Antihypertensive efficacy of candesartan in comparison to losartan: the CLAIM study. Comparative effects of candesartan cilexetil and losartan in patients with systemic hypertension. Candesartan Versus Losartan Efficacy Comparison (CANDLE) Study Group. A new approach to assessing antihypertensive therapy: effect of treatment on pulse pressure. Candesartan cilexetil in Hypertension Ambulatory Measurement of Blood Pressure (CHAMP) Study Investigators. Effectiveness of Add-On Low-Dose Diuretics in Combination Therapy for Hypertension: Losartan/Hydrochlorothiazide vs. Candesartan/Amlodipine The antihypertensive effect and tolerability of candesartan cilexetil, a new generation angiotensin II antagonist, in comparison with losartan. Comparison of angiotensin II receptor blockers: impact of missed doses of candesartan cilexetil and losartan in systemic hypertension. Effects of Candesartan on Cardiovascular Outcomes in Japanese Hypertensive Patients Candesartan and hydrochlorothiazide in isolated systolic hypertension Evaluation of candesartan cilexetil in black patients with systemic hypertension: the ABC Trial. Candesartan in the prevention of relapsing atrial fibrillation. Comparison of Candesartan versus Metoprolol for treatment of systemic hypertension after repaired aortic coarctation. Candesartan- and Atenolol-Based Treatments Induce Different Patterns of Carotid Artery and Left Ventricular Remodeling in Hypertension 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. Cost-Effectiveness Analysis of Hypertension Treatment: Controlled Release Nifedipine and Candesartan Low-Dose Combination Therapy in Patients with Essential Hypertension —The Nifedipine and Candesartan Combination (NICE-Combi) Study— Antihypertensive efficacy of candesartan-lisinopril in combination vs. up-titration of lisinopril: the AMAZE trials. Comparison of the AT1-receptor blocker, candesartan cilexetil, and the ACE inhibitor, lisinopril, in fixed combination with low dose hydrochlorothiazide in hypertensive patients 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.
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 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 BACKGROUND A high pulse pressure is an independent cardiovascular risk factor . It has therefore been suggested that antihypertensive treatment should not only reduce systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) , but should also decrease pulse pressure ( SBP minus DBP ) . In a previous analysis , we showed that two angiotensin II type 1 (AT1)-receptor blockers , c and esartan cilexetil and losartan , differed in their effects in reducing SBP and DBP . OBJECTIVE To compare the efficacy of c and esartan cilexetil and losartan according to a new approach -- their effect on pulse pressure-- and to describe the dose-effect relationship for SBP , DBP and pulse pressure , in a placebo-controlled study . METHODS After a 4-week placebo run-in period , 268 patients with mild-to-moderate hypertension were allocated r and omly to groups to receive placebo , c and esartan cilexetil ( 8 mg once daily ) or losartan ( 50 mg once daily ) , for 4 weeks . The doses were then doubled to 16 and 100 mg , respectively , for the final 4 weeks of the study . Clinic blood pressure was measured 24 and 48 h after each dose of drug or placebo , and ambulatory blood pressure was monitored from 0 to 36 h after each dose , at baseline and after 4 and 8 weeks of treatment . RESULTS C and esartan cilexetil decreased ambulatory pulse pressure significantly ( P < 0.05 ) more than did losartan during both daytime and night-time , and over the 24 h period after the previous dose . A different dose-effect relationship on SBP , DBP and pulse pressure was observed . The duration of action of c and esartan cilexetil was greater than that of losartan . After a missed dose ( i.e. approximately 24 - 36 h after the previous dose ) , mean ambulatory pulse pressure values after 4 and 8 weeks of treatment with c and esartan cilexetil were lower than those observed with losartan ( P < 0.005 ) . Clinic pulse pressure measurements were consistent with these ambulatory measurements . CONCLUSIONS AT1 -receptor