厄贝沙坦与氯沙坦治疗轻、中度高血压病的比较

目的比较厄贝沙坦与氯沙坦对轻中度高血压病患者的降压疗效.方法采用随机、双盲研究方法.经2周的单盲、安慰剂导入期,72例坐位舒张压在95～115mmHg之间的高血压患者被随机分入厄贝沙坦75mg/天组(n=36)或氯沙坦50mg/天组(n=36).4周末,如坐位舒张压仍≥90mmHg,每日剂量加倍(厄贝沙坦150mg/天或氯沙坦100mg/天),总疗程8周.结果两组患者服药后血压均显著降低(P<0.01).经8周治疗,厄贝沙坦组平均坐位收缩压与舒张压分别降低15.0%与13.3%,在氯沙坦组分别为13.7%与14.0%.两药的有效率无显著性差别(厄贝沙坦75.0%,氯沙坦71.4%,P>0.05).与厄贝沙坦不同,氯沙坦组血尿酸水平显著降低.结论在轻中度高血压的治疗中,厄贝沙坦与氯沙坦一样有效与安全.     

厄贝沙坦与氯沙坦治疗轻、中度高血压病的比较

目的 比较厄贝沙坦与氯沙坦对轻中度高血压病患者的降压疗效。方法 采用随机、双盲研究方法。经2周的单盲、安慰剂导入期,72例坐位舒张压在95－115mmHg之间的高血压患者被随机分入厄贝沙坦75mg/天组（n=36)或氯沙坦50mg/天组（n=36)。4周末,如坐位舒张仍≥90mmHg,每日剂量加倍（厄贝沙坦150mg/天或氯沙坦100mg／天）,总疗程8周。结果 两组患者服药后血压均显著降低（P＜0．01）。经8周治疗,厄贝沙坦组平均坐位收缩压与舒张压分别降低15．0％与13．3％,在氯沙坦组分别为13．7％与14．0％。两药的有效率无显著性差别（厄贝沙坦75．0％,氯沙坦71．4％,P＞0．05）。与厄贝沙坦不同,氯沙坦组血尿酸水平显著降低。结论 在轻中度高血压的治疗中,厄贝沙坦与氯沙坦一样有效与安全。     

氯沙坦、苯那普利及二者联合治疗高血压病的对比性研究

目的对比氯沙坦、苯那普利及二者联合治疗轻、中度原发性高血压(EH)的降压效果及耐受性.方法入选的轻、中度EH患者(坐位舒张压90～109 mmHg)经1周药物冲洗期及2周安慰剂期后,随机分为3组(1)L组,口服氯沙坦 50 mg/天;(2)B组,口服苯那普利 10 mg/天;(3)L+B组,口服氯沙坦 50 mg/天,苯那普利 10 mg/天.疗程8周.共入选病例67例,完成8周观察者63例,L组22例,B组20例,L+B组21例.于服安慰剂期末及治疗1、2、4、6、8周末测诊室血压、心率(HR)并记录不良反应.治疗前后测血浆肾素活性(PRA)、血管紧张素Ⅱ(AngⅡ)、醛固酮(ALD)浓度.结果治疗8周后三组血压均下降,其中L组下降10.8±6.2/17.5±5.5 mmHg,总有效率59.1%;B组下降11.2±5.4/16.4±4.6 mmHg,总有效率65.0%;L+B组下降26.4±5.7/32.1±11.0 mmHg,总有效率95.2%.L+B组降压幅度最大,与L组、B组比较有统计学意义(P＜0.001).L组与B组的降压幅度及有效率无显著差异(P＞0.05).三组血浆ALD浓度在治疗后均下降,其中L+B组ALD下降较L组与B组显著(P＜0.001).氯沙坦组不良反应少.结论氯沙坦有明显降压作用,与苯那普利合用有叠加效应.     

