9 mm Hg ( 95 % confidence interval [ CI ] , -4.5 to -9.3 mm Hg ) vs -2.0 mm Hg ( 95 % CI , 0.3 to -4.3 mm Hg ; P = .009 ) for placebo , and the mean change in diastolic BP for allopurinol was -5.1 mm Hg ( 95 % CI , -2.5 to -7.8 mm Hg ) vs -2.4 ( 95 % CI , 0.2 to -4.1 ; P = .05 ) for placebo . Mean change in mean 24-hour ambulatory systolic BP for allopurinol was -6.3 mm Hg ( 95 % CI , -3.8 to -8.9 mm Hg ) vs 0.8 mm Hg ( 95 % CI , 3.4 to -2.9 mm Hg ; P = .001 ) for placebo and mean 24-hour ambulatory diastolic BP for allopurinol was -4.6 mm Hg ( -2.4 to -6.8 mm Hg ) vs -0.3 mm Hg ( 95 % CI , 2.3 to -2.1 mm Hg ; P = .004 ) for placebo . Twenty of the 30 participants achieved normal BP by casual and ambulatory criteria while taking allopurinol vs 1 participant while taking placebo ( P < .001 ) . CONCLUSIONS In this short-term , crossover study of adolescents with newly diagnosed hypertension , treatment with allopurinol result ed in reduction of BP . The results represent a new potential therapeutic approach , although not a fully developed therapeutic strategy due to potential adverse effects . These preliminary findings require confirmation in larger clinical trials . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00288184 OBJECTIVE To evaluate the efficacy , tolerability , and blood pressure ( BP ) lowering effect of extended release metoprolol succinate ( ER metoprolol ) in children 6 to 16 years of age with established hypertension . STUDY DESIGN Patients were r and omized to one of four treatment arms : placebo or ER metoprolol ( 0.2 mg/kg , 1.0 mg/kg , or 2.0 mg/kg ) . Data were analyzed on 140 intent-to-treat patients . RESULTS Mean age ( + /-SD ) was 12.5 + /- 2.8 years and mean baseline BP was 132/78 + /- 9/9 mmHg . Following 4 weeks of treatment , mean changes in sitting BP were : placebo = -1.9/-2.1 mmHg ; ER metoprolol 0.2 mg/kg = -5.2/-3.1 mmHg ; 1.0 mg/kg = -7.7/-4.9 mmHg ; 2.0 mg/kg = -6.3/-7.5 mmHg . Compared with placebo , ER metoprolol significantly reduced systolic blood pressure ( SBP ) at the 1.0 and 2.0 mg/kg dose ( P = .027 and P = .049 , respectively ) , reduced diastolic blood pressure ( DBP ) at the 2.0 mg/kg dose ( P = .017 ) , and showed a statistically significant dose response relationship for the placebo-corrected change in DBP from baseline . There were no serious adverse events or adverse events requiring study drug discontinuation among patients receiving active therapy . CONCLUSION These data indicate that ER metoprolol is an effective and well-tolerated treatment for hypertension in children Background Few antihypertensive drugs are available in appropriate formulations for infants . Method We investigated c and esartan cilexetil liquid suspension in a 4-week , r and omized double-blind dose-ranging study followed by a 1-year open-label treatment phase ( NCT00244621 ) . The drug was administered at 0.05 , 0.2 or 0.4 mg/kg per day in 93 hypertensive children aged 1–5 years , of whom 74 had underlying renal disorders . Results A single-dose pharmacokinetic profile was obtained in 10 patients . At 4 weeks , SBP declined dose dependently by 6 , 9 and 12 mmHg in the three dose groups ( P = 0.01 ) , and DBP by 5 , 8 and 11 mmHg ( P = 0.03 ) . During the 1-year follow-up , responder rates ( both SBP and DBP < 95th percentile ) ranged from 48.2 to 54.1 % . C and esartan lowered the blood pressure regardless of age , sex , BMI or cause of hypertension . The pharmacokinetic profile was independent of age , sex and weight , and was similar to that in older children and adults . In participants with proteinuric renal disease ( urinary albumin/creatinine ratio > 30 mg/g ) , a 57 % median decline in albumin/creatinine ratio was observed at 4 weeks , which was dose related ( P = 0.007 ) and persisted with long-term administration . There were no notable electrocardiographic or laboratory abnormalities . A mild decline in estimated glomerular filtration rate observed at 4 weeks was not progressive with long-term dosing . C and esartan was generally well tolerated ; two patients withdrew for adverse events ( fatigue and worsening glomerulopathy ) . One patient died , probably from acute-on-chronic renal failure . Conclusion C and esartan cilexetil dose-dependently decreases blood pressure and albuminuria  in hypertensive infants and is generally well tolerated The efficacy and safety of captopril were studied in 10 patients with secondary hypertension ( renal parenchymal disease , four patients ; renal artery stenosis , two ; and renal transplant rejection , four ) .  