血管紧张素Ⅱ受体拮抗剂的临床应用

血管紧张素Ⅱ(AngⅡ)受体拮抗剂(ARBs),是继血管紧张素转换酶抑制剂(ACEI)之后的新一类作用于肾素-血管紧张素系统(RAS)的重要药物,被越来越多地应用于高血压的治疗.这类药物在预防心肌梗死后重塑、治疗充血性心力衰竭、动脉硬化、糖尿病肾病等具有良好作用.与ACEI比较,它作用于RAS的末端受体水平,更充分、更直接、更具选择性地阻断RAS,且很少有干咳、血管神经性水肿等副作用.随着ARBs类药物的不断涌现,临床应用日趋广泛,已被世界卫生组织和国际高血压联盟列为6大类抗高血压药物之一.     

某院2009-2011年血管紧张素受体Ⅱ拮抗剂应用分析

目的调查分析某院血管紧张素受体Ⅱ拮抗剂(ARB)的临床使用情况。方法利用该院计算机管理软件检索2009-2011年ARB与钙拮抗剂(CCB)、血管紧张素转换酶抑制剂(ACEI)的销售数量和金额,利用限定日剂量法进行药物利用分析。结果 ARB的销售金额和所占比例始终位居第一,厄贝沙坦的用药频度(DDDs)连续3年排名第一,缬沙坦与厄贝沙坦氢氯噻嗪增长速度最快。结论 ARB占据该院降压治疗主导地位,厄贝沙坦、厄贝沙坦氢氯噻嗪患者选用倾向较大,销售前景看好。     

2013年我院门诊血管紧张素Ⅱ受体拮抗药使用合理性分析

目的:了解我院门诊血管紧张素Ⅱ受体拮抗药(ARB)类药物的使用现状,为促进临床合理用药提供参考。方法:统计2013年我院门诊使用ARB类药物治疗高血压的处方共2 460张,综合分析该类药物的使用情况。结果:2013年度我院门诊采用ARB类药物治疗高血压的比例为36.22%,常用ARB类药物依次为厄贝沙坦片、厄贝沙坦氢氯噻嗪片、缬沙坦胶囊、替米沙坦片。我院治疗高血压处方多为二联用药,其中ARB类药物常见的联用方式为ARB+钙离子拮抗药(CCB)和ARB+保钾利尿药;而ARB类药物的三联用药方式主要为ARB+β受体阻滞药(β-RB)+CCB和ARB+CCB+保钾利尿药。在2 460张应用ARB类药物治疗高血压的处方中,不合理用药处方有1 103张,占44.84%。其中ARB与保钾利尿药联用且不具有明确指征的处方有77张,占6.98%;ARB与ACEI联用且不具有明确指征的处方有39张,占3.54%;ARB与β受体阻滞药联用且不具有明确指征的处方有330张,占29.92%;ARB用药频次不当的处方有617张,占55.94%;其他情况的不合理用药处方有40张,占3.63%。结论:ARB类药物是我院门诊常用的降压药物,然而临床治疗中却存在诸多不合理使用的问题,故应采取适当干预措施,通过医师、药师及医院的共同努力,促进临床合理用药。     

血管紧张素Ⅱ受体拮抗剂延缓慢性肾病进展的效果比较观察

目的比较观察血管紧张素Ⅱ受体拮抗体(ARBs)延缓慢性肾病进展的效果。方法按服用ARBs药物的不同将慢性肾病患者152例随机分为替米沙坦组64例、厄贝沙坦组48例和缬沙坦组40例。观察3组治疗前后血压、血清肌酐、内生肌酐清除率、24h尿蛋白定量变化情况。结果 3组治疗后血压、内生肌酐清除率、24h蛋白定量均改善,差异均有统计学意义(P<0.05)。3组间血压、血清肌酐、内生肌酐清除率及24h蛋白定量比较差异均无统计学意义(P>0.05)。3组均耐受良好,无因不良反应而停药病例。结论 ARBs可延缓已出现肾功能不全慢性肾病患者的肾功能衰竭进展速率,保护肾功能。ARBs对已出现肾功能不全的慢性肾病患者有明确的治疗意义。     

