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Effect of irbesartan monotherapy compared with ACE inhibitors and calcium-channel blockers on patient compliance in essential hypertension patients: a multicenter, open-labeled, three-armed study. 厄贝沙坦单药治疗与ACE抑制剂和钙通道阻滞剂对原发性高血压患者依从性的影响:一项多中心、开放标记、三臂研究
Pub Date : 2005-07-01
Nevres Koylan, Esmeray Acarturk, Aykan Canberk, Nail Caglar, Sali Caglar, Serap Erdine, Sema Guneri, Baris Ilerigelen, Giray Kabakci, Remzi Onder, Olcay Sagkan, Kemalettin Buyukozturk

Objectives: This multicenter, three-armed, open-labeled study investigated patient compliance of patients receiving irbesartan, angiotensin-converting enzyme (ACE) inhibitors or calcium-channel blockers (CCB) for essential hypertension for a 6-month period. Patients were either newly diagnosed or switched from existing antihypertensive medication due to lack of efficacy or side-effects.

Methods: Patients were started monotherapy with irbesartan (n=377), ACE inhibitors (n=298) or CCB (n=308) and were reevaluated on 1st, 3rd, and 6th months of the treatment. The primary endpoint was patient compliance, assessed by proportion of patients who had taken their study medication every day. Efficacy was recorded as mean reductions in blood pressure and the proportion of patients whose blood pressure normalized. Tolerability was assessed by reported adverse events.

Results: Significantly more patients receiving irbesartan had complied with study medication after 3 and 6 months of treatment than ACE inhibitors or CCB. Significantly fewer patients receiving irbesartan needed to change their antihypertensive medication. All three study treatments exhibited similar efficacy profiles, but irbesartan had significantly less adverse events.

Conclusions: This study demonstrated that patient compliance to irbesartan was significantly superior to other study treatments. Irbesartan is therefore a suitable first-line therapy for essential hypertension in everyday clinical practice.

目的:这项多中心、三组、开放标签的研究调查了接受厄贝沙坦、血管紧张素转换酶(ACE)抑制剂或钙通道阻滞剂(CCB)治疗原发性高血压患者6个月的依从性。患者要么是新诊断的,要么是由于缺乏疗效或副作用而从现有的抗高血压药物中切换过来的。方法:患者开始厄贝沙坦(n=377), ACE抑制剂(n=298)或CCB (n=308)的单药治疗,并在治疗的第1、3和6个月重新评估。主要终点是患者的依从性,通过每天服用研究药物的患者比例来评估。疗效记录为血压的平均降低和血压恢复正常的患者比例。通过报告的不良事件来评估耐受性。结果:接受厄贝沙坦治疗的患者在治疗3个月和6个月后的依从性明显高于ACE抑制剂或CCB。接受厄贝沙坦治疗的患者需要改变抗高血压药物的人数明显减少。所有三种研究治疗都显示出相似的疗效,但厄贝沙坦的不良事件显著减少。结论:本研究表明,患者对厄贝沙坦的依从性明显优于其他研究治疗。因此,厄贝沙坦在日常临床实践中是原发性高血压的一种合适的一线治疗药物。
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引用次数: 0
Nifedipine OROS in Chinese patients with hypertension--results of a post-marketing surveillance study in Taiwan. 硝苯地平OROS在中国高血压患者中的应用——台湾上市后监测研究的结果
Pub Date : 2005-07-01 DOI: 10.1080/08038020510040630
Kwo-Chang Ueng, Zhih-Cheng Chen, Poh-Shiow Yeh, Kuo-Chun Hung, Shao-An Hu, Yi-Jen Hung, Harald Landen

Aims: This post-marketing surveillance study assessed the efficacy, safety, and tolerability of the treatment with nifedipine OROS in hypertensive patients in Taiwan.

Results: A total of 2044 patients were included in 204 outpatient clinics. Patients received 30 mg or 60 mg of nifedipine OROS. Mean treatment duration was 15.8 weeks. At endpoint, 91.4% of patients were receiving 30 mg nifedipine OROS. Mean blood pressure reduction was 20.6/10.3 mmHg; 46.1% of patients had a systolic blood pressure < 140 mmHg and 66.8% had a diastolic blood pressure <90 mmHg. Total blood pressure control was achieved in 41.2% of all patients. Beta-blockers were the most commonly used (24.0%) concomitant antihypertensive therapy. A total of 2.3% of patients experienced adverse events. Subjective physicians' assessments of efficacy, tolerability, and patient acceptance of nifedipine OROS treatment had ratings of "very good" and "good" in 82.3% (efficacy), 87.5 (tolerability) and 88.1% (patient acceptance) of the study cohort.

