Rakugi Hiromi, Tsuchihashi Takuya, Shimada Kazuyuki, Numaguchi Hirotaka, Nishida Chisato, Yamaguchi Hiroya, Fujimoto Go, Azuma Kyoichi, Shirakawa Masayoshi, Hanson Mary E, Fujita Kenji P
Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.
Steel Memorial Yawata Hospital, Fukuoka, Japan.
Hypertens Res. 2014 Dec;37(12):1042-9. doi: 10.1038/hr.2014.114. Epub 2014 Jul 3.
Two randomized studies were designed to assess the safety, tolerability and efficacy of losartan 100 mg (L100) plus hydrochlorothiazide 12.5 mg (H12.5) in a single fixed-dose combination. In one study, subjects received losartan 50 mg (L50) plus H12.5 during an 8-week filter period. They were then randomized to either L100/H12.5 or L50/H12.5 for another 8 weeks, followed by L100/H12.5 for 44 weeks. The primary end point was safety of L100/H12.5 for 52 weeks. In the second study, subjects received L100 during an 8-week filter period. Subjects were then randomized to receive either L100/H12.5 or L100 for a further 8 weeks. The primary end point was change from baseline in sitting diastolic blood pressure (SiDBP) at week 8. Safety was assessed throughout both studies. L100/H12.5 reduced SiDBP and sitting systolic blood pressure (SiSBP) at 8 weeks, and when compared with L100, the differences were statistically significant for both measures (P<0.001). L100/H12.5 reductions SiDBP for 8 weeks were comparable to L50/H12.5. The efficacy of L100/H12.5 was maintained to week 52. Drug-related adverse events with an incidence ⩾ 2% in the L100/H12.5 group during the 52-week extension period were an increase in aspartate aminotransferase and in blood uric acid. Additionally, mean uric acid levels were reduced by 0.57 mg dl(-1) from baseline with long-term treatment with L100/H12.5 in subjects whose baseline uric acid level was >7.0 mg dl(-1). In conclusion, L100/H12.5 was shown to be more effective than L100 at reducing SiDBP and SiSBP and showed good tolerability in Japanese patients with essential hypertension.
两项随机研究旨在评估氯沙坦100毫克（L100）加氢氯噻嗪12.5毫克（H12.5）单一固定剂量组合的安全性、耐受性和疗效。在一项研究中，受试者在为期8周的筛选期内接受氯沙坦50毫克（L50）加H12.5。然后他们被随机分为L100/H12.5或L50/H12.5，持续另外8周，随后接受L100/H12.5治疗44周。主要终点是L100/H12.5治疗52周的安全性。在第二项研究中，受试者在为期8周的筛选期内接受L100。然后受试者被随机分为接受L100/H12.5或L100，再持续8周。主要终点是第8周时坐位舒张压（SiDBP）相对于基线的变化。在两项研究中均对安全性进行了评估。L100/H12.5在8周时降低了SiDBP和坐位收缩压（SiSBP），与L100相比，这两项指标的差异均具有统计学意义（P<0.001）。L100/H12.5在8周内降低SiDBP的效果与L50/H12.5相当。L100/H12.5的疗效维持到第52周。在52周延长期内，L100/H12.5组中发生率≥2%的与药物相关的不良事件是天门冬氨酸转氨酶升高和血尿酸升高。此外，在基线尿酸水平>7.0毫克/分升的受试者中，长期接受L100/H12.5治疗后，平均尿酸水平较基线降低了0.57毫克/分升。总之，在降低SiDBP和SiSBP方面，L100/H12.5比L100更有效，并且在日本原发性高血压患者中显示出良好的耐受性。