血管紧张素Ⅱ受体拮抗药的临床应用与不良反应

随着人们对肾素-血管紧张素-醛固酮系统（RAAS）认识的不断深入，血管紧张素Ⅱ受体拮抗药（ARB）已成为一类重要的高血压治疗药物，是继血管紧张素转换酶抑制剂（ACEI）后，又一类作用于肾素-血管紧张素系统（RAS）的新型降压药，具有高效、长效、安全、可口服、耐受性好等特点。ARB属非肽类化合物，目前经美国食品与药品管理局（H）A）批准应用于临床的ARB有氯沙坦、缬沙坦、伊贝沙坦、替米沙坦、坎地沙坦、     

我院门诊ARB类抗高血压药的应用及其作用分析

目的：分析本院门诊电子处方中高血压药物的应用,主要分析血管紧张素ⅡAT1受体拮抗剂（ ARB）类抗高血压药物的应用情况及临床作用。方法收集我医院2015年4月门诊已确诊高血压患者的电子处方,统计我院高血压药物的出现频率和销售金额,并采用WTO推荐的限定日剂量（ DDD）药物的用药频率（ DDDs）等方法对ARB类药物的使用情况进行分析。结果抗高血压药物处方占处方总数的7．6％,共4973张,钙离子拮抗药（ CCB）1410张,占28．35％;ARB类1372张,占27．59％,缬沙坦的DDDs最高,且ARB类的药物利用指数（ DUI）符合合理用药标准;联合用药方案在高血压处方也占一定比例。结论 ARB类药物凭借降压效果明确、不良反应少、患者用药依从性较高的优点,使其得到广泛应用。     

血管紧张素Ⅱ受体阻断剂药理作用及合理用药

血管紧张素Ⅱ受体（AngⅡ）阻断剂是继血管紧张素转换酶（ACE）抑制剂后应用于临床的一类新的抗高血压药物，目前临床主要有氯沙坦（络沙坦）、缬沙坦、厄贝沙坦等。     

我院血管紧张素受体阻断剂使用调查

目的 调查和分析我院门诊处方中血管紧张素受体阻断剂(ARB)的使用及其合理应用情况. 方法选取2007年9和10月两月中我院门诊处方,分析ARB的使用及其与说明书适应证的相符性. 结果替米沙坦使用频率最高,缬沙坦(代文)、氯沙坦钾-氢氯噻嗪和氯沙坦钾的药物利用指数(DUI)均>1,提示存在药物不合理使用现象,ARB使用与其适应证的相符率为88.45%.结论 我院ARB类抗高血压药物使用基本合理.     

全国8市712192例高血压患者口服钙通道阻滞剂的使用分析

目的:分析2017年全国8个城市使用钙通道阻滞剂(calcium channel blockers,CCBs)高血压患者的特征和药品使用情况,为临床合理用药提供参考。方法:基于2017年《医院处方分析项目》随机抽取的处方数据,采用世界卫生组织推荐的药物利用分析方法,对CCBs类降血压药物使用情况进行分析。结果:共抽取8个城市105家医院的712 192例高血压患者口服CCBs类降血压药物的处方。北京地区患者最多,占25.28%。平均年龄(65.60±14.07)岁。患者主要于门诊购药,占86.12%。处方科室主要为内科,占78.62%。可报销药品占比79.75%。7.65%的高血压患者合并肾病。处方数量和处方金额最大的3种药品是一致的,依次为氨氯地平、硝苯地平和左旋氨氯地平;其处方日剂量/限定日剂量(prescribed daily dose/defined daily dose,PDD/DDD)值均>1:氨氯地平(1.27±0.53)、硝苯地平(1.27±0.53)和左旋氨氯地平(1.64±0.91);合并肾病患者的PDD/DDD值高于患者平均水平:氨氣地平(1.53 vs.1.25),硝苯地平(1.64 vs.1.23),左旋氨氣地平(1.85 vs.1.63)。结论:氨氣地平、硝苯地平和左旋氨氣地平为临床最常用的3种CCBs,其临床日剂量均高于成人常用日剂量,合并肾病的高血压患者的日剂量更高。     