Captopril was administered according to a dose titration protocol that r and omized the initial three doses ( 0.5 , 1.0 , and 2.0 mg/kg ) of drug to one of six possible sequences . All patients received diuretics prior to and during captopril therapy . A significant reduction in mean blood pressure was observed in all 10 patients during the initial dose titration . No correlation was observed between captopril dose and magnitude of the blood pressure reduction . The onset of antihypertensive action began approximately 15 minutes after each orally administered dose and reached the nadir approximately 1 1/2 hours later . Blood pressure returned to predrug levels between 6 and 10 hours after the dose . A significant reduction in systolic and diastolic blood pressure was noted in all subjects after 1 week of captopril treatment and was maintained during the course of continuous therapy in nine of 10 patients . Captopril combined with hydrochlorothiazide produced a satisfactory therapeutic response in five patients ; in four others , additional antihypertensive drugs were required . No significant adverse effects were observed . Plasma renin activity determined prior to initiation of captopril was not predictive of blood pressure response to the drug . The clearance of captopril from patients with kidney failure ranged from 14.1 to 18.8 ml/min/kg in five subjects with creatine clearance between 10 and 21 ml/min/1.73 m2 The effectiveness and safety of valsartan have not been assessed in hypertensive children . Therefore , hypertensive patients aged 6 to 16 years ( n=261 ) were r and omized to receive weight-stratified low- ( 10/20 mg ) , medium- ( 40/80 mg ) , or high-dose ( 80/160 mg ) valsartan for 2 weeks . After 2 weeks , patients were r and omized to a 2-week placebo-controlled withdrawal phase . Dose-dependent reductions in sitting systolic blood pressure ( SSBP ) and sitting diastolic blood pressure ( SDBP ) were observed after 2 weeks ( low dose , -7.9/-4.6 mm Hg ; medium dose , -9.6/-5.8 mm Hg ; high dose , -11.5/-7.4 mm Hg [ P<.0001 for all groups ] ) . During the withdrawal phase , SSBP and SDBP were both lower in the pooled valsartan group than in the pooled placebo group ( SSBP , -2.7 mm Hg [ P=.0368 ] ; SDBP , -3.0 mm Hg [ P=.0047 ] ) . Similar efficacy was observed in all subgroups . Valsartan was well tolerated and headache was the most commonly observed adverse event during both the double-blind and 52-week open-label phases BACKGROUND The aim of this study was to determine the dose-response relationship for losartan , 2.5 to 100 mg , and to assess the safety and tolerability of losartan in hypertensive children 6 to 16 years of age . METHODS This was a multicenter , r and omized , double-blind , dose-response study . In Period 1 , a total of 175 patients were stratified by weight ( < 50 kg and > /=50 kg ) and r and omized to one of three dose groups by stratum ( low , 2.5/5.0 mg ; middle , 25/50 mg ; or high , 50/100 mg ) for 3 weeks . The ratio of the three dose levels for both weight strata was 1:10:20 . In Period 2 , patients in each dose group were r and omized to continue the same treatment or placebo washout for 2 additional weeks . RESULTS In Period 1 , sitting trough diastolic blood pressure ( DBP ) decreased in a dose-dependent manner ( P < .0001 ) . At week 3 , changes in DBP from baseline in the low- , middle- , and high-dose groups were -6.0 mm Hg , -11.7 mm Hg , and -12.2 mm Hg , respectively . In Period 2 , DBP increased significantly in patients who switched from middle- and high-dose losartan to placebo ( mean increase 6.0 mm Hg , P = .003 ) relative to DBP in patients who remained on active treatment ; however , these levels remained stable in those patients who switched from low-dose losartan to placebo ( mean increase 1.1 mm Hg , P = .628 ) . CONCLUSIONS In hypertensive children 6 to 16 years of age , losartan given once daily reduced blood pressure in a dose-dependent fashion . A once-daily starting dose of losartan , 0.75 mg/kg ( maximum 50 mg ) effectively lowered DBP within 3 weeks . Losartan up to a dosage of 1.44 mg/kg ( maximum 100 mg ) once daily is generally well tolerated Despite widespread use to treat childhood hypertension , enalapril has never been studied systematic ally to determine effectiveness , dose response , and safety in a pediatric population . This study was conducted prospect ively in 110 hypertensive children ages 6 to 16 years in two sequential phases . The primary outcome variable for both phases of the study was trough ( 24-h postdose ) sitting diastolic blood pressure . The primary objective of the first phase of the study was to determine whether enalapril lowered blood pressure in children in a dose-dependent manner . During a 2-week , double-blind , r and omized , dose-response period , patients were stratified by weight ( < 50 kg or > or = 50 kg ) , then assigned to one of three dosing groups : low(0.625 or 1.25 mg ) , middle ( 2.5 or 5 mg ) , or high dose ( 20 or 40 mg ) . Reduction in blood pressure was examined as a function of dose ratio ( 1:4:32 ) and on a weight-adjusted basis . On completion of the dose-response phase of the study , patients entered a 2-week , double-blind , r and omized withdrawal to either enalapril or placebo .  