氯沙坦治疗轻、中度高血压病的疗效和安全性评价

目的 评价氯沙坦（ｌｏｓａｒｔａｎ,ＬＯＳ）治疗轻、中度高血压病（ＥＨ）的临床疗效和安全性。方法 选取轻中度ＥＨ患［坐位舒张压（ＳｉＤＢＰ）９０￣１１４ｍｍＨｇ（１ｍｍＨｇ＝０．１３３ｋＰａ］,一组采用随机、双盲８周的平行对照,另一组服ＬＯＳ采用开放的８周２４小时动态血压监测（ＡＢＰＭ）和２４周的诊室血压研究。经１周药物冲洗期及２周安慰剂期后,服双盲药ＬＯＳ（６１例）５０ｍｇ／ｄ或对照药赖诺普利     

卡托普利对急性心肌梗死患者早期血压、心率的影响——中国心脏研究－Ⅰ暨血管紧张素转换酶抑制剂治疗急性心肌梗死大型随机临床试验专题报告之二

探讨血管紧张素转换酶抑制剂卡托普利对急性心肌梗死病人早期血压、心率、死亡率及临床事件的影响。方法多中心随机双盲安慰剂对照临床试验，给发病３６ｈ内的急性心肌梗死病人随机口服卡托普利（ｎ＝７４６８，１２．５ｍｇ３／ｄ）或安慰剂（ｎ＝７４９４）治疗４周。结果基础血压＜１００ｍｍＨｇ或舒张压＜７０ｍｍＨｇ、心率＜７０ｍｉｎ－１者，卡托普利组４周总死亡率略高于安慰剂对照组；基础收缩压≥１００ｍｍＨｇ或舒张压≥７０ｍｍＨｇ、心率≥７０ｍｉｎ－１（尤其心率偏快）者，卡托普利组死亡率均低于对照组。用首剂（６．２５ｍｇ）药后２ｈ收缩压或舒张压较前下降１０％～１９％者卡托普利组死亡率（８．５％，７．１％）均明显低于对照组（１０．７％，Ｐ＝０．０４；１０．０％，Ｐ＝０．００３），而血压下降幅度＜１０％者两组死亡率相似。基础收缩压＜１００ｍｍＨｇ者卡托普利组休克发生率（１０．０％）高于对照组（７．８％），低血压发生率（３６．５％ｖｓ２４．０％）更高。基础心率＜６０ｍｉｎ－１者卡托普利组心力衰竭（１３．４％）、休克（５．８％）、室颤（２．８％）发生率均略高于对照组（１１．９％，３．６％，１．３％）；心率≥６０ｍｉｎ－１者卡托普利     

用动态血压监测的方法评价塞利洛尔的降压疗效

目的用２４ｈ动态血压监测的方法评价塞利洛尔降压疗效及作用持续时间。方法符合入选条件的轻中度高血压病患者３２例，平均４８．６±７．８岁。服安慰剂２周后，每天服用塞利洛尔１００～３００ｍｇ共６周，治疗前后分别监测２４ｈ动态血压。结果治疗后２４ｈ、白天、夜间的ＳＢＰ和ＤＢＰ均有明显下降（Ｐ＜０．０１）；血压负荷值亦明显减小（Ｐ＜０．０１）；ＳＢＰ及ＤＢＰ谷峰比值均＞５０％。心率无明显变化（Ｐ＞０．０５）。结论：塞利洛尔的降压作用能持续２４ｈ以上，且安全有效。     

非洛地平缓释片每日一次治疗高血压病的疗效观察

本研究采用自身对照开放试验方法，观察了非洛地平缓释片对轻、中度高血压病患者治疗的疗效和耐受性。本研究共收入２０４例病人，其舒张压在９５ｍｍＨｇ至１１５ｍｍＨｇ（１ｍｍＨｇ＝０．１３３ｋＰａ）之间，经两周观察期，给予非洛地平缓释片（２．５、５、１０、２０ｍｇ）治疗。经８周治疗，病人的收缩压／舒张压下降了２４．１±１３．５／１７．１±６．１ｍｍＨｇ，与治疗前血压相比差异有非常显著性（Ｐ＜０．００１），显效率为８８．２％（１８０／２０４），总有效率为９６．５％（１９７／２０４），不良反应多为轻中度头痛、踝部水肿等。其中有４８例接受了半年的长期治疗，结果显示血压仍然得到稳定的控制且无耐药性产生，平均收缩压／舒张压波动范围１２８．０～１５０．０／８２．６～９０．０ｍｍＨｇ。有２１例病人接受２４小时动态血压监测，结果显示：２４小时平均收缩压／舒张压较治疗前分别下降了１９．５／１２．６ｍｍＨｇ（Ｐ＜０．００１），收缩压／舒张压的谷峰值比率值分别为６７．６％和７９．１％。由此可见，非洛地平缓释片是有效且易于耐受的抗高血压药物。     