我院抗高血压药物临床应用情况调查分析

目的了解该院抗高血压药物应用情况。方法随机抽取该院2008年2～10月中高血压患者病历60例,对用药品种、应用天数、药物消耗量、联合用药情况进行分析。结果用药例次排前4位的分别是：钙拮抗剂、血管紧张素Ⅱ受体（ATI）拮抗剂、利尿剂、β受体阻滞剂。用药总量排前3位的是：厄贝沙坦、尼莫地平和硝苯地平;用药时间排前3位的是：厄贝沙坦、硝苯地平和氨氯地平;限定日剂量（DDD）值排前3位的是：厄贝沙坦、尼莫地平和卡托普利;用药频度（DDDS）排序前3位的分别是：氨氯地平、硝苯地平控释片、厄贝沙坦片。氯沙坦、缬沙坦和氨氯地平的DUI最高。结论该院抗高血压药物利用指数均≤1,无药物滥用情况。     

The value of irbesartan in the management of hypertension

Elevated blood pressure levels are highly prevalent and are a major reason for cardiovascular events and thus place a significant financial burden on healthcare systems worldwide. Guidelines recommend five first-line anti-hypertensive drug classes, but compelling indications may indicate favoring one drug class over another. Angiotensin receptor blockers (ARBs) have demonstrated a blood pressure lowering efficacy which is at least comparable with other drug classes, including ACE inhibitors (ACE-I), β-blockers, calcium channel blockers and diuretics. They have, in addition, a lower side effect profile than other drug classes and patients on ARBs are more persistent with therapy. Compelling indications for the use of ARBs are heart failure, post-myocardial infarction, diabetic nephropathy, proteinuria/microalbuminuria, left ventricular hypertrophy, atrial fibrillation, metabolic syndrome and ACE-I induced cough. The ARB irbesartan has demonstrated a high efficacy in lowering blood pressure, which has been shown to be at least comparable with ACE-Is and superior to other ARBs such as losartan and valsartan. This translated into a better cost-effectiveness for irbesartan than for valsartan and losartan in the treatment of hypertension. In addition, irbesartan has been shown to be effective in both early and late stage diabetic nephropathy. It has further demonstrated considerable cost savings over standard therapy including β-blockers, diuretics and non-dihydropyridine calcium channel blockers at all stages of kidney disease. Based on efficacy data from the Irbesartan Diabetic Nephropathy Trial and Reduction of Endpoints in NIDDM (non insulin dependant diabetes melitis) with the Angiotensin II Antagonist Losartan Study, it has also demonstrated cost savings over losartan in late stage renal disease. While both losartan and irbesartan are registered for the treatment of late stage diabetic nephropathy, irbesartan is also registered for early stage diabetic nephropathy in the EU. In summary, the data from randomized clinical trials on the efficacy of antihypertensive drugs provides an indication of their real value to patients. In addition observational data from clinical practice and proven end-organ protection in diabetic nephropathy provides further evidence of the true value of irbesartan compared to other ARBs in the treatment of hypertension.     

全国多中心左旋氨氯地平药物利用分析

目的探讨2017年全国8个城市左旋氨氯地平的使用特征,为临床合理用药提供参考。方法基于2017年《医院处方分析项目》随机抽取的处方数据,采用世界卫生组织推荐的药物利用分析方法,以氨氯地平为对照,分析左旋氨氯地平使用情况。结果抽得8个城市103家医院的388 848张处方,北京地区患者最多(24. 26%),男女比例为1. 08∶1,平均年龄为66. 31岁,65岁及以上患者占比为55. 75%,门诊处方药物占86. 19%,左旋氨氯地平处方量占34. 56%,北京地区处方量最大(23. 06%)。左旋氨氯地平的平均处方金额低于氨氯地平(80. 90元比95. 65元)。左旋氨氯地平和氨氯地平的处方日剂量/限定日剂量(PDD/DDD)均值分别为1. 79和1. 72,广州地区最高(2. 92和2. 99),杭州地区最低(1. 02和0. 98)。老年高血压、高血压合并肾病患者左旋氨氯地平的PDD/DDD均高于普通人群。结论各地左旋氨氯地平和氨氯地平品种选择、平均日剂量存在差异,老年、合并肾病的高血压人群用药有待进一步深入研究。     

