Combination Therapy with Olmesartan Medoxomil and Hydrochlorothiazide

Background

The combination of olmesartan medoxomil and hydrochlorothiazide (HCTZ) [olmesartan medoxomil/HCTZ] has previously been shown to produce significantly greater SBP/DBP reductions than monotherapy with either agent alone in a randomized, double-blind, factorial study in patients with stage 2 hypertension. Compared with the evaluation of a single mean BP reduction in a patient population, determining the efficacy of an antihypertensive agent in achieving multiple BP targets provides additional information about the range of BP reductions attainable within this study population.

Objective

To conduct a secondary analysis of this study to evaluate the proportion of patients achieving combined SBP/DBP targets recommended in current hypertension treatment guidelines as well as individual SBP and DBP targets.

Methods

A total of 502 patients with DBP ≥100 and ≤115 mmHg were randomized to 8 weeks of treatment with placebo, HCTZ 12.5 or 25 mg/day, olmesartan medoxomil 10, 20, or 40 mg/day, or olmesartan medoxomil/HCTZ 10/12.5, 10/25, 20/12.5, 20/25, 40/12.5, or 40/25 mg/day. Mean baseline SBP ranged from 151.9 to 156.6 mmHg and mean baseline DBP ranged from 102.6 to 104.4 mmHg across the twelve treatment arms. The chi-squared test was used to compare the proportion of patients achieving each BP goal in each of the 11 active treatment regimens with that in the placebo group.

Results

The proportion of patients achieving an SBP <140 or <130 mmHg, DBP <90, <85, or <80 mmHg and combined SBP/DBP <140/90, <130/85, <130/80, or <120/80 mmHg typically increased with escalating dosages of olmesartan medoxomil and HCTZ when administered alone or in combination, but was always highest in those treated with the combination. As the BP goal became progressively more stringent, the proportion of patients achieving the BP goal decreased in each treatment group, although the trend toward greater reductions in patients treated with combination therapy remained intact. All combined SBP/DBP goals were achieved by a statistically significant proportion of patients (p<0.05) in the olmesartan medoxomil/HCTZ 20/25, 40/12.5, and 40/25 treatment groups.

Conclusions

A majority of patients with uncomplicated stage 2 hypertension can achieve recommended BP goals when treated with the combination of olmesartan medoxomil and HCTZ.     

Efficacy and Safety Study of Olmesartan Medoxomil,Amlodipine, and Hydrochlorothiazide Combination Therapy in Patients with Hypertension Not Controlled with Olmesartan Medoxomil and Hydrochlorothiazide Combination Therapy: Results of a Randomized,Double-Blind,Multicenter Trial

Background

This study was to evaluate the efficacy and safety of triple fixed-dose combination (FDC) therapy with olmesartan medoxomil (OM) 20  mg, amlodipine (AML) 5 mg, and hydrochlorothiazide (HCTZ) 12.5 mg (OM/AML/HCTZ 20/5/12.5) in Korean patients with moderate hypertension not controlled with dual FDC therapy (OM/HCTZ 20/12.5).

Methods

In this multicenter, randomized, double-blind, parallel-group study, Korean patients aged 20 to 75 years with stage 2 hypertension who had a mean seated diastolic blood pressure (msDBP) ≥100 mmHg were enrolled when their BP was uncontrolled [mean seated systolic BP (msSBP)/msDBP >140/90 mmHg or msSBP/msDBP >130/80 mmHg with diabetes or chronic kidney disease] with 4-week dual FDC therapy (OM/HCTZ 20/12.5). The patients were randomized to receive either OM/AML/HCTZ 20/5/12.5 or OM/HCTZ 20/12.5 once daily for 8 weeks. At the end of 8 weeks, patients with uncontrolled BP were assigned to receive either OM/AML/HCTZ 40/5/12.5 or OM/AML/HCTZ 20/5/12.5 in an additional 8-week open-label extension period.

