坎地沙坦加氢氯噻嗪对轻中度高血压的疗效和安全性

目的 评价坎地沙坦加氢氯噻嗪(复方坎地沙坦酯片)对原发性高血压的降压疗效和安全性.方法 对原发性高血压患者经过2周清洗期后,进入坎地沙坦酯片8 mg单药治疗期,对4周后血压未达标者(达标血压为＜140/90 mm Hg),以随机、双盲双模拟、平行对照、多中心试验方法 ,分别服复方坎地沙坦酯片(坎地沙坦酯16.0mg/氢氯噻嗪12.5 mg)或坎地沙坦酯片16 mg单药治疗8周.结果 经过2周清洗期,共有392例进入单药治疗期,坎地沙坦酯8 mg单药治疗(n=353)2周后,血压下降值(10.2±0.6)/(6.5±5.7)mm Hg;4周的下降值为(10.8±10.9)/(6.6±6.1)mm Hg,4周血压达标率为15.3%(54/353例),组内比较,差异有非常显著意义(P＜0.01).在以后8周随机双盲对照期,复方坎地沙坦酯组(134例)与坎地沙坦酯单药组(142例)4周时的血压分别下降为(9.3±11.7)/(8.7±6.2)和(5.4±10.8)/(5.4±6.1)mm Hg;8周时为(11.1±11.2)/(10.7±6.6)和(7.8±11.1)/(7.8±6.3)mm Hg(组内及组间比较P＜0.01).随机期4周时联合治疗组血压达标率分别为64.9%(87/134),单药组为39.4%(56/142),8周时分别为79.9%(107/134)和51.4%(73/142)(组间比较P＜0.01).不良反应事件,在单药治疗期为6.2%(22/353),复方坎地沙坦组为2.9%(4/134),坎地沙坦酯组2.8%(4/142),组间比较差异无统计学意义(P＞0.05).结论 复方坎地沙坦酯片较之单用坎地沙坦对原发性高血压患者有较好的降压效果和耐受性.     

无创性动态血压监测评价复方坎地沙坦酯片治疗原发性高血压患者的疗效

目的用无创性动态血压监测仪评价国产复方坎地沙坦酯片(坎地沙坦酯16 mg/氢氯噻嗪12.5 mg)对原发性高血压患者的降压疗效.方法原发性高血压患者经过2周清洗期后,进入坎地沙坦酯片8 mg单药治疗期,对4周后坐位血压未达标者(达标为血压＜140/90 mmHg),进行24小时动态血压监测,以随机双盲、平行对照试验方法,分别服用复方坎地沙坦酯片(复方坎地沙坦酯组,28例)或16 mg坎地沙坦酯片(坎地沙坦酯组,27例)治疗8周.比较两组服药前后24小时动态血压参数变化.观察组内与组间服药前后的不同时段的血压变化,谷峰比值及血压平滑指数.结果共55例患者完成动态血压监测,两组基础指标比较无差异.复方坎地沙坦酯组与坎地沙坦酯组药后收缩压/舒张压/平均动脉压全日平均值(24小时)、日间平均值(600～2200)、夜间平均值(2200～600)均明显下降,与同组基线值比较均有极显著性差异(P＜0.01).组间比较,复方坎地沙坦酯组收缩压/舒张压/平均动脉压全日平均值(24小时)、日间平均值(600～2200)、夜间平均值(2200～600)的降低幅度与坎地沙坦酯组比较均有极显著性差异(P＜0.01).服药谷峰比值(SBP/DBP)复方坎地沙坦酯组分别为99.36%(19.16/19.28 mmHg)和87.36%(10.14/11.61 mmHg),复方坎地沙坦酯组分别为54.42%(7.30/13.41 mmHg)和64.86%(6.43/9.91 mmHg).血压平滑指数(SBP/DBP)在复方坎地沙坦酯组为4.53/3.91,坎地沙坦酯组为1.29/1.52.结论复方坎地沙坦酯片对原发性高血压患者有较好的降压作用,复方制剂比单药降压幅度大、持续时间长.动态血压平均下降幅度日间＞全天＞夜间,收缩压＞舒张压.复方坎地沙坦酯控制血压更平稳.     