Conclusions: Nifedipine OROS proved to be effective and well tolerated for the treatment of hypertension in 2044 Chinese patients. The results confirm the findings and experience of previously performed controlled clinical studies.

目的:本上市后监测研究评估硝苯地平OROS治疗台湾高血压患者的有效性、安全性和耐受性。结果:204家门诊共纳入患者2044例。患者接受30mg或60mg硝苯地平OROS治疗。平均治疗时间15.8周。在终点,91.4%的患者接受30mg硝苯地平OROS治疗。平均血压降低20.6/10.3 mmHg;结论:2044例中国患者中硝苯地平OROS治疗高血压有效且耐受性良好。结果证实了以前进行的对照临床研究的发现和经验。
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引用次数: 11
Effects of nifedipine GITS 20 mg or enalapril 20 mg on blood pressure and inflammatory markers in patients with mild-moderate hypertension. 硝苯地平GITS 20mg或依那普利20mg对轻中度高血压患者血压和炎症指标的影响
Pub Date : 2005-07-01 DOI: 10.1080/08037050510034257
Enrico Agabiti Rosei, Patrizia Morelli, Damiano Rizzoni

Objective: Calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors and other drug classes either alone or in combination have been recommended for the treatment of hypertension. Nifedipine gastrointestinal therapeutic system (GITS) 20 mg is a new low-dose formulation with an improved tolerability. The aim of the present study was to compare the effects of nifedipine GITS 20 mg and enalapril 20 mg on blood pressure and circulating adhesion molecules in hypertensive patients.

Methods: This randomized, double-blind, multicentre trial compared the blood pressure lowering effects of a 12-week treatment of nifedipine GITS 20 mg vs enalapril 20 mg in 264 patients with mild-to-moderate hypertension.

Results: Nifedipine GITS 20 mg induced a reduction of clinic blood pressure, which was similar to that observed with enalapril 20 mg. Nifedipine GITS and enalapril lowered mean sitting diastolic blood pressure by 11.8 and 12.4 mmHg, respectively, while systolic blood pressure was reduced by 15.3 and 16.3 mmHg, respectively. Ambulatory blood pressure monitoring-derived blood pressure data showed similar results in both groups without any statistically significant differences between treatments. Both enalapril and nifedipine tended to reduce ICAM-1 and E-selectin, while only nifedipine reduced von Willebrand factor. Both treatments were well tolerated.

Conclusions: Our findings demonstrate a similar antihypertensive effectiveness of a low dose (20 mg) of nifedipine GITS in comparison with a standard dose of enalapril (20 mg). Given its clinical efficacy and good tolerability, low-dose nifedipine GITS may be considered a valuable treatment option for hypertensive patients.

目的:钙拮抗剂、血管紧张素转换酶(ACE)抑制剂和其他药物类别单独或联合已被推荐用于治疗高血压。硝苯地平胃肠道治疗系统(GITS) 20mg是一种新的低剂量制剂,具有更好的耐受性。本研究的目的是比较硝苯地平GITS 20mg和依那普利20mg对高血压患者血压和循环黏附分子的影响。方法:这项随机、双盲、多中心试验比较了264例轻中度高血压患者服用硝苯地平(20mg)和依那普利(20mg)治疗12周的降压效果。结果:硝苯地平GITS 20mg可使临床血压降低,其效果与依那普利20mg相似。硝苯地平GITS和依那普利分别降低平均坐位舒张压11.8和12.4 mmHg,收缩压分别降低15.3和16.3 mmHg。动态血压监测得出的血压数据在两组中显示相似的结果,治疗之间没有统计学上的显著差异。依那普利和硝苯地平均有降低ICAM-1和e -选择素的趋势,而硝苯地平仅能降低血管性血友病因子。两种治疗方法均耐受良好。结论:我们的研究结果表明,与标准剂量依那普利(20mg)相比,低剂量(20mg)硝苯地平GITS具有相似的降压效果。鉴于其临床疗效和良好的耐受性,小剂量硝苯地平GITS可能被认为是高血压患者的一种有价值的治疗选择。
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引用次数: 25
Fixed combination of manidipine and delapril in the treatment of mild to moderate essential hypertension: evaluation by 24-hour ambulatory blood pressure monitoring. 曼地平联合地普利固定联合治疗轻中度原发性高血压:24小时动态血压监测评价。
Pub Date : 2005-07-01 DOI: 10.1080/08038020510040621
Amedeo Mugellini, Alvaro Vaccarella, Aldo Celentano, Flavio Scanferla, Annalisa Zoppi, Roberto Fogari

