氢氯噻嗪与螺内酯或卡托普利长期合用对原发性高血压患者左室质量参数的影响

目的 探讨氢氯噻嗪(HCTZ)与螺内酯或卡托普利长期联用对高血压病患者左室质量参数的影响.方法 采用多中心随机双盲研究设计.选择9所开滦矿区医院,筛选出轻、中度高血压病患者.人选患者经安慰剂洗脱2周后随机分为螺内酯组(HCTZ 12.5 mg,1次/d 螺内酯20 mg,1次/d,,n=112)和卡托普利组(HCTZ 12.5mg,1次/d 卡托普利25 mg,2次/d,n=109).共服药36月.治疗期间每月随访1次,监测血压.洗脱期末和治疗12、24、36月末行超声心动图检查并计算左室质量指数(LVMI或LVMIh),采静脉血进行生化检查.结果 1)治疗12个月末,两组患者的LVMI均较治疗前显著下降(螺内酯组一8.9%,P(O.05;卡托普利组一12.6%,P<0.01);随治疗时间延长,两组患者的LVMI进一步下降(36月末与12月末比较,螺内酯组:-8.9% VS-17.5%,P<0.05;卡托普利组:-12.6% VS-19.2%,P>0.05),下降幅度组间比较无统计学意义(P>0.05);2)治疗12、24、36月末两组患者血压均显著下降(P0.05).结论 HCTZ与螺内酯或卡托普利联用均能有效降低血压和LVMI或LVMIh,且随治疗时间延长疗效更为显著.     

氢氯噻嗪与螺内酯、卡托普利联合治疗原发性高血压

目的评价小剂量氢氯噻嗪(HCTZ)与螺内酯、卡托普利联用的降压疗效和安全性.方法采用多中心、随机、双盲、平行对照试验,选择轻中度高血压患者829例,经2周安慰剂洗脱期、6周HCTZ导入期后随机进入HCTZ 12.5 mg q.d组HCTZ 12.5 mg与螺内酯20 mg q.d组HCTZ 12.5 mg q.d与卡托普利25 mg b.i.d组治疗,共12个月,随访1次/月.治疗前、治疗6周末和治疗12个月末分别进行血生化检查并评估降压疗效及安全性.结果①治疗6周末,3组的坐位收缩压及舒张压(以下血压值均指坐位血压值)较治疗前明显下降(P＜0.01,P＜0.01).治疗12个月末3组的血压值仍明显下降.HCTZ组、螺内酯组和卡托普利组患者的收缩压下降值分别为(10.5±17.3),(13.3±15.8),(14.6±17.4)mmHg,卡托普利组下降幅度较HCTZ组明显(P=0.034).②HCTZ组、螺内酯组和卡托普利组降压达标率分别为34.9%、44.3%和47.1%,HCTZ组达标率低于其他两组(44.3%vs 34.9%P=0.038;47.1%vs34.9%P＜0.001),螺内酯和卡托普利2组间无统计学差异.③3组间副反应发生率无统计学差异.结论小剂量HCTZ与螺内酯、卡托普利联用降压安全有效.     

氢氯噻嗪与螺内酯、卡托普利联合治疗原发性高血压

目的评价小剂量氢氯噻嗪(HCTZ)与螺内酯、卡托普利联用的降压疗效和安全性。方法采用多中心、随机、双盲、平行对照试验,选择轻中度高血压患者829例,经2周安慰剂洗脱期、6周HCTZ导入期后随机进入HCTZ12.5mg q.d组HCTZ12·5mg与螺内酯20mg q.d组HCTZ12·5mg q.d与卡托普利25mg b.i.d组治疗,共12个月,随访1次/月。治疗前、治疗6周末和治疗12个月末分别进行血生化检查并评估降压疗效及安全性。结果①治疗6周末,3组的坐位收缩压及舒张压(以下血压值均指坐位血压值)较治疗前明显下降(P<0·01,P<0·01)。治疗12个月末3组的血压值仍明显下降。HCTZ组、螺内酯组和卡托普利组患者的收缩压下降值分别为(10·5±17·3),(13·3±15·8),(14·6±17·4)mmHg,卡托普利组下降幅度较HCTZ组明显(P=0·034)。②HCTZ组、螺内酯组和卡托普利组降压达标率分别为34·9%、44·3%和47·1%,HCTZ组达标率低于其他两组(44·3%vs34·9%P=0·038;47·1%vs34·9%P<0·001),螺内酯和卡托普利2组间无统计学差异。③3组间副反应发生率无统计学差异。结论小剂量HCTZ与螺内酯、卡托普利联用降压安全有效。     

