血管紧张素转换酶和醛固酮合成酶基因多态性与氢氯噻嗪降压疗效的关系

目的研究血管紧张素转换酶(ACE)基因I/D多态性和醛固酮合成酶(CYP11B2)基因-344T/C多态性与氢氯噻嗪降压疗效的关系。方法829例高血压病(EH)患者同时服用氢氯噻嗪12·5mg(1次/d),6周后资料完整的785例患者按不同ACE基因型和CYP11B2基因型分组,比较不同基因型和不同基因型组合间血压下降值有无差别。结果服用氢氯噻嗪6周后,ACE基因II、ID、DD型患者收缩压分别下降(5·1±14·8)mmHg(1mmHg=0·133kPa)、(4·8±16·3)mmHg和(9·4±15·7)mmHg,DD型患者下降值大于II、ID型患者,组间比较差异有统计学意义(P<0·00);CYP11B2基因TT、TC、CC型患者收缩压下降值分别为(5·8±16·2)mmHg、(5·5±14·9)mmHg和(7·6±16·1)mmHg,组间比较差异无统计学意义。DD+CC基因型患者收缩压下降值为(10·6±12·3)mmHg,高于其他基因型组合患者,但差异无统计学意义(P>0·05)。多因素分析结果表明DD基因型和治疗前醛固酮浓度是影响患者坐位收缩压下降的主要因素。结论ACE基因的DD型与氢氯噻嗪的降压疗效相关,CYP11B2基因CC型、DD+CC型患者对氢氯噻嗪的降压反应可能优于其他基因组合患者。     

血管紧张素转换酶基因型与氢氯噻嗪降压疗效的相关性研究

目的　探讨高血压病患者血管紧张素转换酶 (ACE)基因不同基因型与氢氯噻嗪降压疗效的关系。方法　 5 18例高血压病患者同时服用氢氯噻嗪 12 5mg ,每日 1次 ,共 6周。资料完整的 5 0 4例患者按II、ID、DD三种基因型分组 ,比较不同基因型间的降压疗效。结果　II、ID、DD基因型患者收缩压下降值分别为 5 7mmHg(1mmHg =0 133kPa)、5 1mmHg、10 4mmHg ,DD基因型患者收缩压下降值大II、ID两型患者 ,差异具有统计学意义 (P <0 0 5 ) ;三组间舒张压下降值、平均动脉压下降值差异无统计学意义 (P >0 0 5 ) ;多元线性回归结果表明DD基因型、治疗前醛固酮水平、血钠水平是影响收缩压下降值的主要因素。结论　不同ACE基因型患者对氢氯噻嗪的反应存在差异 ,DD基因型患者收缩压下降最明显。     

不同剂量氢氯噻嗪治疗老年高血压病的临床观察

目的观察两种剂量氢氯噻嗪治疗老年高血压病的降压疗效及其安全性。方法选择门诊1~2级老年高血压病患者60例,随机给予氢氯噻嗪12.5mg和25mg两种剂量,每日晨起1次口服,观察8周。比较两种剂量氢氯噻嗪的降压疗效及生化指标的变化。结果(1)12.5mg组和25mg组氢氯噻嗪治疗前后的收缩压和舒张压都有明显下降,差异有统计学意义(P<0.05)。但它们的降压幅度、总有效率差异均无统计学意义。(2)生化指标:12.5mg和25mg氢氯噻嗪治疗后,患者均出现血清钾下降及血尿酸值增加,但服用25mg氢氯噻嗪对患者影响更明显,且出现血糖升高,与治疗前相比差异有统计学意义(P<0.05)。结论每日服用12.5mg剂量的氢氯噻嗪可有效降低1、2级老年高血压病患者的血压,与每日25mg剂量的氢氯噻嗪相比,降压作用相当,但对生化影响及出现的不良反应较小。     