This present study assessed the antihypertensive efficacy of the fixed combination of manidipine and delapril by ambulatory blood pressure monitoring in patients with hypertension inadequately controlled by monotherapy with either component. After a 2-week placebo period, 55 mild to moderate hypertensive patients were randomized to manidipine 20 mg o.d. or delapril 30 mg b.i.d. for 4 weeks. After this period, 30 patients, aged 30-76 years (18 males and 12 females) whose diastolic blood pressure was not adequately controlled (> or = 90 mmHg) by monotherapy were treated with the fixed combination of manidipine 10 mg plus delapril 30 mg o.d. for 8 weeks. A 24-h ambulatory blood pressure monitoring recording was performed at the end of the placebo washout, of the monotherapy and of the combination therapy. Blood pressure control over the 24 h was quantified by the trough-to-peak ratio and the smoothness index. As compared to placebo, the fixed combination of manidipine and delapril produced a statistically significant (p<0.01) decrease in sitting clinic (18 +/- 9/14 +/- 5 mmHg) and 24-h blood pressure (12 +/- 7/10 +/- 5 mmHg) without affecting heart rate. This reduction was greater than that observed with single components. At the end of the 8-week combination treatment period, the rate of normalilized patients was 73%. Treatment with the fixed combination was associated with a positively high smoothness index (1.2 +/- 0.7/13.8 +/- 0.8) and with a relatively good trough-to-peak ratio (0.46/0.60). The combination of manidipine and delapril produced significant and smooth reductions in blood pressure values, which persisted over the 24-h dosing interval. These results support the use of fixed manidipine-delapril combination in the treatment of mild to moderate hypertensive patients inadequately controlled by monotherapy.

本研究通过动态血压监测对单药治疗控制不充分的高血压患者,评估了曼地平和德拉普利固定联合治疗的降压效果。在2周的安慰剂期后,55名轻中度高血压患者被随机分配到每日20mg的曼尼地平组或每日30mg的delapril组,持续4周。在此期间,30例患者,年龄30-76岁(男性18例,女性12例),舒张压单药控制不充分(>或= 90mmhg),采用固定联合曼尼地平10mg + delapril 30mg o.d治疗8周。在安慰剂洗脱期、单药治疗和联合治疗结束时,进行24小时动态血压监测记录。通过波谷峰比和平滑度指数对24 h血压控制进行量化。与安慰剂相比,曼尼地平和德拉普利的固定组合产生了统计学意义上的显著差异(p
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引用次数: 12
Effect of eprosartan on pulse pressure and blood pressure components in patients with isolated systolic hypertension. 依泊沙坦对孤立性收缩期高血压患者脉压和血压成分的影响。
Pub Date : 2004-12-01 DOI: 10.1080/08038020310026781
Alejandro de la Sierra, Anna Munoz, Emma Arcos, Juan Salvador Lopez, Jordi Relats

Background: Systolic blood pressure (SBP) and pulse pressure (PP) are accurate predictors of cardiovascular events in the elderly population. In these patients, isolated systolic hypertension (ISH) is an important risk factor for cardiovascular morbidity and mortality.

Study design: A multicentre, observational, prospective study, evaluated the effects of 16 weeks of eprosartan treatment on PP and other blood pressure (BP) parameters. Data from a subgroup of patients from this study, who had ISH, are presented here.

Results: Eprosartan monotherapy reduced SBP, PP and mean blood pressure (MBP) over the duration of treatment, whereas diastolic blood pressure (DBP) remained unchanged. There was no difference in the reductions of these parameters between eprosartan monotherapy and combination therapy. In addition, a high proportion of patients responded to eprosartan therapy. The response to eprosartan therapy was significantly influenced by family history of early cardiovascular disease, but not by gender, body mass index (BMI), raised low-density lipoprotein (LDL)-cholesterol, smoking, left ventricular hypertrophy, or previous history of cardiovascular disease. Patients aged > or =70 years had a decreased reduction in DBP and MBP components. Eprosartan therapy was well tolerated, with only 1% of patients reporting an adverse event.