Antihypertensive effectiveness , defined as the difference in sitting diastolic blood pressure between the placebo and enalapril groups , was determined . Adverse events were carefully recorded throughout the study . The dose-response relationship for enalapril had a negative slope and was linear over the chosen dosing range , suggesting that larger doses of enalapril were associated with a greater reduction in blood pressure . R and omized withdrawal to active drug orplacebo confirmed the antihypertensive effectiveness of enalapril in the middle- and high-dose groups . The antihypertensive effect of enalapril was maintained across age , gender , race , and Tanner stage . Enalapril appears to be an effective and generally well-tolerated antihypertensive agent in children ages 6 to 16 years . An initial dose of 2.5 mg in children weighing < 50 kg and 5 mg in children weighing > 50 kg ( mean = 0.08 mg/kg ) administered once daily effectively lowered blood pressure within 2 weeks in most patients . Blood pressure was reduced in a dose-dependent fashion , with larger doses result ing in a greater reduction BACKGROUND Despite widespread use in hypertensive children , the safety and effectiveness of lisinopril had not been previously tested in a controlled study . METHODS This study explored the dose-response relationship and safety of lisinopril in 115 hypertensive children , aged 6 to 16 years . Patients were r and omized in a double-blind fashion for 2 weeks to one of three doses by body weight at baseline : < 50 kg : low ( 0.625 mg ) , middle ( 2.5 mg ) , high ( 20 mg ) , and > or = 50 kg : low ( 1.25 mg ) , middle ( 5 mg ) , high ( 40 mg ) . The dose-response for lisinopril was evaluated by analyzing the change in slope in sitting diastolic and systolic blood pressure ( BP ) by dose after 2 weeks of therapy compared to baseline . Patients then entered a double-blind withdrawal , where patients were either switched to placebo or continued their current lisinopril treatment for up to 2 weeks . Patients completed period II when their BP returned to baseline . Antihypertensive effectiveness , between placebo and lisinopril was determined for all doses . Adverse events were carefully monitored . RESULTS There was a dose-response relationship between the lowest and each of the higher doses of lisinopril . Blood pressure in the placebo group increased after withdrawal of lisinopril . The dose-response relationship was consistent across all subgroups ( ie , age , Tanner stage , ethnicity , gender ) . CONCLUSIONS Lisinopril , once daily , is an effective and well-tolerated antihypertensive in children aged 6 to 16 years . An initial dose of 0.07 mg/kg , administered once daily , effectively lowered BP within 2 weeks . Blood pressure was reduced in a dose-dependent fashion We evaluated the efficacy , safety , and dose – response relationship of fosinopril in children aged 6 to 16 years with hypertension or high-normal blood pressure with an associated medical condition requiring treatment . The study was a prospect i ve , double-blind , placebo-controlled trial conducted in 78 clinical sites in the United States , Russia , and Israel . There were 4 phases : a screening phase of 10 days maximum , a 4-week dose – response phase , a placebo withdrawal phase of 2 weeks maximum , and a 52-week open-label safety phase . The primary objective of the dose – response phase was to determine whether low ( 0.1 mg/kg ) , medium ( 0.3 mg/kg ) , or high ( 0.6 mg/kg ) doses of fosinopril based on established adult dosing affect trough seated systolic blood pressure . During the dose – response phase , all 3 doses were equally effective in lowering systolic blood pressure . During the placebo withdrawal phase , there was an adjusted mean systolic blood pressure increase of 5.2 mm Hg for the placebo group and 1.5 mm Hg for the fosinopril group , a net withdrawal effect of 3.7 mm Hg ( P=0.013 ) . Fosinopril was well tolerated ; serious adverse events occurred infrequently and were generally not attributed to fosinopril . Because children appear to be more sensitive to lower doses of fosinopril than adults , starting doses for children should be ≤0.1 mg/kg BACKGROUND Although inhibition of the renin-angiotensin system delays the progression of renal failure in adults with chronic kidney disease , the blood-pressure target for optimal renal protection is controversial . We assessed the long-term renoprotective effect of intensified blood-pressure control among children who were receiving a fixed high dose of an angiotensin-converting-enzyme ( ACE ) inhibitor .  