Results

A total of 623 patients received a 4-week run-in treatment with OM/HCTZ, 341 patients were randomized, and finally, 167 patients in the OM/AML/HCTZ group and 171 patients in the OM/HCTZ group were analyzed for the full analysis set. Non-responders after the 8 weeks of double-blind treatment continued the 8-week open-label treatment with OM/AML/HCTZ 40/5/12.5 mg (n = 32) or OM/AML/HCTZ 20/5/12.5 mg (n = 71). After 8 weeks of double-blind treatment, the changes in msDBP were ?9.50 (8.46) mmHg in the OM/AML/HCTZ group and ?4.23 (7.41) mmHg in the OM/HCTZ group (both p < 0.0001 vs. baseline; p < 0.0001 between groups). The response rates for both msSBP and msDBP at week 8 were 65.27 % in the OM/AML/HCTZ group and 37.43 % in the OM/HCTZ group (p < 0.0001 between groups). The response rates for both msSBP and msDBP at week 16 after open-label treatment were 18.75 % in the OM/AML/HCTZ 40/5/12.5 group and 46.48 % in the OM/AML/HCTZ 20/5/12.5 group (p = 0.0073 between groups). All medications were well tolerated.

Conclusion

In Korean patients with moderate hypertension not controlled with dual FDC therapy (OM/HCTZ 20/12.5) as first-line therapy, switching to triple FDC therapy (OM/AML/HCTZ 20/5/12.5) was associated with significant BP reductions and greater achievement of BP goals, and was well tolerated (ClinicalTrials.gov Identifier: NCT01838850).

     

Effect of an Olmesartan Medoxomil-Based Treatment Algorithm on Systolic Blood Pressure in Patients with Stage 1 or 2 Hypertension

Background and Objective

Elevated systolic BP (SBP) is a major contributor to cardiovascular disease. SBP control reduces the occurrence of stroke, heart failure, and cardiovascular and total mortality. The aim of this study was to analyze the magnitude of SBP reductions and the achievement of individual SBP targets in the original BENIFORCE study.

Methods

An olmesartan medoxomil-based treatment algorithm was evaluated in a double-blind, placebo-controlled titration study in 276 patients with stage 1 (47.1%) or 2 (52.9%) hypertension. After placebo run-in, patients were randomized to placebo (12 weeks) or olmesartan medoxomil 20 mg/day (weeks 1–3). Olmesartan medoxomil was uptitrated to 40 mg/day (weeks 4–6), then olmesartan medoxomil/hydrochlorothiazide (HCTZ) 40/12.5 mg per day (weeks 7–9), and olmesartan medoxomil/HCTZ 40/25 mg per day (weeks 10–12) if BP remained ≥120/80 mmHg at any time interval.

Setting

The BENIFORCE study was a multicenter (29 sites) study conducted between January and October 2007 in the US.

Results

In patients receiving olmesartan medoxomil-based therapy, 81.0%, 67.2%, and 46.6% of patients with stage 1 hypertension and 70.4%, 49.4%, and 23.5% of patients with stage 2 hypertension achieved SBP targets of <140, <130, and <120 mmHg, respectively (all p<0.01 vs placebo). The proportions of patients achieving SBP targets increased with escalating doses of olmesartan medoxomil and HCTZ, administered alone or in combination, and was highest for combination therapy. Similarly, escalating doses of olmesartan medoxomil or olmesartan medoxomil/HCTZ increased the proportion of patients achieving SBP reductions of >15 but ≤30, >30 but ≤45, and >45 mmHg compared with placebo.

Conclusion

An olmesartan medoxomil-based treatment algorithm effectively reduced SBP and achieved SBP targets in patients with stage 1 or 2 hypertension. This regimen resulted in >80% of patients achieving SBP reductions of ≥15 mmHg while 44% achieved SBP reductions of >30 mmHg.     

奥美沙坦酯治疗轻中度原发性高血压的疗效和安全性

目的评价奥美沙坦酯治疗轻中度原发性高血压的疗效和安全性。方法随机、双盲、双模拟、阳性药物(氯沙坦钾)平行对照。40例轻中度原发性高血压患者随机分为奥美沙坦酯或氯沙坦钾组,均治疗8周,观察两组治疗前后的血压、心率、心电图和血、尿常规等实验室检查结果的变化。结果奥美沙坦酯组与氯沙坦钾组比较,患者平均坐位收缩压和舒张压的降低程度均有显著性差异,分别为(18.9±8.7)mmHg和(12.6±7.6)mmHg(P<0.01);(13.8±3.5)mmHg和(11.7±3.3)mmHg(P<0.05)。治疗前后两组血压降低幅度均有显著差异,心率无明显变化。奥美沙坦酯和氯沙坦钾组降压显效率分别为63.2%和57.9%,总有效率分别为84.2%和68.4%,组间无显著差异。两组共出现3例头晕,实验室检查无异常改变。结论奥美沙坦酯治疗轻中度原发性高血压的疗效良好,不良反应发生率低。     