NEDD4L基因与四川藏族高血压氢氯噻嗪疗效的关联分析

目的:研究四川藏族轻度高血压患者对小剂量氢氯噻嗪治疗的反应和耐受性,并比较神经前体细胞表达发育调控样蛋白4(NEDD4L)基因SNP位点与降压反应的关联。方法:对符合纳入排除标准的120例初发藏族轻度高血压患者,进行问卷调查、体格检查、血清学检测;提取其外周血白细胞DNA进行PCR扩增,使用分子质谱法对NEDD4L基因3个SNP位点rs2288774、rs3865418和rs4149601进行分型。并对所有入选患者进行为期1个月的小剂量氢氯噻嗪(12.5mg,qd)干预。结果:该群体用药前的平均收缩压为153.73mmHg(1mmHg=0.133kPa),用药后的平均收缩压为143.52 mmHg,显著下降10.21 mmHg;用药前的平均舒张压为90.94mmHg,用药后的平均舒张压为85.16mmHg,显著下降5.78mmHg。40例血压达标,达标率为36.70%。协方差分析未发现上述位点不同基因型携带者的血压下降值有显著差异。多元线性回归也未发现上述位点与血压下降值有显著关联。结论:小剂量氢氯噻嗪可在短期内显著降低藏族轻度高血压患者的血压;但未发现以上SNP位点对降压有显著影响。     

长期服用氢氯噻嗪对中心动脉压的影响

目的:观察长期服用单药氢氯噻嗪对高血压患者中心动脉压的影响。方法:回顾性分析了参加非洛地平降低心血管事件试验(FEVER)的3个研究中心的受试者资料,选择其中只服用氢氯噻嗪且完成3年以上脉搏波检查随访的76例患者的资料。脉搏波检查在入组时做1次作为基线值,随后每12个月1次至研究结束。观察的中心动脉脉搏波主要指标包括:中心动脉第一峰收缩压、中心动脉第二峰收缩压、中心动脉舒张压、反射波增压及反射波增压指数。结果:与基线值比较,12、24和36个月随访时肱动脉的收缩压和舒张压及中心动脉第一峰收缩压和中心动脉舒张压均有极显著的下降(P<0.001),反射波增压有所下降(P<0.05),而反射波增压指数和心率无显著变化(P>0.05)。结论:长期服用小剂量氢氯噻嗪降低肱动脉压及中心动脉压一样,对反射波增压指数无影响,提示不能产生额外的中心动脉降压获益。     

氢氯噻嗪分别与氯沙坦或卡托普利联合应用的降压疗效和安全性的比较观察

目的:比较联合应用氯沙坦和氢氯噻嗪与卡托普利和氢氯噻嗪治疗高血压的疗效和安全性。方法:72例新诊断或经2周洗脱期后基线平均舒张压为95～115mmHg,平均收缩压<180mmHg的高血压病患者,随机分成A、B两组各36例。A组每天服用氯沙坦50mg和氢氯噻嗪12.5mg,B组每天服用卡托普利50mg和氢氯噻嗪25mg。用药后每周测血压,以基线值与第4周末血压的平均变化作为疗效指标,并记录药物不良反应,结合实验室检查结果作安全性评估。结果:两治疗组第4周平均舒张压及平均收缩压降低无显著差异(P>0.10)。但与药物相关的不良反应A组显著低于B组(8.4％对16.7％)。结论:联合应用氯沙坦和氢氯噻嗪与卡托普利和氢氯噻嗪降压疗效相似,但前者的安全性和耐受性较好。     

