复方缬沙坦与血脂康联合治疗原发性高血压的临床研究

目的评价复方缬沙坦(缬沙坦80mg/氢氯噻嗪12.5mg)联合血脂康(600mg)治疗轻、中度原发性高血压患者的疗效和安全性。方法采用随机、双盲对照研究。将280例轻、中度高血压患者随机分为缬沙坦组和对照组。缬沙坦组患者给予复方缬沙坦(缬沙坦80mg/氢氯噻嗪12.5mg,1次/d)和血脂康(600mg,2次/d)治疗,对照组患者降压药物单用缬沙坦(80mg,1次/d)。治疗中每周测量血压。在治疗8周和结束时评价药物安全性和有效性。结果对于轻、中度原发性高血压患者,缬沙坦组较对照组血压进一步下降,达标率显著高于对照组。治疗结束时平均坐位收缩压均降低5mmHg,平均坐位舒张压多下降3mmHg,缬沙坦组和对照组患者中,血压控制<140/90mmHg者分别占54.1%和40.7%。结论轻、中度原发性高血压患者采用复方缬沙坦联合血脂康治疗,降压效果和达标率均优于单用缬沙坦。     

卡托普利联合尼群地平治疗高血压的临床分析

目的评价卡托普利联合尼群地平治疗高血压的疗效和安全性。方法共入选100例轻、中度高血压患者(90mmHg≤坐位舒张压110mmHg;145mmHg≤坐位收缩压≤170mmHg)。单药卡托普利25mg,2次/d治疗4周,结束后坐位舒张压仍大于90mmHg的72例患者按1∶1随机、双盲分为两组,联合组:卡托普利12.5mg,2次/d,联合尼群地平10mg,2次/d。单药组:卡托普利25mg,2次/d,继续治疗8周。治疗结束时评价药物安全性及有效性。结果联合组比单药组患者血压下降明显,达标率高。结论轻中度原发性高血压患者采用卡托普利联合尼群地平治疗达标率优于单用卡托普利。     

缬沙坦/氨氯地平复方片剂对单药控制不良的轻中度高血压患者的疗效观察

目的 评价缬沙坦(80 mg)/氨氯地平(5 mg)复方片剂(复方片剂)治疗经氨氯地平5 mg或缬沙坦80 mg控制不良的轻、中度原发性高血压患者疗效和安全性.方法 采用多中心、双盲、双模拟、随机、活性药物对照、平行试验方法进行两项临床研究.在两项研究中对经1～4周洗脱期的轻、中度原发性高血压患者[坐位舒张压≥95 mm Hg(1 mm Hg=0.133 kPa)且<110 mm Hg]分别采用单药氨氯地平5 mg或缬沙坦80 mg治疗4周,在单药导入结束后,坐位舒张压仍然≥90mm Hg且<110 mm Hg的患者随机进入复方片剂组或继续原有的单药治疗,共8周.其间,在治疗4周和试验结束时评估药物的安全性及有效性.结果 治疗结束时,复方片剂组平均坐位收缩压/平均坐位舒张压下降幅度较氨氯地平单药治疗组多4.4mm Hg/3 mm Hg(P<0.0001);较缬沙坦80 mg组多6.4 mm Hg/4.2 mm Hg(P<0.0001).两项研究中复方片剂组的血压控制率(血压<140/90 mmHg)分别为71.0%及71.2%,显著优于氨氯地平或缬沙坦单药治疗组,不良事件发生率与单药治疗组相当.结论 复方片剂组的血压控制率显著优于其两种成分(氨氯地平5 mg或缬沙坦80 mg)单药的治疗,且具有良好的安全性和耐受性.     

