Comparative effects of candesartan cilexetil and losartan in patients with systemic hypertension. Candesartan Versus Losartan Efficacy Comparison (CANDLE) Study Group. Effectiveness of Add-On Low-Dose Diuretics in Combination Therapy for Hypertension: Losartan/Hydrochlorothiazide vs. Candesartan/Amlodipine Differing anti-proteinuric action of candesartan and losartan in chronic renal disease. Antihypertensive efficacy of candesartan in comparison to losartan: the CLAIM study. Comparison of angiotensin II receptor blockers: impact of missed doses of candesartan cilexetil and losartan in systemic hypertension. 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. 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. The antihypertensive effect and tolerability of candesartan cilexetil, a new generation angiotensin II antagonist, in comparison with losartan. 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. A forced titration study of antihypertensive efficacy of candesartan cilexetil in comparison to losartan: CLAIM Study II Cost-effectiveness of candesartan versus losartan in the primary preventive treatment of hypertension Renoprotective Effects of Various Angiotensin II Receptor Blockers in Patients with Early-Stage Diabetic Nephropathy Stroke prevention with the angiotensin II type 1-receptor blocker candesartan in elderly patients with isolated systolic hypertension: the Study on Cognition and Prognosis in the Elderly (SCOPE).
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 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 It has becoming clear that angiotensin receptor blockers ( ARBs ) show varying levels of angiotensin II type 1 ( AT1 ) receptor blocking activity . Although the duration of activity and the efficacy on blood pressure of ARB are reported to vary , depending on the agents used , it has not been examined whether the effects on proteinuria and urinary nitrite/nitrate ( NOx ) excretion differ in hypertensive patients with chronic renal disease . In the present study , patients with hypertension ( > 140 and /or 90 mmHg ) and chronic renal disease ( proteinuria > 0.5g/day ; serum creatinine < 265 micromol/l or creatinine clearance > 30 ml/min/1.72 m2 ) were r and omly assigned to perindopril- ( n = 15 ) , tr and olapril- ( n = 15 ) , c and esartan- ( n = 17 ) , and losartan-treated groups ( n = 15 ) , and were followed up for 96 weeks . All agents decreased blood pressure to the same level , and none of them had any effect on creatinine clearance .  C and esartan , perindopril , and tr and olapril reduced proteinuria markedly ( from 3.0 + /- 0.6 to 1.8 + /- 0.5 g/day , 2.7 + /- 0.5 to 1.6 + /- 0.4 g/day , and 2.7 + /- 0.5 to 1.7 + /- 0.4 g/day , respectively ) at 12 weeks , and the beneficial effect persisted throughout the study . The effect of losartan , however , diminished over the study period . Whereas perindopril , tr and olapril , and c and esartan markedly increased urinary NOx excretion ( from 257 + /- 23 to 1,011 + /- 150 micromol/day , 265 + /- 70 to 986 + /- 130 micromol/day , and 260 + /- 62 to 967 + /- 67 micromol/day at 12 weeks , respectively ) , a relatively blunted increase was observed with losartan ( from 309 + /- 42 to 596 + /- 64 micromol/day ) . In conclusion , renal action of ARB varies , with relatively less proteinuria-sparing , as well as NOx-enhancing , effects observed with c and esartan showing the greatest reduction of proteinuria and greatest enhancement of NOx . Furthermore , renal nitric oxide may contribute to the renal protective action of these agents when administered to patients with chronic renal disease 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 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 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 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 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 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 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 Background Although angiotensin receptor blockers have different receptor binding properties , no comparative r and omized studies with cardiovascular event endpoints have been performed for this class of drugs . The aim of this study was to assess the long-term cost-effectiveness of c and esartan ( Atac and ® ) versus generic losartan in the primary preventive treatment of hypertension . Methods A decision-analytic model was developed to estimate costs and health outcomes over a patient ’s