Dunlay M C, Fitzpatrick V, Chrysant S, Francischetti E A, Goldberg A I, Sweet C S
Clinical Cardiovascular Research, Merck Research Laboratories, West Point, PA 19486, USA.
J Hum Hypertens. 1995 Nov;9(11):861-7.
This 12-week, open-label study was conducted to gain experience with losartan potassium, an angiotensin II receptor antagonist, in patients with severe hypertension. Patients were either untreated or withdrawn from current therapy for at least 48 h before initiation of losartan 50 mg once daily. Patients were titrated to 100 mg as needed to achieve a goal of sitting diastolic blood pressure (SiDBP) 90 or 95 mm Hg. Hydrochlorothiazide (12.5 mg once daily titrated to 25 mg) was added and followed by either a dihydropyridine calcium channel blocker (CCB) and/or atenolol, if BP was not controlled. A total of 179 patients with a pretreatment mean baseline BP of 172 +/- 17/112 +/- 18 mm Hg enrolled in the trial and BP was recorded 24 h after dosing at baseline and weeks 2, 4, 8 and the final week (10-12 weeks). The mean reductions in SiDBP from baseline were 7.3, 9.3, 15.9 and 18.9 mm Hg, respectively, and these changes from baseline were statistically significant, P < 0.001. At the end of the trial, 22% of patients remained on losartan monotherapy, 30% required the addition of hydrochlorothiazide (HCTZ) and 31% required both HCTZ and a CCB; 11% required HCTZ and atenolol while 4% required HCTZ, a CCB and atenolol; 2% of patients were on regimens not specified by the protocol. SiDBP < 90 mm Hg was achieved in 68 patients by the final visit; 24% of these patients were treated with losartan monotherapy (50 or 100 mg), 41% achieved control with the addition of HCTZ (12.5 or 25 mg) and 24% required triple therapy which included losartan, HCTZ and a CCB. As assessed by the investigator, 25% of the patients in the study had drug-related clinical adverse experiences. Headache was the most frequently reported clinical adverse event (26% of patients). No clinically significant changes in laboratory parameters were observed. It is concluded that losartan potassium can be used as initial therapy for patients with severe hypertension and can be administered concurrently with hydrochlorothiazide, calcium channel blockers and atenolol.
这项为期12周的开放标签研究旨在积累使用血管紧张素II受体拮抗剂氯沙坦钾治疗重度高血压患者的经验。患者在开始每日一次服用50毫克氯沙坦之前，要么未接受治疗，要么从当前治疗中撤药至少48小时。根据需要将患者剂量滴定至100毫克，以实现坐位舒张压（SiDBP）达到90或95毫米汞柱的目标。如果血压未得到控制，则添加氢氯噻嗪（每日一次12.5毫克，滴定至25毫克），随后加用二氢吡啶类钙通道阻滞剂（CCB）和/或阿替洛尔。共有179例患者入组该试验，其治疗前平均基线血压为172±17/112±18毫米汞柱，在基线、第2、4、8周和最后一周（10 - 12周）给药后24小时记录血压。SiDBP较基线的平均降低值分别为7.3、9.3、15.9和18.9毫米汞柱，这些与基线的变化具有统计学意义，P < 0.001。在试验结束时，22%的患者仅接受氯沙坦单药治疗，30%的患者需要加用氢氯噻嗪（HCTZ），31%的患者需要同时使用HCTZ和CCB；11%的患者需要HCTZ和阿替洛尔，4%的患者需要HCTZ、CCB和阿替洛尔；2%的患者采用了方案未规定的治疗方案。到最后一次访视时，68例患者的SiDBP < 90毫米汞柱；这些患者中24%接受氯沙坦单药治疗（50或100毫克），41%通过加用HCTZ（12.5或25毫克）实现血压控制，24%需要三联治疗，包括氯沙坦、HCTZ和CCB。根据研究者评估，该研究中25%的患者有与药物相关的临床不良事件。头痛是最常报告的临床不良事件（占患者的26%）。未观察到实验室参数有临床显著变化。结论是氯沙坦钾可作为重度高血压患者的初始治疗药物，并且可与氢氯噻嗪、钙通道阻滞剂和阿替洛尔联合使用。