西尼地平和氨氯地平对原发性高血压患者交感神经系统活性的影响

目的利用握力试验激活交感神经系统,评价服用西尼地平和氨氯地平8周后交感神经系统活性的变化.方法50例轻中度原发性高血压患者经2周安慰剂期后,随机分入西尼地平组(n=25,西尼地平5 mg,每日1次)和氨氯地平组(n=25,氨氯地平5 mg,每日1次).于安慰剂期末和药物治疗8周末各进行1次握力试验,并记录静息血压和心率.结果西尼地平组和氨氯地平组用药8周后分别与用药前比较静息时收缩压和舒张压均显著降低(P均＜0.01).服药前两组握力试验中血压和心率增加幅度相似,但用药后握力试验中西尼地平组血压增量从(30.7±8.63)/(20.7±3.44)mmHg降至(20.3±10.42)/(14.7±4.58)mmHg(P＜0.01),而氨氯地平组血压增加幅度与用药前无显著性差异.结论服用西尼地平不仅可降低静息时血压,而且可降低负荷状态下的血压增加幅度.氨氯地平仅降低静息血压,对负荷状态下交感神经系统激活无影响.     

国产苯磺酸氨氯地平治疗轻中度原发性高血压的疗效和安全性

目的评价国产苯磺酸氨氯地平(安内真)治疗轻、中度原发性高血压的疗效和安全性.方法在12个研究中心选择轻、中度原发性高血压患者,采用随机、双盲、平行对照的方法,经2周单盲安慰剂洗脱期后,随机分入安内真组或进口苯磺酸氨氯地平(络活喜)组,分别服用安内真或络活喜5 mg每日一次,治疗4周末坐位DBP<90 mmHg者继续原剂量治疗至8周末;坐位DBP≥90 mmHg者剂量分别加倍至10 mg每日一次治疗至8周末.于安慰剂洗脱期末及治疗2、4、6、8周末测量诊室血压、心率、心律及体征并记录不良反应.试验开始前及结束时进行实验室检查.结果共266 例原发性高血压患者进入随机试验,安内真组134例,络活喜组132例;243 例完成试验,其中安内真组124 例,络活喜组119 例.两组服药后2、4、6、8周坐位收缩压和舒张压与服药前比较均有明显降低,差别有统计学意义(P<0.001);两组服药后2、4、6、8周坐位舒张压下降幅度组间比较无统计学差异(P>0.05);服药8周后,安内真组和络活喜组总有效率分别为96.77% 和 94.12%,组间比较无统计学差异.两组不良反应轻而少,组间比较无显著性差别;两组试验结束时主要实验室检查指标与试验前比较无统计学差异.结论安内真5～10 mg每日一次治疗轻、中度原发性高血压安全有效.     

CARLOS:坎油沙坦+双氢克尿噻与氯沙坦+双氢克尿噻对比研究

作　　者　KoeningW标　　题　中、重度高血压病人服用坎迪沙坦+双氢克尿噻复合制剂(cilexetil)与氯沙坦+双氢克尿噻复合制剂有效性及耐受性的对比研究。参考文献　ClinDrugInvest,2 0 0 0 ,19:2 39～2 4 6　　疾　　病　高血压病目　　的　比较中、重度高血压病人服用坎迪沙坦+双氢克尿噻复合制剂(cilexetil)与氯沙坦+双氢克尿噻复合制剂有效性及耐受性。研究设计　随机、双盲、双安慰剂、平行队列研究。随　　访　6周。试验病人　16 0名没接受治疗或控制的高血压病人,10 0mmHg <坐位舒张压≤12 0mmHg ,其中81名患者接受坎迪沙坦+双氢克…     

依普利酮与氯沙坦对轻中度原发性高血压患者动脉僵硬度及中心动脉压的影响

目的探讨依普利酮与氯沙坦对收缩压及舒张压均增高的双期轻中度原发性高血压患者动脉僵硬度及中心动脉压(CAP)的影响。方法随机、双盲、双模拟、阳性药物平行对照设计,将84例轻中度原发性高血压患者[舒张压90～<110mm Hg(1mm Hg=0.133kPa)且收缩压140～<180mm Hg]分为依普利酮组和氯沙坦组,每组各42例,经服用安慰剂2周后进入12周的试验期,分别给予依普利酮50mg或氯沙坦50mg,口服1次/d,复诊1次/2周,4周后如舒张压≥90mm Hg,则改为依普利酮100mg分2次口服或氯沙坦100mg,口服1次/d。安慰剂治疗2周后及12周试验期结束前分别进行肝肾功能、电解质、血糖、血脂、血常规、尿常规、动态血压监测、臂踝脉搏波传导速度(baPWV)和CAP的测定。结果依普利酮组高血压患者完成试验37例,失访5例,氯沙坦组完成试验40例,失访2例;与治疗前相比,依普利酮组及氯沙坦组患者坐位收缩压及舒张压、动态血压参数、baPWV及CAP均明显降低;治疗12周末,两组患者的坐位收缩压及舒张压下降幅度差异无统计学意义[(18.3±8.6)比(21.4±9.4),(14.0±5.3)比(15.1±6.6)mm Hg,均P>0.05];依普利酮组的24h平均收缩压及平均舒张压、昼平均收缩压及平均舒张压、夜平均收缩压及平均舒张压、baPWV、CAP及总的不良事件发生率,与氯沙坦组相比差异无统计学意义(均P>0.05)。结论依普利酮与氯沙坦均能明显降低轻中度收缩压及舒张压均增高的双期原发性高血压患者的动脉僵硬度及中心动脉压。     

