title: Reproducibility and clinical value of the trough-to-peak ratio of the antihypertensive effect: evidence from the sample study. Antihypertensive efficacy of candesartan in comparison to losartan: the CLAIM study. A forced titration study of antihypertensive efficacy of candesartan cilexetil in comparison to losartan: CLAIM Study II A placebo-controlled comparison of the efficacy and tolerability of candesartan cilexetil, 8 mg, and losartan, 50 mg, as monotherapy in patients with essential hypertension, using 36-h ambulatory blood pressure monitoring. The smoothness index: A new, reproducible and clinically relevant measure of the homogeneity of the blood pressure reduction with treatment for hypertension Comparative antihypertensive effects of losartan 50 mg and losartan 50 mg titrated to 100 mg in patients with essential hypertension. Safety and tolerability of losartan potassium, an angiotensin II receptor antagonist, compared with hydrochlorothiazide, atenolol, felodipine ER, and angiotensin-converting enzyme inhibitors for the treatment of systemic hypertension. Effects of losartan and candesartan monotherapy and losartan/hydrochlorothiazide combination therapy in patients with mild to moderate hypertension. Losartan Trial Investigators. Implications of small reductions in diastolic blood pressure for primary prevention. Comparative effects of candesartan cilexetil and losartan in patients with systemic hypertension. Candesartan Versus Losartan Efficacy Comparison (CANDLE) Study Group. A comparison of the efficacy and duration of action of candesartan cilexetil and losartan as assessed by clinic and ambulatory blood pressure after a missed dose, in truly hypertensive patients: a placebo-controlled, forced titration study. Candesartan/Losartan study investigators. The antihypertensive effect and tolerability of candesartan cilexetil, a new generation angiotensin II antagonist, in comparison with losartan. Efficacy and tolerability of a combination tablet of candesartan cilexetil and hydrochlorothiazide in insufficiently controlled primary hypertension--comparison with a combination of losartan and hydrochlorothiazide.
abstract: The objectives of our study were to assess the reproducibility of the trough-to-peak ratio ( T/P ) and to see whether a high T/P is accompanied by more organ protection or vice versa . The study included 175 ( mean+/-SD age , 51+/-9 years ) subjects with mild-moderate essential hypertension who had echocardiographic evidence of left ventricular ( LV ) hypertrophy taken from the SAMPLE study ( Study on Ambulatory Monitoring of Blood Pressure and Lisinopril Evaluation ) , an open-label multicenter study . The study included a 3-week washout pretreatment period , a 12-month treatment period with lisinopril ( n=84 ) or lisinopril plus hydrochlorothiazide ( n=91 ) once daily , and a 4-week placebo follow-up period . Results of 24-hour ambulatory blood pressure monitoring and echocardiographic determination of left ventricular mass index ( LVMI ) were obtained before and after 3 and 12 months of treatment . T/Ps were computed in each patient by dividing the systolic and diastolic blood pressure changes at trough ( changes in the last 2 hours of the monitoring period ) by those at peak ( average of the 2 adjacent hours with the maximal blood pressure reduction between the 2nd and 8th hour from drug intake ) after 3 and 12 months of treatment . Average 24-hour blood pressure was similarly reduced at 3 and 12 months . Trough blood pressure changes at 3 and 12 months were closely correlated , as were the corresponding peak blood pressure changes . However , the 3- and 12-month T/Ps correlated to a lesser degree ( r<0.42 ) . Furthermore , the reduction of LVMI induced by treatment was similarly correlated with the treatment-induced reduction in 24-hour average , trough , and peak blood pressures but not with the T/Ps . This was also evident when the contribution to LV hypertrophy regression by 24-hour blood pressure changes and T/Ps was assessed in a multivariate regression analysis . In patients with a T/P > /=0.5 or < 0.5 , the regression of LVMI was similar . In conclusion , peak and trough blood pressure changes are reproducible and predict the regression of LVMI induced by treatment as well as average 24-hour blood pressure . T/Ps are less