高血压病患者不同治疗依从性对临床终点事件的影响

目的 探讨不同治疗依从件对高血压病患者临床终点事件的影响.方法 选择轻、中度高血压病患者853例,入选患者经安慰剂洗脱2周和氢氯噻嗪(HCTZ)导人6周后随机给予HCTZ12.5 mg/d或HCTZ 12.5 mg/d+螺内酯20 mg/d或HCTZ 12.5 ms/d+卡托普利25 mg 2次/d.根据患者的依从件分为依从组和非依从组.治疗期间每月随访1次,监测血压,记录终点事件,每年进行1次血牛化指标枪测.随访4年.结果 (1)第4年时依从组和非依从组的收缩压与基线值比较分别降低(19.4.±20.6)am Hg(1 mm Hg:0.133 kPa)和(7.3±18.2)mm Hg,舒张压与基线值比较分别降低(10.7±13.5)nun Hg和(3.5±10.2)mm Hg.依从组血压与基线值和非依从组血压比较均降低(P<0.001).(2)第4年时依从组血清尿素氮、肌酐、尿酸水平较基线值升高;血清K、总胆固醇、低密度脂蛋白胆固醇水平较基线值低;两组问血牛化值比较,依从组m清尿素氮、尿酸水平较非依从组高,而血清K、总胆固醇水平较非依从组降低.(3)第4年时依从组发生临床终点事件10例(致死性2例,非致死性8例).非依从组发生临床终点事件28例(致死性7例,非致死性21例).第4年时依从组无事件率高于非依从组(P<0.05).结论 在依从性良好的情况下,以噻嗪类利尿剂作为基础降压药物长期治疗高血压不但能够有效降低患者血压,还能减少高血压病患者临床终点事件的发生.     

螺内酯对无症状左室收缩功能障碍患者心室重构的影响

目的:探讨螺内酯对无症状左室收缩功能障碍患者心室重构的影响.方法:入选我院2007-12-2009-06门诊及住院无症状左室收缩功能障碍[左室射血分数(LVEF)＜40%,左室舒张末期容积指数(LVEDVI)＞75 ml/m2,纽约心脏病协会心功能分级Ⅰ级]患者63例,在常规治疗的基础上随机分为螺内酯干预组32例(螺内酯40 mg/d),对照组31例,所有患者在入选前及药物应用6个月后行超声心动图检查评估LVEDVI、左室收缩末期容积指数(LVESVI)、左室质量指数(LVMI)和LVEF的变化.结果:治疗6个月后,2组LVEDVI、LVESVI、 LVMI和 LVEF均较治疗前有明显改善,且差异有统计学意义(均P<0.05),螺内酯组改善更为显著(均P<0.05).结论:在常规治疗的基础上加用螺内酯治疗可进一步改善无症状左室收缩功能障碍患者的心室重构.     

氢氯噻嗪所致血糖升高对心脑血管事件的影响

目的 探讨以氢氯噻嗪为基础的降压治疗期间,血糖升高对原发性高血压患者心脑血管事件的影响.方法 选择轻中度原发性高血压患者829例,入选患者经安慰剂洗脱2周和氢氯噻嗪导人6周后随机给予氢氯噻嗪12.5 mg/d或(氢氯噻嗪12.5mg/d+螺内酯20mg/d)或(氢氯噻嗪12.5 mg/d+卡托普利25 mg两次/d)治...     