上皮细胞钠通道α亚单位（α-ENaC）基因单核苷酸多态性与四川藏族高血压氢氯噻嗪疗效的关联分析

目的：研究四川省甘孜州藏族僧尼群体轻度高血压患者对小剂量氢氯噻嗪治疗的反应和耐受性,并比较α-ENaC基因四个SNP位点不同基因型/等位基因携带者降压反应的差异。 方法：对符合纳入排除标准的120名初发藏族轻度高血压患者,进行问卷调查、体格检查、血清学检测;提取其外周血白细胞DNA进行PCR扩增,使用分子质谱法对α-ENaC基因四个SNP位点rs2228576、rs10849447、rs13306613和rs3782727进行分型。并对所有入选患者进行为期一月的小剂量氢氯噻嗪（12.5mg qd）干预。 结果：该研究群体用药前的平均收缩压为153.73mmHg,用药后的平均收缩压为143.52mmHg,较用药前血压值显著下降10.21mmHg;用药前的平均舒张压为90.94mmHg,用药后的平均舒张压为85.16mmHg,较用药前血压值显著下降5.78mmHg。药物达标总人数为40人,达标率为：36.70%。协方差分析未发现上述四个位点不同基因型携带者的血压下降值具有显著差异。多元线性回归也未发现上述SNP位点的突变与血压下降值有显著关联。 结论：小剂量氢氯噻嗪可以在短期内显著降低藏族轻度高血压患者的血压水平;但未发现以上SNP位点对降压程度有显著影响。     

醛固酮合成酶基因多态性对氢氯噻嗪降压疗效的影响

采用PCR技术检测734例同时服用氢氯噻嗪患者醛固酮合成酶（CYP11B2）基因型,比较不同基因型间的降压疗效。结果TT、TC、CC基因型间舒张压及平均动脉压下降值差异均无统计学意义（P均〉0.05）,但CC基因型患者收缩压下降值大于其他两型。提示高血压病患者不同CYP基因型对氢氯噻嗪的降压疗效存在一定影响。     

氢氯噻嗪、阿替洛尔、卡托普利对高血压病人24小时脉压的影响

目的 探讨不同降压药对高血压病患者24小时平均脉压的影响。方法符合1999年中国高血压联盟颁布的《中国高血压防治指南》中诊断标准的高血压病1、2级患者300例，随机分成三组，分别服用氢氯噻嗪、阿替洛尔、卡托普利，服药前及服药后8周分别进行动态血压检查。结果用药8周后收缩压(SBP)、舒张压(DBP)、脉压(PP)较用药前均有明显下降，但氢氯噻嗪组脉压下降比其它组明显。结论氢氯噻嗪对高血压病人不但降低收缩压及舒张压，对其24小时平均脉压的降低也有明显的作用。     

氢氯噻嗪分别与氯沙坦或卡托普利联合应用的降压疗效和安全性的比较观察

目的比较联合应用氯沙坦和氢氯噻嗪与卡托普利和氢氯噻嗪治疗高血压的疗效和安全性。方法72例新诊断或经2周洗脱期后基线平均舒张压为95～115mmHg，平均收缩压＜180mmHg的高血压病患者，随机分成A、B两组各36例。A组每天服用氯沙坦50mg和氢氯噻嗪12.5mg，B组每天服用卡托普利50mg和氢氯噻嗪25mg。用药后每周测血压，以基线值与第4周末血压的平均变化作为疗效指标，并记录药物不良反应，结合实验室检查结果作安全性评估。结果两治疗组第4周平均舒张压及平均收缩压降低无显著差异(P＞0.10)。但与药物相关的不良反应A组显著低于B组(8.4％对16.7％)。结论联合应用氯沙坦和氢氯噻嗪与卡托普利和氢氯噻嗪降压疗效相似，但前者的安全性和耐受性较好。     

国产比索洛尔对高血压2型糖尿病患者糖代谢的影响

目的观察国产比索洛尔对高血压合并2型糖尿病患者糖代谢及血压的影响情况。方法将符合纳入标准的高血压合并2型糖尿病患者随机分组。观察治疗前后患者糖化血红蛋白(HbA1c)、空腹血糖、糖耐量和血压等的变化。结果共有92例患者完成研究,其中比索洛尔组47例,卡托普利组45例。治疗前和经12周治疗后两组HbA1c、空腹血糖、餐后2h血糖、收缩压和舒张压差异均无统计学意义(P=0.05)。结论本研究表明比索洛尔作为高选择性β1受体阻滞剂,对于原发性高血压合并2型糖尿病患者糖代谢无明显不良影响,同时具有良好的降压效果。     

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.     