METHODS After a 6-month run-in period , 385 children , 3 to 18 years of age , with chronic kidney disease ( glomerular filtration rate of 15 to 80 ml per minute per 1.73 m(2 ) of body-surface area ) received ramipril at a dose of 6 mg per square meter of body-surface area per day . Patients were r and omly assigned to intensified blood-pressure control ( with a target 24-hour mean arterial pressure below the 50th percentile ) or conventional blood-pressure control ( mean arterial pressure in the 50th to 95th percentile ) , achieved by the addition of antihypertensive therapy that does not target the renin-angiotensin system ; patients were followed for 5 years . The primary end point was the time to a decline of 50 % in the glomerular filtration rate or progression to end-stage renal disease . Secondary end points included changes in blood pressure , glomerular filtration rate , and urinary protein excretion . RESULTS A total of 29.9 % of the patients in the group that received intensified blood-pressure control reached the primary end point , as assessed by means of a Kaplan-Meier analysis , as compared with 41.7 % in the group that received conventional blood-pressure control ( hazard ratio , 0.65 ; confidence interval , 0.44 to 0.94 ; P=0.02 ) . The two groups did not differ significantly with respect to the type or incidence of adverse events or the cumulative rates of withdrawal from the study ( 28.0 % vs. 26.5 % ) . Proteinuria gradually rebounded during ongoing ACE inhibition after an initial 50 % decrease , despite persistently good blood-pressure control . Achievement of blood-pressure targets and a decrease in proteinuria were significant independent predictors of delayed progression of renal disease . CONCLUSIONS Intensified blood-pressure control , with target 24-hour blood-pressure levels in the low range of normal , confers a substantial benefit with respect to renal function among children with chronic kidney disease . Reappearance of proteinuria after initial successful pharmacologic blood-pressure control is common among children who are receiving long-term ACE inhibition . ( Clinical Trials.gov number , NCT00221845 .
target: The adverse events associated with the antihypertensive agents were mostly minor and included headaches , dizziness and upper respiratory infections .
  The most data are available for c and esartan , for which there is low- quality evidence of a modest lowering effect on blood pressure .
  We did not find evidence of a consistent dose response relationship for escalating doses of angiotensin receptor blockers , calcium channel blockers or angiotensin-converting enzyme inhibitors .
  All agents appear safe , at least in the short term
background: BACKGROUND Hypertension is a major risk factor for stroke , coronary artery disease and kidney damage in adults .
  There is a paucity of data on the long-term sequelae of persistent hypertension in children , but it is known that children with hypertension have evidence of end organ damage and are at risk of hypertension into adulthood .
  The prevalence of hypertension in children is rising , most likely due to a concurrent rise in obesity rates .
  In children with hypertension , non-pharmacological measures are often recommended as first-line therapy , but a significant proportion of children will eventually require pharmacological treatment to reduce blood pressure , especially those with evidence of end organ damage at presentation or during follow-up .
  A systematic review of the effects of antihypertensive agents in children has not previously been conducted .
  OBJECTIVES To determine the dose-related effects of different classes of antihypertensive medications , as monotherapy compared to placebo ; as combination therapy compared to placebo or a single medication ; or in comparisons of various doses within the same class , on systolic or diastolic blood pressure ( or both ) in children with hypertension .