霉酚酸酯分散片治疗狼疮性肾炎的血药浓度分析

目的：霉酚酸酯（MMF）已被广泛用于治疗狼疮性肾炎（LN）和其它重症。肾小球肾炎，监测其血药浓度有助于减少并发症。近年国内研制的MMF分散片，其药代动力学和血药浓度有何特点尚缺乏研究，本文就此作初步探索。方法：10例[女7例，男3例，平均年龄[（25．0±8．4）岁]活动性Ⅳ型LN患者，采用激素联合MMF分散片（赛可平，0．75g2／d）治疗。MMF分散片服用方法随机分成两组，每组5例：一组先空腹服药，1周后改进餐时服药；另一组先进餐时服药，1周后改空腹服药。两组均在服药1周时采集12个点血样（0、15min、30min、45min．1h、1．5h．2h、4h、6h、8h、10h、12h）。HPLC法测定血浆霉酚酸（MPA），采用直接法和三点法（C0，C0.5h，C2h）计算MPA-AUC0-12h。结果：（1）MMF分散片空腹服药Tmax、Cmax、AUC0-12h分别为（0．57±0．26）h、（16．06±5．30）mg／L和（34．53±8．89）mg·h／L；餐时服药时分别为（0．87±0．42）h、（11．00±4．41）mg／L和（32．05±9．82）mg·h／L。（2）与空腹服药相比，餐时服药时Cmax平均值下降31．5％（P〈0．05），AUC0-12h平均值下降7．2％（P〉0．05）。（3）20例次血药浓度AUC，三点法平均值为（34．06±8．39）mg·h／L，直接法为（33．29±9．21）mg·h／L。两者之间无统计学差异（P〉0．05）。相关分析显示，三点法与直接法之间具有较强的相关性（r=0．94，P〈0．05）。（4）2例患者在空腹服药时出现胃肠道反应，在餐时服药时症状减轻。结论：LN患者服用1．5g／d MMF分散片能获得满意的血药浓度。餐时服药明显降低峰值Cmax减轻胃肠道反应，但对AUC0-12h影响较小。三点法仍可用于计算MMF分散片MPA AUC0-12h。     

应用动态血糖监测系统评价双相门冬氨酸胰岛素30对老年2型糖尿病患者的疗效

目的应用动态血糖系统（CGMS）观察老年人2型糖尿病（T2DM）患者中性鱼精蛋白锌胰岛素NPH与双相门冬氨酸胰岛素30（BI-Asp30）治疗的疗效和安全性。方法T2DM患者22例，分别接受BIAsp30和NPH治疗12w，治疗结束即时进行72h CGMS观察。结果12w时BI-Asp30组糖化血红蛋白（HbAlC）显著低于NPH组（7．46±0．94％vs 7．90±0．93）。CGMS检查显示，BIAsp30组早餐后（9．3±2．4mmol／L vs 10．3±2．5mmol／L）和晚餐后2h血糖（PG）（9．1±2．2mmol／L vs 10．1±3．1mmol／L）降低更明显，血糖≥10mmol／L时间百分比明显降低（14．5±10．1 vs 20．8±11．4），凌晨3点PG不过低（5．2±0．8mmol／L vs 4．1±1．0mmol／L）。BIAsp30组夜间低血糖发生率（1例次）显著少于NPH组（3例次），夜间血糖≤3．0mmo／L时间百分比亦明显减少（1．93±1．37 vs 5．03±1．33）。结论BIAsp30治疗更接近生理胰岛素分泌模式，能更好地控制餐后PG，减少低血糖发生。     