A Review of the Efficacy of Fixed-Dose Combinations Olmesartan Medoxomil/ Hydrochlorothiazide and Amlodipine Besylate/ Benazepril in Factorial Design Studies

In order to adequately control hypertension, the majority of patients will require treatment with more than one antihypertensive agent. Fixed-dose combination therapy offers several advantages, including improved efficacy, tolerability, and treatment compliance. Certain combinations have benefits in specific patient populations, such as the elderly or those with comorbidities. In this review, we evaluate the BP-lowering efficacy of olmesartan medoxomil/hydrochlorothiazide (HCTZ) and amlodipine besylate/benazepril in similarly designed, randomized, placebo-controlled studies in similar patient populations. This indirect comparison showed that both combinations significantly improve both systolic and diastolic BP compared with monotherapy with the individual agents or placebo; it also demonstrated that the combinations were well tolerated. Both combination therapies significantly improved response rates, but olmesartan medoxomil/HCTZ achieved the highest control rates compared with the individual agents. On the basis of an indirect comparison of published factorial design studies, olmesartan medoxomil/HCTZ appears to be at least as effective as amlodipine besylate/benazepril and may provide quantitatively greater reductions in diastolic BP at commonly used dosages. A randomized clinical trial comparing the two combinations is needed to confirm these findings.     

Efficacy and Safety of Olmesartan Medoxomil and Hydrochlorothiazide Compared with Benazepril and Amlodipine Besylate

BACKGROUND: Most patients with stage 2 hypertension require two or more antihypertensive agents in order to achieve the BP goals recommended in current treatment guidelines. Accordingly, combinations of two drugs with different mechanisms of antihypertensive action are widely used. OBJECTIVE: The aim of this randomized, double-blind, multicenter 12-week study was to compare the efficacy, safety, and tolerability of a combination of olmesartan medoxomil/hydrochlorothiazide (HCTZ) with that of benazepril plus amlodipine besylate in patients with stage 2 hypertension. METHODS: Patients were eligible for randomization following a 3- to 4-week placebo run-in period if they had either (i) mean seated DBP>or=90 mm Hg but<115 mm Hg and mean seated SBP>or=160 mm Hg but <200 mm Hg, or (ii) mean seated DBP>or=100 mm Hg but<115 mm Hg. The difference in mean seated SBP measured on two separate visits during the run-in period was required to beor=95 mm Hg and<115 mm Hg or SBP>145 mm Hg and相似文献   

Spectrophotometric Estimation of Olmesartan Medoxomil and Hydrochlorothiazide in Tablet

A simultaneous determination of olmesartan medoxomil and hydrochlorothiazide by absorption ratio spectrophotometric method has been developed in combined tablet dosage form. The method is based on measurements of absorbance at isoabsoptive point. The Beer''s law obeys in the range of 10–30 μg/ml for both olmesartan medoxomil and hydrochlorothiazide respectively. The proposed method was validated by performing recovery study and statistically.     

奥美沙坦酯对原发性高血压患者血压及左心室肥厚的影响

目的观察血管紧张素Ⅱ型受体拮抗剂奥美沙坦酯对高血压患者血压及左心室肥厚的影响。方法采用前瞻性、随机双盲、阳性药物对照研究方法,将54例原发性高血压合并左心室肥厚的患者随机分为奥美沙坦组(治疗组)27例,口服奥美沙坦酯20mg/d,1次/d;缬沙坦组(对照组)27例,口服缬沙坦80mg/d,1次/d,共24周,服药前后分别测量血压,并行心脏超声检查。结果2组治疗前后血压明显下降(P<0.05);左室后壁厚度(PWT)、左心室舒张期室间隔厚度(IVST)、左室重量指数(LVM I)与治疗前相比有明显的统计学意义(P<0.05),2组间比较无差异性(P>0.05)。结论奥美沙坦酯在降低原发性高血压患者血压的同时,可逆转左心室肥厚。     