应用动态血压监测评价氯沙坦治疗原发性高血压的降压疗效

目的：应用动态血压监测（ＡＢＰＭ）评估氯沙坦（ｌｏｓａｒｔａｎ）５０～１００ ｍｇ,每日１次,对轻、中度原发性高血压（ＥＨ）患者的２４小时降压效果。 方法：轻、中度ＥＨ患者 ３３例,服用 ２周安慰剂,坐位舒张压仍在 ９５～１１４ ｍｍＨｇ（１ ｍｍＨｇ＝０．１３３ ｋＰａ）者予氯沙坦５０ ｍｇ／ｄ,服药 ２周末血压下降未达有效标准者氯沙坦增加至 １００ ｍｇ／ｄ,氯沙坦治疗疗程共 ６周。于服安慰剂末及治疗２、４、６周末测诊室血压,于服安慰剂末及治疗６周末应用ＡＢＰＭ。 结果;氯沙坦治疗６周,降压总有效率为８７．５％;２４小时各时点血压均较治疗前显著下降（Ｐ＜０．０５、Ｐ＜０．０１）,不伴有心率及血压昼夜节律的改变;降低收缩压和舒张压的谷／峰值分别为５２．９％和６３．６％。能明显降低血尿酸（Ｐ＜０．０５）。除１例因头晕中途退出研究外,余不良反应轻微。 结论：氯沙坦 ５０～１００ ｍｇ,每日１次能平稳、有效地控制 ＥＨ患者 ２４小时血压,且患者总体耐受良好。     

托拉塞米治疗原发性高血压的临床评价

目的　评价托拉塞米 (torasemide)治疗轻、中度原发性高血压的疗效和安全性。方法　选择门诊轻、中度原发性高血压患者 (坐位舒张压 (DBP) 95mmHg～ 1 1 5mmHg) ,以随机、双盲、平行对照的方法 ,经 1～ 2周药物洗脱期后 ,随机分入托拉塞米组或吲哒帕胺缓释片剂 (indapamide)组 ,分别服用托拉塞米 5mg每日一次或吲哒帕胺缓释片剂2 5mg每日一次。治疗 4周末坐位DBP <90mmHg者结束试验 ;坐位DBP≥ 90mmHg者剂量分别加倍至托拉塞米1 0mg每日一次或吲哒帕胺缓释片剂 5mg每日一次 ,继续服用 4周。于洗脱期末及治疗 2、4、6、8周测量诊室血压、心率并记录症状、体征 ;治疗期前、治疗第 2周及试验结束时进行实验室检查。结果　共 1 30例合格的原发性高血压患者进入随机分组 ,1 1 8例完成试验 ,其中托拉塞米组 56例 (4周结束者 30例 ,8周结束者 2 6例 ) ,吲哒帕胺缓释片剂组 62例 (4周结束者 41例 ,8结束者周 2 1例 )。服药 4周后 ,总有效率托拉塞米组 67 86 % (38/ 56例 ) ,吲哒帕胺缓释片剂组 72 58% (45/ 62例 ) ;治疗 8周后 ,加量者总有效率托拉塞米组 34 62 % (9/ 2 6例 ) ,吲哒帕胺缓释片剂组61 90 % (1 3/ 2 1例 ) ,组间比较均无差异 (P =1 0 0 ,P =0 67)。两组药后 2、4、6、8周坐位舒张压的下降幅     

