Casadei B, Conway J, Coats A J, Bird R
Department of Cardiovascular Medicine, John Radcliffe Hospital, Oxford.
Clin Investig. 1992;70 Suppl 1:S37-8. doi: 10.1007/BF00207609.
The blood pressure (BP) lowering effect of low doses of antihypertensive agents is not usually explored because of the difficulty in detecting small changes in BP. Since ambulatory blood pressure monitoring in a cross-over trial design can reliably detect differences of 5 mmHg with less than 20 subjects, we have used this technique to assess the dose-response curve of a new beta-blocker, carvedilol. Twenty subjects were enrolled after diagnostic ambulatory BP monitoring had shown a day-time average diastolic BP of over 90 mmHg. Three doses of carvedilol (6.25, 12.5 and 25 mg daily) and placebo were then given double-blind in random order for periods of 4 weeks each. No period effects were detected. The antihypertensive effect was statistically significant at doses of 12.5 mg and 25 mg daily. There was, however, no evidence that 25 mg/day produced the peak effect. The lowest dose (6.25 mg/day) produced a small fall in both systolic and diastolic BP but neither of these were significant. We conclude that doses of 12.5 and 25 mg carvedilol once a day are adequate for the treatment of hypertension.
由于难以检测到血压的微小变化,低剂量抗高血压药物的降压效果通常未被探究。鉴于交叉试验设计中的动态血压监测能够在受试者少于20人的情况下可靠地检测出5 mmHg的差异,我们采用了该技术来评估新型β受体阻滞剂卡维地洛的剂量反应曲线。在诊断性动态血压监测显示日间平均舒张压超过90 mmHg后,招募了20名受试者。随后,将卡维地洛的三个剂量(每日6.25、12.5和25 mg)和安慰剂以双盲、随机的顺序给药,每个阶段为期4周。未检测到阶段效应。每日剂量为12.5 mg和25 mg时,降压效果具有统计学意义。然而,没有证据表明每日25 mg产生了峰值效应。最低剂量(每日6.25 mg)使收缩压和舒张压均有小幅下降,但两者均无统计学意义。我们得出结论,卡维地洛每日12.5 mg和25 mg的剂量足以治疗高血压。