合并肺动脉高压心脏移植患者术后早期血流动力学分析及处理

目的观察和探讨心脏移植患者术前肺动脉压力和肺循环阻力与术后右心功能不全的关系,及降低因术后早期肺动脉高压造成右心功能损害的临床措施。方法54例接受同种原位心脏移植手术的患者,根据术前肺动脉收缩压（sPAP）≥45nmmHg（1mmHg=0．133kPa）或〈45mmHg,分为Ⅰ组34例和Ⅱ组20例。统计术前血流动力学指标心排指数（CI）、肺循环阻力（PVR）、中心静脉压（CVP）。Swan-Ganz导管连续监测术后60h内的平均肺动脉压（mPAP）、PVR、CI等指标的动态变化。床旁超声分别监测和评价术后3、7、14、21天和1个月时的三尖瓣反流程度。术后肺动脉高压及右心功能维护治疗措施包括利尿、NO吸入、静脉注射前列环素（llomedin 20）、血液滤过等。结果本组患者无术后早期死亡（术后30天内）。Ⅰ、Ⅱ组患者术前的sPAP分别为（60±12）mmHg和（25±9）mmHg（P〈0．01）;PVR分别为（358±150）dyn·s^-1·cm^-5和（140±68）dyn·s^-1·cm^-5（P〈0．01）。术后早期出现右心功能不全的患者Ⅰ组24／34（70．6％）例,Ⅱ组7／20（35．0％）例,两组比较,差异有统计学意义（P=0．01）。Ⅰ组患者术后早期肺动脉压力和PVR仍明显高于Ⅱ组患者,并且在较长的时间后才逐渐下降至正常或仍维持偏高水平。Ⅰ组患者术后早期三尖瓣反流的严重程度高于Ⅱ组患者（P〈0．05）,但随着术后时间的延长,两组患者三尖瓣反流程度差异无统计学意义。结论心脏移植患者术前肺动脉高压的严重程度是影响术后早期右心功能的关键因素。通过有效的降低和防治术后早期肺动脉高压,降低右心负荷,可以明确降低和缩短因肺动脉高压造成术后早期右心功能损害的严重程度和持续时间,有利于术后早期心功能的恢复并维持良好的远期心功能状态。     

复方缬沙坦治疗轻中度原发性高血压患者的疗效观察

目的评价复方缬沙坦（缬沙坦80mg／氢氯噻嗪12．5mg复方制剂）治疗经单用缬沙坦80mg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。对经2周洗脱期的轻、中度原发性高血压患者[坐位舒张压≥95mmHg（1mmHg=0．133kPa）且〈110mmHg]采用单药缬沙坦80mg／d治疗4周,在单药导入结束后,坐位舒张压仍〉190mmHg的864例患者按1：1随机、双盲分为复方缬沙坦组或缬沙坦80mg／d组,继续治疗8周。在治疗4周和结束时评估药物安全性及有效性。结果在轻、中度原发性高血压患者中复方缬沙坦每日1次比单用缬沙坦80mg／d血压进一步下降、达标率提高。治疗结束时平均坐位收缩压多降低3．5mmHg,平均坐位舒张压多下降2．2mmHg,血压控制〈140／90mmHg的患者在复方缬沙坦组和单用缬沙坦80mg／d组分别为53．9％及40．9％。结论轻、中度原发性高血压患者采用复方缬沙坦治疗组降压有效率及达标率均优于每日1次服用缬沙坦80mg／d组。复方缬沙坦适用于缬沙坦单药控制不良的轻、中度原发性高血压患者。     

A comparison of the efficacy and safety of irbesartan/HCTZ combination therapy with irbesartan and HCTZ monotherapy in the treatment of moderate hypertension