不同剂量螺内酯联合贝那普利治疗舒张性心力衰竭的临床疗效及安全性评价

目的探讨不同剂量螺内酯联合贝那普利治疗舒张性心力衰竭(DHF)的临床疗效及安全性。方法选取144例DHF病人随机分为对照组、20 mg/d螺内酯组、60 mg/d螺内酯组,每组48例。对照组给予贝那普利,20 mg/d螺内酯组给予20 mg/d螺内酯联合贝那普利治疗,60 mg/d螺内酯组给予60 mg/d螺内酯联合贝那普利治疗。比较3组治疗前后舒张早期血流峰速率(E)、舒张晚期血流峰速率(A)、E/A值、左室质量指数(LVMI)、左房容积指数(LAVI)、纽约心脏病协会(NYHA)心功能分级、N末端脑钠肽原(NT-proBNP)、超敏C反应蛋白(hs-CRP)、肿瘤坏死因子-α(TNF-α)水平、不良反应发生情况及临床疗效。结果治疗后,20 mg/d螺内酯组、60 mg/d螺内酯组E、E/A较对照组增高(P0.05),A、LVMI、LAVI、NT-proBNP、hs-CRP、TNF-α水平及NYHA心功能分级较对照组降低(P0.05);60 mg/d螺内酯组E、A、E/A、LVMI、LAVI、NT-proBNP、hs-CRP、TNF-α、NYHA心功能分级变化较20 mg/d螺内酯组更明显(P0.05)。60 mg/d螺内酯组临床疗效优于对照组(P0.05)。60 mg/d螺内酯组乳房胀痛发生率明显高于对照组和20 mg/d螺内酯组(P0.05)。结论 20 mg/d、60 mg/d螺内酯联合贝那普利治疗DHF均有效,但60 mg/d螺内酯组效果更明显。     

小剂量螺内酯抑制急性前壁心肌梗死患者的左室重构

目的 探讨小剂量螺内酯对急性前壁心肌梗死患者血清脑利钠肽（BNP）水平和左室重构的影响.方法 选择急性前壁心肌梗死患者90例,在常规治疗基础上,随机分为3组：常规治疗组30例,接受转换酶抑制剂、β受体阻滞剂、抗血小板、调脂药物等常规处理;小剂量螺内酯组30例,在上述治疗基础上每日给予螺内酯20 mg;中剂量螺内酯组30例,在上述治疗基础上每日给予螺内酯40 mg.结果 6个月时小剂量螺内酯组、中剂量螺内酯组和常规治疗组左室射血分数显著升高（P＜0.05）.治疗后常规治疗组BNP水平显著下降（P＜0.05）,小剂量螺内酯组和中剂量螺内酯组BNP水平下降更显著（P＜0.01）;小剂量螺内酯组与中剂量螺内酯组比较差异无统计学意义.结论 小剂量螺内酯抑制急性前壁心肌梗死患者的左室重构,血清BNP水平下降.     

合适剂量呋塞米和螺内酯联合治疗老年舒张性心力衰竭的临床疗效

目的分析呋塞米(20 mg/d)联合螺内酯(40 mg/d)对老年舒张性心力衰竭(DHF)〔纽约心脏病协会(NYHA)1~2级〕患者的临床效果。方法 DHF老年患者93例根据随机数字法分为呋塞米组(20 mg/d,n=27),合适剂量组(呋塞米20 mg/d+螺内酯40 mg/d,n=36)和大剂量组(呋塞米40 mg/d+螺内酯100 mg/d,n=30),治疗1个月后对比分析各组NYHA分级、左室射血分数(LVEF)、左室舒张末内径(LVEDd)、左室壁节段运动的差异性及心衰再住院率和电解质紊乱发生率的差异性。结果治疗后3组NYHA分级均较前降低(P0.05),而治疗后3组NYHA分级差异无统计学意义(P0.05)。合适剂量组治疗后LVEF较前升高,LVEDd较前减小,室壁运动平均收缩期运动速度(Sm)和舒张期早期运动速度(Em)较前减小(P0.05);其他两组与治疗前差异无统计学意义(P0.05);治疗后合适剂量组比其他两组改善更明显(P0.05)。治疗后合适剂量组的心衰再住院率和电解质紊乱发生率显著少于其他两组(P0.05)。结论呋塞米20 mg/d+螺内酯40 mg/d对老年DHF(NYHA 1~2级)患者可能显著改善临床症状,提高远期预后。     

辛伐他汀对高血压左室重构的影响

目的探讨辛伐他汀对高血压左室重构的影响.方法选择1级、2级高血压病患者62例,随机分成辛伐他汀组(32例)和对照组(30例).均以卡托普利(25 mg, Tid)和双克(12.5～25 mg, Qd)控制血压.辛伐他汀组加用辛伐他汀20 mg, Qd.观察治疗12周.分别于药物治疗前后测定左室重量指数(LVMI)和血清Ⅲ型前胶原(PCⅢ)浓度.结果两组患者药物治疗后在血压降低的同时LVMI及血清PCⅢ浓度也较治疗前降低(P<0.05或P<0.01).辛伐他汀组对血清PCⅢ浓度的降低较对照组更明显(P<0.05),而对LVMI的降低两组间则无显著性差异.结论辛伐他汀可能具有逆转高血压心肌纤维化改善左室重构的作用,这些治疗引起的变化可能发生于左室重构逆转之前.     