动态血压参数正常参照值协作研究

国内七个医疗单位检测２８３例年龄２０～７９岁临床健康者的动态血压，结果表明，国人２４小时动态血压均值１１１／６８±９．６／６，３ｍｍＨｇ（１ｍｍＨｇ＝０．１３３ｋＰａ），男（１１３．９／６９．２±９．０／６．０ｍｍＨｇ）女（１０７．０／６６．３±８．９／６．３ｍｍＨｇ）性别之间差异有非常显著性（Ｐ＜０．００１），各年龄组之间相差数值较小，各地区动态血压参数值无明显大的差距。推荐２４小时动态血压均值＜１３０／８０ｍｍＨｇ，白昼均值＜１３５／８５ｍｍＨｇ，夜间均值＜１２５／７５ｍｍＨｇ，夜间血压下降率≥１０％可作为暂时的动态血压正常参照值工作标准。     

静脉注射依那普利拉治疗重症高血压的疗效及安全性

目的验证国产依那普利拉（Ｅ）治疗重症高血压的降压疗效及安全性，以提供高血压急症的新药。方法对上海、镇江、扬州等４家医院收治的１７２例高血压病重症患者，男１１８例，女５４例，平均年龄（５３±９）岁，静脉注射Ｅ。分组：（１）对三组高血压病（各１０例）分别静脉注射Ｅ１．２５ｍｇ、２．５ｍｇ、５ｍｇ；（２）Ｅ与甲磺酸酚妥拉明（Ｐ）各５４例单次静脉注射开放平行比较试验；（３）３４例为２４小时内多次静脉注射Ｅ（ｑ６ｈ），观察２４小时内血压、心率及不良反应。结果结果显示：（１）不同剂量Ｅ静脉注射以２５ｍｇ降压效果最好；（２）两组比较：用药后２、４、６小时Ｅ组降压幅度优于Ｐ组（Ｐ＜０．０５），总有效率为９６．３％，Ｐ组总有效率９０７％；（３）２４小时多次给Ｅ，总有效率达１００％。Ｅ主要不良反应：轻度头昏（６／１１８）、头痛（２／１１８）、肢体麻木（４／１１８）及咳嗽（５／１１８）。结论国产Ｅ是一种安全有效的治疗高血压急症用药，我们推荐静脉首选剂量２．５ｍｇ为宜。     

24小时动态血压参数正常参照值的研究

目的　探讨国人２４ 小时动态血压（２４ ｈ ＡＢＰ）参数的正常参照值。方法　采用无创性携带式动态血压监测仪检测３００ 例，年龄２０～７９ 岁临床健康者的动态血压。结果　国人２４ 小时动态血压均值：（１１１－８／６８－２ ±８－５／６－１）ｍｍＨｇ（１ ｍｍＨｇ ＝ ０－１３３ ｋＰａ），白昼（１１３－９／７０－１ ±１０－４／６－９）ｍｍＨｇ；夜间（１０７－０／６５－３±９－０／６－０）ｍｍＨｇ。结论　推荐２４ 小时动态血压均值＜ １３０／８０ ｍｍＨｇ；白昼均值＜ １３５／８５ ｍｍＨｇ，夜间均值＜ １２５／７７ ｍｍＨｇ；夜间／白昼比值≤０－９０，即夜间血压下降率≥１０％ 可暂时作为动态血压参数的正常参照值。     

氯沙坦治疗老年高血压伴肾损害的疗效观察

搪塞氯沙坦在老年高血压伴肾损害病人中，对蛋白尿的影响。方法 ３０例老年高血压病患，平均年龄７７．３６±５．６岁，口服氯沙坦，疗程１２周，治疗前后观察血压，２４小时尿蛋白，肾功能变化。结果 氯沙坦能有效地降低尿蛋白排泄（２４小时尿蛋白；０．９９±０．３３降至０．７８±０．３１，与其他降压药联合服用有更好的降压作用。绫 对高血压合并肾损害患，每日１次氯沙坦５０ｍｇ或１００ｍｇ能有效降低尿蛋白排泄     