blockers differ both in their ability to reduce pulse pressure and in their duration of effect , c and esartan cilexetil having a greater and more sustained effect than losartan . Different dose-effect relationships on SBP , DBP or pulse pressure were observed . Further prospect i ve studies based on pulse pressure are needed to analyse the mechanism of reduction of pulse pressure and to determine its prognostic value In guidelines , a combination therapy of two or more antihypertensives is recommended for treatment of hypertension where monotherapy is ineffective . Although diuretics or calcium channel blockers are commonly used as add-ons to angiotensin receptor blocker ( ARB ) , the most effective and safe combination has not been established . In this r and omized 4-month study , the efficacy and safety were compared between an ARB/diuretics ( losartan/hydrochlorothiazide [ HCTZ ] ) combination and the most prescribed combination , ARB/calcium channel blocker ( c and esartan/amlodipine ) in hypertensive patients for whom 8 mg/day of c and esartan proved ineffective . After 36 patients were recruited and allocated into two groups , changes in blood pressure ( BP ) and laboratory values were analyzed in 31 patients : 16 patients received losartan ( 50 mg/day)/HCTZ ( 12.5 mg/day ) ( L/H group ) , and 15 patients received c and esartan ( 8 mg/day)/amlodipine ( 5 mg/day ) ( C/A group ) after 5 patients were withdrawn . After 4 months , L/H significantly ( p<0.001 ) reduced mean systolic BP (SBP)/diastolic BP ( DBP ) from baseline 160/89±13/11 mmHg to 140/80±9/8 mmHg , and C/A reduced BP from 161/90±10/11 mmHg to 141/79±10/7 mmHg . The efficacy in reducing BP was similar between the two combination therapies . L/H significantly reduced serum potassium , but within the normal range , and did not increase serum uric acid or serum triglyceride . With L/H , the percentage of patients who attained the BP goal in SBP was higher in elderly patients than in younger patients . As L/H is more cost-effective than c and esartan/amlodipine and has fewer adverse effects on uric acid and other metabolic parameters than diuretic monotherapy , it is concluded to be useful for the management of hypertension 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 Blood pressure remains poorly controlled in the hypertensive population due in large part to low or unsatisfactory patient compliance . Clinical studies that incorporate an intentionally missed dose have been design ed to evaluate the impact of poor patient compliance on the effectiveness of antihypertensive medications . In these studies , ambulatory blood pressure monitoring is continued throughout the dosing interval and beyond in order to determine when systolic and diastolic blood pressure increase into the hypertensive range . In an 8-week , r and omized , double-blind , placebo-controlled trial in patients with mild-to-moderate hypertension , the antihypertensive effects of c and esartan cilexetil 16 mg were maintained after a missed dose , whereas systolic and diastolic blood pressure increased toward baseline levels after a missed dose of losartan 100 mg . C and esartan cilexetil provided a significantly greater reduction in sitting systolic ( p = 0.004 ) and diastolic blood pressure ( p = 0.008 ) than losartan when measured 48 hours after the last dose . Moreover , the homogeneity of antihypertensive effects was greater after c and esartan cilexetil than losartan based on calculation of the smoothness index from ambulatory systolic and diastolic measurements during the first 24-hour period after dosing and during the 12-hour period after the missed dose . These results demonstrate that missing or delaying a dose of c and esartan cilexetil has less impact on antihypertensive efficacy than missing or delaying a dose of losartan In recent years , angiotensin receptor blockers ( ARBs ) have begun to represent a markedly larger percentage of the antihypertensive agents used in Japan . However , it remains uncertain whether ARBs are effective for protecting against hypertension-related organ damage in the general Japanese population . In the present report , we describe the results