lifetime . Data from a clinical registry study were used to estimate event rates for cardiovascular complications , such as myocardial infa rct ion and heart failure . Costs and quality of life data were from published sources . Costs were in Swedish kronor and the outcome was quality -adjusted life-years ( QALYs ) . Results Due to reduced rates of cardiovascular complications , c and esartan was associated with a QALY gain and lower health care costs compared with generic losartan ( 0.053 QALYs gained and reduced costs of approximately 4700 Swedish kronor for women ; and 0.057 QALYs gained and reduced costs of approximately 4250 Swedish kronor for men ) . This result was robust in several sensitivity analyses . Conclusion When modeling costs and health outcomes based on event rates for cardiovascular complications from a real-world registry study , c and esartan appears to bring a QALY gain and a reduction in costs compared with generic losartan in the primary preventive treatment of hypertension in Sweden Background : There is increasing evidence that inhibition of the renin-angiotensin system provides renoprotection independent of blood pressure lowering . The aim of the present study was to determine whether various angiotensin II receptor blockers ( ARBs ) affect urinary albumin excretion ( UAE ) , urinary liver-type fatty acid-binding protein ( L-FABP ) and 8-hydroxy-2′-deoxyguanosine ( 8-OHdG ) levels in early-stage diabetic nephropathy patients with microalbuminuria . Methods : Sixty-eight diabetic nephropathy patients with microalbuminuria were r and omly allocated to 1 of 4 treatment groups : losartan 100 mg/day ( group A ) , c and esartan 12 mg/day ( group B ) , olmesartan 40 mg/day ( group C ) , or telmisartan 80 mg/day ( group D ) . Treatment was continued for 12 months . UAE , L-FABP and 8-OHdG excretion , serum creatinine , and 24-hour creatinine clearance ( Ccr ) were measured . Results : The serum creatinine and 24-hour Ccr were not affected during the experimental period in any of the groups . Systolic and diastolic blood pressures , UAE , urinary L-FABP and 8-OHdG excretion were significantly reduced after 6 and 12 months compared with baseline in any of the groups . ΔL-FABP and Δ8-OHdG were significantly greater in group D than in the other 3 groups after 12 months . Conclusions : ARBs have renoprotection and this effect of telmisartan appears to be more potent than that of losartan , c and esartan , or olmesartan in early-stage diabetic nephropathy patients OBJECTIVES The aim of this study was to test the hypothesis that the angiotensin II type 1 receptor blocker ( ARB ) c and esartan can reduce the risk of stroke in elderly patients with isolated systolic hypertension ( ISH ) . BACKGROUND Isolated systolic hypertension is the predominant form of hypertension in the elderly , and stroke is the most common cardiovascular ( CV ) complication . METHODS In the Study on Cognition and Prognosis in the Elderly ( SCOPE ) , 4,964 patients age 70 to 89 years were r and omly assigned to double-blind c and esartan or placebo with open-label antihypertensive therapy ( mostly thiazide diuretics ) added as needed to control blood pressure . Of the 4,964 patients , 1,518 had ISH ( systolic blood pressure > 160 mm Hg and diastolic blood pressure < 90 mm Hg ) . The present study is a predefined subgroup analysis of outcome results in the ISH patients . RESULTS Of the ISH patients , 754 were r and omized to the c and esartan group and 764 to the control group . Over the study period , blood pressure was reduced by 22/6 mm Hg in the c and esartan group and by 20/5 mm Hg in the control group ( difference between treatments 2/1 mm Hg ; p = 0.101 and 0.064 ) . A total of 20 fatal/non-fatal strokes occurred in the c and esartan group ( 7.2/1,000 patient-years ) and 35 in the control group ( 12.5/1,000 patient-years ) ; relative risk ( RR ) was 0.58 ( 95 % confidence interval 0.33 to 1.00 ) , that is , a RR reduction of 42 % ( p = 0.050 unadjusted , p = 0.049 adjusted for baseline risk ) . There were no marked or statistically significant differences between the treatment groups in other CV end points or all-cause mortality . CONCLUSIONS In elderly patients with ISH , antihypertensive treatment based on the ARB c and esartan result ed in a significant 42 % RR reduction in stroke in comparison with other antihypertensive treatment , despite little difference in blood pressure reduction
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 .