四种抗高血压药物对单纯收缩期高血压患者短期降压疗效的研究

目的 探讨双氢克尿噻、阿替洛尔、硝苯地平缓释片、卡托普利在中国乡镇农村社区未治疗单纯收缩期高血压中的短期降压疗效.方法 442例单纯收缩期高血压患者随机分配4组：双氢克尿噻组（给予双氢克尿噻 12.5 mg/d,qd）113例;阿替洛尔组（给予阿替洛尔 12.5 mg/d,bid）66例;硝苯地平组（给予硝苯地平缓释片 10 mg/d,bid）130例;卡托普利组（给予卡托普利 12.5 mg/d,bid）133例,比较4周后四种抗高血压药物的降压疗效.结果 4周后收缩压、舒张压在各组中均明显下降.阿替洛尔降低收缩压作用低于双氢克尿噻（P=0.033）和硝苯地平缓释片（P=0.005）;双氢克尿噻降低舒张压作用明显低于硝苯地平缓释片（P=0.015）;双氢克尿噻降低脉压作用明显大于阿替洛尔（P=0.006）和卡托普利（P=0.019）;硝苯地平缓释片降低脉压作用明显高于阿替洛尔（P=0.026）.双氢克尿噻1年的费用约为11元.结论 从降压疗效及经济学上,双氢克尿噻是适合中国农民单纯收缩期高血压的首选一线药物.从降低血压各组分上,双氢克尿噻及硝苯地平缓释片优于阿替洛尔和卡托普利.     

Angiotensin II receptor antagonist telmisartan in isolated systolic hypertension (ARAMIS) study: efficacy and safety of telmisartan 20, 40 or 80 mg versus hydrochlorothiazide 12.5 mg or placebo

OBJECTIVE: To identify telmisartan doses that are more effective than placebo and non-inferior to hydrochlorothiazide (HCTZ) 12.5 mg, and are well tolerated, in lowering systolic blood pressure (SBP) in patients with isolated systolic hypertension (ISH). PATIENTS AND METHODS: A 2-4-week single-blind placebo run-in was followed by randomization of 1039 patients (age 36-84 years) with ISH [seated SBP 150-179 mmHg and seated diastolic blood pressure (DBP) < 90 mmHg] to once-daily double-blind treatment with telmisartan 20, 40 or 80 mg, HCTZ 12.5 mg, or placebo. The change in seated trough SBP after 6 weeks compared with baseline was the primary end point. Secondary end points were the percentage achieving the target fall in SBP and the change from baseline in seated trough DBP. Incidence and severity of adverse events and physical examination and laboratory parameters were monitored for the safety evaluation. RESULTS: Baseline demographics in telmisartan 20 mg (n = 206), 40 mg (n = 210), 80 mg (n = 207), HCTZ 12.5 mg (n = 205) and placebo (n = 211) treatment groups were comparable: (mean +/- SD) age, 63.0 +/- 10.9 years; SBP, 162.9 +/- 8.1 mmHg; and DBP 83.4 +/- 5.0 mmHg. No previous antihypertensive therapy had been received by 66% of the patients. Mean reductions in seated trough SBP (adjusted for baseline and country) were: telmisartan 20 mg, 15.6 mmHg (n = 204); 40 mg, 17.9 mmHg (n = 209); and 80 mg, 16.9 mmHg (n = 205), compared with placebo, 11.4 mmHg (n = 208), and HCTZ 12.5 mg, 15.7 mmHg (n = 204). The target fall in seated trough SBP (< or =140 mmHg or reduction by > or =20 mmHg) was achieved in 46.6% (telmisartan 20 mg), 51.7% (telmisartan 40 mg), 53.9% (telmisartan 80 mg), 27.4% (placebo) and 42.7% (HCTZ 12.5 mg); the response rate was significantly higher for telmisartan 80 mg than for HCTZ 12.5 mg (P = 0.03). All-causality adverse events occurred in 19.9, 17.6 and 20.3% receiving telmisartan 20, 40 and 80 mg, respectively; 20.9% receiving placebo and 22.0% receiving HCTZ 12.5 mg. No drug-related serious adverse events occurred. CONCLUSIONS: All doses of telmisartan (20-80 mg) were significantly superior to placebo in reducing SBP in patients with ISH and clinically comparable to HCTZ 12.5 mg. Tolerability of telmisartan was similar to that of placebo.     

