White William B, Lacourciere Yves, Davidai Giora
Section of Hypertension and Clinical Pharmacology, University of Connecticut School of Medicine, Farmington, Connecticut 06032, USA.
Am J Hypertens. 2004 Apr;17(4):347-53. doi: 10.1016/j.amjhyper.2004.02.016.
Ambulatory blood pressure (BP) monitoring has shown that BP typically declines by 10% to 20% during sleep and increases fairly rapidly in the early morning period. Because the early morning period has been associated with both loss of hypertension control and increased rates of myocardial infarction and stroke, there has been interest in evaluating the effects of antihypertensive therapy at this particular time of the day. The purpose of this study was to assess the effects of a long half-life (telmisartan, 24 h) versus intermediate half-life (valsartan, 6 to 9 h) on early morning BP in two scenarios: after an active dose and after a missed dose of each agent.
The study was a double-blind, randomized trial that compared telmisartan (40 to 80 mg once daily) versus valsartan (80 to 160 mg once daily) on early morning BP in 490 patients with hypertension. Ambulatory BP recordings were performed at baseline after a placebo period and again after 6 and 8 weeks of double-blind therapy in a randomized cross-over design. The monitoring patients received either an active dose or a placebo dose (to mimic a "missed" dose). The primary study end point was reduction in the BP in the early morning period (last 6 h of the dosing period).
After the active dose, telmisartan reduced the BP during the last 6 h of the dosing period by -11/-7.6 +/- 0.8/0.6 mm Hg compared to -8.7/-5.8 +/- 0.8/0.6 mm Hg on valsartan (P = .02 for systolic BP and.01 for diastolic BP). On the day of the missed dose, telmisartan reduced the early morning BP by -9.0/-6.3 +/- 0.7/0.6 mm Hg versus -7.4/-5.1 +/- 0.7/0.4 mm Hg on valsartan (P = .09 for systolic BP and.06 for diastolic BP). On the day of the missed dose, reductions in 24-h average BP for the two antihypertensive agents were -10.3/-6.9 mm Hg for telmisartan versus -8.7/-5.9 mm Hg for valsartan (P = .06 for systolic BP and.056 for diastolic BP).
On a day of active therapy, telmisartan lowered both systolic and diastolic BP to a greater extent than valsartan for the last 6 h of the dosing interval. On a day in which a dose was missed, there was a notable trend for greater BP reduction during the latter part of the dosing interval on telmisartan versus valsartan. These results demonstrate that telmisartan achieved a greater effect than valsartan on BP during the early morning period in patients with hypertension.
动态血压监测显示，血压通常在睡眠期间下降10%至20%，并在清晨时段迅速上升。由于清晨时段与高血压控制不佳以及心肌梗死和中风发生率增加相关，因此人们对评估一天中这个特定时间段的抗高血压治疗效果产生了兴趣。本研究的目的是评估在两种情况下，长效半衰期（替米沙坦，24小时）与中效半衰期（缬沙坦，6至9小时）对清晨血压的影响：每种药物服用有效剂量后和漏服一剂后。
该研究是一项双盲随机试验，比较了替米沙坦（每日一次，40至80毫克）与缬沙坦（每日一次，80至160毫克）对490例高血压患者清晨血压的影响。在安慰剂期后基线时以及双盲治疗6周和8周后，采用随机交叉设计进行动态血压记录。监测患者接受有效剂量或安慰剂剂量（模拟“漏服”剂量）。主要研究终点是清晨时段（给药期的最后6小时）血压的降低。
服用有效剂量后，替米沙坦在给药期的最后6小时使收缩压/舒张压降低了-11/-7.6±0.8/0.6毫米汞柱，而缬沙坦为-8.7/-5.8±0.8/0.6毫米汞柱（收缩压P = 0.02，舒张压P = 0.01）。在漏服药物当天，替米沙坦使清晨血压降低了-9.0/-6.3±0.7/0.6毫米汞柱，而缬沙坦为-7.4/-5.1±0.7/0.4毫米汞柱（收缩压P = 0.09，舒张压P = 0.06）。在漏服药物当天，两种抗高血压药物的24小时平均血压降低值，替米沙坦为-10.3/-6.9毫米汞柱，缬沙坦为-8.7/-5.9毫米汞柱（收缩压P = 0.06，舒张压P = 0.056）。
在积极治疗日，在给药间隔的最后6小时，替米沙坦降低收缩压和舒张压的程度均大于缬沙坦。在漏服一剂的当天，在给药间隔后期，替米沙坦降低血压的幅度比缬沙坦有明显更大的趋势。这些结果表明，在高血压患者中，替米沙坦在清晨时段对血压的影响比缬沙坦更大。