reproducible , and their value does not predict regression of organ damage by antihypertensive treatment An 8-week , multicenter , double-blind , r and omized , parallel-group , forced-titration study was conducted to evaluate the antihypertensive efficacy of c and esartan vs. losartan in 654 hypertensive patients with a diastolic blood pressure between 95 and 114 mm Hg from 72 sites throughout the U.S. Eligible patients were r and omized to c and esartan cilexetil 16 mg once daily , or losartan 50 mg once daily . Two weeks following r and omization , patients doubled the respective doses of their angiotensin receptor blockers for an additional 6 weeks . At week 8 , c and esartan cilexetil lowered trough systolic/diastolic blood pressure by a significantly greater amount than did losartan ( 13.3/10.9 mm Hg with c and esartan cilexetil vs. 9.8/8.7 mm Hg with losartan ; p less than 0.001 ) . At the same period , c and esartan cilexetil also lowered peak blood pressure by a significantly greater amount than did losartan ( 15.2 to 11.6 mm Hg with c and esartan cilexetil vs. 12.6 to 10.1 mm Hg with losartan ; p less than 0.05 ) . There were statistically significantly ( p less than 0.05 ) higher proportions of responders and controlled patients in the c and esartan cilexetil group ( 62.4 % and 56.0 % , respectively ) than in the losartan group ( 54.0 % and 46.9 % , respectively ) . Both treatment regimens were well tolerated ; 1.8 % in the c and esartan cilexetil group and 1.6 % in the losartan group withdrew because of adverse events . In conclusion , this forced-titration study confirms that c and esartan cilexetil is more effective than losartan in lowering blood pressure when both are administered once daily at maximum doses . Both drugs were well tolerated . (c)2001 by Le Jacq An 8-week , multicentre ( 72 sites in the US ) , double-blind , r and omised , parallel group , forced titration study compared the antihypertensive efficacy of c and esartan cilexetil and losartan .  A total of 611 patients with essential hypertension ( diastolic blood pressure 95 to 114 mm Hg ) were r and omised initially to c and esartan cilexetil 16 mg once daily or losartan 50 mg once daily . After 2 weeks of r and omised treatment , the doses of c and esartan cilexetil and losartan were doubled to 32 mg and 100 mg once daily and continued respectively for 6 weeks . At week 8 , c and esartan cilexetil lowered the blood pressure ( BP ) at 24 h ( trough ) , 6 h ( peak ) and 48 h post dose to a significantly greater extent ( P < 0.05 ) than losartan : c and esartan cilexetil lowered trough BP by 13.4/10.5 mm Hg , peak BP by 15.5/12.9 mm Hg and 48-h BP by 10.5/9.9 mm Hg compared to a reduction of trough BP by 10.1/9.1 mm Hg , peak BP by 12.0/9.5 mm Hg , and 48-h BP by 5.9/7.0 mm Hg by losartan . The responder and control rates were numerically higher in the c and esartan cilexetil group , but the differences did not reach statistical significance ; the responder rates were 58.8 % for the c and esartan cilexetil group and 52.1 % for the losartan group and control rates were 49.0 % for the c and esartan cilexetil group and 44.6 % for the losartan group . Overall , both treatment regimens were well tolerated . A total of 15 of the 611 ( 2.5 % ) patients withdrew from the study due to an adverse event , including nine ( 2.9 % ) in the c and esartan cilexetil group and six ( 2.0 % ) in the losartan group . In conclusion , this forced titration study confirms that c and esartan cilexetil is more effective in lowering BP than losartan when compared at once daily maximum doses This double-blind , r and omised , controlled study compared the efficacy of c and esartan cilexetil 8 mg ( n = 87 ) and losartan 50 mg ( n = 89 ) , once daily for 6 weeks , relative to placebo  ( n = 80 ) in patients with mild-to-moderate essential hypertension ( diastolic blood pressure ( DBP ) : 95 - 115 mmHg ) . Ambulatory BP measurements were done every 15 min over 36 h. At the end of the 6-week treatment , the mean change in DBP between the baseline and the 0 - 24-h period after the last dose of study medication was greater in patients receiving c and esartan cilexetil 8 mg ( -7.3 mmHg + /- 6.9 mmHg ) compared with losartan 50 mg ( -5.1 mmHg + /- 4.9 mmHg ) ( p < 0.05 ) or placebo ( 0.3 mmHg + /- 6.5 mmHg ) ( p < 0.001 ) . The mean change in systolic BP ( SBP ) during this time was greater in patients receiving c and esartan cilexetil 8 mg ( -10.8 mmHg + /- 11.3 mmHg ) , or losartan 50 mg ( -8.8 mmHg + /- 8.9 mmHg ) than placebo ( 1.2 mmHg + /- 9.9 mmHg ) ( p < 0.001 ) . C and esartan cilexetil 8 mg was associated with a greater reduction in DBP and SBP , relative to placebo , when compared with losartan 50 mg , during both daytime and night-time , and between 12 and 24 h after dosing ( p < 0.001 ) . Both active treatments were well tolerated . In patients with mild-to-moderate essential hypertension , c and esartan cilexetil 8 mg therefore had greater , more consistent antihypertensive efficacy throughout the day and the night , and long-lasting efficacy after the last dose , compared with losartan 50 mg . This greater efficacy is maintained with an excellent tolerability associated with members of the angiotensin Il type 1-receptor blocker class Objective To introduce a new method , the smoothness index , for assessing the homogeneity of 24 h blood pressure reduction by antihypertensive treatment and to compare it with the trough : peak ratio ; and to assess the ability of both indices to predict a reduction in the left ventricular mass index induced by treatment . Patients and methods In 174 patients with essential hypertension and left ventricular hypertrophy , enrolled in the Study on Ambulatory Monitoring of Pressure and Lisinopril Evaluation ( SAMPLE ) , aged 20–65 years , we measured clinic blood pressure , 24 h ambulatory blood pressure and the left ventricular mass index ( echocardiography ) before and after treatment with lisinopril at 20 mg with the addition of 12.5 or 25 mg hydrochlorothiazide as needed to reach a sufficient blood pressure reduction . The following parameters were computed for systolic and diastolic ambulatory blood pressure : ( 1 ) hourly and 24 h blood pressure averages ( ± SD ) at baseline and after 3 and 12 months of treatment ; ( 2 ) hourly blood pressure changes from baseline after 3 and 12 months of treatment , and their average ( ± SD ) over 24 h ; ( 3 ) the trough : peak ratio after 3 and 12 months of treatment ; and ( 4 ) the smoothness index after 3 and 12 months of treatment . Similar calculations were also performed at the end of a final study month during which active treatment was withdrawn and placebo was substituted ( n = 164 ) . Results The smoothness index for systolic and diastolic ambulatory blood pressure computed after 3 months of treatment was more closely related to its corresponding values after 12 months of treatment than the trough : peak ratio values computed after the same time periods were ( r = 0.68 versus 0.38 for systolic and 0.68 versus 0.42 for diastolic blood pressure , respectively ) . The smoothness index showed an inverse correlation with the 24 h st and ard deviation of systolic and diastolic blood pressure ( r = −0.25 and −0.16 , P < 0.01 and < 0.05 , respectively , for 12 months of treatment ) , while the trough : peak ratio did not ( r = −0.01 to −0.12 , NS ) . A treatment-induced reduction in the left ventricular mass index was related to the smoothness index for systolic and diastolic blood pressure ( r = −0.35 and −0.32 , P < 0.001 with 12 months of treatment ) , but not to the corresponding trough : peak ratios . Conclusions The smoothness index identifies the occurrence of a balanced 24 h blood pressure reduction with treatment and correlates with the favourable effects of treatment on left ventricular hypertrophy better than the commonly used trough : peak ratio The antihypertensive activity of losartan potassium ( losartan , Cozaar ) , an angiotensin II receptor antagonist , was evaluated in a parallel 12-week , double-blind , placebo-controlled trial in hypertensive patients with mild-to-moderate hypertension . After a 4-week , single-blind , placebo lead-in period , which included monitoring of baseline variables , 366 patients with a group mean sitting diastolic blood pressure of 101 + /- 5 ( s.d . ) mmHg were assigned r and omly to one of three treatment groups : placebo , losartan 50 mg , or losartan 50 mg with the option to titrate to 100 mg after the first 6 weeks if the target sitting diastolic blood pressure ( < 90 mmHg ) was not reached . To assess the potential blood pressure response