严重充血性心力衰竭患者自主神经功能与心率变异的关系及地高辛的影响

对２５例重度充血性心力衰竭（ＣＨＦ）患者在地高辛治疗前后测定血浆去甲肾上腺素（ＮＥ）及心率变异（ＨＲＶ）。结果显示：ＮＥ基础值与ＨＲＶ时域指标基础水平均呈负相关（Ｐ＜０．０５或＜０．０１）。地高辛治疗前后的ＮＥ相比（２９１±８０ｐｇ／ｍｌｖｓ２１３±８２ｐｇ／ｍｌ），Ｐ＜０．００１。２４小时平均ＲＲ间期及２４小时正常ＲＲ间期标准差由治疗前的７２７±１２３ｍｓ及６７．７±２１．８ｍｓ分别增加至７７７±１２２ｍｓ及８７．２±２９．２ｍｓ（Ｐ均＜０．０５）；２４小时相邻ＲＲ间期差值的均方根（ＲＭＳＳＤ）、２４小时正常相邻ＲＲ间期之差大于５０ｍｓ的心搏数所占百分比（ＰＮＮ５０）及高频（ＨＦ）由治疗前的３６．３±３０．６ｍｓ、５．３±５．５％及３７．１±２１．２ｍｓ２分别增加至５６．１±４３．７ｍｓ、１０．８±１０．６％及７９．９±５８．２ｍｓ２（Ｐ值＜０．０５至＜０．０１）；低频（ＬＦ）由治疗前的１１８．９±１３３．２ｍｓ２增加至１７１．２±１７２．８ｍｓ２（Ｐ＜０．００５）；ＮＥ下降幅度与时域指标增加幅度均呈正相关。ＨＲＶ多数时域指标增加幅度及其绝对值与血清地高辛浓度呈正相关，以ＲＭＳＳＤ和ＰＮＮ５０尤为显著（Ｐ?     

氯沙坦治疗对高血压病患者近期肾功能影响

目的：评估氯沙坦治疗对高血压病人肾功能的影响。方法４７例高血压病病人随机分为两组：氯沙坦组（５０ｍｇ，１次／日，２３例）；依那普利组（１０ｍｇ，１次／日，２４例）。若经２周治疗后，舒张压仍超过９０ｍｍＨｇ，则剂量加倍。疗程８周。治疗前后观察血压血压及肾功能指标变化，并进行比较。结果①两组经治疗后血压均明显降低，氯沙查组由（１６４．７±１４．９／１０１．２±６．１）ｍｍＨｇ降至（１４５．７±９．７／ 7     

氯沙坦治疗原发性高血压的疗效和对尿清蛋白的影响

目的 探讨氯沙坦治疗轻、中度原发性高血压的疗效和对尿清蛋白的影响。方法 82例高血压患者随机分两组,氯沙坦组(治疗组,43例)50～100mg·d-1口服,疗程12周;培哚普利组(对照组,39例)4～8mg·d-1服,疗程12周。治疗前后做动态血压及肝、肾功能、血脂、血糖等检查,测定尿液中清蛋白(Alb),血清肌酐(Scr)及血尿素氮(BUN)的变化。结果 治疗组降压总有效率75％(33例),降压幅度(以mmHg计)收缩压(SBP)为21.舒张压(DBP)为13,谷/峰(T/P)比值SBP为0.73,DBP为0.71。对照组总有效率74％(29例),降压幅度SBP为22,DBP为12,谷/峰比值SBP为O.71,DBP为O.72,两组结果相似。治疗后两组尿Alb减低(P<0.01)。氯沙坦不良反应轻微。结论 氯沙坦对高血压有确切疗效,干咳发生率低,减少尿清蛋白的排泄,对肾脏有保护作用。     