血管紧张素转换酶抑制剂和血管紧张素Ⅱ受体拮抗剂联用治疗糖尿病肾病的不良反应文献分析

目的探讨国内血管紧张素转换酶抑制剂（ACEI）与血管紧张素Ⅱ受体拮抗剂（ARB）联用治疗糖尿病肾病的安全性。方法通过检索中国知网（CNKI）、万方数据库、中文科技期刊数据库（维普）等文献数据库,收集2000年1月-2013年3月国内临床资料进行汇总、分析。结果ACEI和ARB联用组842例患者引起药物不良反应（ADR）114例,ADR发生率低于单用ACEI组,差异有统计学意义（P〈0．05）,与单用ARB组相当,差异无统计学意义（P〉0．05）。贝那普利联用氯沙坦ADR发生率和单用贝那普利或氯沙坦相当（P〉0．05）;贝那普利联用缬沙坦ADR发生率低于单用贝那普利组,差异有统计学意义（P〈0．05）,与缬沙坦相当（P〉0．05）;贝那普利联合缬沙坦咳嗽的发生率远远低于单用贝那普利组,差异有高度统计学意义（P〈0．01）。ACEI和ARB联用组ADR临床表现以呼吸系统、神经系统、其他（高血钾、血肌酐升高）为主,分别占47．37％、29．82％、16．67％。结论ACEI和ARB联用组ADR发生率相当于单用ARB组,低于单用ACEI组。贝那普利联用缬沙坦比联用氯沙坦更为安全,但限于研究数量及质量,以上结论仍需更多、更详实的数据及研究加以验证。     

Angiotensin II Receptor Antagonists Alone and Combined with Hydrochlorothiazide

Angiotensin II receptor antagonists (angiotensin receptor blockers; ARBs) and thiazide diuretics have an accepted place in the management of hypertension. Most patients require combination therapy with two or more drugs to adequately control blood pressure to targets recommended by European and international guidelines. ARBs and the thiazide diuretic hydrochlorothiazide have complementary modes of action. Fixed-dose combinations of an ARB and low-dose hydrochlorothiazide provide a convenient and effective treatment option for patients who do not achieve blood pressure targets on monotherapy, without compromising the placebo-like tolerability of ARBs. In Europe, fixed-dose combinations with hydrochlorothiazide currently are available for the ARBs candesartan, eprosartan, irbesartan, losartan, telmisartan, and valsartan. Recently, a number of studies have focused on the use of ARBs in monotherapy and in combination therapy, in conditions including congestive heart failure, post-myocardial infarction management, hypertension with cardiovascular risk factors, and diabetic and non-diabetic nephropathy. Evidence from these studies suggests a beneficial role beyond the antihypertensive effect of these therapies in providing protection against cardiovascular, renovascular, and cerebrovascular events.     

Cost Effectiveness of Angiotensin Receptor Blocker Monotherapy in Patients with Hypertension in the Netherlands

Background and Objective

Health gains and related cost savings achieved by optimizing treatment in hypertensive patients is highly important. The aim of this study was to evaluate the costs and cost effectiveness of treatment with angiotensin II receptor antagonists (angiotensin II receptor blockers [ARBs]) in patients with essential hypertension and to compare within-trial with real-life dosing of ARBs.