Conclusions: Eprosartan is an effective and well-tolerated antihypertensive therapy for elderly patients with ISH.

背景:收缩压(SBP)和脉压(PP)是老年人心血管事件的准确预测指标。在这些患者中,孤立性收缩期高血压(ISH)是心血管疾病发病率和死亡率的重要危险因素。研究设计:一项多中心、观察性、前瞻性研究,评估依泊沙坦治疗16周对PP和其他血压参数的影响。本研究中患有ISH的亚组患者的数据在此列出。结果:依泊沙坦单药治疗期间降低收缩压、PP和平均血压(MBP),而舒张压(DBP)保持不变。依泊沙坦单药治疗和联合治疗在这些参数的降低方面没有差异。此外,很大比例的患者对依普沙坦治疗有反应。早期心血管疾病家族史对依泊沙坦治疗的反应有显著影响,但不受性别、体重指数(BMI)、低密度脂蛋白(LDL)-胆固醇升高、吸烟、左心室肥厚或既往心血管疾病史的影响。年龄>或=70岁的患者DBP和MBP成分降低。依泊沙坦治疗耐受性良好,只有1%的患者报告了不良事件。结论:依普沙坦是治疗老年ISH患者有效且耐受性良好的降压药物。
{"title":"Effect of eprosartan on pulse pressure and blood pressure components in patients with isolated systolic hypertension.","authors":"Alejandro de la Sierra,&nbsp;Anna Munoz,&nbsp;Emma Arcos,&nbsp;Juan Salvador Lopez,&nbsp;Jordi Relats","doi":"10.1080/08038020310026781","DOIUrl":"https://doi.org/10.1080/08038020310026781","url":null,"abstract":"<p><strong>Background: </strong>Systolic blood pressure (SBP) and pulse pressure (PP) are accurate predictors of cardiovascular events in the elderly population. In these patients, isolated systolic hypertension (ISH) is an important risk factor for cardiovascular morbidity and mortality.</p><p><strong>Study design: </strong>A multicentre, observational, prospective study, evaluated the effects of 16 weeks of eprosartan treatment on PP and other blood pressure (BP) parameters. Data from a subgroup of patients from this study, who had ISH, are presented here.</p><p><strong>Results: </strong>Eprosartan monotherapy reduced SBP, PP and mean blood pressure (MBP) over the duration of treatment, whereas diastolic blood pressure (DBP) remained unchanged. There was no difference in the reductions of these parameters between eprosartan monotherapy and combination therapy. In addition, a high proportion of patients responded to eprosartan therapy. The response to eprosartan therapy was significantly influenced by family history of early cardiovascular disease, but not by gender, body mass index (BMI), raised low-density lipoprotein (LDL)-cholesterol, smoking, left ventricular hypertrophy, or previous history of cardiovascular disease. Patients aged > or =70 years had a decreased reduction in DBP and MBP components. Eprosartan therapy was well tolerated, with only 1% of patients reporting an adverse event.</p><p><strong>Conclusions: </strong>Eprosartan is an effective and well-tolerated antihypertensive therapy for elderly patients with ISH.</p>","PeriodicalId":8974,"journal":{"name":"Blood pressure. Supplement","volume":"2 ","pages":"5-10"},"PeriodicalIF":0.0,"publicationDate":"2004-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/08038020310026781","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25057826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 15
Automated office and home phone-transmitted blood pressure recordings in uncontrolled hypertension treated with valsartan and hydrochlorothiazide. 使用缬沙坦和氢氯噻嗪治疗的未控制高血压患者的自动办公室和家庭电话传输血压记录。
Pub Date : 2004-12-01 DOI: 10.1080/08038020410004756
Xavier Girerd, Thierry Denolle, Caroline Yau, Béatrice Fiquet, Patrick Brunel, Bruno Moulin, Daniel Herpin