国产尼索地平片治疗原发性高血压的疗效观察

本研究采用自身对照开放试验方法,观察国产尼索地平片对轻、中度原发性高血压患者的疗效和耐受性.共有268例患者进入研究,其舒张压在95-114mmHg之间.经过7—10天的观察期,给予国产尼索地平片10mg-20mg,每日2次.治疗6周后病人收缩压和舒张压分别从162.26±16.92mmHg和103.63±7.15mmHg降至139.90±12.65mmHg和88.36±9.10mmHg(P<0.005),降压显效率达75.37%(202/268),有效率达21.27%(57/268).总有效率达96.63%.不良反应多为轻中度头痛、面红、踝部浮肿等.其中60例患者接受了单用尼索地平片6个月的长期治疗,结果显示血压得到稳定的控制,平均收缩压和舒张压分别波动在136.3—141.2 mmHg和86.3—88.0mmHg.16例病人进行了24h动态血压监测,结果显示24h平均收缩压和平均舒张压分别从143.20±20.68mmHg和88.87±10.20mmHg降至136.87±13.58mmHg和84.93±9.66mmHg(p<0.05).由此可见,国产尼索地平片是一种有效且易于耐受的抗高血压药物.     

Comparison of telmisartan versus losartan: meta-analysis of titration-to-response studies

OBJECTIVES: To compare the ability of telmisartan and losartan to reduce mean diastolic blood pressure (DBP) during the last 6 h of the 24-h dosing interval in a prospectively planned meta-analysis of ambulatory blood pressure monitoring (ABPM) data from two independent studies. METHODS: Data were from two independent randomized, double-blind, double-dummy, titration-to-response studies conducted in patients with mild-to-moderate hypertension (seated cuff DBP 95-109 mmHg, 24-h mean ambulatory DBP >or=85 mmHg). After a 4-week placebo run-in period, patients received once-daily telmisartan 40 mg or losartan 50 mg, with up-titration after 4 weeks to telmisartan 80 mg or losartan 100 mg, respectively, if seated trough cuff DBP >or=90 mmHg. Blood pressures were recorded using ABPM immediately before randomization and after 8 weeks of active treatment. In addition, seated trough cuff blood pressures were measured at baseline and after 4 and 8 weeks of active treatment. RESULTS: Titration to the higher dose was required in 60.1% of telmisartan patients and 69.5% of losartan patients (P=0.01). Reductions from baseline in the last 6 h mean ambulatory DBP with telmisartan and losartan were 6.6+/-0.4 and 5.1+/-0.4 mmHg, respectively (P<0.01, adjusted for baseline and study); the effects were homogeneous across the two studies. During the last 6 h of the 24-h dosing interval, telmisartan produced greater reductions in each of the observed hourly mean ambulatory DBP values. Telmisartan-induced reductions were also greater for the majority of the observed hourly mean ambulatory DBP values over the entire 24-h dosing interval. Reductions from baseline in the last 6 h adjusted mean ambulatory systolic blood pressure (SBP) for telmisartan and losartan were 9.9+/-0.6 and 7.8+/-0.6 mmHg, respectively (P=0.01). The 24-h profiles of ambulatory SBP hourly mean reductions were similar to those for DBP. Both telmisartan and losartan were found to be safe and well tolerated. CONCLUSIONS: Telmisartan 40/80 mg is superior to losartan 50/100 mg in controlling DBP and SBP during the last 6 h of the 24-h dosing interval.     

Effect of eprosartan and losartan on uric acid metabolism in patients with essential hypertension.

OBJECTIVE: The influence of angiotensin II AT-1 receptor antagonists on uric acid metabolism, and the potential differences among them with regard to this effect, remains to be precisely established. This study was designed to compare the effects of losartan and eprosartan on uric acid metabolism in patients with mild to moderate essential hypertension. DESIGN: Randomized, double-blind, parallel-group study in hypertensive patients. SETTING: Outpatient clinic. PATIENTS: Following a 2- to 3-week single-blind placebo run-in period, 60 patients with sitting diastolic blood pressure > or = 95 and < or = 114 mmHg were randomized. Fifty-eight patients completed the study. INTERVENTIONS: Patients were randomized to receive losartan 50 mg or eprosartan 600 mg once daily for 4 weeks. MAIN OUTCOME MEASURES: The primary endpoint was the change in the ratio of urinary uric acid/creatinine in the period 0-4 h of a 24 h urine collection after 4 weeks of treatment. Secondary endpoints included 24 h urinary uric acid excretion, as well as serum urate and anti-hypertensive efficacy. RESULTS: Mean urinary uric acid/creatinine changes from baseline were 0.14 (day 1) and 0.11 (week 4) for losartan and -0.04 for eprosartan (at both day 1 and week 4; P < 0.01 between groups at both time-points). The mean increase in 24 h urinary uric acid excretion with losartan was 0.7 mmol/24 h (25% increase from baseline) at both day 1 and week 4. No significant difference was observed in the change of serum urate levels versus baseline between both treatment groups after 4 weeks (- 23.4 and - 19.5 micromol/l for losartan and eprosartan, respectively). Patients with hyperuricaemia in both treatment groups showed similar modifications of uric acid metabolism compared with non-hyperuricaemic subjects. Blood pressure control (sitting diastolic blood pressure < 90 mmHg or < 100 mmHg with a decrease of at least 10 mmHg from baseline) was achieved in 22 patients (73%) with eprosartan and in 16 (53%) with losartan. CONCLUSIONS: Losartan increased uric acid excretion in hypertensive patients, whilst eprosartan did not Neither AT-1 receptor antagonist substantially modified serum urate concentrations.     