复方替米沙坦对单药控制不良高血压患者的有效性和安全性

目的 评价复方替米沙坦在替米沙坦单药治疗无充分反应时中国高血压患者中的有效性和安全性.方法 多中心、随机、双盲、双模拟临床试验.经1周安慰剂筛选期,699例符合入选标准的轻、中度高血压患者进入80 mg替米沙坦单药开放治疗期.345例对替米沙坦单药开放治疗8周无充分反应[平均坐位舒张压≥90 mm Hg(1 mm Hg=0.133 kPa)]的患者进入为期8周的随机双盲治疗期.175例患者进入复方替米沙坦治疗组(80 mg替米沙坦加12.5 mg氢氯噻嗪),170例进入80 mg替米沙坦单药治疗组.每次随访测量坐位和立位的收缩压和舒张压谷值,记录不良事件.筛选期以及开放和随机双盲治疗期结束时进行实验室和心电图检查.结果 (1)与开放治疗期结束(基线)比较,随机双盲治疗8周后,复方替米沙坦组坐位舒张压谷值平均下降10.1 mm Hg,替米沙坦单药组平均下降7.7 mm Hg,两组间比较P=0.0017.复方替米沙坦组坐位收缩压谷值平均下降14.2 mm Hg,替米沙坦单药组平均下降7.4 mm Hg,两组间比较P＜0.0001.(2)与基线比较,随机双盲治疗8周后,复方替米沙坦组立位舒张压和收缩压谷值平均下降幅度大于替米沙坦单药组,两组间比较P=0.0350和P＜0.0001.(3)按照平均坐位舒张压谷值＜90 mm Hg和(或)与基线值相比降低≥10 mm Hg评价,随机双盲治疗8周后,复方替米沙坦组有效率为74.6%(129例患者),替米沙坦单药组为59.2%(100例患者),两组间比较P=0.0016.(4)在随机双盲期,两组与试验药物有关的不良事件发生率分别为3.5%和3.6%,两组间比较P＞0.05.结论 替米沙坦单药治疗无充分反应的中国高血压患者,复方替米沙坦每日口服一次能够进一步降低血压,且安全性良好.     

伊贝沙坦治疗轻、中度原发性高血压疗效观察

目的通过伊贝沙坦(国产)与缬沙坦(合资)的对比研究来评价伊贝沙坦对轻、中度原发性高血压的降压疗效和安全性.方法53例轻、中度原发性高血压患者被随机、双盲分为两组,经口服安慰剂2周后,分别每日口服1次伊贝沙坦75～150mg(伊贝沙坦组)或缬沙坦80～160mg(缬沙坦组),治疗4周,观察用药前后坐位血压、心率变化,对比用药前后血生化、血尿常规检查结果,记录患者用药后的不良反应.结果治疗4周后,伊贝沙坦组舒张压降低13.3±8.7mmHg(1mmHg＝0.133kPa)缬沙坦组舒张压降低16.5士9.3mmHg.两组治疗后与治疗前相比,血压下降有非常显著差异(P＜0.01),心率变化、血生化及血尿常规检查结果比较无显著差异(P＞0.05).总有效率及不良反应发生出率两组间比较均无显著差异(P＞0.05).结论口服伊贝沙坦75～150mg,每日1次,对轻、中度原发性高血压降压疗效确切,患者耐受性好.     

缬沙坦与赖诺普利治疗原发性高血压患者在耐受性、安全性和疗效上的比较

目的 :评价缬沙坦 (valsartan)治疗原发性高血压患者的耐受性、安全性和疗效。　　方法 :146例轻、中度原发性高血压患者采用随机双盲的研究方法分为缬沙坦组 (n=75 )和赖诺普利 (lisinopril)组 (n=71) ,分别接受缬沙坦 80 mg/d或赖诺普利 10 mg/d,4周后血压控制不满意者 (舒张压≥ 90 mm Hg,1mm Hg=0 .133k Pa) ,接受缬沙坦 16 0 mg/d或赖诺普利 2 0 mg/d。　　结果 :缬沙坦与赖诺普利均能有效降低血压。治疗总有效率分别为 6 0 .3%和 6 4.1% ,降压程度及治疗有效率比较统计学无显著性差异 (P>0 .0 5 )。缬沙坦组具有良好的耐受性 ,未见干咳现象 ,而赖诺普利组干咳发生率达 5 .6 %。　　结论 :缬沙坦是治疗轻、中度原发性高血压安全有效的药物。     

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.     