托拉塞米治疗原发性高血压的临床评价

目的评价托拉塞米(torasemide)治疗轻、中度原发性高血压的疗效和安全性.方法选择门诊轻、中度原发性高血压患者(坐位舒张压(DBP)95 mmHg～115 mmHg),以随机、双盲、平行对照的方法,经1～2周药物洗脱期后,随机分入托拉塞米组或吲哒帕胺缓释片剂(indapamide)组,分别服用托拉塞米5 mg每日一次或吲哒帕胺缓释片剂2.5 mg每日一次.治疗4周末坐位DBP<90 mmHg者结束试验;坐位DBP≥90 mmHg者剂量分别加倍至托拉塞米10 mg每日一次或吲哒帕胺缓释片剂5 mg每日一次,继续服用4周.于洗脱期末及治疗2、4、6、8周测量诊室血压、心率并记录症状、体征;治疗期前、治疗第2周及试验结束时进行实验室检查.结果共130例合格的原发性高血压患者进入随机分组,118例完成试验,其中托拉塞米组56例(4周结束者30例,8周结束者26例),吲哒帕胺缓释片剂组62例(4周结束者41例,8结束者周21例).服药4周后,总有效率托拉塞米组67.86%(38/56例),吲哒帕胺缓释片剂组72.58%(45/62例);治疗8周后,加量者总有效率托拉塞米组34.62%(9/26例),吲哒帕胺缓释片剂组61.90%(13/21例),组间比较均无差异(P=1.00,P=0.67).两组药后2、4、6、8周坐位舒张压的下降幅度和下降率组间比较无统计学差异.治疗2周和试验结束时吲哒帕胺缓释片剂组的血钾、钠、氯均较托拉塞米组低(P<0.01或0.05).结论托拉塞米5～10 mg每日一次治疗轻、中度原发性高血压的疗效与吲哒帕胺缓释片剂2.5～5 mg每日一次相似,但对血钾、钠、氯的影响较吲哒帕胺缓释片剂轻.     

Antihypertensive efficacy and safety of fixed-dose combination therapy with losartan plus hydrochlorothiazide in Japanese patients with essential hypertension.

A randomized, double-blind, placebo-controlled, parallel-group multicenter study was conducted to evaluate the antihypertensive efficacy and safety of 8-week treatment with one of three fixed-dose combinations-losartan 50 mg plus hydrochlorothiazide 12.5 mg, losartan 50 mg plus hydrochlorothiazide 6.25 mg, or losartan 25 mg plus hydrochlorothiazide 6.25 mg-in comparison with those of hydrochlorothiazide 12.5 mg alone, losartan 50 mg alone, or placebo in Japanese patients with essential hypertension. Significant reductions in sitting diastolic blood pressure (DBP) and systolic blood pressure (SBP) were seen in all three combination groups compared with the placebo group (each p<0.001). The greatest reductions in DBP and SBP were observed in the losartan 50 mg plus hydrochlorothiazide 12.5 mg group (12.7 and 18.0 mmHg, respectively). The reductions in the losartan 50 mg plus hydrochlorothiazide 12.5 mg group were significantly greater (each p<0.001) than those in the placebo group and each of the monotherapy groups. There were no significant differences in the incidences of clinical and laboratory drug-related adverse events between any of the combination groups and the placebo group. All combination groups showed improved hypokalemia and hyperuricemia compared to the hydrochlorothiazide 12.5 mg group. These results demonstrated that once-daily, fixed-dose combination therapy with losartan 50 mg plus hydrochlorothiazide 12.5 mg is well tolerated and more efficacious in lowering DBP and SBP than monotherapy in Japanese hypertensive patients.     

Effect of delapril-manidipine combination vs irbesartan-hydrochlorothiazide combination on fibrinolytic function in hypertensive patients with type II diabetes mellitus

The aim of this double-blind, double-dummy, parallel group study was to compare the effects of delapril-manidipine combination vs a irbesartan-hydrochlorothiazide combination on plasma tissue plasminogen activator (t-PA) and plasmogen activator inhibitor type I (PAI-l) activities in hypertensive patients with type II diabetes mellitus. After a 4-week run-in placebo period, 80 patients (37 male and 43 female), aged 41-65 years, were randomly allocated to an 8-week treatment with delapril 30 mg once daily or irbesartan 150 mg once daily. Thereafter, manidipine l0 mg once daily was added to delapril treatment and hydrochlorothiazide 12.5 mg to irbesartan treatment for a further 8 weeks. Blood pressure (BP), plasma t-PA and PAI-l activities were evaluated at the end of the run-in period, after 4-week monotherapy treatments, and at the end of the combination treatment periods. Both combination treatments, delapril-manidipine and irbesartan-hydrochlorothiazide, produced a greater reduction in systolic BP/diastolic BP (SBP/DBP) values (-27.6/21.8 mmHg and -26.4/20.2 mmHg, respectively) than the respective monotherapies (-15.2/11.7 mmHg with delapril and -16.3/11.3 mmHg with irbesartan). Delapril monotherapy significantly decreased plasma PAI-l activity (-10.4 IU/mI; P<0.05). The addition of manidipine produced a significant increase in t-PA activity (+0.27 IU/mI); P<0.05). Irbesartan monotherapy did not significantly affect the fibrinolytic balance, whereas the addition of hydrochlorothiazide worsened it, producing a significant increase in PAI-l activity (+9.5 IU/ml; P<0.05). In hypertensive patients with type II diabetes mellitus, the combination delapril-manidipine may determine a greater improvement of the fibrinolytic function than the respective monotherapy, while the association irbesartan-hydrochlorothiazide may worsen it.     