Antihypertensive effect of valsartan 80 mg and hydrochlorothiazide 12.5 mg evaluated by ambulatory blood pressure monitoring

OBJECTIVE: The aim of the study was to evaluate by ambulatory blood pressure measurement (ABPM) the 24 hours antihypertensive efficacy of the fixed combination therapy, valsartan 80 mg + hydrochlorothiazide 12.5 mg (V + H), once daily, after 6 weeks of treatment, in patients with mild to moderate hypertension. STUDY DESIGN: It was a French, multicenter, double blind, randomized trial in parallel groups comparing V + H and placebo. After an initial two weeks placebo period, patients were assigned to receive either V + H or placebo for six weeks. Were eligible those with clinical arterial blood pressure, measured by sphygmomanometer, between 160/95 and 209/114 mmHg after monotherapy. A 26 hours ABPM, with Spacelabs 90,207, was done at J0 and J42 (one measurement every 15 minutes, in day time and at night). Responders were defined as a fall in day diastolic blood pressure > or = 5 mmHg and/or day diastolic blood pressure < 90 mmHg with ABPM. RESULTS: 123 of the 138 randomized patients had two interpretative measurements. Their average age was 59 + 10 years. 57% (78) of them were males and their average ABPM before treatment was 143 +/- 15/88 +/- 11 mmHg. With V + H, the reduction of the systolic and the diastolic blood pressure measured by ABPM, was significantly more important than with placebo (SBP: -15.4 +/- 10.9 mmHg versus -0.6 +/- 7.7 mmHg, p < 0.001; DBP: -9.1 +/- 7 mmHg versus -0.4 +/- 5.4 mmHg, p < 0.001). Pulse pressure (PP) was also significantly reduced with the combination therapy V + H, but it was not modified with placebo (-6.3 + 5.5 mmHg versus -0.2 + 4.1 mmHg, p < 0.001). ABPM responder rate was 73% with V + H versus 24% with placebo (p < 0.001). Trough/peak ratio was 80.3% for systolic blood pressure and 57.3% for diastolic blood pressure. The combination V + H was as well tolerated as placebo. CONCLUSION: The fixed combination V + H used for treatment of hypertension, after failure of monotherapy, is very effective in reducing pulse pressure, systolic and diastolic blood pressure, over 24 hours, homogeneously, and is as well tolerated as placebo.     

An inpatient trial of the safety and efficacy of losartan compared with placebo and enalapril in patients with essential hypertension

Summary The antihypertensive activity and safety of losartan, a specific and selective antogonist of angiotensin II (subtype 1) receptors, was evaluated in 100 inpatients with mild to moderate essential hypertension. After a 2-week, single-blind, out patient placebo lead-in period, the last 2 days of which included inpatient monitoring of baseline blood pressure, the patients were assigned randomly to receive once-daily doses of either placebo; 50, 100, or 150 mg losartan; or 10 mg enalapril. Patients were treated double blind for 5 days, followed by a day for the study of drug withdrawal. Beginning with the first dose, the three doses of losartan and enalapril significantly decreased peak and trough systolic and diastolic blood pressures compared with placebo (p<-0.05). The area under the blood pressure curve was analyzed as an assessment of total blood pressure change throughout the day. On day 1, total blood pressure reduction with losartan (50–150 mg) was slightly less than with enalapril. By day 5 of double-blind treatment, the reduction in blood pressure in these groups was similar, suggesting that losartan has a slower onset of action than enalapril. No rebound hypertension was observed after study-drug discontinuation. Losartan was well tolerated in this trial, with an adverse event profile similar to placebo and enalapril.     