This prospective, double-blind, parallel-group study randomized patients with moderate hypertension (seated systolic blood pressure (SeSBP) 160-179 mm Hg when seated diastolic blood pressure (SeDBP) <110 mm Hg; or SeDBP 100-109 mm Hg when SeSBP <180 mm Hg) 3:1:1 to treatment with irbesartan 300 mg/hydrochlorothiazide (HCTZ) 25 mg combination therapy (n=328), irbesartan 300 mg monotherapy (n=106) or HCTZ monotherapy 25 mg (n=104). Treatment was initiated at half dose, with forced titration to full dose after two weeks followed by ten further weeks' treatment. The primary efficacy variable was the mean reduction in SeSBP from baseline to week 8. Baseline characteristics were similar between groups, with mean baseline blood pressure approximately 162/98 mm Hg; the mean age was 55 years. At week 8 there was a reduction in SeSBP of 27.1 mm Hg with irbesartan/HCTZ, compared with 22.1 mm Hg with irbesartan monotherapy (P=0.0016) and 15.7 mm Hg with HCTZ (P<0.0001). Both the rate of decline and the total degree of decline achieved were greatest with irbesartan/HCTZ and least with HCTZ. A significantly greater percentage of patients reached a treatment goal of SeSBP <140 mm Hg and SeDBP <90 mm Hg by week 8 with irbesartan/HCTZ (53.4%), compared with irbesartan (40.6%; P=0.0254) and HCTZ (20.2%; P<0.0001) alone. Treatment was well tolerated in all three-treatment groups with a slight increase in adverse events in the combination therapy group. In conclusion, irbesartan/HCTZ (300/25 mg) is well tolerated and achieves rapid and sustained reductions in both systolic blood pressure and diastolic blood pressure in patients with moderate hypertension.     

Treatment of hypertension in the elderly with a new calcium channel blocking drug, nitrendipine

PURPOSE: Treatment of hypertension in the elderly decreases cardiovascular morbidity and mortality. We hypothesized that nitrendipine would be efficacious in the treatment of hypertension in the elderly. We evaluated potential differences between nitrendipine and the commonly used drug hydrochlorothiazide (HCTZ). PATIENTS AND METHODS: The study was conducted as a double-blind randomized clinical trial of nitrendipine or HCTZ. Thirty hypertensive subjects over age 60 with a median sitting blood pressure greater than or equal to 95 mm of Hg were recruited into the study. A diastolic blood pressure with treatment of less than 95 mm Hg with a 5 mm Hg or greater decrease from baseline was considered a successful response. RESULTS: Nitrendipine decreased mean (+/- SEM) blood pressure from 163 +/- 3/102 +/- 1 to 142 +/- 2/89 +/- 2 mm Hg, and HCTZ decreased it from 164 +/- 4/102 +/- 1 to 143 +/- 5/91 +/- 2 mm Hg. A greater proportion of patients had a successful response with nitrendipine (81 percent) than with HCTZ (64 percent). The antihypertensive effect of nitrendipine twice daily appeared to be sustained for 24 hours. Blood pressure response to exercise was attenuated with both drugs. HCTZ caused gout, leg pains, muscle aches, hypokalemia, increased uric acid levels, and increased total cholesterol and triglyceride levels. Nitrendipine caused edema and tachycardia. CONCLUSION: Nitrendipine significantly reduces blood pressure with few side effects and no adverse metabolic effects, and offers a reasonable alternative for treating hypertension in the elderly.     

The JNC 7 approach compared to conventional treatment in diabetic patients with hypertension: a double-blind trial of initial monotherapy vs. combination therapy

The JNC 7 states that persons with blood pressure (BP) more than 20/10 mm Hg above goal should be started on combination drug therapy. This criterion includes patients with BP >160/100 mm Hg and diabetics with hypertension. The goal BP for persons with diabetes mellitus is <130/80 mm Hg. A randomized, double-blind trial force titrated initial combination therapy utilizing an angiotensin receptor blocker (ARB) combination (losartan/hydrochlorothiazide [LOS/HCTZ]) compared with an angiotensin-converting enzyme (ACE) inhibitor (ramipril), for 8 weeks, and tested the hypothesis that combination therapy is more likely to achieve goal BP vs. monotherapy. At 4 weeks, 30.5% of LOS/HCTZ and 14.4% of ramipril recipients achieved goal diastolic BP (p<0.001). More participants achieved goal systolic BP in the ARB/HCTZ group at 4 weeks (29.8% vs. 14.4%; p<0.001). At 4 weeks, mean diastolic BP had decreased 10.2+/-7.4 mm Hg in the LOS/HCTZ group compared with 6.4+/-6.8 mm Hg in the ramipril group (p<0.001), and systolic BP had fallen 15.4+/-13.1 mm Hg in the ARB/HCTZ compared with 9.2+/-10.2 mm Hg in the ACE-inhibitor group (p<0.001). Significant differences favoring the combination were also noted at 8 weeks. Drug-related adverse experiences were 10.3% for the combination compared with 12.7% for the monotherapy group. Initial combination therapy with an ARB/HCTZ was more effective than ACE-inhibitor monotherapy in achieving BP goals in participants with diabetes with no significant differences in the incidence of adverse experiences. These observations confirm other studies of combination therapies, such as b blocker/diuretic, ACE inhibitor/diuretic, or ACE inhibitor/calcium channel blocker. The use of two medications will achieve goal BP in more patients than monotherapy. This observation is important in treatment of high-risk patients with diabetes.     