Methods

Cost effectiveness was estimated based on a published clinical trial comparing the BP-lowering effects of olmesartan, losartan, valsartan, and irbesartan. BP lowering after 8 weeks of treatment was entered into the Framingham risk functions to estimate cardiovascular complications after 1 and 5 years, using an international health economics model that was adapted to the Netherlands. Dutch costs (2006 values) and complications derived from the model were discounted at 4% and 1.5%, respectively, and cost effectiveness was expressed in net costs per cardiovascular complication averted. In a drug-utilization study, pharmacy dispensing records were used to evaluate differences between within-trial and daily-practice dosing and related costs for treatment in the Netherlands.

Results

After 8 weeks, the trial-based analysis showed that treatment with olmesartan versus losartan, valsartan, and irbesartan resulted in a significantly larger decrease in BP (11.5 vs 8.2, 7.9 and 9.9 mmHg [p<0.05], respectively) and consequently more complications averted. Cost effectiveness for olmesartan, losartan, valsartan, and irbesartan was estimated at €39 100, €77 100, €70 700, and €50 900 per cardiovascular complication averted, respectively. The incremental cost-effectiveness analysis indicated the most favorable cost-effectiveness outcome for olmesartan, with lower costs and less cardiovascular complications for olmesartan compared with the other three ARBs. The drug-utilization analysis showed that the dosing followed within clinical trials was not found in daily practice. On average, losartan, valsartan, and irbesartan were administered at doses above those used in clinical trials, whereas olmesartan was dosed lower than in clinical trials, resulting in relatively lower costs.

Conclusion

Based on the exact trial data, olmesartan was estimated to be the most favorable option of the four ARBs based on within-trial decreases in BP levels after 8 weeks and in terms of cost-effectiveness for this particular Dutch setting. However, for definite conclusions to be drawn, this hypothesis-generating study requires confirmation from further prospective studies comparing ARBs based on comparable BP control and including hard endpoints.     

Angiotensin II Receptor Blockers Inhibit the Generation of Epoxyeicosatrienoic Acid from Arachidonic Acid in Recombinant CYP2C9, CYP2J2 and Human Liver Microsomes

Cytochrome P450 (CYP) 2C9, CYP2C8 and CYP2J2 enzymes, which metabolize arachidonic acid (AA) to epoxyeicosatrienoic acids, have cardioprotective effects including anti‐inflammation and vasodilation. We have recently shown that some angiotensin II receptor blockers (ARBs) may inhibit AA metabolism via CYP2C8. Using recombinant CYP2C9, CYP2J2 and human liver microsomes (HLMs), the aim was now to compare the ability of six different clinically used ARBs to inhibit AA metabolism in vitro. The rank order of the ARBs for the 50% inhibitory concentration (IC₅₀) of AA metabolism was losartan <telmisartan <irbesartan <candesartan <olmesartan <valsartan via CYP2C9, and telmisartan <irbesartan <olmesartan <losartan <candesartan and valsartan via CYP2J2. The order for the HLMs was losartan <telmisartan <irbesartan <olmesartan <candesartan <valsartan. Some ARBs having lower concentration of IC₅₀ indicate that these ARBs might inhibit the AA metabolism in the liver.     

Switch strategies in the management of hypertension: a cost minimisation analysis of angiotensin receptor blocker based regimen

ABSTRACT

Background and objective: Budgetary pressures within health care systems have led many health care providers to consider the switching of patients on long term anti­hypertensive medication to agents with the lowest acquisition price. The long term success of this strategy hinges on price differentials remaining stable, an assumption that may not be valid in drug classes where patent expiry times vary. The treatment of hypertension using angiotensin receptor blockers (ARBs) represents just such a case. The present study, therefore, modelled the 5-year cost consequences of treatment based on losartan, candesartan, valsartan and irbesartan, based on expected patent expiry dates.

Methods: A Markov model was constructed, applying dose-specific blood-pressure lowering and costs to a cohort of uncontrolled mild–moderate hypertensive patients and assessing the anticipated cost of treatment over a 5 year period. A probabilistic approach was adopted to account for between-patient and between-treatment differences.

