Azilsartan medoxomil: a review of its use in hypertension

Azilsartan medoxomil (Edarbi?; Ipreziv?) is an orally administered angiotensin II receptor type 1 antagonist (blocker) used in the treatment of adults with essential hypertension. This article reviews data on the clinical efficacy and tolerability of azilsartan medoxomil in adults with essential hypertension and provides a summary of its pharmacological properties. Azilsartan medoxomil is a prodrug that undergoes rapid hydrolysis in the gastrointestinal tract after oral administration to the bioactive moiety azilsartan, before systemic absorption. Azilsartan medoxomil produces antihypertensive effects by selectively blocking the binding of angiotensin II to the angiotensin type 1 (AT(1)) receptor, thereby antagonizing the pressor response activity of angiotensin II. In vitro, azilsartan produced greater and more sustained AT(1) receptor binding/blockade activity than several comparator angiotensin II receptor antagonists. Azilsartan medoxomil reduces blood pressure (BP) in hypertensive adults. In addition, the drug has been shown to have pleiotropic effects (i.e. effects beyond AT(1) receptor blockade). In adults with essential hypertension, azilsartan medoxomil 20, 40 or 80?mg effectively reduced BP over a 24-hour period with once-daily administration in three major, randomized, controlled trials in which the primary endpoints were changes from baseline in 24-hour mean systolic BP (SBP) at week 6 (two trials) or week 24, assessed by ambulatory BP monitoring (ABPM). In the two 6-week trials, azilsartan medoxomil showed dose-dependent efficacy over all evaluated dosages and was more effective than placebo in lowering SBP. At the maximum approved dosage of 80?mg once daily, azilsartan medoxomil was significantly more effective than maximum dosages of olmesartan medoxomil (40?mg once daily) or valsartan (320?mg once daily), based on primary endpoint assessments. Mean reductions in clinic measurements of SBP and diastolic BP (DBP) measurements were also generally greater with azilsartan medoxomil 80?mg once daily than with the comparator drugs in these 6-week studies. Over a longer treatment period of 24 weeks, azilsartan medoxomil showed sustained BP-lowering efficacy, with the reduction in 24-hour mean SBP at week 24 significantly greater with azilsartan medoxomil 40 or 80?mg once daily than with valsartan 320?mg once daily. Mean reductions from baseline in mean clinic SBP and DBP as well as DBP by ABPM were also significantly greater with azilsartan medoxomil 40 or 80?mg once daily than with valsartan. Azilsartan medoxomil was generally well tolerated, with a tolerability profile similar to that of placebo in the 6-week trials. Across the three major trials, headache and dizziness were among the most common adverse events. Overall, rates of treatment discontinuation as a result of adverse events were low in the 6-week and 24-week trials. In conclusion, once-daily azilsartan medoxomil effectively lowers BP in adults with essential hypertension and has shown better antihypertensive efficacy than maximum therapeutic dosages of olmesartan medoxomil or valsartan in major trials of up to 24 weeks' duration. Azilsartan medoxomil is generally well tolerated and the low rates of discontinuation due to adverse events suggest that patients are likely to persist with long-term treatment. Azilsartan medoxomil is therefore a useful and attractive new option for lowering BP in patients with essential hypertension, particularly for those not able to tolerate other antihypertensive drugs. Further studies are required to evaluate the effects of azilsartan medoxomil on cardiovascular morbidity and mortality.     

奥美沙坦酯氢氯噻嗪治疗高血压的临床研究

目的观察奥美沙坦酯氢氯噻嗪片治疗高血压的临床疗效。方法选取2013年5月—2015年5月于北京市房山区良乡地区社区卫生服务中心就诊的120例高血压患者,用随机数表法分为对照组和治疗组,每组各60例。对照组口服氯沙坦钾片,1片/次,1次/d。治疗组口服奥美沙坦酯氢氯噻嗪片,1片/次,1次/d。两组均连续治疗8周。于患者治疗前1天和服药8周后进行两组患者的24 h动态血压监测,并测定心血管危险因素高敏C反应蛋白(hs CRP)、同型半胱氨酸(Hcy)水平。结果治疗后治疗组的总有效率为85.0%,对照组的总有效率为73.3%,两组总有效率比较差异具有统计学意义(P0.05)。治疗后治疗组24 h平均收缩压、24 h平均舒张压、白昼平均收缩压、白昼平均舒张压、夜间平均收缩压、夜间平均舒张压、白昼收缩压变异、白昼舒张压变异、夜间收缩压变异、夜间舒张压变异明显低于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组hs CRP、Hcy水平显著降低,同组治疗前后差异有统计学意义(P0.05);且治疗组的降低程度优于对照组,两组比较差异有统计学意义(P0.05)。结论奥美沙坦酯氢氯噻嗪片治疗高血压病不仅降压作用强,且血压变异性小,还能降低心血管危险因素,具有一定的临床推广应用价值。     