Safety and Tolerability of Fixed-Dose Irbesartan/Hydrochlorothiazide for Rapid Control of Severe Hypertension

This prospective, double-blind, multicenter trial compared the safety and tolerability of irbesartan/hydrochlorothiazide (HCTZ) fixed-dose combination therapy with irbesartan monotherapy in patients with severe hypertension (seated diastolic blood pressure (SeDBP) ≥110 mm Hg, mean BP 172/113 mm Hg at baseline). Patients were randomized 2:1 to 7 weeks' irbesartan/HCTZ 150/12.5 mg to 300/25 mg (n = 468) or irbesartan 150 mg to 300 mg (n = 227). The incidence of treatment-related adverse events (AEs) was similar with combination and monotherapy (11.3% and 10.1%), and most AEs were mild-to-moderate. The combined incidence of prespecified AEs was lower with irbesartan/HCTZ than with irbesartan (8.8% vs. 11.5%). There were no treatment-related serious AEs or deaths. At week 5, more patients achieved SeDBP < 90 mm Hg compared to irbesartan (47% vs. 33%; P = 0.0005). Despite more rapid and aggressive BP lowering, initial fixed-dose irbesartan/HCTZ demonstrated a comparable AE profile to irbesartan monotherapy in patients with severe hypertension.     

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.     

Initial Combination Therapy With Irbesartan/Hydrochlorothiazide for Hypertension: An Analysis of the Relationship Between Baseline Blood Pressure and the Need for Combination Therapy

Hypertension treatment guidelines recommend initiating 2-drug therapy whenever blood pressure (BP) is ≥20 mm Hg systolic or ≥10 mm Hg diastolic above goal. This post hoc pooled analysis of 2 multicenter, randomized, double-blind, active-controlled forced-titration studies in 1235 patients with moderate and severe hypertension examined how baseline BP levels relate to the need for combination therapy by comparing the antihypertensive efficacy and tolerability of once-daily fixed-dose irbesartan/hydrochlorothiazide (HCTZ) 300/25 mg compared with irbesartan 300-mg or HCTZ 25-mg monotherapies. In study 1, patients with severe hypertension (seated diastolic BP [SeDBP] ≥110 mm Hg) were treated for 7 weeks with irbesartan or irbesartan/HCTZ combination therapy, with forced-titration after week 1. In study 2, patients with moderate hypertension (seated systolic BP [SeSBP] 160–180 mm Hg or SeDBP 100–110 mm Hg) were treated for 12 weeks with irbesartan/HCTZ, irbesartan monotherapy, or HCTZ monotherapy, with forced-titration after week 2. The relationship between baseline BP and the likelihood of achieving BP goals (SeSBP <140 mm Hg or SeDBP <90 mm Hg; SeSBP <130 mm Hg or SeDBP <80 mm Hg) as well as the antihypertensive response was evaluated at week 7/8. The need for combination therapy increased with increasing baseline BP and lower BP goals across the range of BP levels studied, with a comparable adverse effect profile to monotherapy. These results suggest that the likelihood of achieving an early BP goal for a given BP severity should be considered when choosing initial combination therapy vs monotherapy.