associated with the act of titration , patients in the placebo and losartan 50 mg treatment groups with a sitting diastolic blood pressure of > or = 90 mmHg at week 6 were mock titrated ( changed to a new tablet containing the same study medication and dose ) . Sitting diastolic blood pressure was also evaluated at the end of the trial during a 1-week off-drug period to assess for rebound hypertension . At week 6 , patients in the active-drug-treatment arms experienced significantly greater peak ( 6 h post-dose ) and trough ( 24 h post-dose ) reduction in systolic and diastolic sitting blood pressures compared with placebo ( p < or = 0.01 ) . Based on trough blood pressures at week 12 , active drug ( both arms ) was more effective than placebo in lowering sitting diastolic blood pressure , with a very small additional benefit associated with increasing the dose of losartan to 100 mg in patients who did not reach the target blood pressure after the first 6 weeks on losartan 50 mg . There was no evidence of rebound hypertension during 1 week after withdrawal of losartan . The correlation between baseline plasma renin activity and reduction in peak and trough blood pressure at week 12 , although statistically significant , was generally poor in the active treatment groups . In this trial , losartan was efficacious and well tolerated , and was similar to placebo with regard to adverse-experience profile . Adverse experiences that could reasonably be related to excessive lowering of blood pressure were not common and there was no evidence of rebound hypertension This report presents data on the safety and tolerability of losartan potassium ( losartan ) , a selective antagonist of the angiotensin II AT-1 receptor , in approximately 2,900 hypertensive patients treated in double-blind clinical trials . In these studies , headache ( 14.1 % ) , upper respiratory infection ( 6.5 % ) , dizziness ( 14.1 % ) , asthenia/fatigue ( 3.8 % ) , and cough ( 3.1 % ) were the clinical adverse experiences most often reported in patients treated with losartan .  These adverse experiences were also frequently reported in patients receiving placebo : 17.2 % , 5.6 % , 2.4 % , 3.9 % , and 2.6 % , respectively . Dry cough as an adverse event was reported in 8.8 % of patients treated with angiotensin-converting enzyme inhibitors , and in 3.1 % and 2.6 % of patients treated with losartan or placebo , respectively . Only dizziness was considered " drug-related " more often in losartan-treated ( 2.4 % ) than placebo-treated ( 1.3 % ) patients . In controlled clinical trials , losartan was better tolerated than other antihypertensive agents as determined by the incidence of patients reporting any drug-related adverse experiences . Rates of discontinuation due to clinical adverse experiences in patients who received losartan monotherapy or losartan+hydrochlorothiazide were 2.3 % and 2.8 % , respectively , compared with placebo ( 3.7 % ) . No laboratory adverse experiences were unexpected or of clinical importance . First-dose hypotension rarely occurred with losartan or with losartan plus hydrochlorothiazide , and withdrawal effects such as rebound hypertension were not observed in clinical trials . There were no clinical ly important differences in the clinical or laboratory safety profiles in the demographic subgroups for age , gender , or race . In controlled clinical trials , losartan demonstrated an excellent tolerability profile OBJECTIVE The goal of this multicenter , double-blind , r and omized , parallel-group study was to compare the effects of losartan potassium ( hereafter referred to as losartan ) , c and esartan cilexitil ( hereafter referred to as c and esartan ) , and losartan/hydrochlorothiazide ( HCTZ ) in patients with mild to moderate hypertension ( sitting diastolic blood pressure [ SiDBP ] 95 - 115 mm Hg ) . METHODS A total of 1161 patients were r and omized in a 2:2:1 ratio to 12 weeks of treatment with losartan 50 mg QD , possibly titrated to 100 mg QD ( n = 461 ) ; c and esartan 8 mg QD , possibly titrated to 16 mg QD ( n = 468 ) ; or losartan 50 mg QD , possibly titrated to losartan 50 mg plus HCTZ 12.5 mg QD ( n = 232 ) . At 6 weeks , the regimens of patients not reaching a goal SiDBP < 90 mm Hg were titrated as described , whereas patients achieving this goal continued with