老年慢性心力衰竭患者血清瘦素水平变化及其与血压的关系

该文探讨慢性心力衰竭（CHF）患者血清瘦素水平变化及其与血压的关系。方法：观察慢性心力衰竭患者35例及健康对照组30例血清瘦素、左心室射血分数（LVEF）及血压水平，分析瘦素水平与血压及LVEF之间的关系。结果：CHF组与对照组比较，血清瘦素水平分别为（11．4±5．8）、（7．3±3．1）μg／L，收缩压分别为（142．1±19．7）、（127．0±17．6）mmHg，舒张压分别为（85．0±12．9）、（78．4±9．7）mmHg，两组比较，差异有统计学意义（P〈0．05和P〈0．01）。CHF患者按LVEF程度分为2组，LVEF〈30％组瘦素水平为（12．4±7．8）μg／L，30％～40％组瘦素水平为（10．8±1．8）μg／L，两组间比较差异有统计学意义（P〈0．05），表明LVEF水平越低，瘦素水平越高。多元回归分析显示，CHF患者血清瘦素水平分别与体重指数（r=0．910，P〈0．01）、收缩压（r=0．859，P〈0．01）、舒张压（r=0．680，P〈0．05）呈正相关，与LVEF呈负相关（r=-0．729，P〈0．01）。结论：老年CHF患者血清瘦素水平较健康对照组高。并与LVEF程度呈负相关；CHF患者血压明显高于健康对照组。且瘦素水平与血压呈正相关。提示血清瘦素水平与高血压之间存在密切联系。共同促进CHF发展。     

氯沙坦对兔快速心房起搏的电生理作用观察

28只新西兰大耳白兔，随机分为氯沙坦组和对照组各14只。前者灌胃法给予氯沙坦15mg／（kg·d），后者单纯饲料喂养，两组均喂养4周。4周后，颈内静脉切开置入4F电极导管，快速心房起搏1h后，记录起搏前后的心房有效不应期（AERP）；然后猝发S1S1刺激诱发心房颤动（AF），观察AF的诱发率、房颤周长（AFCL）和持续时间。结果①起搏前后AERP缩短值氯沙坦组明显小于对照组[（17．44±5．58）msVS（30．71±8．86）ms，P〈0．01]。②AF的诱发率氯沙坦组少于对照组（28．57％vs85．71％，P〈0．05）。③AF发作的持续时间氯沙坦组短于对照组[（47．5±9．6）sVS（115．0±8．0）s，P〈0．01]。④AFCL氯沙坦组长于对照组[（85．0±10．0）msvs（45．0±8．0）ms，P〈0．01]。认为氯沙坦能阻止兔快速心房起搏引起的AERP缩短和诱发AF等心房电重构现象。     

辛伐他汀并缬沙坦对单纯收缩期高血压患者脉压的影响

目的观察辛伐他汀和缬沙坦联合用药对老年单纯收缩期高血压（ISH）患者脉压（PP）的影响。方法66例老年ISH患者被随机分为两组,对照组33例用缬沙坦（80mg／d）,治疗组33例用缬沙坦（80mg／d）加辛伐他汀（20mg／d）,观察12周。每2周随访血压1次并记录。结果在治疗12周时,对照组PP从治疗前（74．67±7．77）mmHg降至（67．37±5．13）mmHg;治疗组PP从治疗前（75．06±6．96）mmHg降至（59．75±5．92）mmHg。治疗后两组PP的差异有显著性（t=5．255。P〈0．01）。结论辛伐他汀和缬沙坦联合用药有助于改善老年ISH患者的PP。     