氯沙坦治疗老年人单纯收缩期高血压临床研究

目的研究氯沙坦对老年人收缩期高血压的临床作用。方法对比82例老年单纯性收缩期高血压患者应用氯沙坦治疗前及治疗2周、4周、8周后的血压及心率变化；治疗前后血浆内血管紧张素Ⅱ（AngⅡ）、醛固酮、内皮素的变化；治疗前后血、尿常规、肝肾功能、血脂、血糖、电解质、心电图变化。结果降压总有效率为86．5％。治疗后AngⅡ显著增高（P〈0．01），醛固酮、内皮素显著降低（P〈0．05）。血、尿常规、肝肾功、血脂、血糖、电解质及心电图均无明显变化。不良反应发生率低。结论氯沙坦治疗老年人收缩期高血压疗效好，降压作用持续稳定，耐受性良好，不良反应轻微。     

奥美沙坦酯对老年高血压患者肌酐清除率的影响

目的：评价奥美沙坦酯对老年高血压患者肌酐清除率的影响。方法：42例老年高血压患者随机接受奥美沙坦酯20mg或氯沙坦50mg,qd治疗,总疗程8周。结果：奥美沙坦酯组和氯沙坦组治疗前后肌酐清除率均有不同程度上升,但与治疗前相比无统计学差异,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不良反应。结论：老年高血压患者应用奥美沙坦酯后肌酐清除率有轻度上升,提升对肾脏有保护作用。     

奥美沙坦酯对2型糖尿病高血压尿微量蛋白影响

目的探讨奥美沙坦酯对2型糖尿病患者的血压及尿微量白蛋白的影响。方法80例24小时尿微量白蛋白排泄量(UAE)在30～300mg的2型糖尿病患者随机分为两组:奥美沙坦酯组40例,口服奥美沙坦酯20mg/d;依那普利组40例口服马来酸依那普利10～20mg/d,疗程12周。分别测量两组治疗前后血压(BP)、尿微量白蛋白(ALB)、血肌酐(Scr)并计算内生肌酐清除率(Ccr)。结果两组治疗后BP、Scr及ALB均显著下降(P<0.05),Ccr明显上升(P<0.05),组间比较无显著性差异(P>0.05);依那普利组咳嗽发生率25%,其中有6例不能耐受咳嗽而退出试验,奥美沙坦酯组无咳嗽病例发生。结论奥美沙坦酯不仅能有效降低血压,而且能降低尿微量白蛋白,不良反应少,依从性好。     

Triple-Combination Therapy with Olmesartan, Amlodipine, and Hydrochlorothiazide in Black and Non-Black Study Participants with Hypertension

Background Although awareness of hypertension in Black patients has increased, blood pressure (BP) is frequently inadequately controlled. Objective This prespecified subgroup analysis of the TRINITY study evaluated the efficacy and safety of olmesartan medoxomil (OM) 40 mg, amlodipine besylate (AML) 10 mg, and hydrochlorothiazide (HCTZ) 25 mg triple-combination treatment compared with the component dual-combination treatments in Black and non-Black study participants. Study Design TRINITY was a 12-week, randomized, double-blind, parallel-group evaluation. The first patient was enrolled in May 2008 and the last patient completed the study in February 2009. The study consisted of a 3-week washout period for participants receiving antihypertensive therapy and a 12-week double-blind treatment period. For the treatment phase, all study participants were stratified by age, race, and diabetes mellitus status and randomized to a treatment sequence that led to their final treatment assignment, which they received from weeks 4 to 12 (OM 40 mg/AML 10 mg/HCTZ 25 mg, OM 40 mg/AML 10 mg, OM 40 mg/HCTZ 25 mg, or AML 10 mg/HCTZ 25 mg). In the first 2 weeks of the double-blind treatment period, all participants received either dual-combination treatment or placebo. Participants assigned to dual-combination treatment continued treatment until week 4, and participants receiving placebo were switched at week 2 to receive one of the dual-combination treatments until week 4. At week 4, participants either continued dual-combination treatment or randomly received triple-combination treatment until week 12. Setting 317 clinical sites in the USA and Puerto Rico were included in the study. Patients Study participants eligible for randomization (N = 2492) were ≥18 years of age with mean seated blood pressure (SeBP) ≥140/100 mmHg or ≥160/90 mmHg (off antihypertensive medication). Intervention The intervention was with dual- or triple-combination antihypertensive treatment: OM 40 mg/AML 10 mg/HCTZ 25 mg, OM 40 mg/AML 10 mg, OM 40 mg/HCTZ 25 mg, or AML 10 mg/HCTZ 25 mg. Main Outcome Measure The primary efficacy variable was the change in least squares (LS) mean seated diastolic BP (SeDBP) from baseline to week 12. Secondary efficacy variables included the LS mean change in seated systolic BP (SeSBP), percentage of study participants reaching BP goal, and safety parameters. >Results In both Black and non-Black participants, triple-combination treatment resulted in significant and similar mean reductions in SeDBP and SeSBP (p≤0.0001 vs each dual-combination treatment) with a greater proportion of participants reaching BP goal compared with dual-combination treatments, regardless of race. Most treatment-emergent adverse events were mild or moderate in severity and no new safety concerns were identified. Conclusion Triple-combination treatment provided greater BP reductions than dual-combination treatments regardless of race. Clinical Trial Registration Registered at ClinicalTrials.gov as NCT00649389.     