low-dose monotherapy . The single primary end point at 12 weeks tested the equivalence of the 2 monotherapy regimens , predefined as a maximum between-treatment difference in the mean change from baseline trough SiDBP of 2.5 mm Hg . RESULTS At 12 weeks , changes in SiDBP/sitting systolic blood pressure ( SiSBP ) of -12.4/-14.4 mm Hg with losartan 50 mg/100 mg and -13.1/-15.8 mm Hg with c and esartan 8 mg/16 mg demonstrated equivalence between the 2 monotherapy regimens ( 95 % CI for difference in SiDBP , -1.6 to 0.2 ) . At 12 weeks , the losartan 50 mg/50 mg plus HCTZ 12.5 mg regimen had reduced SiDBP/SiSBP significantly more ( -14.3/-18.0 mm Hg ) than either the c and esartan 8 mg/16 mg ( SiDBP , P = 0.045 ; SiSBP , P = 0.017 ) or losartan 50 mg/100 mg regimen ( SiDBP and SiSBP , P = 0.001 ) . During the last 6 weeks , patients whose regimen had been titrated to losartan 50 mg plus HCTZ 12.5 mg ( n = 114 ) showed a greater reduction in SiDBP/SiSBP ( -14.5/ -18.7 mm Hg ) than did those whose regimen had been titrated to either losartan 100 mg ( -10.5/-12.3 mm Hg ; n = 211 ) or c and esartan 16 mg ( -11.5/-13.2 mm Hg ; n = 206 ) , representing a clinical ly meaningful > or = 2.5-mm Hg ) difference . All 3 treatments were well tolerated , with few patients experiencing drug-related adverse events ( 6.9 % losartan 50 mg/100 mg , 7.5 % c and esartan 8 mg/16 mg , 3.0 % losartan 50 mg/ 50 mg plus HCTZ 12.5 mg ) . C and esartan 8 mg/16 mg increased serum uric acid levels ( 0.13 mg/dL ; 95 % CI , 0.04 to 0.23 ) , whereas losartan 50 mg/100 mg decreased them ( -0.14 mg/dL ; 95 % CI , -0.24 to -0.04 ) , and losartan 50 mg/50 mg plus HCTZ 12.5 mg left them unchanged ( 0.06 mg/dL ; 95 % CI , -0.07 to 0.20 ) . CONCLUSIONS Losartan 50 mg/100 mg and c and esartan 8 mg/16 mg were comparable treatments in terms of blood pressure reduction . After titration , losartan 50 mg plus HCTZ 12.5 mg was superior to either c and esartan 16 mg or losartan 100 mg in reducing hypertension .  Losartan , but not c and esartan , lowered serum uric acid levels and attenuated the expected increase in uric acid levels with HCTZ 12.5 mg OBJECTIVES To estimate the impact of small reductions in the population distribution of diastolic blood pressure ( DBP ) , such as those potentially achievable by population -wide lifestyle modification , on incidence of coronary heart disease ( CHD ) and stroke . DESIGN Published data from the Framingham Heart Study , a longitudinal cohort study , and from the National Health and Nutrition Examination Survey II , a national population survey , were used to examine the impact of a population -wide strategy aim ed at reducing DBP by an average of 2 mm Hg in a population including normotensive subjects . SETTING / PARTICIPANTS White men and women aged 35 to 64 years in the United States . MAIN OUTCOME MEASURES Incidence of CHD and stroke , including transient ischemic attacks ( TIAs ) . RESULTS Data from overviews of observational studies and r and omized trials suggest that a 2-mm Hg reduction in DBP would result in a 17 % decrease in the prevalence of hypertension as well as a 6 % reduction in the risk of CHD and a 15 % reduction in risk of stroke and TIAs . From an application of these results to US white men and women aged 35 to 64 years , it is estimated that a successful population intervention alone could reduce CHD incidence more than could medical treatment for all those with a DBP of 95 mm Hg or higher . It could prevent 84 % of the number prevented by medical treatment for all those with a DBP of 90 mm Hg or higher . For stroke ( including TIAs ) , a population -wide 2-mm Hg reduction could prevent 93 % of events prevented by medical treatment for those with a DBP of 95 mm Hg or higher and 69 % of events for treatment for those with a DBP of 90 mm Hg or higher . A combination strategy of both a population reduction in DBP and targeted medical intervention is most effective and could double or triple the impact of medical treatment alone . Adding a population -based intervention to existing levels of hypertension treatment could prevent an estimated additional 67,000 CHD events ( 6 % ) and 34,000 stroke and TIA events ( 13 % ) annually among all those aged 35 to 64 years in the United States . CONCLUSIONS A small reduction of 2 mm Hg in DBP in the mean of the population