异莲心碱防止高血压大鼠左室肥厚的可能机制

背景既往报告异莲心碱是从莲子心中分离的一种双苄基喹啉生物碱单体，具有抗心律失常、Ca^2＋拮抗及阻断α受体作用，对高血压左室肥厚有不同程度的改善。高血压左室肥厚心肌肌浆网钙泵（SERCA）活力较正常心肌降低。目的探讨异莲心碱对高血压大鼠左室肥厚及SERCA活力的影响。方法将二肾一夹肾血管性高血压大鼠（RHR）模型，随机分为3组：正常对照组、肾血管性高血压大鼠对照组（未治疗RHR组）和异莲心碱治疗组。在异莲心碱治疗组持续给药10周后，分别测定各组大鼠的血压、左室质量／体质量，以及左室心肌SERCA活力。结果治疗后，异莲心碱治疗组血压（136．4±14．6）mmHg较未治疗RHR组（189．8±4．4）mmHg显著降低（P〈0．01）；异莲心碱治疗组左室质量／体质量（2．23±0．43）也较未治疗RHR组（2．93±0．52）显著降低（P〈0．05）；异莲心碱治疗组左室心肌SERCA活力[（0．91±0．18）μmol／（gprotein·min）]较未治疗RHR组[（0．61±0．23）μmol／（gprotein·min）]显著升高（P〈0．05），但仍较正常对照组[（1．32±0．18）μmol／（gprotein·min）]低（P〈0．01）。结论异莲心碱能降低RHR的血压，减低RHR的左室质量／体质量，对高血压左室肥厚具有一定的防治作用；其机制可能与异莲心碱能升高RHR肥厚心肌肌浆网SERCA活力，改善心肌细胞内钙超载有关。     

GNB3基因C825T多态性与中国高血压患者服用坎地沙坦酯或坎地沙坦酯／氢氯噻嗪复方制剂降压疗效的相关性研究

目的探讨GNB3C825T基因多态性与坎地沙坦酯及复方坎地沙坦酯（坎地沙坦酯＋氢氯噻嗪）降压疗效的相关性。方法62名原发性高血压患者随机分组，分别给予坎地沙坦酯片及坎地沙坦酯＋氢氯噻嗪片治疗8周，定期随访取得血压下降数据。采用聚合酶链式反应．限制性片断长度多态性（PCR-RFLP）方法检测GNB3基因型。利用协方差分析各基因型与两药物降压疗效的关系。结果服用坎地沙坦酯／氢氯噻嗪复方的病人血压下降值明显高于单独服用坎地沙坦酯的病人血压下降值（P〈0．05）。GNB3825T等位基因在入选的高血压病人中频率为45．16％。与多数国人报道结果一致。协方差分析结果显示服用两种药后收缩压和舒张压的下降幅度在GNB3C825T各基因型高血压患者问比较均无统计学差异（P〉0．05）。结论GNB3C825T基因多态性可能与坎地沙坦酯及坎地沙坦酯＋氢氯噻嗪降压疗效不相关。     

食欲刺激素抑制血管紧张素Ⅱ诱导的人脐静脉内皮细胞活性氧生成及内皮素1表达

目的研究食欲刺激素（Ghrelin）在不同浓度下对血管紧张素Ⅱ（AngⅡ）体外诱导人脐静脉内皮细胞（HUVECs）活性氧（ROS）生成和内皮素1（ET-1）表达的影响。方法体外培养人脐静脉内皮细胞，用AngⅡ和Ghrelin联合干预细胞18h后，采用流式细胞术测定细胞内ROS水平，放射免疫方法测定ET-1含量，用RT0-PCR法测定ET-1mRNA表达。结果AngⅡ明显增加HUVECs的ROS生成[（21．4±2．2）比（2．9±0．9）10μmol／L]和ET-1分泌（111．3±7．9比43．2±9．7）ng／L，P〈0．05；Ghrelin对基础ROS及ET-1分泌无影响，但在10^-8～10^-6mol／L范围内剂量依赖性地抑制AngII诱导ROS生成[（14．2±0．7）、（10．4±1．4）和（6．6±0．5）10^-7mol／L]及ET-1分泌[（119．3±7．2）、（101．5±2．8）和（72．3±8．8）ng／L]与AngⅡ组（40．5±12．7）ng／L比较，P均〈0．05；RT—PCR显示AngⅡ明显增加ET-1mRNA表达，此作用可为Ghrelin所抑制，且在10^-8～10^-6mol／L浓度范围呈浓度依赖性。结论Ghrelin能够抑制AngⅡ诱导的HUVECs ROS的生成，ET-1的释放及ET-1 mRNA表达，且在一定的浓度范围内（10^-8～10^-6mol／L）呈浓度依赖性。     