of a single blind , r and omized , prospect i ve study conducted in 1999–2002 and employing a total of 2,048 essential hypertensive subjects ( sitting blood pressure 140–180/90–110 mmHg ) aged 35–79 years . Subjects were r and omly assigned to receive the ARB c and esartan , 2 to 12 mg daily , or conventional antihypertensive drugs other than angiotensin converting enzyme inhibitors or ARBs . We used Cox regression analysis to compare the two regimens . The primary outcome was assessed by hospitalization due to stroke , myocardial infa rct ion , and congestive heart failure . Blood pressure was reduced from 162.1/91.1 to 140.1/78.9 mmHg in the c and esartan group and from 165.9/95.9 to 138.4/81.1 mmHg in the conventional therapy group . The main outcomes were as follows : there was a 39 % reduction in hospitalization for stroke ( 5.8 vs. 9.4 cases : relative risk [ RR ] : 0.61 ; 95 % confidence interval [ CI ] : 0.41–0.84 ; p<0.05 ) and a 57 % reduction in hospitalization for myocardial infa rct ion ( RR : 0.44 ; CI : 0.21–0.84 ; p<0.05 ) with the c and esartan-based treatment compared with the conventional treatment . In spite of a significant difference in the total incidence of both stroke and myocardial infa rct ion , there was no significant reduction in the incidence of congestive heart failure ( 15 % reduction : 4.3 vs. 5.0 ; RR : 0.85 ; CI : 0.57–1.26 ) . Further analysis in stratifying the subjects with or without a past history of cardiovascular diseases including stroke and myocardial infa rct ion revealed that c and esartan reduced the incidence of stroke ( 61 % reduction ; RR : 0.39 ; CI : 0.15–0.43 ; p<0.01 ) and congestive heart failure ( 49 % reduction ; RR : 0.51 ; CI : 0.23–0.92 ; p<0.05 ) but not myocardial infa rct ion ( RR : 0.74 ; CI : 0.36–1.48 ; p=0.1 ) in hypertensive patients with a past history . However , conventional treatment was superior to c and esartan-based treatment in reducing the incidence of stroke in the patients without a past history of cardiovascular diseases ( 66 % reduction ; RR : 0.34 ; CI : 0.16–0.69 ; p<0.05 ) . This is the first demonstration that an ARB-based antihypertensive treatment was superior to the conventional treatment for reducing the risk of stroke and myocardial infa rct ion in Japanese hypertensive patients , especially in the patients with a past history of cardiovascular diseases Aim : We investigated the efficacy and safety of daily c and esartan 8/16 mg and hydrochlorothiazide 12.5 mg as monotherapy and in combination in older patients with systolic hypertension . Methods : The study used a double-blind r and omized placebo-controlled crossover design . Treatment phases were of 6 weeks duration . For inclusion , patients were aged 55 - 84 years with sitting systolic blood pressure ( SBP ) 160 - 210 mmHg and diastolic blood pressure ( DBP ) < 95 mmHg . Nineteen patients ( 11 male , eight female , median age 68 years ) completed the study . Major findings : Compared with the placebo phase , clinic and ambulatory SBP was significantly reduced with both dose-adjusted c and esartan and fixed-dose hydrochlorothiazide as monotherapy , the effect of c and esartan being greater than that of hydrochlorothiazide . In combination , the effects of the two drugs were additive . Both drugs were well tolerated either as monotherapy or in combination . Conclusion : Both c and esartan and a low dose of hydrochlorothiazide are effective and well-tolerated antihypertensive agents in isolated systolic hypertension with additive effects in combination . C and esartan was more effective than hydrochlorothiazide , although it is possible that dose adjustment only of c and esartan could have enhanced its relative effectiveness To assess the efficacy and tolerability of the angiotensin-II receptor blocker c and esartan cilexetil , the Association of Black Cardiologists ( ABC ) coordinated a 12-week , multicenter , double-blind , placebo-controlled clinical trial in 304 black adults with a sitting diastolic blood pressure ( DBP ) of 91 to 105 mmHg , inclusive . The goal of the ABC Trial was to address previous reports suggesting that drugs that block the renin-angiotensin-aldosterone