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
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
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DOI：
10.1016/s0895-7061(99)00142-9
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发表时间：
1999-12-01
影响因子：
3.2
通讯作者：
Asmar, R
中科院分区：
文献类型：
--
作者：
Lacourcière, Y;Asmar, R
这项双盲、强制剂量调整研究的目的是比较坎地沙坦酯（与人AT（1）受体具有持久结合作用）与氯沙坦对动态血压（ABP）的降压作用持续时间，不仅在24小时给药间隔内，而且在漏服剂量当天。在4周的安慰剂导入期后，268例坐位舒张压95 - 110 mm Hg和平均清醒动态舒张压大于或等于85 mm Hg的患者随机接受8 mg坎地沙坦、50 mg氯沙坦或安慰剂治疗4周。此后，所有患者的剂量增加一倍，再持续4周。给药后36 h动态血压监测和48 h门诊血压监测结果显示，坎地沙坦酯（16 mg）降低ABP的程度明显大于氯沙坦（100 mg），尤其是对白天收缩期ABP的降低（P < .05），夜间（P < .05），24小时（P < .01）周期，收缩期0 - 36 h之间的收缩压（P <0.01）和舒张压（P <0.05），以及漏服剂量当天的收缩压（P <0.001）和舒张压（P < 0.001）。仅坎地沙坦16 mg组在给药后48小时的门诊血压显著降低。坎地沙坦8 mg组和氯沙坦50 mg组在白天（P <0.01）、夜间（P <0.05）、24 h（P <0.01）、0 - 36 h（P <0.05）和漏服当天（P <0.05）的收缩压ABP降低差异有统计学意义。此外，尽管氯沙坦并没有以剂量相关的方式显著降低动态血压，但坎地沙坦16 mg组的动态收缩压和舒张压降低幅度显著大于（P <0.01和<0.001）在ABP支持剂量-反应关系的每个阶段期间，与使用8 mg坎地沙坦观察到的那些相比。这项在动态高血压患者中进行的强制滴定研究表明，坎地沙坦西酯在8 - 16 mg每日一次的剂量范围内，在临床和动态血压方面均提供了显著的剂量依赖性降低。此外，坎地沙坦酯在降低收缩期ABP和控制漏服剂量当天的收缩期和舒张期ABP方面优于氯沙坦上级。两种药物之间观察到的差异最可能归因于坎地沙坦酯与受体结合位点的结合更紧密，解离更缓慢。美国高血压杂志1999;12：1181-1187（C）1999美国高血压杂志有限公司。
The purpose of this double-blind, forced titration study was to compare the antihypertensive effect duration of candesartan cilexetil, which has a long-lasting binding to the human AT(1)-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 greater than or equal to 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) 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 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. Am J Hypertens 1999;12:1181-1187 (C) 1999 American Journal of Hypertension, Ltd.