Candesartan and hydrochlorothiazide in isolated systolic hypertension

AIM: We investigated the efficacy and safety of daily candesartan 8/16mg and hydrochlorothiazide 12.5 mg as monotherapy and in combination in older patients with systolic hypertension. METHODS: The study used a double-blind randomized placebo-controlled crossover design. Treatment phases were of 6 weeks duration. For inclusion, patients were aged 55-84 years with sitting systolic blood pressure (SBP) 160-210 mmHg and diastolic blood pressure (DBP) < 95 mmHg. Nineteen patients (11 male, eight female, median age 68 years) completed the study. MAJOR FINDINGS: Compared with the placebo phase, clinic and ambulatory SBP was significantly reduced with both dose-adjusted candesartan and fixed-dose hydrochlorothiazide as monotherapy, the effect of candesartan being greater than that of hydrochlorothiazide. In combination, the effects of the two drugs were additive. Both drugs were well tolerated either as monotherapy or in combination. CONCLUSION: Both candesartan and a low dose of hydrochlorothiazide are effective and well-tolerated antihypertensive agents in isolated systolic hypertension with additive effects in combination. Candesartan was more effective than hydrochlorothiazide, although it is possible that dose adjustment only of candesartan could have enhanced its relative effectiveness.     

Clinical efficacy and tolerability of candesartan cilexetil. Candesartan Study Groups in Japan

Clinical trials of candesartan cilexetil conducted in Japan are reviewed. Candesartan cilexetil inhibited the pressor response to intravenous angiotensin II in healthy volunteers, with peak effects observed at 4 or 8 h after oral dosing; suppressing effects persisted up to 24 h. In 14 multicentre studies with 928 hypertensive patients treated for 8 to 12 weeks, candesartan cilexetil had an efficacy rate (reduction of systolic/diastolic blood pressure > or = 20/10 mm Hg and/or mean blood pressure > or = 13 mm Hg) of 72% and 63%, and an adverse effect rate of 9.9% and 7.3%, in patients with mild-to-moderate essential hypertension and those with impaired renal function, respectively. When data for elderly patients were analysed, there was no difference in efficacy and tolerability compared to non-elderly patients. In a double-blind comparative study, candesartan cilexetil was superior to enalapril in hypertensive patients: efficacy rate, 74% vs 66% (NS); adverse symptom rate, 10.4% vs 27.3% (P < 0.01); incidence of cough, 1.5% vs 14.8% (P < 0.01). Treatment with 2-8 mg of candesartan cilexetil once daily for 8 to 12 weeks reduced the left ventricular mass index without deterioration of cardiac function. In conclusion, 4-12 mg of candesartan cilexetil once daily is effective and well tolerated in patients with essential hypertension, including elderly patients, those with severe hypertension, and hypertensive patients with renal insufficiency. Its improved tolerability profile over angiotensin-converting enzyme inhibitors, as well as its end-organ protective effects, suggest that candesartan cilexetil is useful as a first-line antihypertensive drug.     