奥美沙坦酯联合氨氯地平与奥美沙坦酯联合氢氯噻嗪治疗原发性高血压的对比

目的比较奥美沙坦酯联合氨氯地平与奥美沙坦酯联合氢氯噻嗪在治疗原发性高血压中的降压疗效。方法 80例原发性高血压患者随机分为奥美沙坦-氨氯地平组和奥美沙坦-氢氯噻嗪组,每组40例。奥美沙坦-氨氯地平组给予奥美沙坦酯20 mg和氨氯地平5 mg,口服,qd;奥美沙坦-氢氯噻嗪组给予奥美沙坦酯20 mg和氢氯噻嗪12.5 mg,口服,qd;疗程均为8周。观察患者24 h动态血压变化情况、血压昼夜波动节律,检测治疗前后实验室指标并记录不良反应发生情况。结果两组患者治疗后白昼、夜间平均收缩压和舒张压均降低(P<0.05),两组降低幅度无显著差异(P>0.05)。奥美沙坦-氨氯地平组治疗后白昼、夜间收缩压和舒张压变异均低于奥美沙坦-氢氯噻嗪组(P<0.05)。奥美沙坦-氨氯地平组血压昼夜节律异常逆转率为79%(11/14),高于奥美沙坦-氢氯噻嗪组(25%,4/16,P<0.05)。两组实验室指标均无明显变化。两组均无明显不良反应发生。结论奥美沙坦酯联合氨氯地平与奥美沙坦酯联合氢氯噻嗪治疗原发性高血压的降压效果相当,但前者在降低血压变异性、改善高血压患者血压昼夜节律变化方面效果更佳,具有平稳降压的作用。     

The role of olmesartan medoxomil in the management of hypertension

Intensive blood pressure control is a desirable and obtainable goal in patients with hypertension, according to the most recent treatment guidelines from Europe and the US. Achieving target blood pressure depends on the efficacy of antihypertensive treatment and patient compliance. Olmesartan medoxomil, a non-peptidergic angiotensin AT1 receptor antagonist, has been shown to be effective and well tolerated. Continuation of initial treatment is higher with AT1 receptor antagonists than for any other class of antihypertensive drugs. Olmesartan medoxomil may also have end-organ protective effects that provide additional clinical benefit. Optimal blood pressure control may be achieved faster if initial treatment contains the most efficacious and well tolerated antihypertensive drug or drugs. The ongoing European study, known as OLMEBEST (Efficacy and safety of OLMEsartan: reduction of Blood pressure in the treatment of patients suffering from mild to moderate ESsenTial hypertension), will provide important information on the use of olmesartan medoxomil as an initial treatment for hypertension.     

奥美沙坦酯与氨氯地平联合氢氯噻嗪治疗高血压的临床研究

目的 探讨奥美沙坦酯与氨氯地平联合氢氯噻嗪治疗高血压的疗效对比。方法 选取2017年2月—2019年2月新疆喀什地区第二人民医院治疗的100例高血压患者为研究对象,根据随机数字表法将患者分为对照组和观察组,每组各50例。对照组患者口服苯磺酸氨氯地平片,5 mg/次,1次/d;氢氯噻嗪片,25 mg/次,1次/d。观察组患者口服奥美沙坦酯片,20 mg/次,1次/d。氢氯噻嗪片用法同对照组。两组均连续治疗2个月。观察两组患者的临床疗效,同时比较两组患者治疗前后的24 h动态血压情况和血清因子水平。结果 治疗后,观察组患者的降压总有效率为92.00%,显著高于对照组的74.00%（P<0.05）。治疗后,两组患者24 h动态血压均明显降低（P<0.05）,且观察组显著低于对照组（P<0.05）。治疗后,两组患者同型半胱氨酸（Hcy）、超敏C反应蛋白（hs-CRP）水平均明显降低（P<0.05）,且观察组各血清因子水平均显著低于对照组（P<0.05）。结论 奥美沙坦酯联合氢氯噻嗪可有效控制血压水平,降低血清因子水平,对促进高血压患者病情康复具有积极意义。     