The study objective was to evaluate, by means of automated office and phone-transmitted home blood pressure (OBP and HBP) recordings, the effects of a fixed combination of valsartan 160 mg and hydrochlorothiazide (HCTZ) 25 mg in hypertensive patients previously uncontrolled with the combination of an angiotensin receptor antagonist and HCTZ. From 241 selected patients, 171 (71%) had uncontrolled hypertension OBP and HBP [mean baseline OBP and HBP systolic and diastolic (SBP/DBP): 157/91 and 152/87 mmHg]. In this open-design study, patients were directly switched from other angiotensin receptor blocker combination products to valsartan/HCTZ for 6 weeks. The same validated automated device was used for OBP and HBP recordings. At baseline, mean HBP was 152 +/- 15/87 +/- 10 mmHg and mean OBP was 157 +/- 12/91 +/- 9 mmHg. After 6 weeks of treatment with valsartan 160 mg and HCTZ 25 mg, a significant decrease in BP was observed both at home (146 +/- 17/83 +/- 12 mmHg) and at the office (151 +/- 18/87 +/- 11 mmHg), with a difference from baseline of -4 mmHg, p < 0.001 for DBP and of -6 mmHg for SBP, p < 0.001. The percentage of patients with office and home control was 24% and 23% respectively, with a kappa index at 0.459. Elevated OBP only (office hypertension) was observed in 3.6% and elevated HBP only (masked hypertension) in 10% of patients. In conclusion, treatment with valsartan and HCTZ 25 mg in patients with confirmed uncontrolled hypertension induced a clinically relevant decrease in BP with approximately 23% of additional patients strictly controlled with a single tablet. The use of an automated oscillometric device at the office and at home allowed the detection of controlled subjects with good agreement.

研究目的是通过自动办公室和电话传输的家庭血压(OBP和HBP)记录,评估缬沙坦160 mg和氢氯噻嗪(HCTZ) 25 mg固定联合使用血管紧张素受体拮抗剂和HCTZ联合控制的高血压患者的效果。在241例选定的患者中,171例(71%)高血压不受控制的OBP和HBP[平均基线收缩压和舒张压(SBP/DBP): 157/91和152/87 mmHg]。在这项开放设计的研究中,患者直接从其他血管紧张素受体阻滞剂组合产品切换到缬沙坦/HCTZ 6周。使用相同的经过验证的自动化设备进行OBP和HBP记录。基线时,平均HBP为152 +/- 15/87 +/- 10 mmHg,平均OBP为157 +/- 12/91 +/- 9 mmHg。缬沙坦160 mg和HCTZ 25 mg治疗6周后,在家中(146 +/- 17/83 +/- 12 mmHg)和办公室(151 +/- 18/87 +/- 11 mmHg)观察到血压显著下降,与基线相比差异为-4 mmHg,舒张压p < 0.001,收缩压-6 mmHg, p < 0.001。办公室控制和家庭控制的患者比例分别为24%和23%,kappa指数为0.459。3.6%的患者仅有OBP升高(办公室高血压),10%的患者仅有HBP升高(隐蔽性高血压)。综上所述,缬沙坦和HCTZ 25mg治疗确认不受控制的高血压患者可导致与临床相关的血压下降,另有约23%的患者使用单片严格控制。在办公室和家中使用自动振荡测量装置,可以很好地检测受控对象。
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引用次数: 4
Candesartan plus hydrochlorothiazide fixed combination vs previous monotherapy plus diuretic in poorly controlled essential hypertensive patients. 坎地沙坦加氢氯噻嗪固定联合治疗与既往单药加利尿剂治疗控制不良的原发性高血压患者的比较。
Pub Date : 2004-12-01 DOI: 10.1080/08038020410035574
Giuseppe Mancia, Stefano Omboni

Objective: To assess efficacy and tolerability of candesartan cilexetil (CC) plus hydrochlorothiazide (HCTZ) fixed combination vs previous monotherapy (PM) plus HCTZ in hypertension.

Design and methods: After 2-4 weeks of run in, 409 outpatients (diastolic blood pressure, DBP >90 and < or =110 mmHg; systolic blood pressure, SBP < or =180 mmHg), aged 26-79 years, under monotherapy, were randomized in a PROBE multicenter trial to CC 16 mg plus HCTZ 12.5 mg or PM plus HCTZ 12.5 mg for 8 weeks. HCTZ was doubled after the first 4 weeks in non-responders (DBP > or =90 mmHg or SBP > 180 mmHg).

Results: Automatic oscillometric (Omron 705 CP) DBP and SBP were similarly reduced by CC + HCTZ and PM + HCTZ after 4 (12/15 and 10/13 mmHg) and 8 weeks (13/20 and 12/18 mmHg) in the intention-to-treat (ITT, n = 398) population. HCTZ dose was doubled in 18.1 and 31.2% of patients in the CC + HCTZ and PM + HCTZ group, respectively (p < 0.05). Rate of normalized patients (DBP <90 and/or SBP < 140 mmHg) after 8 weeks of treatment was greater (p < 0.05) under CC + HCTZ (82.0 vs 72.6% vs PM + HCTZ). Pulse pressure was comparably reduced by CC + HCTZ and PM + HCTZ, at 4 (3 mmHg for both) and 8 weeks (7 and 6 mmHg, respectively). Heart rate was unchanged. Results of per-protocol analysis (n = 316) did not differ from those of ITT analysis. Rate of adverse events was low and comparable between groups.