Effects of up-titration of candesartan versus candesartan plus amlodipine on kidney function in type 2 diabetic patients with albuminuria

In the present study, we tested the hypothesis that up-titrating the dose of an angiotensin receptor blocker (ARB) is superior to combined treatment with an ARB and a calcium channel blocker for the same degree of blood pressure (BP) reduction, with respect to urinary albumin excretion in diabetic patients treated with a standard dose of the ARB. Hypertensive patients with type 2 diabetes mellitus and albuminuria (≥30?mg?g(-1) creatinine) were enroled in the study, and were either started on or switched to candesartan (8?mg per day) monotherapy. After a 12-week run-in period, baseline evaluations were performed and patients with BP ≥130/80?mm?Hg were randomly assigned to receive either candesartan (12?mg per day) or candesartan (8?mg per day) plus amlodipine (2.5?mg per day) for a further 12 weeks. The primary end-point was a reduction in urinary albumin levels. Although there was no significant difference in the BP reduction between the two groups, the reduction in urinary albumin was greater in the up-titrated than the combination therapy group (-40±14% vs -9±38%, respectively; P<0.0001). Thus, up-titration of candesartan more effectively reduces urinary albumin excretion than combined candesartan plus amlodipine in hypertensive patients with diabetes for the same degree of BP reduction.     

Antihypertensive Efficacy of Candesartan in Comparison to Losartan: The CLAIM Study

An 8-week, multicenter, double-blind, randomized, parallel-group, forced-titration study was conducted to evaluate the antihypertensive efficacy of candesartan vs. losartan in 654 hypertensive patients with a diastolic blood pressure between 95 and 114 mm Hg from 72 sites throughout the U.S. Eligible patients were randomized to candesartan cilexetil 16 mg once daily, or losartan 50 mg once daily. Two weeks following randomization, patients doubled the respective doses of their angiotensin receptor blockers for an additional 6 weeks. At week 8, candesartan cilexetil lowered trough systolic/diastolic blood pressure by a significantly greater amount than did losartan (13.3/10.9 mm Hg with candesartan cilexetil vs. 9.8/8.7 mm Hg with losartan; p < 0.001). At the same period, candesartan cilexetil also lowered peak blood pressure by a significantly greater amount than did losartan (15.2 to 11.6 mm Hg with candesartan cilexetil vs. 12.6 to 10.1 mm Hg with losartan; p < 0.05). There were statistically significantly ( p < 0.05) higher proportions of responders and controlled patients in the candesartan cilexetil group (62.4% and 56.0%, respectively) than in the losartan group (54.0% and 46.9%, respectively). Both treatment regimens were well tolerated; 1.8% in the candesartan cilexetil group and 1.6% in the losartan group withdrew because of adverse events. In conclusion, this forced-titration study confirms that candesartan cilexetil is more effective than losartan in lowering blood pressure when both are administered once daily at maximum doses. Both drugs were well tolerated.     

The Antihypertensive Effect and Tolerability of Candesartan Cilexetil, a New Generation Angiotensin II Antagonist, in Comparison with Losartan

This multicentre study compared the antihypertensive effect and tolerability of the novel angiotensin II antagonist candesartan cilexetil with those of losartan and placebo. Men and women aged 20-80 years, with primary hypertension and sitting diastolic blood pressure (DBP) 95-114 mm Hg after a 4-week placebo run-in period, were randomized to once daily double-blind treatment with candesartan cilexetil 8 mg (n = 82), candesartan cilexetil 16 mg (n = 84), losartan 50 mg (n = 83) or placebo (n = 85) for 8 weeks. Blood pressure was measured 6 and 24 h after dose, i.e. at peak and trough. Differences between treatments were analysed by analysis of covariance, and the primary effect variable was reduction in trough sitting DBP. Compared with placebo treatment, trough DBP was significantly reduced by a mean (95% CI) of 8.9 (6.0; 11.8) mm Hg with 8 mg and 10.3 (7.4; 13.2) mm Hg with 16 mg candesartan cilexetil. The 8 mg dose was as effective as losartan 50 mg, while 16 mg candesartan cilexetil was significantly more effective, with a difference between treatments of 3.7 (0.8; 6.7) mm Hg (p = 0.013). The placebo corrected trough/peak ratio was 0.9-1.1 with candesartan cilexetil and 0.7 with losartan. Candesartan cilexetil was similarly well tolerated as placebo. In conclusion, candesartan cilexetil 8 mg or 16 mg once daily is an effective and well tolerated antihypertensive treatment. Candesartan cilexetil 16 mg is significantly more effective than losartan 50 mg once daily.     