Results: For both undiscounted and discounted models, a losartan-based regimen represents the least costly option of the four agents tested. Median (IQR) discounted expenditure per patient for each agent was: losartan: £506 (£441–£650), candesartan: £610 (£542–£766), valsartan: £809 (£796–£1078), irbesartan £696 (£694–£934).

Conclusion: Switching hypertensive patients taking ARBs to the agent with the lowest current acquisition cost may yield only transient budgetary savings. Once patent expiry is taken into account, this model suggests that maintaining or switching patients to losartan would yield considerably greater savings over 5 years.     

Irbesartan: a review of its use in hypertension and in the management of diabetic nephropathy

Irbesartan (Avapro, Aprovel) is a potent and selective angiotensin II subtype 1 receptor antagonist indicated for use in patients with hypertension, including those with type 2 diabetes mellitus and nephropathy. Once-daily administration of irbesartan provided 24-hour control of blood pressure (BP). In patients with mild-to-moderate hypertension irbesartan was as effective as enalapril, atenolol and amlodipine, and more effective than valsartan in terms of absolute reduction in BP and response rates. Irbesartan produced a greater reduction in diastolic BP at trough than once-daily losartan, but had a smaller effect than olmesartan; the reduction in systolic BP achieved with irbesartan was similar or greater than that with losartan and similar to that seen with olmesartan. The combination of irbesartan with hydrochlorothiazide produced additive effects on BP reduction. Irbesartan also induced regression of left ventricular mass in patients with hypertension and left ventricular hypertrophy. In two large studies (IRbesartan MicroAlbuminuria type 2 diabetes mellitus in hypertensive patients [IRMA 2] and the Irbesartan Diabetic Nephropathy Trial [IDNT]) irbesartan exerted a renoprotective effect in hypertensive patients with type 2 diabetes at both the early and later stages of diabetic nephropathy. The renoprotective effect was at least partly independent of the BP-lowering effect. In the IRMA 2 trial, the proportion of patients progressing to overt nephropathy was significantly lower for recipients of irbesartan 300mg once daily than placebo. In patients with overt nephropathy in the IDNT, irbesartan 300mg once daily provided significantly greater renoprotection than amlodipine 10mg once daily or placebo. The relative risk of doubling of serum creatinine was significantly lower with irbesartan than amlodipine or placebo. Irbesartan is well tolerated in hypertensive patients, including those with type 2 diabetes and incipient or overt nephropathy. The overall incidence of adverse events with irbesartan was similar to that with placebo. Irbesartan was associated with a lower incidence of cough than enalapril and was not associated with ankle oedema or with any clinically significant drug interactions. In conclusion, irbesartan is a well tolerated and effective antihypertensive agent. It also slows the progression of renal disease in hypertensive patients with type 2 diabetes at both the early and later stages of diabetic nephropathy. Thus, irbesartan is a valuable agent in the management of patients with these indications.     

Therapeutic Effects of Angiotensin (AT1) Receptor Antagonists

Blockade of the renin-angiotensin system improves morbidity and mortality of patients with cardiovascular diseases, e.g. arterial hypertension, renal failure, following myocardial infarction and in congestive heart failure. The angiotensin II type 1 (AT(1)) receptor antagonists (angiotensin receptor blockers; ARBs), i.e. losartan, eprosartan, irbesartan and valsartan were developed by computer-based molecule design. Early observations already indicate that the ARBs elicit pleiotropic effects developing anti-aggregatory, anti-inflammatory and anti-mitogenic effects independent from their actions at the AT(1) receptor. Losartan metabolism indicates a number of known active intermediates and pointed to further interactions of these derivatives with other receptors and cellular signaling systems. Here we discuss a compilation of detailed pharmacokinetic and pharmacodynamic data of active metabolites of ARBs indicating their mode of action and suggest novel therapeutic implications. The clinical observations that ARBs elicit potencies in patients with cardiovascular diseases via the regulation of inflammatory, growth and homeostatic factors lead us to focus on specific, reactive metabolites, which hold potential for future indications and possible drug interactions in cardiovascular diseases.