Conclusions: CC plus HCTZ fixed combination is an effective and safe alternative to other antihypertensive drugs, given either as monotherapy or in combination when they do not satisfactorily control patient's blood pressure.

目的:评价坎地沙坦西列地酯(CC)联合氢氯噻嗪(HCTZ)固定联合与既往单药(PM)联合HCTZ治疗高血压的疗效和耐受性。设计与方法:经2 ~ 4周磨合,409例门诊患者(舒张压、舒张压>90、<或=110 mmHg;收缩压,收缩压<或=180 mmHg),年龄26-79岁,接受单药治疗,在PROBE多中心试验中随机分为CC 16 mg + HCTZ 12.5 mg或PM + HCTZ 12.5 mg,持续8周。无应答者(舒张压>或=90 mmHg或收缩压> 180 mmHg)的HCTZ在前4周后翻倍。结果:在意向治疗(ITT, n = 398)人群中,CC + HCTZ和PM + HCTZ在4周(12/15和10/13 mmHg)和8周(13/20和12/18 mmHg)后,自动振荡测量(Omron 705 CP)舒张压和收缩压类似地降低。CC + HCTZ组和PM + HCTZ组分别有18.1%和31.2%的患者HCTZ剂量增加一倍(p < 0.05)。结论:CC + HCTZ固定联合治疗在血压控制效果不理想时,可作为其他降压药物的一种安全有效的替代方案。
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引用次数: 11
Experimental evidences of nitric oxide-dependent vasodilatory activity of nebivolol, a third-generation beta-blocker. 第三代β受体阻滞剂奈比洛尔血管扩张活性的实验证据。
Pub Date : 2004-10-01
Louis J Ignarro

Nebivolol is a new and selective beta1-adrenergic receptor antagonist whose haemodynamic profile is different from that of classical beta-blockers. The blood pressure lowering effects of nebivolol are, at least partially, due to the direct vasodilation as a result of nitric oxide (NO) release from endothelial cells. Several in vitro studies unequivocally show that, at least in certain vascular districts (particularly in small diameter, non-conduit vessels) and in platelets, nebivolol can stimulate an increase of endothelial NO, which becomes available at the smooth muscle layers and induces vasorelaxation. Nebivolol appears to interact with the endothelial NO pathway in two complementary ways: it increases NO synthase (NOS) activity and reduces the NO-scavenging radical superoxide anion, by re-directing deranged NOS activity, from superoxide to NO production. Nebivolol appears also to possess a complementary antioxidant activity, through which the pathological ROS-induced depression of intracellular NO levels can be prevented. Depending on the studies, evidences for a role of different receptors have been obtained. Although the interaction of nebivolol with cell receptors and the mechanisms of signal transduction into eNOS activation are not yet fully delineated, that nebivolol increases NO production and extracellular release has been proved not only by confirming its inhibition by NOS blockers, but also by measuring NO levels in mediums and cells in several different experimental settings.

奈比洛尔是一种新的选择性β -肾上腺素能受体拮抗剂,其血流动力学特征不同于经典的β受体阻滞剂。奈比洛尔的降压作用至少部分是由于内皮细胞释放一氧化氮(NO)而直接舒张血管所致。几项体外研究明确表明,至少在某些血管区(尤其是小直径、非导管血管)和血小板中,奈比洛尔可以刺激内皮NO的增加,而内皮NO在平滑肌层中可用,并诱导血管松弛。奈比洛尔似乎以两种互补的方式与内皮细胞NO通路相互作用:通过将紊乱的NOS活性从超氧化物重定向到NO生成,增加NO合成酶(NOS)活性,降低NO清除自由基超氧阴离子。奈比洛尔似乎还具有互补的抗氧化活性,通过它可以防止病理性ros诱导的细胞内NO水平的降低。根据不同的研究,已经获得了不同受体作用的证据。虽然奈比洛尔与细胞受体的相互作用以及信号转导到eNOS激活的机制尚未完全描述,但奈比洛尔增加NO的产生和细胞外释放已经被证实,不仅通过证实其对NOS阻滞剂的抑制作用,而且通过在几种不同的实验环境中测量培养基和细胞中的NO水平。
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引用次数: 0
Clinical pharmacodynamics of nebivolol: new evidence of nitric oxide-mediated vasodilating activity and peculiar haemodynamic properties in hypertensive patients. 奈比洛尔的临床药效学:高血压患者一氧化氮介导的血管舒张活性和特殊血流动力学特性的新证据。
Pub Date : 2004-10-01 DOI: 10.1080/08038020410016548
Alberto Zanchetti