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     

缬沙坦治疗轻、中度高血压病40例疗效观察

目的：观察缬沙坦治疗轻、中度高血压的疗效。方法：本研究为双盲对照试验。轻、中度原发性高血压病人40例，男32例，女8例，年龄39—63岁，随机均分成缬沙坦组和卡托普利组(各20例)，分别给予缬沙坦80mg，口服，1次／日，或卡托普利12．5mg，口服，3次／日；2周后按血压决定维持量，缬沙坦维持量增加到160mg，口服，1次／日；卡托普利维持量增加到25mg，口服，3次／日；总疗程4周。结果：缬沙坦治疗4周末的总有效率为75％，卡托普利组总有效率70％，两组疗效无显差异(P＞0．05)。结论：缬沙坦治疗轻、中度原发性高血压疗效明显，每日服药1次，疗效持久、稳定。     

缬沙坦与苯那普利治疗老年高血压的对照研究

目的观察比较缬沙坦与苯那普利治疗老年人轻、中度原发性高血压的疗效和安全性。方法选择103例老年高血压患者,随机分为治疗组52例和对照组51例,治疗组给予缬沙坦80～160mg/d,对照组给予苯那普利10～20mg/d,观察两组患者4周和8周的疗效。结果两组患者治疗第2周后平均收缩压、舒张压较治疗前明显降低(P＜0．01),在整个治疗期间血压持续平稳下降；缬沙坦与苯那普利治疗4周降低舒张压总有效率分别为86．4%及84．3%,8周降低舒张压总有效率分别为92．3%及90．2%,两组比较差别无显著性意义(P＞0．05)。结论缬沙坦是一种安全、有效、长效。耐受性好不良反应少的降压药物。     

Time to achieve blood-pressure goal: influence of dose of valsartan monotherapy and valsartan and hydrochlorothiazide combination therapy

BACKGROUND: Our objective was to assess time to achieve blood-pressure (BP) goal with incremental doses of valsartan alone, and together with hydrochlorothiazide (HCTZ), in patients with uncomplicated hypertension. METHODS: This analysis pooled patient-level data from nine randomized, double-blind, fixed-dose, placebo-controlled trials (N = 4278) of once-daily valsartan 80 mg, 160 mg, and 320 mg, and valsartan/hydrochlorothiazide (HCTZ) 80/12.5 mg, 160/12.5 mg, 160/25 mg, 320/12.5 mg, and 320/25 mg. Kaplan-Meier methods estimated the cumulative proportion of patients achieving BP <140/90 mm Hg over 8 weeks and the median time to BP goal. The HCTZ 12.5-mg and 25-mg doses were pooled for the time-to-goal analysis in patients receiving combinations with valsartan 160 mg or 320 mg. RESULTS: Overall, the median time-to-goal was 8.1 weeks with valsartan 160 mg, 6.1 weeks with valsartan 320 mg, 2.6 weeks with valsartan 160 mg/HCTZ, and 2.1 weeks with valsartan 320 mg/HCTZ. In patients with stage 2 hypertension, the median time-to-goal was 4.3 weeks with valsartan 160 mg/HCTZ and 2.4 weeks with valsartan 320 mg/HCTZ. Goal rates by Week 4 for valsartan/HCTZ exceeded rates by Week 8 with the same doses of valsartan alone. Overall, the proportion that achieved BP goal by Week 8 was 32.6% with valsartan 80 mg, 48.4% with valsartan 160 mg, 54.2% with valsartan 320 mg, 74.6% with valsartan 160 mg/HCTZ, and 84.8% with valsartan 320 mg/HCTZ, versus 24.2% with placebo. With valsartan 320 mg/HCTZ, 75.8% of stage 2 patients and 94% of stage 1 patients reached BP goal by Week 8. Discontinuation rates due to adverse events were generally low across doses. CONCLUSIONS: In both stage 1 and stage 2 hypertension, BP control is achieved more frequently and promptly when patients receive higher doses of valsartan monotherapy or valsartan combination therapy, with a favorable benefit-risk profile.     