system may not be effective in controlling BP in hypertensive black individuals . Patients were r and omized to receive c and esartan cilexetil 16 mg ( n = 156 ) or placebo ( n = 148 ) , once daily after a 4- to 5-week single-blind , placebo run-in period . C and esartan cilexetil and placebo doses were doubled if the trough ( 24 + /- 3 hours after dose ) sitting DBP was 90 mmHg or higher after 4 weeks . If the DBP was 90 mmHg or higher at week 8 , hydrochlorothiazide 12.5 mg was added to both placebo or c and esartan cilexetil 32 mg . C and esartan cilexetil was significantly more effective than placebo in reducing trough sitting systolic BP ( SBP ) and DBP at week 8 ( 6.4/5.1 mmHg versus 1.3/2.7 mmHg ) and at week 12 ( 9.3/7.5 mmHg versus 5.7/5.2 mmHg ) . Hydrochlorothiazide was added in 27 and 50 % of patients in the c and esartan cilexetil and placebo groups , respectively . Control and responder rates were consistently higher in the c and esartan cilexetil treatment group at weeks 8 and 12 . Discontinuation and adverse event rates were similar in the two groups . C and esartan cilexetil once daily was effective in reducing BP in a substantial proportion of an exclusively black hypertensive population . The combination of c and esartan cilexetil plus hydrochlorothiazide demonstrated additional efficacy while maintaining an excellent tolerability profile BACKGROUND Several studies have indicated that treatment with angiotensin converting enzyme ( ACE ) inhibitors and angiotensin II type 1 receptor blockers ( ARBs ) may reduce the incidence of atrial fibrillation ( AF ) in hypertensive patients and patients with left ventricular dysfunction . However , there is limited data on the effect of ACE-inhibitors and ARBs in patients undergoing electrical cardioversion for persistent AF . We hypothesized that treatment with the ARB c and esartan , without adjunct antiarrhythmic therapy , would reduce the recurrence rate of AF after successful cardioversion . METHODS In a double blind , placebo-controlled study , 171 patients with persistent AF were r and omized to receive c and esartan 8 mg once daily ( n=86 ) or placebo ( n=85 ) for 3 - 6 weeks before and c and esartan 16 mg once daily or placebo for 6 months after electrical cardioversion . Primary endpoint was recurrence of AF . RESULTS A total of 68 patients in the c and esartan group and 69 patients in the placebo group were successfully cardioverted . Forty-eight patients ( 71 % ) in the c and esartan group and 45 ( 65 % ) in the placebo group had a recurrence of AF during 6 months follow-up . Median time to recurrence was 8 and 9 days in the c and esartan and placebo groups , respectively . The differences between the groups were not statistically significant . CONCLUSION Treatment with the ARB c and esartan for 3 - 6 weeks before and 6 months after electrical cardioversion had no effect on the recurrence rate of AF Even after successful repair , hypertension is one of the main determinants of cardiovascular morbidity and mortality in patients with aortic coa rct ation ( CoA ) . We compared the effect of c and esartan ( angiotensin II receptor blockade ) and metoprolol ( beta-adrenergic receptor blockade ) on blood pressure , large artery stiffness , and neurohormonal status in hypertensive patients after repair of CoA. In the present open-label , crossover study , hypertensive patients after CoA repair were first r and omly assigned to treatment with c and esartan 8 mg or metoprolol 100 mg once per day . After 8 weeks of treatment with one of the drugs , the other treatment was given for 8 weeks . The treatment effects were assessed with 24-hour ambulatory blood pressure monitoring , measurement of large artery stiffness , and neurohormonal plasma levels at baseline and after 8 weeks of either treatment . Sixteen patients ( mean age 37 + /- 12 years , 26 + /- 15 years after repair , 63 % men ) completed the study . The 24-hour mean arterial pressure at baseline was 97.7 + /- 6.2 mm Hg . Metoprolol ( mean dose 163 + /- 50 mg/day ) decreased the mean arterial pressure ( 7.0 + /- 4.2 and 4.1 + /- 3.6 mm Hg , respectively ) more than did c and esartan ( mean dose 13 + /- 4 mg/day ; p = 0.018 , 95 % confidence interval 0.6 to 5.5 ) . Large artery stiffness did not change with either treatment . With metoprolol , plasma B-type natriuretic peptide increased and plasma renin decreased . With c and esartan , the plasma renin and noradrenaline levels increased and aldosterone levels decreased . In conclusion , in adult hypertensive patients after CoA repair , metoprolol had more of an antihypertensive effect than did c and esartan . Moreover , the neurohormonal outcome did not support a significant role for the renin-angiotensin system in the causative mechanism of hypertension after Background and Purpose — Angiotensin receptor blocker (ARB)–based treatment reduces cardiovascular events and stroke more than does β-blocker – based treatment despite similar blood pressure ( BP ) reduction . We investigated whether these treatments have different effects on cardiac and large-artery remodelling and evaluated the relation of arterial remodelling to hemodynamic changes in subjects with hypertension . Methods — We compared the treatment effects of an ARB ( c and esartan cilexetil)-based regimen and a β-blocker (atenolol)–based regimen for 52 weeks on common carotid artery ( CCA ) and left ventricular structure in hypertensive patients in a r and omized , double-blind study .  Clinic brachial BP and 24-hour ambulatory BP , carotid BP , left ventricular mass index , CCA intima-media thickness , lumen diameter , intima-media area , and carotid blood flow were measured . Distensibility , circumferential tensile stress , Young ’s elastic modulus ( Em ) , and shear stress ( & tgr ; ) in the CCA were also calculated . Results — Both c and esartan and atenolol  reduced intima-media thickness and intima-media area and increased distensibility to similar extents after 52 weeks of treatment . Despite similar reductions in BP , treatment with atenolol result ed in a lesser reduction in left ventricular mass index , a decrease in lumen diameter , and a reduction in carotid blood flow compared with c and esartan . Conclusions — BP-independent effects of ARB on cardiac and arterial structure may contribute to the beneficial effects of these agents on cardiovascular disease 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 Societal interest in pharmaco-economic analysis is increasing in Japan . In this study , the cost-effectiveness of low-dose combination therapy with controlled release nifedipine plus c and esartan and up-titrated monotherapy with c and esartan was estimated , based on the results of the NICE-Combi study . The NICE-Combi study was a double-blind , parallel arm , r and omized clinical trial to compare the efficacy of low-dose combination therapy of controlled release nifedipine ( 20 mg/day ) plus c and esartan ( 8 mg/day ) vs. up-titrated monotherapy of c and esartan ( 12 mg/day ) on blood pressure control in Japanese patients with mild to severe essential hypertension who were not sufficiently controlled by the conventional dose of c and esartan ( 8 mg/day ) . The incremental cost effectiveness of each cohort during the 8-week r and omization period was compared , from the perspective of a third-party payer ( i.e. , insurers ) . The average total cost per patient was 29,943 Japanese yen for the combination therapy group and 33,182 Japanese yen for the c and esartan monotherapy group , while the rate of achievement of the target blood pressure was significantly higher in the combination therapy group than in the up-titrated monotherapy group . In the combination therapy group , higher efficacy and lower incremental treatment cost ( “ Dominance ” ) were observed when compared to the monotherapy group . The sensitivity analyses also supported the results . In conclusion , these results suggest that combination therapy with controlled release nifedipine and low-dose c and esartan ( 8 mg ) is “ dominant ” to up-titrated c and esartan monotherapy for the management of essential hypertension . This conclusion was robust to sensitivity analysis The AMAZE ( A Multicenter Trial Using Atac and and Zestril vs. Zestril to Evaluate the Effects on Lowering Blood Pressure ) program included two identical studies sponsored by AstraZeneca LP . The oral form of c and esartan is c and esartan cilexetil ; for simplicity , the term " c and esartan " is used throughout this manuscript . Two identical multicenter , r and omized , double-blind studies were performed to determine if addition of the angiotensin receptor blocker c and esartan was more effective in lowering blood pressure than up-titration of lisinopril .  