New evidence from recently completed clinical studies performed with nebivolol, a highly selective beta-1 beta-blocker, endowed with additional vasodilating activity mediated by nitric oxide (NO) endothelial release, confirm previous findings that nebivolol differs from other beta-blocking agents and that the combination of beta-1 blockade and NO-mediated vasodilation not only potentiates the blood pressure lowering activity, but leads to a broader favourable haemodynamic profile, which is clinically relevant to the treatment of hypertensive patients. In particular, six new studies focusing on the vasodilation properties of nebivolol demonstrated that: (i) its blood pressure lowering effect is accompanied by a vasodilating action that is seen after single and chronic administration of the usual antihypertensive oral dose of 5 mg once daily; (ii) the vasodilation can be documented systemically, at various regional vascular beds and skin microcirculation, and is accompanied by increased small arterial distensibility; (iii) the NO-endothelium-dependency of its vasodilating action is shown by the model of forearm or cutaneous vasodilating response to acetylcholine and by the blockade of the nebivolol-induced local vasodilation by a blocker of the arginine-NO cascade, L-NMMA. Two more studies demonstrated the ability of nebivolol to increase NO concentrations through preservation of NO from oxidative degradation, and not only by stimulation of its synthesis. Finally, two studies confirmed the favourable haemodynamic action of nebivolol on both systolic and diastolic function and, in particular, an increase in stroke volume, associated with reduction in vascular resistance, resulting in a maintained cardiac output despite reduced heart rate. These properties consistently differentiate nebivolol from non-vasodilating beta-blockers, such as those used for the active comparative studies, i.e. atenolol, metoprolol or bisoprolol. The observation that nebivolol enhances or restores NO-mediated vasodilation in hypertensive patients has important therapeutic implications in view of the well-established protective role of NO against cardiovascular risk factors, and particularly the development of atherosclerosis. Similarly, the favourable haemodynamic profile of nebivolol, as described by the new investigations (preservation of cardiac output, reduction of peripheral resistance and improved diastolic function) appear to have clinically relevant benefits on the impairment in systolic and/or diastolic function often complicating the hypertension.

最近完成的关于奈比洛尔的临床研究的新证据证实,奈比洛尔是一种高度选择性的β -1 β受体阻滞剂,具有由一氧化氮(NO)内皮释放介导的额外血管舒张活性,证实了奈比洛尔不同于其他β -受体阻滞剂的发现,β -1阻滞剂和NO介导的血管舒张的结合不仅增强了降血压活性,而且导致了更广泛的有利的血流动力学特征。这对高血压患者的治疗有临床意义。特别是,六项关于奈比洛尔血管舒张特性的新研究表明:(1)其降压作用伴随着血管舒张作用,这是在常规降压口服剂量5mg每日一次的单次和慢性给药后看到的;(ii)血管舒张可在不同区域血管床和皮肤微循环中系统性记录,并伴有小动脉扩张性增加;(iii)其血管舒张作用的no -内皮依赖性通过对乙酰胆碱的前臂或皮肤血管舒张反应模型以及通过精氨酸- no级联的阻断剂L-NMMA阻断奈比洛尔诱导的局部血管舒张来显示。另外两项研究表明,奈比洛尔不仅通过刺激一氧化氮合成,而且通过保护一氧化氮免受氧化降解而增加一氧化氮浓度。最后,两项研究证实了奈比洛尔对收缩期和舒张期功能的有利血流动力学作用,特别是与血管阻力降低相关的卒中容量增加,从而在心率降低的情况下维持心输出量。这些特性将奈比洛尔与非血管扩张受体阻滞剂(如用于活性比较研究的阿替洛尔、美托洛尔或比索洛尔)区分开来。鉴于一氧化氮对心血管危险因素的保护作用,特别是对动脉粥样硬化的发展,奈比洛尔增强或恢复一氧化氮介导的高血压患者血管舒张的观察具有重要的治疗意义。同样,新的研究表明,奈比洛尔有利的血流动力学特征(保持心输出量,降低外周阻力和改善舒张功能)似乎对高血压合并的收缩期和/或舒张期功能损害具有临床相关益处。
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引用次数: 80
Doxazosin GITS versus hydrochlorothiazide as add-on therapy in patients with uncontrolled hypertension. Doxazosin GITS与氢氯噻嗪作为不受控制的高血压患者的附加治疗。
Pub Date : 2003-12-01 DOI: 10.1080/08038020310016369
Carlos Campo, Julian Segura, Cecilia Roldán, José M Alcázar, José L Rodicio, Luis M Ruilope