Efficacy and tolerability of a fixed-dose combination of telmisartan plus hydrochlorothiazide in patients uncontrolled with telmisartan monotherapy.

The antihypertensive effects of a telmisartan 80 mg/hydrochlorothiazide (HCTZ) 12.5 mg fixed-dose combination and telmisartan 80 mg monotherapy were compared in patients with a history of mild-to-moderate essential hypertension and inadequate BP control (DBP > or = 90 mm Hg) following 8 weeks of telmisartan monotherapy. At the end of this period, 491 patients (62.9% men; mean age 55.3 years) whose DBP was > or = 90 mm Hg were double-blind randomised to once-daily telmisartan 80 mg/HCTZ 12.5 mg (n = 246) or telmisartan 80 mg (n = 245). Trough (24 h post-dose) clinic BP was measured after 4 and 8 weeks of double-blind therapy. At the end of double-blind treatment, patients receiving telmisartan 80 mg/HCTZ 12.5 mg had significant additional decrements in clinic SBP/DBP over telmisartan 80 mg of -5.7/-3.1 mm Hg (P < 0.01). Most of the additional effect occurred during the first 4 weeks of treatment. The proportion of patients with normalised BP (SBP < 140 mm Hg and DBP < 90 mm Hg) was significantly greater in the telmisartan 80 mg/HCTZ 12.5 mg group than the telmisartan 80 mg group (41.5%vs 26.1%;P < 0.05). Both treatments were well tolerated. The incidence of adverse events was similar except for diarrhoea, which occurred more frequently in the telmisartan 80 mg/HCTZ 12.5 mg group, and oedema, which occurred more frequently in the telmisartan group. Our results indicate that a telmisartan 80 mg/HCTZ 12.5 mg fixed-dose combination confers significant additional BP reductions compared with continuation of telmisartan monotherapy in non-responders.     

Effects of high dose olmesartan medoxomil plus hydrochlorothiazide on blood pressure control in patients with grade 2 and grade 3 hypertension

High dose (40 mg) olmesartan medoxomil (OM) blocks the angiotensin II receptor, significantly reducing blood pressure (BP). Adding hydrochlorothiazide (HCTZ) to OM increases efficacy, but has not been evaluated in patients inadequately controlled by OM 40 mg. Patients with grade 2 and grade 3 hypertension with inadequately controlled BP (seated diastolic blood pressure [SeDBP] 90-115 mm Hg and seated systolic blood pressure [SeSBP] 140-180 mm Hg, plus ambulatory BP criteria) after 8 weeks of OM 40 mg open-label treatment were randomized to 8 weeks of double-blind treatment with OM/HCTZ 40/25 (n=140), 40/12.5 (n=278), 20/12.5 mg (n=280) or OM 40 mg (n=274). Treatment with OM/HCTZ 40/25 mg and 40/12.5 mg significantly reduced SeDBP (-5.3 and -3.4 mm Hg, respectively), and SeSBP (-7.4 and -5.2 mm Hg, respectively), vs OM 40 mg monotherapy (P<0.0001 for each) in patients inadequately controlled on OM 40 mg alone. OM/HCTZ 40/12.5 mg reduced SeSBP significantly more than OM/HCTZ 20/12.5 mg (-2.6 mm Hg, P=0.0255), and also produced a further reduction in SeDBP vs the lower dose. All treatments were well tolerated, with similar low proportions of patients reporting treatment-emergent adverse events in all treatment groups. In conclusion, adding HCTZ to OM 40 mg significantly improves BP reductions and target BP rates in harder-to-treat patients and a clear dose-response was observed for efficacy.     