distribution , in addition to medical treatment , could have a great public health impact on the number of CHD and stroke events prevented . Whether such DBP reductions can be achieved in the population through lifestyle interventions , in particular through sodium reduction , depends on the results of ongoing primary prevention trials as well as the cooperation of the food industry , government agencies , and health education professionals The antihypertensive efficacy and tolerability of the novel angiotensin-II ( A-II ) receptor blocker c and esartan cilexetil and the prototype A-II receptor blocker , losartan , were compared in an 8-week , multicenter , double-blind , r and omized , parallel-group , titration-to-effect study of 332 adults ( 42 % women , 12 % black ) with systemic hypertension ( sitting diastolic blood pressure [ DBP ] 95 - 114 mmHg , inclusive ) . In patients with a mean trough ( 24 + /- 3 hours after dose ) sitting DBP of 90 mmHg or higher after 4 weeks of once daily administration of c and esartan 16 mg or losartan 50 mg , dose was titrated up to c and esartan 32 mg or losartan 100 mg once daily . The c and esartan regimen was significantly more effective than the losartan regimen in reducing trough sitting DBP at week 8 ( 11.0 mmHg versus 8.9 mmHg ) . C and esartan also produced numerically greater reductions in secondary blood pressure parameters , including sitting systolic blood pressure ( SBP ) , trough st and ing DBP and SBP , and peak ( 6 + /- 2.5 hours after dose ) sitting and st and ing DBP and SBP . Responder rates ( sitting DBP < 90 mmHg or reduction in blood pressure of > or = 10 mmHg ) and control rates ( sitting DBP < 90 mmHg ) were higher with c and esartan ( 64 % versus 54 % and 54 % versus 43 % , respectively ) . A total of 1.9 % of the patients taking c and esartan and 6.5 % of those taking losartan discontinued prematurely because of adverse events or lack of efficacy The purpose of this double-blind , forced titration study was to compare the antihypertensive effect duration of c and esartan cilexetil , which has a longlasting binding to the human AT1-receptor , to that of losartan on ambulatory BP ( ABP ) not only during the 24-h dosing interval but also during the day of a missed dose intake . After a 4-week placebo lead-in period , 268 patients with sitting diastolic BP 95 to 110 mm Hg and mean awake ambulatory DBP > or = 85 mm Hg were r and omized to receive either 8 mg of c and esartan , 50 mg of losartan , or placebo for a 4-week period . Thereafter , the doses were doubled in all patients for an additional 4-week period . Ambulatory BP monitoring was performed for 36 h after dosing and clinic BP measured 48 h after dosing . C and esartan cilexetil ( 16 mg ) reduced ABP to a significantly greater extent than 100 mg of losartan , particularly for systolic ABP during daytime ( P<.05 ) , nighttime ( P<.05 ) , and 24-h ( P<.01 ) periods , systolic ( P<.01 ) and diastolic ( P<.05 ) ABP between 0 and 36 h , and both systolic ( P<.001 ) and diastolic ( P<0.001 ) ABP during the day of a missed dose . Clinic BP at 48 h after dosing was significantly reduced exclusively with 16 mg of c and esartan . The differences in BP reduction between 8 mg of c and esartan and 50 mg of losartan were statistically significant for systolic ABP during daytime ( P<.01 ) , nighttime ( P<.05 ) , 24-h ( P<.01 ) , 0 to 36 h ( P<.05 ) and during the day of missed dose ( P<.05 ) . Moreover , although losartan did not significantly reduce ambulatory BP in a dose-related manner , ambulatory systolic and diastolic BP reductions with 16 mg of c and esartan were significantly greater ( P<.01 and < .001 ) than those seen with 8 mg of c and esartan during every period at the ABP supporting a dose-response relationship . In conclusion , this forced titration study in ambulatory hypertensive patients demonstrates that c and esartan cilexetil provides significant dose-dependent reduction in both clinic and ambulatory BP in doses ranging from 8 to 16 mg once daily . Furthermore , c and esartan cilexetil is superior to losartan in reducing systolic ABP and in controlling both systolic and diastolic ABP on the day of a missed dose . The differences observed between both agents are most likely attributable to a tighter binding to , and a slower dissociation from , the receptor binding site with c and esartan cilexetil This multicentre study compared the antihypertensive effect and tolerability of the novel angiotensin II antagonist c and esartan cilexetil with those of losartan and placebo .  