奥美沙坦酯片联合苯磺酸氨氯地平治疗老年高血压的临床效果观察

目的 观察奥美沙坦酯片联合苯磺酸氨氯地平治疗高血压的临床疗效.方法 将2011年7月-2013年7月收治的老年高血压患者116例随机分为研究组及对照组各58例.研究组给予奥美沙坦酯片联合苯磺酸氨氯地平治疗,对照组给予单纯苯磺酸氨氯地平治疗.治疗后比较2组临床疗效,血压值及不良反应发生情况.结果 研究组总有效率为94.8%高于对照组的82.8%,差异有统计学意义（P＜0.05）.治疗后研究组收缩压、舒张压均低于对照组,差异均有统计学意义（P＜0.05）.116例患者服药后出现不良反应3例,发生率为2.58%,主要表现为轻微头痛,患者可耐受,不影响治疗.结论 奥美沙坦酯片联合苯磺酸氨氯地平治疗高血压的临床疗效优于单纯苯磺酸氨氯地平治疗,且不良反应少,值得临床推广应用.     

阿齐沙坦与奥美沙坦酯治疗轻中度原发性高血压的疗效比较

目的 比较阿齐沙坦与奥美沙坦酯治疗轻中度原发性高血压的临床疗效。方法 2015年9月—2017年2月从全国多家研究中心筛选轻、中度原发性高血压304例,随机分为奥美沙坦酯组和阿齐沙坦组。受试者从起始剂量开始,阿齐沙坦片20 mg/次和奥美沙坦酯片模拟剂,1次/d,或奥美沙坦酯片20 mg/次和阿齐沙坦片模拟剂,1次/d,开始治疗。用药后第8周末对受试者进行血压评价,如果服药前（药物浓度谷值时）坐位收缩压≥140 mmHg（1 mmHg=133 Pa）和/或舒张压≥90 mmHg则试验药物剂量加倍（阿齐沙坦片40 mg/次口服或奥美沙坦酯片40 mg/次,1次/d）继续治疗8周,如果服药前（药物浓度谷值时）坐位收缩压<140 mmHg且舒张压<90 mmHg则维持原剂量继续治疗8周。治疗总周期16周。观察两组的有效率和达标率。比较两组治疗前,治疗8、12、16周收缩压、舒张压,血压与治疗前差值的变化情况。结果 用药8、16周,奥美沙坦酯组有效率分别是66.89%、69.59%;阿齐沙坦组有效率分别是59.60%、58.94%,两组有效率比较差异没有统计学意义。用药8、16周,奥美沙坦酯组达标率分别是62.16%、61.49%;阿齐沙坦组达标率分别是56.95%、56.29%,两组达标率比较差异均没有统计学意义。治疗8、12、16周,两组受试者的坐位收缩压、舒张压逐渐降低,与同组治疗前比较差异均有统计学意义（P<0.05）;治疗后,两组血压比较差异无统计学意义。用药后两组受试者的坐位收缩压和舒张压均逐渐降低,至16周末时,两组间坐位舒张压下降值比较差异具有统计学意义（P<0.05）;16周末时两组收缩压下降值差异均没有统计学意义。结论 有效性方面,阿齐沙坦组疗效未达非劣效于奥美沙坦酯组,但阿齐沙坦自身的降压效果显著并具临床意义;安全性方面,阿齐沙坦组与奥美沙坦酯组不良事件、严重不良事件、不良反应发生率相当,安全性良好。     

Olmesartan medoxomil: in children and adolescents with hypertension

Olmesartan medoxomil is an orally administered angiotensin II receptor antagonist, selective for the angiotensin II type 1 receptor, which has established antihypertensive efficacy in adults. In children and adolescents with hypertension (n?=?302), oral olmesartan medoxomil significantly and dose-dependently reduced seated systolic blood pressure (BP) and seated dystolic BP from baseline (the primary endpoint) in a 3-week, dose-response period in a well designed phase II/III clinical trial. Patients received olmesartan medoxomil high dose (20 or 40?mg once daily depending on bodyweight) or low dose (2.5 or 5.0?mg once daily depending on bodyweight). The response was significant for both cohorts, which were stratified by race (cohort A was mixed race [62% White] and cohort B was 100% Black). In addition, BP control was maintained in olmesartan recipients relative to placebo recipients in cohort A and the combined cohort A?+?B, but not for patients in cohort B, during a placebo-controlled withdrawal period of this trial. Oral olmesartan medoxomil was generally well tolerated in children and adolescents with hypertension. The majority of adverse events were of mild to moderate intensity.     