动态血压评价替米沙坦、氯沙坦治疗轻、中度高血压的临床疗效

目的　比较选择性血管紧张素Ⅱ受体拮抗剂替米沙坦、氯沙坦治疗轻、中度原发性高血压的疗效及安全性。方法　对 77例原发性高血压患者分成两组 ,分别予以替米沙坦 80mg,氯沙坦 5 0mg ,每日一次 ,6周后观察动态血压 (ABPM)评价降压效果。结果　替米沙坦和氯沙坦两组 2 4小时平均动态收缩压 (SBP)、舒张压 (DBP)均明显降低 ,替米沙坦 80mg的降压效果比氯沙坦 5 0mg更好 (P <0 .0 5 ) ,特别是在给药间期的最后 4～ 6小时 ,SBP/DBP替米沙坦降低了12 .3± 14 /7.2± 0 .9mmHg ,氯沙坦降低了 6.0± 1.6/3 .8± 0 .9mmHg(P <0 .0 5 )。结论　替米沙坦 80mg每日用药一次 ,可以保持正常的血压昼夜节律 ,提供 2 4小时血压控制的效果     

Telmisartan vs losartan plus hydrochlorothiazide in the treatment of mild-to-moderate essential hypertension--a randomised ABPM study

The objective of this prospective, randomised, open-label, blinded-end point parallel-group, multicentre study was to show that telmisartan 80 mg is not inferior to a fixed-dose combination of losartan 50 mg/hydrochlorothiazide (HCTZ) 12.5 mg in patients with mild-to-moderate hypertension. The criterion for noninferiority was a treatment difference of < or =3.0 mmHg in the reduction of 24-h mean ambulatory diastolic blood pressure (DBP) from the end of the 4-week placebo washout period to the end of the 6-week active treatment period. In the intent-to-treat analysis, the mean reduction in 24-h DBP was 8.3+/-6.7 mmHg among telmisartan-treated patients (n=332) and 10.3+/-6.3 mmHg among losartan/HCTZ-treated patients (n=350). The mean adjusted difference in 24-h DBP between the two treatment groups was 1.9 mmHg, allowing rejection of the a priori null hypothesis of a treatment difference of >3 mmHg. The reduction in mean 24-h systolic blood pressure was 13.2+/-10.2 mmHg with telmisartan and 17.1+/-10.3 mmHg with losartan/HCTZ. Both drugs provided effective control over the 24-h dosing interval. Analyses of morning (0600-1159) ambulatory blood pressure monitoring DBP means and trough cuff DBP confirmed the noninferiority hypothesis of the protocol for telmisartan 80 mg vs losartan 50 mg/HCTZ 12.5 mg. The reductions in office blood pressures measured at trough in patients treated with telmisartan were -16.3/-9.6 and -18.5/-11.1 mmHg in the patients treated with losartan/HCTZ (difference -2.4/-1.2 mmHg). There were no differences between the side-effect profiles of the two treatments.     

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.     

Central and peripheral hemodynamic effects of losartan and in combination with hydrochlorothiazide in mild to moderate essential hypertension

Background: Angiotensin II antagonists have proved to be effective antihypertensive agents with organoprotective properties. We aimed to clarify the effects of losartan and its combination with hydrochlorothiazide on 24-h blood pressures (BPs), central hemodynamics and microcirculation in essential hypertension (EH). Methods: Forty patients with mild to moderate EH were randomly allocated to receive losartan 50 mg (group I) or losartan 50 mg in combination with hydrochlorothiazide, 12.5 mg (group II). At baseline, week 2 and 8, ambulatory BP monitoring (ABPM), central hemodynamics monitoring and microcirculation investigation were performed. Results: In both groups, 24-h, daytime and night-time systolic (SBP) and diastolic (SBP) significantly decreased at week 8. DBP decreased more than SBP. Both drug regimens led to significant decrease in total peripheral vascular resistance; stroke and cardiac indexes remained unchanged. Losartan and its combination with hydrochlorothiazide improved main parameters of microcirculation. The index of microcirculation increased, as did the amplitude of cardiodependent and low frequency waves. Conclusions: Losartan monotherapy and losartan in combination with hydrochlorothiazide are effective antihypertensive agents. The BP-lowering effect is realized through reduction of total peripheral vascular resistance. Moreover, both drug regimens significantly improve parameters of microcirculation.