Document Detail

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.
MedLine Citation:
PMID:  10619580     Owner:  NLM     Status:  MEDLINE    
The purpose of this double-blind, forced titration study was to compare the antihypertensive effect duration of candesartan 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 randomized to receive either 8 mg of candesartan, 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. Candesartan 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 candesartan. The differences in BP reduction between 8 mg of candesartan 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 candesartan were significantly greater (P<.01 and <.001) than those seen with 8 mg of candesartan during every period at the ABP supporting a dose-response relationship. In conclusion, this forced titration study in ambulatory hypertensive patients demonstrates that candesartan cilexetil provides significant dose-dependent reduction in both clinic and ambulatory BP in doses ranging from 8 to 16 mg once daily. Furthermore, candesartan 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 candesartan cilexetil.
Y Lacourcière; R Asmar
Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of hypertension     Volume:  12     ISSN:  0895-7061     ISO Abbreviation:  Am. J. Hypertens.     Publication Date:  1999 Dec 
Date Detail:
Created Date:  2000-01-20     Completed Date:  2000-01-20     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  8803676     Medline TA:  Am J Hypertens     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1181-7     Citation Subset:  IM    
Hypertension Research Unit, Centre Hospitalier de l'Université Laval, Québec, Canada.
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MeSH Terms
Aged, 80 and over
Angiotensin Receptor Antagonists*
Antihypertensive Agents / therapeutic use*
Benzimidazoles / therapeutic use*
Biphenyl Compounds / therapeutic use*
Blood Pressure / drug effects,  physiology*
Blood Pressure Monitoring, Ambulatory*
Circadian Rhythm / physiology
Delayed-Action Preparations
Dose-Response Relationship, Drug
Double-Blind Method
Hypertension / drug therapy*,  physiopathology
Losartan / therapeutic use*
Middle Aged
Treatment Outcome
Reg. No./Substance:
0/Angiotensin Receptor Antagonists; 0/Antihypertensive Agents; 0/Benzimidazoles; 0/Biphenyl Compounds; 0/Delayed-Action Preparations; 0/Tetrazoles; 114798-26-4/Losartan; R85M2X0D68/candesartan cilexetil

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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