抗高血压药物阿齐沙坦酯

日本武田制药公司研发的血管紧张素Ⅱ受体阻滞剂阿齐沙坦酯（azilsartan medoxomil,商品名：Edar-bi）于2011年2月25日获美国FDA批准用于成人高血压的治疗。该药目前有80 mg和40 mg两种规格,推荐剂量为80 mg,每日1次口服使用。     

奥美沙坦酯氢氯噻嗪片治疗原发性高血压患者的临床有效性及安全性分析

目的 观察原发性高血压患者应用奥美沙坦酯氢氯噻嗪片治疗的效果及安全性.方法 80例原发性高血压患者,依据用药方案不同分为对照组和观察组,每组40例.对照组患者应用氯沙坦钾片进行治疗,观察组患者应用奥美沙坦酯氢氯噻嗪片进行治疗.对比两组患者的舒张压(DBP)、收缩压(SBP)、临床疗效、血清超敏C反应蛋白(hs-CRP)...     

阿奇沙坦的合成

3.硝基邻苯二甲酸-1-甲酯经Curtius重排、与2'-氰基-4-溴甲基联苯进行N-烷基化、脱叔丁氧羰基保护、Pd/C催化氢化、闭环制得1-[(2'-氰基[1,1'-联苯基]-4-基)甲基]-2-乙氧基-1H-苯并咪唑-7-羧酸甲酯,再经缩合、酯化及闭环反应成噁二唑环,最后水解得抗高血压药阿奇沙坦,总收率约14%.     

Evaluation of olmesartan medoxomil in the rat monocrotaline model of pulmonary hypertension

It is suggested that angiotensin II is involved in the pathogenesis of pulmonary hypertension and subsequent right ventricular hypertrophy; therefore, an angiotensin AT1 receptor antagonist could be beneficial for the treatment of this disease. We tested the effect of the new AT1 receptor antagonist olmesartan medoxomil on monocrotaline-induced pulmonary hypertension in rats. At 3 weeks after a single subcutaneous injection of monocrotaline (50 mg/kg), the lung/body weight ratio, the right ventricle/(left ventricle plus septum) weight ratio [RV/(LV+S)], and right ventricular systolic pressure were increased, indicating establishment of pulmonary hypertension and right ventricular hypertrophy. Oral administration of olmesartan medoxomil (2 or 5 mg/kg/day for 3 weeks) restored RV/(LV+S) and right ventricular systolic pressure, and a higher dose (5 mg/kg/day) improved the lung/body weight ratio. Pulmonary arteries isolated from monocrotaline-treated rats exhibited an increase in basal tone in the resting state, indicating that they had intrinsic tone. Three weeks of treatment with olmesartan decreased this intrinsic tone. These data suggest that long-term treatment with olmesartan has beneficial effects on monocrotaline-induced pulmonary hypertension and subsequent right ventricular hypertrophy.     

Olmesartan medoxomil: a review of its use in the management of hypertension

Olmesartan medoxomil (Olmetec, Benicar) is an angiotensin II type 1 (AT(1)) receptor antagonist (angiotensin receptor blocker [ARB]) that inhibits the actions of angiotensin II on the renin-angiotensin-aldosterone system, which plays a key role in the pathogenesis of hypertension. Oral olmesartan medoxomil 10-40 mg once daily is recommended for the treatment of adult patients with hypertension. In those with inadequate BP control using monotherapy, fixed-dose olmesartan medoxomil/hydrochlorothiazide (HCTZ) [Olmetec plus, Benicar-HCT] combination therapy may be initiated. Extensive clinical evidence from several large well designed trials and the clinical practice setting has confirmed the antihypertensive efficacy and good tolerability profile of oral olmesartan medoxomil, as monotherapy or in combination with HCTZ, in patients with hypertension, including elderly patients with isolated systolic hypertension (ISH). Notably, BP control is sustained throughout the 24-hour dosage interval, including during the last 4 hours of this period. In clinical trials, olmesartan medoxomil monotherapy provided better antihypertensive efficacy than losartan, candesartan cilexetil or irbesartan monotherapy, and was at least as effective as valsartan treatment, with a faster onset of action than other ARBs in terms of reductions from baseline in diastolic BP (DBP) and, in most instances, systolic BP (SBP). Combination therapy with olmesartan medoxomil plus HCTZ was superior to that with benazepril plus amlodipine, as effective as that with losartan plus HCTZ, noninferior to that with atenolol plus HCTZ, but less effective than that with telmisartan plus HCTZ, in individual trials. Data from ongoing clinical outcome trials are required to more fully determine the relative position of olmesartan medoxomil therapy in the management of hypertension. In the meantime, the consistent antihypertensive efficacy during the entire 24-hour dosage interval and good tolerability profile of olmesartan medoxomil, with or without HCTZ, make it a valuable option for the treatment of adult patients with hypertension, including the elderly.     

