Lacourcière Yves, Krzesinski Jean-Marie, White William B, Davidai Giora, Schumacher Helmut
Hypertension Research Unit, Centre Hospitalier l'Université de Quebec, Ste Foy, Quebec, Canada.
Blood Press Monit. 2004 Aug;9(4):203-10. doi: 10.1097/00126097-200408000-00005.
Early morning blood pressure (BP) surge and 24 h mean BP are linked to target-organ damage and cardiovascular events. Antihypertensive agents should sustain BP control, particularly in the last 6 h of the dosing interval or if dosing is missed. The efficacies of the long half-life telmisartan compared with shorter half-life valsartan in the last 6 h of the dosing interval following active treatment and during 24 h after a missed dose were compared.
In two identically designed multinational, randomized, double-blind, forced-titration studies, hypertensive patients (seated diastolic blood pressure (DBP), 95-109 mm Hg, 24 h mean ambulatory DBP, > or = 85 mm Hg) received once-daily telmisartan (40- 80 mg) or valsartan (80-160 mg) for a total of 8 weeks; uptitration occurred after 2 weeks low-dose treatment. After 4 weeks high-dose treatment, patients were given either 1 days double-blind active therapy or placebo (that is, missed dose). Following a further 2 weeks active treatment, a cross-over was performed: patients who had previously received 1 days placebo received active therapy and vice versa. At baseline and after the two active or missed doses, 24 h ambulatory BP monitoring was performed. Data from the studies were pooled, as prospectively planned and analyzed using the intent-to-treat population.
After active therapy, last 6 h mean DBP was reduced by 7.6+/-7.9 mm Hg with telmisartan (n=447) compared with 5.8+/-7.8 mm Hg with valsartan (n=430) (P=0.0044). Last 6 h mean systolic blood pressure (SBP) was reduced by 11.1 mm Hg with telmisartan compared with 9.1 mm Hg with valsartan (P=0.0066). After a missed dose, 24 h mean DBP was reduced by 7.2+/-6.5 mm Hg with telmisartan (n=437) compared with 5.5+/-6.2 mm Hg with valsartan (n=431) (P=0.0004). The reduction in 24 h mean SBP after a missed dose was 10.7 mm Hg with telmisartan and 8.7 mm Hg with valsartan (P=0.0024). Absence of treatment-by-study interaction indicated that pooling of studies was appropriate. All 24 hourly mean reductions in DBP and SBP were greater for telmisartan than valsartan. Both treatments were well tolerated.
Due to its longer half-life, telmisartan offers more sustained BP control, especially at the end of the dosing period and provides sustained efficacy in poorly compliant patients in the event of a missed dose with a statistical superiority compared with valsartan.
清晨血压骤升和24小时平均血压与靶器官损害及心血管事件相关。抗高血压药物应维持血压控制，尤其是在给药间隔的最后6小时或漏服药物时。比较了长效半衰期替米沙坦与短效半衰期缬沙坦在积极治疗后给药间隔的最后6小时以及漏服药物后24小时内的疗效。
在两项设计相同的跨国、随机、双盲、强制滴定研究中，高血压患者（坐位舒张压（DBP）为95 - 109 mmHg，24小时动态平均DBP≥85 mmHg）每日服用一次替米沙坦（40 - 80 mg）或缬沙坦（80 - 160 mg），共8周；低剂量治疗2周后进行剂量滴定。高剂量治疗4周后，患者接受1天的双盲积极治疗或安慰剂（即漏服剂量）。再经过2周的积极治疗后，进行交叉：之前接受1天安慰剂的患者接受积极治疗，反之亦然。在基线以及两次积极治疗或漏服剂量后，进行24小时动态血压监测。如预先计划，汇总研究数据并使用意向性治疗人群进行分析。
积极治疗后，替米沙坦组（n = 447）最后6小时平均DBP降低7.6±7.9 mmHg，缬沙坦组（n = 430）降低5.8±7.8 mmHg（P = 0.0044）。替米沙坦组最后6小时平均收缩压（SBP）降低11.1 mmHg，缬沙坦组降低9.1 mmHg（P = 0.0066）。漏服剂量后，替米沙坦组（n = 437）24小时平均DBP降低7.2±6.5 mmHg，缬沙坦组（n = 431）降低5.5±6.2 mmHg（P = 0.0004）。漏服剂量后，替米沙坦组24小时平均SBP降低10.7 mmHg，缬沙坦组降低8.7 mmHg（P = 0.0024）。研究间无治疗交互作用表明汇总研究是合适的。替米沙坦组DBP和SBP的所有24小时平均降低幅度均大于缬沙坦组。两种治疗耐受性均良好。
由于替米沙坦半衰期更长，其能提供更持久的血压控制，尤其是在给药期结束时，并且在患者漏服药物时对依从性差的患者也能提供持续疗效，与缬沙坦相比具有统计学优势。