Antihypertensive effects of valsartan/hydrochlorothiazide combination in essential hypertension.

Fixed-dose combination therapy has received increased interest since publication of JNC-VI report and WHO/ISH guidelines 1999. We compared in a randomized, double-blind study the efficacy and tolerability of valsartan 80 mg combined with hydrochlorothiazide (HCTZ) 12.5 mg to monotherapy with either HCTZ 12.5 mg or 25 mg in patients with essential hypertension inadequately controlled by previous HCTZ 12.5 mg monotherapy. Two hundred and seventeen patients whose blood pressure (BP) control remained poor (95 mmHg < or = sitting diastolic BP < 115 mmHg) after a 4-week single-blind period with HCTZ 12.5 mg were randomized to receive either combination therapy with valsartan 80 mg plus HCTZ 12.5 mg (V/HCTZ) or monotherapy with HCTZ 12.5 mg or HCTZ 25 mg for 8 weeks. Reduction of sitting trough diastolic BP between baseline and week 8 as well as tolerability was evaluated. Reduction in trough diastolic BP was most pronounced in the V/HCTZ group (-11.3 mmHg) and significantly greater than in the HCTZ 12.5 mg group (-2.9 mmHg, p < 0.001) and the HCTZ 25 mg group (-5.7 mmHg, p < 0.001). Tolerability of study medication was comparable between all three groups. In conclusion, switching to V/HCTZ combination therapy provides an additional lowering of BP compared to dosage increase of the thiazide in patients with BP insufficiently controlled by HCTZ 12.5 mg monotherapy.     

Comparison of the antihypertensive efficacy of irbesartan/HCTZ and valsartan/HCTZ combination therapy: impact of age and gender

This analysis aimed to explore whether low-dose irbesartan/hydrochlorothiazide (HCTZ) has superior blood pressure (BP)-lowering efficacy over low-dose valsartan/HCTZ in the elderly and across both genders. This is a post-hoc analysis of data from a multicenter, parallel group, open-label, blinded-endpoint study in patients with hypertension uncontrolled with HCTZ monotherapy. The reduction in systolic BP (SBP)/diastolic BP (DBP) and rate of BP control achieved following 8 weeks of treatment with irbesartan/HCTZ 150/12.5 mg or valsartan/HCTZ 80/12.5 mg were analyzed for older (≥65 years) vs. younger (<65 years) patients and for men vs. women. Blood pressure measurements were by home BP monitoring (HBPM). In the age and gender subgroups, both treatments significantly decreased home SBP and DBP (p < 0.0001). The reduction in home SBP and DBP was numerically greater with irbesartan/HCTZ compared to valsartan/HCTZ for all subgroups: the difference in DBP was significant for all except the elderly (p < 0.05), and the difference in SBP was significant in the elderly and in men (p < 0.03). In all subgroups, more patients achieved BP control (HBPM ≤135/85 mmHg) in the irbesartan/HCTZ arm (range 45%-58%) than in the valsartan/HCTZ arm (range, 23%-39%; p < 0.02). Both combination therapies were well tolerated and safety parameters were similar in both age and gender subgroups. More patients with mild or moderate hypertension, uncontrolled in HCTZ monotherapy alone, had their BP controlled with irbesartan/HCTZ 150/12.5 mg than with valsartan/HCTZ 80/12.5 mg, irrespective of age or gender.     