Aggressive antihypertensive therapy based on hydrochlorothiazide, candesartan or lisinopril as initial choice in hypertensive type II diabetic individuals: effects on albumin excretion, endothelial function and inflammation in a double-blind, randomized clinical trial

We investigated the effects of aggressive antihypertensive therapy based on hydrochlorothiazide, candesartan or lisinopril on urinary albumin excretion, endothelial function and inflammatory activity in hypertensive type II diabetic individuals. A total of 70 hypertensive type II diabetic individuals were treated with three antihypertensive strategies in a randomized, double-blind, double-dummy design. Blood pressure was titrated to levels below 130/85 mmHg or a decrease in systolic pressure of 10% with a diastolic pressure below 85 mmHg. After titration, patients were treated for 12 months. Mean blood pressures changed from 157/93, 151/94 and 149/93 at baseline to 135/80, 135/82 and 131/80 mmHg after titration in the hydrochlorothiazide (n=24), candesartan (n=24) and lisinopril (n=22) groups. About 70% reached target blood pressures. However, only 45% had blood pressures <130/85 mmHg. Urinary albumin excretion and levels of soluble vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 decreased (GEE regression coefficients, -2.40 mg/24 h (P<0.001), -85 ng/ml (P=0.01) and -50 ng/ml (P=0.02)), but brachial artery endothelium-dependent and -independent vasodilation and levels of von Willebrand factor and C-reactive protein did not change (GEE regression coefficients, 0.21 mm (P=0.07), 0.04 mm (P=0.43), 0.04 IU/ml (P=0.33) and -1.15 mg/l (P=0.64)). No differences in outcome variables between treatment groups were observed. These data show that achievement of target blood pressures below 130/85 mmHg in hypertensive type II diabetes is difficult. Aggressive antihypertensive therapy can improve urinary albumin excretion, endothelial function and inflammatory activity in hypertensive type II diabetic individuals, regardless of the type of antihypertensive therapy used.     

Renin inhibition with aliskiren provides additive antihypertensive efficacy when used in combination with hydrochlorothiazide

OBJECTIVES: Aliskiren is a novel, orally active renin inhibitor. Its antihypertensive efficacy and safety, alone and in combination with hydrochlorothiazide (HCTZ), were investigated in an 8-week, double-blind, placebo-controlled trial in hypertensive patients. The effects of these treatments on plasma renin activity (PRA) were also assessed. METHODS: A total of 2776 patients aged >or=18 years with mean sitting diastolic blood pressure (MSDBP) 95-109 mmHg were randomized to receive once-daily treatment with aliskiren (75, 150 or 300 mg), HCTZ (6.25, 12.5 or 25 mg), the combination of aliskiren and HCTZ, or placebo, in a factorial design. The primary endpoint was the change in MSDBP from baseline to week 8. PRA was assessed at these timepoints at selected study centers. RESULTS: Aliskiren monotherapy was superior to placebo (P < 0.001; overall Dunnett's test) in reducing MSDBP and mean sitting systolic blood pressure (MSSBP). Combination treatment was superior to both component monotherapies in reducing BP (maximum MSSBP/MSDBP reduction of 21.2/14.3 mmHg from baseline with aliskiren/HCTZ 300/25 mg), and resulted in more responders (patients with MSDBP < 90 mmHg and/or >or=10 mmHg reduction) and better control rates (patients achieving MSSBP/MSDBP < 140/90 mmHg) than either monotherapy. Aliskiren monotherapy reduced PRA by up to 65% from baseline. Although HCTZ monotherapy increased PRA by up to 72%, PRA decreased in all of the combination therapy groups. All active treatments were well tolerated. CONCLUSIONS: Aliskiren monotherapy demonstrated significant BP lowering, and its effect was considerably greater when combined with HCTZ. Renin inhibition with aliskiren neutralized the compensatory rise in PRA induced by HCTZ.     