Long-term efficacy and tolerability of telmisartan as monotherapy and in combination with other antihypertensive medications

This open-label, multicenter, extension study assessed the efficacy and tolerability of telmisartan 80 mg administered alone or with HCTZ and/or other antihypertensive agents over a maximal 1-year treatment period. Of the 690 patients with mild-to-moderate hypertension completing the preceding 6-week, randomized trial (comparing telmisartan 80 mg with losartan 50 mg/HCTZ 12.5 mg combination therapy), 489 patients (70.9%) continued in this extension study. A fixed-titration regimen was employed: all patients received telmisartan 80 mg initially, with the stepwise addition of HCTZ 12.5 mg, HCTZ 25 mg and/or other antihypertensives to attain diastolic blood pressure (DBP) control (<90 mmHg). At the final visit, DBP control was achieved in 70.0% (194/277) of patients maximally titrated to telmisartan 80 mg, 55.8% (48/86) titrated to telmisartan 80 mg + HCTZ 12.5 mg, 54.7% (47/86) titrated to telmisartan 80 mg + HCTZ 25 mg, and 64.7% (22/34) titrated to telmisartan 80 mg + other antihypertensive +/- HCTZ (12.5 or 25 mg). The DBP and systolic blood pressure (SBP) reductions observed in the preceding randomized trial continued during extension treatment. Progressively greater blood pressure reductions occurred with the sequential addition of HCTZ and other antihypertensives. Adding HCTZ 12.5 mg to telmisartan 80 mg was particularly effective at enhancing antihypertensive efficacy. All treatments were well tolerated. Thus, telmisartan 80 mg administered alone or with HCTZ (12.5 or 25 mg) and/or other antihypertensives maintains a clinically significant therapeutic effect over the long term in patients with mild-to-moderate hypertension.     

优化联合治疗老年单纯性收缩期高血压

目的比较卡托普利单药、左旋氨氯地平（施慧达）单药、卡托普利＋左旋氨氯地平、卡托普利＋左旋氨氯地平＋阿托伐他汀四种治疗方案治疗老年单纯性收缩期高血压（ISH）的临床疗效。方法纳入60岁以上ISH患者264例，平均分为4组。卡托普利组：口服卡托普利（12．5～50）mg（bid）。左旋氨氯地平组：晨起顿服左旋氨氯地平2．5mg（qd）。联合治疗组（联合组）：卡托普利（12．5～50）mg（bid）＋左旋氨氯地平2．5mg（qd）。优化联合组（优化组）：在联合治疗组的基础上加用阿托伐他汀10mg（qd）；共治疗12周。并分别比较治疗前、治疗后1周、3周、6周、12周4组血压、血脂水平及心电图变化。结果四组治疗后收缩压均有不同程度的降低，优化组和联合组与卡托普利组、左旋氨氯地平组比较差异具有统计学意义（P≤0．05）。优化组降压、降脂及心肌供血改善尤其显著，且4组治疗前后肝肾功能变化无明显差异。结论左旋氨氯地平联合卡托普利治疗老年ISH安全有效，可改善心肌缺血、降低血脂，联合阿托伐他汀治疗效果更佳。     

A home blood pressure monitoring study comparing the antihypertensive efficacy of two angiotensin II receptor antagonist fixed combinations

BACKGROUND: The objective of this prospective, randomized, open-label, blinded-endpoint study was to compare the antihypertensive efficacy of valsartan 80 mg v irbesartan 150 mg when combined with hydrochlorothiazide (HCTZ) 12.5 mg. METHODS: Untreated or uncontrolled hypertensive adults (n = 800) were enrolled by primary care physicians. After a 5-week open-label lead-in phase in which all patients received 12.5 mg HCTZ once daily, subjects whose blood pressure (BP) remained uncontrolled were randomized (n = 464) to valsartan/HCTZ (80/12.5 mg) or irbesartan/HCTZ (150/12.5 mg) for 8 weeks. Home BP monitoring (HBPM) was performed in the morning and in the evening for 5 days, at baseline, and after 8 weeks. Office BP measurements were obtained at baseline and after 8 weeks. RESULTS: Irbesartan/HCTZ produced greater reductions in average systolic BP (SBP) and diastolic BP (DBP) measured by HBPM than valsartan/HCTZ (SBP: -13.0 v -10.6 mm Hg, P = .0094; DBP: -9.5 v -7.4 mm Hg, P = .0007). These differences were more pronounced in the morning (trough) than in the evening. Office BP measurements also showed greater reductions in trough seated SBP and DBP with irbesartan/HCTZ compared with valsartan/HCTZ. Normalization rates observed with HBPM (SBP <135 mm Hg and DBP <85 mm Hg) were significantly greater with irbesartan/HCTZ than with valsartan/HCTZ (50.2 v 33.2%; P = .0003). The overall safety was similar in the two groups. CONCLUSIONS: The superior BP-lowering potency of the fixed combination irbesartan/HCTZ (150/12.5 mg) over valsartan/HCTZ (80/12.5 mg), evidenced independently from the investigators by HBPM, supports the use of this technique in trials with prospective, randomized, open-label, blinded-endpoint designs.     