Men and women aged 20 - 80 years , with primary hypertension and sitting diastolic blood pressure ( DBP ) 95 - 114 mm Hg after a 4-week placebo run-in period , were r and omized to once daily double-blind treatment with c and esartan cilexetil 8 mg ( n=82 ) , c and esartan cilexetil 16 mg ( n=84 ) , losartan 50 mg ( n=83 ) or placebo ( n=85 ) for 8 weeks . Blood pressure was measured 6 and 24 h after dose , i.e. at peak and trough . Differences between treatments were analysed by analysis of covariance , and the primary effect variable was reduction in trough sitting DBP . Compared with placebo treatment , trough DBP was significantly reduced by a mean ( 95 % CI ) of 8.9 ( 6.0 ; 11.8 ) mm Hg with 8 mg and 10.3 ( 7.4 ; 13.2 ) mm Hg with 16 mg c and esartan cilexetil . The 8 mg dose was as effective as losartan 50 mg , while 16 mg c and esartan cilexetil was significantly more effective , with a difference between treatments of 3.7 ( 0.8 ; 6.7 ) mm Hg ( p=0.013 ) . The placebo corrected trough/peak ratio was 0.9 - 1.1 with c and esartan cilexetil and 0.7 with losartan . C and esartan cilexetil was similarly well tolerated as placebo . In conclusion , c and esartan cilexetil 8 mg or 16 mg once daily is an effective and well tolerated antihypertensive treatment .  C and esartan cilexetil 16 mg is significantly more effective than losartan 50 mg once daily This r and omized , double-blind study compared the antihypertensive effect , safety and tolerability of a c and esartan cilexetil/hydrochlorothiazide ( c and esartan/HCT ; 16/12.5 mg ) combination tablet with that of a losartan/HCT ( 50/12.5 mg ) combination tablet in patients with mild-to-moderate primary hypertension insufficiently controlled on previous monotherapy . Men and women , aged 20 - 80 years , with a sitting diastolic blood pressure ( DBP ) > or = 90 and < or = 110 mmHg and sitting systolic blood pressure ( SBP ) < or = 200 mmHg during treatment with any kind of antihypertensive monotherapy for at least 4 weeks were r and omized to c and esartan/HCT or losartan/HCT once daily for 12 weeks . All BP measurements were performed 24 h after previous dose . Mean values and st and ard deviations ( SD ) or confidence intervals ( CI ) are given . A total of 340 patients were enrolled , of whom 299 ( 144 women and 155 men , mean age 59.5 [ 10.5 ] years ) were r and omized to c and esartan/HCT ( n = 151 ) or losartan/HCT ( n = 148 ) . BPs at r and omization were 159.5 (15.4)/98.4 (5.8)mmHg and 160.5 (16.1)/98.5 (5.4)mmHg , respectively . There was a greater reduction in BP with c and esartan/HCT than with losartan/HCT : DBP -10.4 ( -11.8 ; -8.9 ) vs -7.8 ( -9.3 ; -6.3 ) mmHg , difference between treatments -2.6 ( -4.7 ; -0.5 ) mmHg ( p = 0.016 ) ; SBP -19.4 ( -22.1 ; -16.7 ) vs - 13.7 ( -16.5 ; - 10.9 ) mmHg , difference between treatments -5.7 ( -9.6 ; -1.8 ) mmHg ( p = 0.004 ) . The proportion of patients achieving a DBP < or = 90 mmHg was greater in the c and esartan/HCT group : 60.9 ( 53.1 ; 68.7 ) vs 49.3 ( 41.3 ; 57.4)% ( p = 0.044 ) . There were 12 withdrawals in the c and esartan/HCT group , of which 8 were due to adverse events , and 17 and 12 , respectively in the losartan/HCT group . We conclude that the combination of c and esartan and HCT reduces BP effectively and is well tolerated . BP was normalized in 61 % of these patients who had insufficient response to previous monotherapy . The reduction in BP and the proportion of patients with normalized BP were greater with the c and esartan/HCT 16/12.5 mg combination than with the losartan/ HCT 50/12.5 mg combination
target: Conclusions : C and esartan is superior to losartan in reducing blood pressure .
  C and esartan also causes fewer serious adverse events than losartan
background: Background : C and esartan is a relatively novel antihypertensive agent of the angiotensin receptor blocker ( ARB ) .
  Several clinical trials have compared c and esartan with losartan in the management of essential hypertension .
  However , systematic assessment of efficacy and safety between c and esartan and losartan is still lacking .