Improving Blood Pressure Control: Increase the Dose of Diuretic or Switch to a Fixed‐Dose Angiotensin Receptor Blocker/Diuretic? The Valsartan Hydrochlorothiazide Diuretic for Initial Control and Titration to Achieve Optimal Therapeutic Effect (Val‐DICTATE) Trial

To assess the strategy of increasing the dose of a diuretic compared with using an angiotensin receptor blocker in combination with a diuretic, the authors performed a multicenter, randomized, parallel group trial in hypertensive patients (baseline blood pressure [BP], 153/97 mm Hg) whose BP remained uncontrolled on initial low-dose diuretic monotherapy (hydrochlorothiazide [HCTZ] 12.5 mg Hg). Patients with stage 1 and 2 hypertension were randomized to treatment with valsartan/HCTZ (160/12.5 mg) or to doubling of the HCTZ dose (25 mg). The primary end point was the percentage of patients whose clinic BP values were <140/90 mm Hg following 4 weeks of double-blind therapy. A significantly higher proportion (P<.001) of hypertensive patients met BP control levels in the valsartan/HCTZ (160/12.5 mg) group compared with the HCTZ 25 mg group (37% vs 16%). Changes from baseline in BP were significantly greater (P<.001) for both systolic BP and diastolic BP in the combination therapy arm compared with the diuretic monotherapy arm (-12. 4/-7.5 mm Hg in valsartan/HCTZ 160/12.5 mg group vs -5.6/-2.1 mm Hg in HCTZ 25 mg group). Tolerability and adverse events were similar in the 2 treatment groups. This study suggests that in the management of hypertension, utilizing an angiotensin receptor blocker/diuretic combination was more effective in lowering BP and achieving BP goals when compared with increasing the dose of the diuretic.     

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.     

Evaluation of the dose response with valsartan and valsartan/hydrochlorothiazide in patients with essential hypertension

This patient data meta-analysis included 9 randomized, double-blind, placebo-controlled trials (N=4278) of once-daily valsartan 80, 160, or 320 mg or valsartan/hydrochlorothiazide 80/12.5, 160/12.5, 160/25, 320/12.5, or 320/25 mg given for 4 to 8 weeks. Efficacy variables included: (1) mean change in systolic blood pressure (BP) and diastolic BP; and (2) proportion of patients reaching BP goal (<140/90 mm Hg) at the end of the study. Results showed that incremental systolic and diastolic BP reductions were achieved with increasing doses. Starting doses of valsartan 160 mg provided greater BP reductions and a higher proportion of patients reaching goal than 80 mg; combination therapy was more effective than monotherapy. BP goal rates increased incrementally with higher doses. With valsartan/hydrochlorothiazide 320/25 mg, 74.9% overall, 88.8% of stage 1, and 62.1% of stage 2 patients reached BP goal. The rate of discontinuation due to adverse events was low with both monotherapy and combination treatment. Higher starting doses may enable patients to achieve greater initial BP reductions and reach BP goal more rapidly.     

Efficacy of eprosartan in combination with HCTZ in patients with essential hypertension

This randomised, double-blind study was designed to investigate the efficacy of a once-daily (OD) combination of the AT(1) receptor blocker, eprosartan 600 mg, and the thiazide diuretic, hydrochlorothiazide (HCTZ) 12.5 mg, in patients with mild to moderate hypertension (sitting diastolic blood pressure (sitDBP) > or =98 mm Hg and < or =114 mm Hg) not adequately controlled with eprosartan 600 mg OD. A total of 494 patients entered the open-label monotherapy run-in phase, which consisted of eprosartan 600 mg OD for 3 weeks. Patients who responded to monotherapy were not eligible to enter the randomised phase of the study and were withdrawn. The remaining 309 patients were then randomised to either eprosartan 600 mg plus HCTZ 12.5 mg OD or to continue on eprosartan 600 mg OD. In the eprosartan plus HCTZ combination group, both sitDBP and sitting systolic blood pressure (sitSBP) were significantly reduced compared with the eprosartan monotherapy group. In addition, the response rate was higher in the combination group compared with the monotherapy group. There were no significant effects on reduction of sitDBP due to gender, prior use of antihypertensives or baseline severity of hypertension. The tolerability profile for the combination group was similar to that for the monotherapy group. Headache was the most frequent adverse event in both treatment groups. The majority of adverse events were mild to moderate in intensity. In this study of patients who were unresponsive to eprosartan monotherapy for 3 weeks, a combination product of eprosartan 600 mg and HCTZ 12.5 mg was shown to be an effective and well tolerated treatment.     

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.