The objective of this prospective, randomized, open-label, parallel-arm comparative study, with a 4-month follow-up, was to assess the antihypertensive efficacy, tolerability and metabolic safety of doxazosin GITS (gastrointestinal therapeutic system) 4-8 mg/day vs hydrochlorothiazide (HCTZ) 12.5-25 mg/day as add-on therapy in patients not controlled with monotherapy with other drugs. Ninety-eight patients completed the study (mean age 57.4 +/- 15 years, 53% female). Mean systolic/diastolic blood pressure reduction was 8.2/4.5 mmHg in the HCTZ group and 8.9/5.0 mmHg in the doxazosin GITS group, and a strict blood pressure control was achieved in 79% and 83% of the patients, respectively. The incidence rates of adverse events were low and similar in both groups. However, metabolic differences were seen between the groups, doxazosin GITS vs HCTZ, respectively: total cholesterol (mg/dl) 210 +/- 53 vs 231 +/- 62 (p < 0.05), low-density lipoprotein (LDL) cholesterol (mg/dl) 139 +/- 40 vs 161 +/- 57 (p < 0.01), high-density lipoprotein (HDL) cholesterol (mg/dl) 58 +/- 16 vs 48 +/- 13 (p < 0.01), HDL/total cholesterol ratio 27.6 +/- 8 vs 21.2 +/- 7 (p < 0.001), plasma uric acid (mg/dl) 5.3 +/- 2.6 vs 6.8 +/- 3.1 (p < 0.05) and serum potassium (mEq/l) 4.1 +/- 1.3 vs. 3.7 +/- 1.2 (p < 0.01). In conclusion, doxazosin GITS has a tolerability and efficacy profile similar to low doses of thiazide diuretics, with a better evolution of metabolic and electrolyte parameters. Therefore, in patients not controlled with monotherapy, doxazosin GITS can be considered an alternative to the addition of thiazide diuretics.

这项前瞻性、随机、开放标签、平行对照研究的目的是通过4个月的随访,评估doxazosin GITS(胃肠道治疗系统)4- 8mg /天与氢氯噻嗪(HCTZ) 12.5- 25mg /天作为非单药治疗患者的附加治疗的降压疗效、耐受性和代谢安全性。98例患者完成了研究(平均年龄57.4±15岁,53%为女性)。HCTZ组平均收缩压/舒张压降低8.2/4.5 mmHg, doxazosin GITS组平均收缩压/舒张压降低8.9/5.0 mmHg, 79%和83%的患者分别达到严格的血压控制。两组不良事件发生率低且相似。然而,doxazosin GITS和HCTZ组之间的代谢差异分别是:总胆固醇(mg / dl) 210 + / - 53 vs 231 + / - 62 (p < 0.05),低密度脂蛋白(LDL)胆固醇(mg / dl) 139 + / - 40 vs 161 + / - 57 (p < 0.01),高密度脂蛋白(HDL)胆固醇(mg / dl) 58 + / - 16 vs 48 + / - 13 (p < 0.01),高密度脂蛋白/总胆固醇比率27.6 + / - 8和21.2 + / - 7 (p < 0.001),血浆尿酸(mg / dl) 5.3 + / - 2.6 vs 6.8 + / - 3.1 (p < 0.05)和血清钾(毫克当量/ l) 4.1 + / - 1.3和3.7 + / - 1.2 (p < 0.01)。综上所述,doxazosin GITS具有与低剂量噻嗪类利尿剂相似的耐受性和疗效,但代谢和电解质参数的进化更好。因此,在单药治疗无法控制的患者中,doxazosin GITS可以被认为是噻嗪类利尿剂的替代方案。
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引用次数: 13
期刊
Blood pressure. Supplement
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