贝那普利/氨氯地平复方制剂与贝那普利单药治疗轻中度高血压的多中心随机双盲平行对照研究

目的 评价贝那普利/氨氯地平复方片剂与贝那普利片单药治疗轻、中度高血压患者的有效性和安全性.方法 本研究为多中心、随机、双盲、平行对照研究.356例原发性高血压患者经2周洗脱期后,再给予4周贝那普利片10 mg单药治疗,220例平均坐位舒张压(SeDBP)仍≥90 mm Hg(1 mm Hg=0.133 kPa)的患者随机分为贝那普利(10 mg)/氨氯地平(5 mg)固定剂量复方片剂组(复方制剂组,1片/d,n=113)和贝那普利片单药组(单药治疗组,20 mg/d,n=107),治疗4周末两组诊室SeDBP≥90 mmHg者剂量加倍.SeDBP＜90 mm Hg者续服原剂量,共随机双盲治疗8周.以总有效率和SeDBP下降差值作为主要疗效指标.其中74例患者(复方片剂组38例,单药组36例)完成了24 h动态血压监测,并作为降压疗效的评价指标.结果 随机、双盲治疗8周末,复方片剂组SeDBP下降值为(11.7±6.8)mm Hg、达目的 血压占65.7%、总有效率为88.5%;单药治疗组SeDBP下降值为(7.7±6.9)mm Hg、达目的 血压占35.5%、总有效率为65.5%.两组组间比较差异均有统计学意义(P＜0.001).24 h动态血压监测结果,复方制剂组和单药组的舒张压/收缩压(DBP/SBP)的谷/峰比率(T/P)分别为83.1%/76.0%和85.8%/79.5%(P＜0.05).复方制剂组与单药治疗组的不良反应发生率分别为16.8%和35.5%(P＜0.01).结论 贝那普利/氨氯地平复方制剂治疗原发性高血压患者的降压疗效明显优于贝那普利单药治疗,且有良好的耐受性.

Abstract：

Objective To evaluate the efficacy and tolerability of the fixed combination of amlodipine 5 mg/benazepril 10 mg once-daily therapy, compared with benazepril, 10 mg, monotherapy in patients with mild and moderate hypertension, and to evaluate the 24 h antihypertensive efficacy and the duration of action by ambulatory blood pressure monitoring Methods In a multicenter, randomized,double-blind, parallel controlled trial, 356 cases of hypertensive patients after 2 weeks wash-out, and then given 4 weeks of benazepril 10 mg monotherapy, 220 patients with mean seated diastolic blood pressure (SeDBP)remained ≥90 mm Hg(1 mm Hg = 0. 133 kPa)were randomly divided into benazepril 10 mg/amlodipine 5 mg(BZ10/AML5)fixed-dose combination therapy group(once a day, n = 113), and benazepril monotherapy group(daily 20 mg, n = 107). In the two groups the patients with SeDBP≥90 mm Hg were doubled the dosage of the initial regimen at the end of 4-week treatment for additional 4 weeks , and the patients with SeDBP ＜ 90 mm Hg remained the initial regimen for additional 4 weeks. The primary endpoint was to evaluate the improvement of SeDBP at the end of 8-week treatment. There were 74 patients(the combination therapy group n = 38, monotherapy therapy group n = 36)completed the 24 h ambulatory blood pressure monitoring which was included in the final efficacy analysis. Results The randomized, doubleblind treatment for 8 weeks, the mean value of SeDBP reduction, the reaching target blood pressure rate and total successful response rate to the treatment(a SeDBP ＜ 90 mm Hg or a decrease of 10 mm Hg or more from baseline)were(11.7 ± 6.8)mm Hg, 65.7% and 88.5% in the combination therapy group,respectively, and were(7.7 ±6. 9)mm Hg, 35.5% and 65.5% in the monotherapy group, respectively.There were statistically significant difference between the combination therapy and the monotherapy groups in all the 3 indexs(P ＜ 0. 001). The fixed combination significantly reduced systolic blood pressure(SBP)and diastolic blood pressure(DBP)values throughout the 24 h. The trough to peak ratios of DBP/SBP in the fixed compound of benazepril/amlodipine(10 mg/5 mg)and benazepril(20 mg)alone were 83. 1%/76. 0% and 85.8%/79. 5%, respectively. Adverse events rates were 16. 8% in the combination therapy group and 35.5% in the monotherapy group(P ＜ 0. 001). Conclusions The combination therapy with benazepril/amlodipine was superior to benazepril monotherapy and was well tolerated in patients with essential hypertension and allowing a satisfactory BP control for 24 hours.     