奥美沙坦酯与缬沙坦治疗中度原发性高血压临床研究

目的比较奥美沙坦酯和缬沙坦治疗中度原发性高血压的疗效和安全性。方法入选482例中度原发性高血压患者,按照1∶1随机分组,分别接受奥美沙坦酯20～40 mg/d或缬沙坦80～160 mg/d治疗,共8周。观察并比较其降压效果。结果治疗4周后,奥美沙坦酯组SeDBP平均下降了(10.58±6.82)mmHg,缬沙坦组下降了(9.38±7.16)mmHg;两组比较,P=0.004。奥美沙坦组与缬沙坦组分别有60%、61.74%的患者剂量加倍,加量有效率分别为52.22%、51.85%;治疗8周后,两组SeDBP平均下降(15.72±6.03)mmHg及(14.12±6.79)mmHg;治疗4周后,两组的药物不良反应发生率分别为3.33%、7.5%(P>0.05)。结论口服奥美沙坦酯胶囊20～40 mg/d,1次/d,能保持24 h平稳降压,8周总有效率为79.65%;与缬沙坦80～160 mg/d的降压疗效相近。而两组药物不良反应发生率差异无统计学意义。     

Olmesartan medoxomil/amlodipine/hydrochlorothiazide: fixed-dose combination in hypertension

The antihypertensive agents olmesartan medoxomil, amlodipine and hydrochlorothiazide (HCTZ) are now available as a fixed-dose combination tablet (olmesartan medoxomil/amlodipine/HCTZ). In a 12-week, randomized, double-blind, multicentre trial (TRINITY) in adults with moderate to severe hypertension, olmesartan medoxomil?+?amlodipine?+?HCTZ triple combination therapy produced significantly greater least squares mean reductions from baseline in seated diastolic blood pressure (BP) [primary endpoint] and seated systolic BP than olmesartan medoxomil/amlodipine, olmesartan medoxomil/HCTZ or amlodipine?+?HCTZ. Furthermore, significantly more patients achieved BP goals and targets with the triple combination regimen than with any of the dual combination regimens at week 12, with olmesartan medoxomil?+?amlodipine?+?HCTZ also demonstrating benefit over the dual regimens in terms of ambulatory BP control. According to subgroup analyses of the TRINITY trial, olmesartan medoxomil?+?amlodipine?+?HCTZ was more effective in reducing BP and achieving BP goals than each of the dual therapies, irrespective of hypertension severity, age, sex, race or diabetes mellitus status. Data from a number of smaller clinical studies indicated that olmesartan medoxomil?+?amlodipine?+?HCTZ triple combination therapy provides antihypertensive efficacy in patients whose BP is not adequately controlled with olmesartan medoxomil?+?amlodipine. Olmesartan medoxomil?+?amlodipine?+?HCTZ was generally well tolerated in the TRINITY study, with adverse events usually being mild or moderate in severity.     

奥美沙坦酯治疗老年高血压的疗效及安全性观察

目的：评价奥美沙坦酯治疗老年高血压的疗效和安全性。方法：选取2009年1-8月我院42例老年高血压患者,随机分为两组。治疗组（21例）服用奥美沙坦酯每次20mg,每日1次;对照组（21例）服用氯沙坦每次50mg,每日1次。总疗程均为8周。结果：奥美沙坦酯组和氯沙坦组治疗前后血压下降幅度差异均有统计学意义（P〈0.01）。奥美沙坦酯组和氯沙坦组降压显效率分别为69.0%和68.4%,总有效率分别为90.4%和89.7%,两组间差异无统计学意义（P〉0.05）。奥美沙坦酯组和氯沙坦组均未出现药品不良反应。结论：奥美沙坦酯治疗老年高血压效果明显,安全性好。