Controlled-release nifedipine and candesartan low-dose combination therapy in patients with essential hypertension: the NICE Combi (Nifedipine and Candesartan Combination) Study

OBJECTIVE: To compare the clinical efficacy of low-dose controlled-release (CR) nifedipine (20 mg/day) plus candesartan (8 mg/day) combination therapy with that of up-titrated candesartan (12 mg/day) monotherapy. DESIGN: Randomized, double-blind study. SETTING: Outpatient study. PATIENTS AND PARTICIPANTS: Patients with essential hypertension, who did not achieve their target blood pressure with baseline treatment of candesartan 8 mg/day for 8 weeks. MAIN OUTCOME MEASURES: Blood pressure, pulse pressure, urinary microalbumin excretion. RESULTS: Blood pressure was significantly reduced in both groups (P < 0.05), but the reduction was significantly greater in the combination therapy group (12.1 +/- 1.4/8.7 +/- 0.9 mmHg) than in the up-titrated monotherapy group (4.1 +/- 1.4/4.6 +/- 0.9 mmHg) (P < 0.0001). The reduction in pulse pressure was significantly greater in the combination therapy group (3.3 +/- 1.2 mmHg) than in the up-titrated monotherapy group (0.7 +/- 1.2 mmHg) (P = 0.0031). Urinary microalbumin excretion decreased significantly in the combination therapy group (from 61.9 to 40.5 mg/g creatinine; P < 0.05), but not in the up-titrated monotherapy group. CONCLUSIONS: These findings suggest that the low-dose combination therapy of nifedipine CR and candesartan is superior to the up-titrated monotherapy of candesartan in terms of blood pressure control and renal protection in patients with essential hypertension.     

A forced titration study of antihypertensive efficacy of candesartan cilexetil in comparison to losartan: CLAIM Study II.

An 8-week, multicentre (72 sites in the US), double-blind, randomised, parallel group, forced titration study compared the antihypertensive efficacy of candesartan cilexetil and losartan. A total of 611 patients with essential hypertension (diastolic blood pressure 95 to 114 mm Hg) were randomised initially to candesartan cilexetil 16 mg once daily or losartan 50 mg once daily. After 2 weeks of randomised treatment, the doses of candesartan cilexetil and losartan were doubled to 32 mg and 100 mg once daily and continued respectively for 6 weeks. At week 8, candesartan cilexetil lowered the blood pressure (BP) at 24 h (trough), 6 h (peak) and 48 h post dose to a significantly greater extent (P < 0.05) than losartan: candesartan cilexetil lowered trough BP by 13.4/10.5 mm Hg, peak BP by 15.5/12.9 mm Hg and 48-h BP by 10.5/9.9 mm Hg compared to a reduction of trough BP by 10.1/9.1 mm Hg, peak BP by 12.0/9.5 mm Hg, and 48-h BP by 5.9/7.0 mm Hg by losartan. The responder and control rates were numerically higher in the candesartan cilexetil group, but the differences did not reach statistical significance; the responder rates were 58.8% for the candesartan cilexetil group and 52.1% for the losartan group and control rates were 49.0% for the candesartan cilexetil group and 44.6% for the losartan group. Overall, both treatment regimens were well tolerated. A total of 15 of the 611 (2.5%) patients withdrew from the study due to an adverse event, including nine (2.9%) in the candesartan cilexetil group and six (2.0%) in the losartan group. In conclusion, this forced titration study confirms that candesartan cilexetil is more effective in lowering BP than losartan when compared at once daily maximum doses.     