Comparison of antihypertensive and metabolic effects of losartan and losartan in combination with hydrochlorothiazide--a randomized controlled trial

INTRODUCTION: Losartan is an angiotensin II receptor blocker indicated for treatment of hypertension. It also inhibits platelet agreggation through blockade of thromboxane A2/ prostaglandin H2 receptors, and has a uricosuric effect We determined the effect on ambulatory blood pressure (ABP) of 100 mg losartan monotherapy (L100) versus 50 mg losartan/12.5 mg hydrochlorothiazide (HCTZ) combination therapy (L50H12.5C), in patients uncontrolled on 50 mg losartan. We also assessed the effects of losartan on platelet aggregation and serum urate at these clinically relevant doses. METHODS: This was a randomized, double-blind trial of L100 versus L50H12.5C, in moderate hypertensives (sitting diastolic blood pressure (DBP) >or = 95 mmHg and < 120 mmHg). After 4 weeks of placebo run-in, patients received 50 mg losartan for 6 weeks; patients uncontrolled (sitting DBP > or = 95 mmHg) were randomized to L100 or L50H12.5C for a further 6 weeks. Platelet function was assessed by measuring percentage inhibition of platelet aggregation, and serum uric acid was also measured. RESULTS: Monotherapy with 50 mg losartan reduced ABP by 16.0/9.9 mmHg during the day and 9.8/5.5 mmHg at night However, 16 out of 24 (66%) patients had uncontrolled blood pressure on this treatment L50H12.5C further reduced daytime ABP by 10.7(10.7)/8.4(6.5) mmHg mean (SEM) compared with L100 (-5.3(9.7)/-2.3(4.8), P = 0.013). 50 mg losartan and L100 did not affect platelet function or uric acid levels beyond placebo values; treatment with L50H12.5C was associated with a significant rise in serum urate above levels obtained on 50 mg losartan (366.9(67.6) versus 331.6(65.0), P=0.006), to levels similar to placebo (358.8(80.9)). CONCLUSION: L50H12.5C is an effective antihypertensive regimen in patients with moderate hypertension that is uncontrolled on 50 mg losartan monotherapy, and is the preferred treatment option in these patients compared with increasing the dose of losartan. The additional benefit of losartan on platelet inhibition was not evident in our population at these doses; however, there was evidence to suggest that the uricosuric effects of losartan might ameliorate the uric acid retention effects of therapy with hydrochlorothiazide.     

The efficacy and tolerability of losartan versus atenolol in patients with isolated systolic hypertension. Losartan ISH Investigators Group

OBJECTIVE: To compare the efficacy and tolerability of angiotensin II (Ang II) antagonist losartan and the beta-blocker atenolol in the treatment of patients with isolated systolic hypertension (ISH) after 16 weeks of treatment. METHODS: A double-blind, randomized, multi-country study was carried out in 273 patients with ISH. Patients with a sitting systolic blood pressure (SiSBP) of 160-205 mmHg, and a sitting diastolic blood pressure (SiDBP) < 90 mmHg at screening and at placebo baseline were subjected to a 4-week placebo period and then randomly grouped to receive 50 mg losartan or 50 mg atenolol once daily for 16 weeks. At 8 and 12 weeks, patients not controlled (SiDBP > or = 160 mmHg) were given additional treatment of 12.5 mg hydrochlorothiazide (HCTZ) once daily. RESULTS: Similar significant reductions in SiSBPs (mean +/- SD) were obtained with 50 mg losartan and 50 mg atenolol, from 173.7 +/- 10.3 and 173.5 +/- 10.7 mmHg at baseline to 149.0 +/- 15.5 and 148.2 +/- 15.3 mmHg after 16 weeks of losartan or atenolol treatment respectively. Sixty-seven percent of the losartan-treated and 64% of the atenolol-treated patients remained on monotherapy throughout the study. Only 1.5% of the losartan-treated patients withdrew because of a clinical adverse event (CAE) compared with 7.2% in the atenolol-treatment group (P= 0.035). Drug-related CAEs were observed significantly more frequently with atenolol than with losartan treatment (20.3 versus 10.4%; P = 0.029). CONCLUSION: It is concluded that 50 mg losartan and 50 mg atenolol produced comparable reductions in SiSBP in patients with ISH but losartan was better tolerated. This is the first demonstration of the therapeutic value of selective Ang II receptor blockade with losartan in the treatment of ISH.     

