A comparison of the efficacy and duration of action of candesartan cilexetil and losartan as assessed by clinic and ambulatory blood pressure after amissed dose, in truly hypertensive patients - A placebo-controlled, forcedtitration study

The purpose of this double-blind, forced titration study was to compare the antihypertensive effect duration of candesartan cilexetil, which has a lon g-lasting binding to the human AT(1)-receptor, to that of losartan on ambul atory 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 pa tients with sitting diastolic BP 95 to 110 mm Hg and mean awake ambulatory DBP greater than or equal to 85 mm Hg were randomized to receive either 8 m g of candesartan, 50 mg of losartan, or placebo for a 4-week period. Therea fter, the doses were doubled in all patients for an additional 4-week perio d. 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) ABS 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 ca ndesartan. The differences in BP reduction between 8 mg of candesartan and 50 mg of losartan were statistically significant for systolic ABP during da ytime (P < .01), nighttime (P < .05), 24-h (P < .01), 0 to 36 h (P < .05) a nd during the day of missed dose (P < .05). Moreover, although losartan did not significantly reduce ambulatory BP in a dose-related manner, ambulator y systolic and diastolic BP reductions with 16 mg of candesartan were signi ficantly greater (P < .01 and < .001) than those seen with 8 mg of candesar tan during every period at the ABP supporting-a dose-response relationship. In conclusion, this forced titration study in ambulatory hypertensive patie nts demonstrates that candesartan cilexetil provides significant dose-depen dent reduction in both clinic, and ambulatory BP in doses ranging from 8 to 16 mg once daily. Furthermore, candesartan cilexetil is superior to losart an in reducing systolic ABP and in controlling both systolic and diastolic ABP on the day of a missed dose. The differences observed between both agen ts are most likely attributable to a tighter binding to, and a slower disso ciation from, the receptor binding site with candesartan cilexetil. Am J Hy pertens 1999;12:1181-1187 (C) 1999 American Journal of Hypertension, Ltd.