Effect of an angiotensin II receptor antagonist, candesartan, on insulin resistance and pressor mechanisms in essential hypertension

Candesartan (8 mg/d) was administered for 2 weeks to eight patients with essential hypertension to investigate the effect of an angiotensin II receptor antagonist on insulin sensitivity. The effect of candesartan on sodium-retaining action and the activation of pressor systems by hyperinsulinaemia, which might be related to pressor mechanisms in essential hypertension, was also investigated in this study. In patients with essential hypertension, candesartan restored insulin sensitivity to the level of that in normotensive subjects. Candesartan treatment attenuated the sodium-retaining action of hyperinsulinaemia. These findings suggest that inhibition of angiotensin II action by candesartan can improve insulin sensitivity and inhibit the sodium-retaining action associated with hyperinsulinaemia in essential hypertension.     

Effect of losartan versus candesartan on uric acid, renal function, and fibrinogen in patients with hypertension and hyperuricemia associated with diuretics

BACKGROUND: Hyperuricemia may counter benefits of blood pressure (BP) reduction, although this is controversial. METHODS: We examined the effects of candesartan and losartan on uric acid, creatinine, and fibrinogen. Patients with hypertension and serum uric acid > or = 0.42 mmol/L (7 mg/dL) associated with diuretics were randomized to receive losartan 50 to 100 mg or candesartan 8 to 16 mg for 24 weeks. At randomization and after 24 weeks, systolic and diastolic BP, serum uric acid, creatinine, and fibrinogen were measured. RESULTS: A total of 59 patients were entered into the study (30 in the losartan and 29 in the candesartan group). Mean systolic and diastolic BP were reduced in the candesartan group, from 156 mm Hg at baseline to 132 mm Hg at 24 weeks, and from 90.9 to 80.8 mm Hg respectively, P < .0001), and in the losartan group from 150.3 to 132 mm Hg and from 89.6 to 77.6 respectively, P < 0001). Overall mean values of fibrinogen levels were again reduced from 4.39 g/L at baseline to 4.01 g/L at 24 weeks (P < .02). Mean values of serum uric acid in the losartan and candesartan groups were similar at baseline (0.44 and 0.46 mmol/L, respectively), but they were lower in the losartan group after 24 weeks (0.39 and 0.48 mmol/L, P = .01). Twelve patients (44%) in the candesartan group had a 10% increase in serum creatinine compared with four patients (14.2%) in the losartan group (P < .02). CONCLUSIONS: Candesartan and losartan lowered BP, but only losartan reduced uric acid. The lowering of fibrinogen in both groups may explain the reduction in stroke with angiotensin receptor blockers. The effect of persistent hyperuricemia on renal function requires further study.     

Candesartan cilexetil is not associated with cough in hypertensive patients with enalapril-induced cough. Multicentre Cough Study Group

The aim of this study was to evaluate the occurrence of dry cough during treatment with candesartan cilexetil, enalapril, or placebo in patients with hypertension and a history of angiotensin converting enzyme (ACE)-inhibitor-related cough. Patients with confirmed cough during an enalapril (10 mg) challenge period, followed by no cough during a placebo dechallenge period were randomized to 8 weeks of double-blind treatment with candesartan cilexetil (8 mg) (n = 62), enalapril (10 mg) (n = 66), or placebo (n = 26). Incidence and severity of dry cough was evaluated by the symptom assessment questionnaire, frequency of dry cough by a visual analog scale, and the possible impact on quality of life by the minor symptom evaluation (MSE) profile. The percentage of patients with cough was significantly lower with candesartan cilexetil (35.5%) than with enalapril (68.2%, P < .001), and did not differ between candesartan cilexetil and placebo (26.9%, P > .20). Patients coughed less frequently and with less severe cough with candesartan cilexetil than with enalapril, and similarly with candesartan cilexetil and placebo. Changes in the MSE profile were minor, although candesartan cilexetil had better scores for contentment than placebo (P = .03), and also tended to be associated with better sleep than enalapril (P = .08). In hypertensive patients with ACE-inhibitor-induced cough, the incidence, frequency, and severity of dry cough was significantly lower with candesartan cilexetil than with enalapril, and no different from that found with placebo.