Efficacy of manidipine/delapril versus losartan/hydrochlorothiazide fixed combinations in patients with hypertension and diabetes

BACKGROUND: Hypertension markedly increases the already high risk for cardiovascular complications in patients with diabetes mellitus. Less than one in eight patients with hypertension and type 2 diabetes have adequately controlled blood pressure. As a result, antihypertensive combinations are now widely used in management of hypertension associated with diabetes. METHODS: This double-blind study investigated efficacy of a new fixed dose combination of a calcium antagonist, manidipine 10 mg, and an angiotensin-converting enzyme inhibitor, delapril 30 mg, compared with a combination of an angiotensin receptor blocker, losartan 50 mg, and a diuretic, hydrochlorothiazide 12.5 mg. Patients with hypertension (blood pressure > or = 130/80 mmHg) with controlled type 2 diabetes (HbA1c < or = 7.5%) were randomized to manidipine/delapril (n = 153) or losartan/hydrochlorothiazide (n = 161), administered once daily for 12 weeks. Patients underwent ambulatory blood pressure monitor evaluation at baseline and end of treatment. RESULTS: Mean decreases in 24-h systolic blood pressure were seen with both manidipine/delapril (-9.3 mmHg) and losartan/hydrochlorothiazide (-10.7 mmHg) combinations. The mean (95% confidence interval) treatment difference was -1.4 (-4.5/1.8) mmHg, demonstrating noninferiority of the manidipine/delapril combination. Reduction in 24-h diastolic blood pressure (-4.6 versus -4.5 mmHg) and daytime (systolic blood pressure -10.5 versus -11.1 mmHg) and night-time (systolic blood pressure -7.1 versus -9.3 mmHg) blood pressure were also not significantly different between treatments. Compliance and adverse events were comparable for both groups. CONCLUSION: The study demonstrated that the combination of manidipine and delapril is as effective as losartan and hydrochlorothiazide in treatment of hypertension in type 2 diabetes.     

Long-term efficacy of combination therapy with losartan and low-dose hydrochlorothiazide in patients with uncontrolled hypertension

We evaluated the long-term efficacy of losartan and low-dose hydrochlorothiazide combination therapy in the treatment of hypertension. We enrolled 15 Japanese hypertensive outpatients whose 24-hour ambulatory blood pressure was >or= 135/80 mmHg after candesartan 8 mg (CND group; n = 10) monotherapy or amlodipine 5 mg (AML group; n = 5) monotherapy for 2 months or more. The monotherapy was then switched to losartan 50 mg and hydrochlorothiazide 12.5 mg combination therapy. Ambulatory blood pressure and indices of glucose and lipid metabolism were measured at the end of the monotherapy and after 3 and 12 months of the combination therapy. In the CND group, 24-hour blood pressure decreased significantly from 137 +/- 9/89 +/- 4 to 126 +/- 8/81 +/- 7 mmHg after 3 months (P < 0.05/ P < 0.001) and to 123 +/- 7/81 +/- 4 mmHg after 12 months (P < 0.01/P < 0.001). In the AML group, 24-hour blood pressure decreased significantly from 137 +/- 11/81 +/- 7 to 125 +/- 12/75 +/- 6 mmHg after 3 months (P < 0.05/P < 0.05) and to 124 +/- 9/77 +/- 7 mmHg after 12 months (P < 0.05/NS). There were significant decreases in systolic blood pressure during the daytime (6:00-21:30), nighttime (22:00-5:30) and early morning (6:00-8:00) after 12 months in both groups. No adverse changes in the indices of glucose or lipid metabolism were observed in either group. In conclusion, long-term combination therapy with losartan and low-dose hydrochlorothiazide was effective in the treatment of hypertensive patients whose blood pressure was not controlled by candesartan or amlodipine monotherapy alone.