Hypertensive patients ( N=1,096 ) who were uncontrolled on lisinopril 20 mg daily were r and omized ( 1:1 ) to receive either 8 weeks of high-dose lisinopril ( 40 mg ) or the addition of c and esartan ( 16 mg ) for 2 weeks followed by 32 mg for 6 weeks . Study 1 ( n=538 ) demonstrated decreases in trough sitting systolic/diastolic blood pressures at Week 8 by 6.2/5.9 mm Hg , respectively , for the lisinopril up-titration treatment group and by 11.6/8.3 mm Hg , respectively , for the lisinopril plus c and esartan treatment group ( p<0.01 in comparing both blood pressures reductions between the two treatment groups ) . Corresponding results for Study 2 ( n=558 ) are reductions of 8.7/6.2 mm Hg and 9.5/7.4 mm Hg , respectively , for each of the two treatment groups . For Study 2 , comparisons of systolic/diastolic blood pressures between the two treatment groups were not statistically significantly different ( p=0.51/p=0.08 , respectively ) . Post hoc pooled analysis ( N=1,096 ) demonstrated a slightly greater blood pressure reduction with lisinopril plus c and esartan compared with lisinopril ( 3.1/1.7 mm Hg ) . A 95 % confidence interval limit for the difference in least squares mean change from baseline in systolic blood pressure between the two treatment groups is -4.8 to -1.5 and is -2.8 to -0.7 in mm Hg for diastolic blood pressure . The blood pressure control rates ( < 140/<90 mm Hg ) were 42.7 % and 36.9 % , respectively . Both treatment regimens were well tolerated in all groups . In conclusion , for hypertensive patients not controlled by lisinopril 20 mg once daily , addition of c and esartan ( 32 mg once daily ) or doubling the dose of lisinopril provides safe , additional reduction of blood pressure Aim : To compare c and esartan cilexetil and lisinopril in fixed combination with hydrochlorothiazide with respect to antihypertensive efficacy and tolerability . Methods : This was a double-blind ( double-dummy ) , r and omised , parallel group comparison in patients with a mean sitting diastolic blood pressure 95–115 mm Hg on prior antihypertensive monotherapy . Treatments were c and esartan cilexetil/hydrochlorothiazide 8/12.5 mg once daily ( n = 237 ) and lisinopril/hydrochlorothiazide 10/12.5 mg once daily ( n = 116 ) for 26 weeks . The primary efficacy variable was change in trough sitting diastolic blood pressure . Results : Changes in mean sitting diastolic blood pressure did not differ significantly between the groups ( mean difference 0.5 mm Hg ; 95 % confidence interval −1.6 , 2.7 , P = 0.20 ) . No significant differences between the groups was found for other haemodynamic variables ( sitting systolic blood pressure , st and ing blood pressure , sitting/erect heart rate , and proportion of responders and controlled patients ) . Both drugs were well tolerated but the proportion of patients with at least one adverse event was significantly greater in the lisinopril group ( 80 % vs 69 % , P = 0.020 ) . The proportion of patients spontaneously reporting cough ( 23.1 % vs 4.6 % ) and discontinuing therapy due to adverse events ( 12.0 % vs 5.9 % ) was also higher in the lisinopril group compared with the c and esartan cilexetil group . Conclusions : The fixed combinations of c and esartan cilexetil and hydrochlorothiazide 8/12.5 mg and lisinopril and hydrochlorothiazide 10/12.5 mg once daily are equally effective as antihypertensive agents . The fixed combination containing c and esartan cilexetil is better tolerated than that containing lisinopril 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
Conclusions : C and esartan is superior to losartan in reducing blood pressure .
C and esartan also causes fewer serious adverse events than losartan
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 .