Antihypertensive effects of two fixed-dose combinations of losartan and hydrochlorothiazide versus hydrochlorothiazide monotherapy in subjects with ambulatory systolic hypertension

BACKGROUND: The efficacy of losartan (L) in combination with hydrochlorothiazide (HCTZ) has been demonstrated to reduce blood pressure. However, there are limited data on the effects of L/HCTZ combinations versus HCTZ monotherapies in reducing ambulatory systolic blood pressure. The aim of this study was to compare the effects of these treatment approaches in patients with ambulatory systolic hypertension. METHODS: Patients were randomized to receive L 50 mg (n = 60) or HCTZ 12.5 mg (n = 60) for 6 weeks. Patients were then force-titrated to L 50/HCTZ 12.5 mg and to L 100/HCTZ 25 mg or were sham-titrated to HCTZ 12.5 mg and force-titrated to HCTZ 25 mg, respectively. Clinic and 24-h ambulatory blood pressure (ABP) were measured at baseline and after each 6-week treatment period. RESULTS: We found that L 50 and HCTZ 12.5 induced significant and similar decreases in clinic and ABP. The combinations of L 50/HCTZ 12.5 and L 100/HCTZ 25 provided significantly greater decreases in clinic and ABP than did HCTZ monotherapies. The L 50/HCTZ 12.5 and L 100/HCTZ 25 combinations provided significant additional decreases in systolic/diastolic ABP during daytime (-5.3/-2.0 mm Hg; P <.001 and -5.8/-3.4 mm Hg; P <.001) and the other periods of the 24-h interval compared with the levels achieved by the previous treatment, indicating a clear dose-response relationship. However, increasing the dose of HCTZ from 12.5 mg to 25 mg was not associated with additional ABP reductions. CONCLUSIONS: Combinations of L 50/HCTZ 12.5 and L 100/HCTZ 25 provided greater reductions in clinic and ABP than HCTZ monotherapies, with a clear dose-response relationship with regard to ABP. These results support the use of ABP monitoring when assessing the efficacy of antihypertensive therapies.     

Effects of candesartan cilexetil in patients with severe systemic hypertension. Candesartan Cilexetil Study Investigators.

The efficacy, tolerability, and safety of the potent angiotensin II receptor blocker candesartan cilexetil were evaluated in 217 adult patients (68% men, 41% black) with severe systemic hypertension on background therapy with hydrochlorothiazide (HCTZ) in a 4-week, multicenter, randomized, double-blind, placebo-controlled study. Patients with sitting diastolic blood pressure (BP) > or =110 mm Hg during the placebo run-in received HCTZ 12.5 mg once daily for 1 week. Those with sitting diastolic BP >95 mm Hg after the HCTZ run-in were randomized (2:1) to receive candesartan cilexetil 8 mg once daily (n = 141) or placebo (n = 76), plus HCTZ 12.5 mg. After 1 week of double-blind treatment, patients with sitting diastolic BP > or =90 mm Hg were uptitrated to candesartan cilexetil 16 mg once daily or matching placebo, plus HCTZ 12.5 mg; 84% required uptitration. Primary efficacy measurement was a change in trough (24+/-3 hours after treatment) sitting diastolic BP from the end of the HCTZ run-in to double-blind week 4. Mean changes in systolic and diastolic BP were significantly greater with candesartan cilexetil than with placebo, -11.3/-9.1 mm Hg versus -4.1/-3.1 mm Hg, p <0.001/p <0.001, respectively. Patients with higher sitting diastolic BP at the end of the HCTZ run-in tended to have greater decreases in BP (p <0.05). Most patients (53%) receiving candesartan cilexetil were responders (diastolic BP <90 mm Hg or > or =10 mm Hg decrease) and 32% were controlled (diastolic BP <90 mm Hg). Tolerability and safety profiles were similar in the candesartan and placebo groups. In conclusion, candesartan cilexetil 8 to 16 mg once daily was an effective and well-tolerated therapy for lowering BP when added to HCTZ 12.5 mg in a diverse population of patients with severe systemic hypertension in the United States.