氨氯地平治疗老年单纯性收缩期高血压疗效观察

目的观察氨氯地平治疗老年单纯性高血压临床效果。方法将86例老年单纯性高血压患者用氨氯地平5～10mg,po,qd×8wk。进行治疗结果氨氯地平降压总有效率96.5%,疗效明显。治疗期间心肝肾功能、血与尿等的各项生理指标无明显改变。结论氨氯地平治疗老年单纯性收缩期高血压病疗效好,且不良反应少。     

联合降压治疗老年单纯收缩期高血压的安全性及疗效观察

目的了解贝那普利联合苯磺酸氨氯地平的联合降压治疗对老年单纯收缩期高血压(isolated systolic hypertension,ISH)的安全性及疗效。方法 200例老年ISH患者随机分为治疗组100例,采用贝那普利联合苯磺酸氨氯地平治疗;对照组100例单用贝那普利治疗,4周后对两组的降压有效率,不良反应等指标进行观察。结果 4周治疗组有效率为97.0%(97/100),明显高于对照组,差异有显著性(P<0.05)。两组治疗前收缩压和舒张压比较P>0.05,差异无统计学意义;降压治疗4周后,两组收缩压比较P<0.05,差异有统计学意义;治疗组的降压有效率显著高于对照组,P<0.05,差异有统计学意义;治疗组和对照组出现严重不良反应停药者。结论苯磺酸氨氯地平联合贝那普利治疗老年ISH安全有效,值得各医院推广应用。     

他汀类药物治疗血脂正常单纯收缩期高血压患者的疗效及安全性的Meta分析

目的:系统评价他汀类药物治疗血脂正常单纯性收缩期高血压患者(ISH)的疗效及安全性。方法:计算机检索Pubmed、EMbase、Cochrane图书馆临床对照试验资料库、中国生物医学文献数据库(CBM)、中国期刊全文数据库(CNKI)和万方数据库及万方中华医学会期刊库,检索时间均从建库至2012年5月,手工检索相关文献。收集他汀类药物治疗血脂正常ISH患者的随机对照试验(RCT)。对符合纳入标准的临床研究进行质量评价和资料提取后,采用RevMan5.0软件进行Meta分析。结果:共纳入17项RCT,包括1297例患者。Meta分析结果显示,试验组较对照组能有效地降低收缩压(SBP)[MD=-4.56,95%CI(-5.60,-3.53),P<0.00001],防止舒张压(DBP)的过度降低[MD=3.26,95%CI(1.42,5.09),P=0.0005],还能有效地缩小脉压差(PP)[MD=-8.41,95%CI(-10.44,-6.38),P<0.00001]。试验组对总胆固醇、甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇和不良反应发生率的影响与对照组比较,差异无统计学意义。结论:对于血脂正常的ISH患者,他汀类药物能有效地降低SBP,缩小PP,不良反应发生率低。     

Efficacy and Safety of a Fixed Combination of Irbesartan/Hydrochlorothiazide in Chinese Patients with Moderate to Severe Hypertension

Background and Objectives

In a multi-center, single-arm, prospective study, we investigated the efficacy and safety of the fixed irbesartan/hydrochlorothiazide combination in Chinese patients with moderate to severe hypertension.

Methods

Eligible patients were aged 18–75 years, with a blood pressure of 160–199 mmHg systolic or 100–119 mmHg diastolic during a 1-week wash-out phase off antihypertensive medication. The enrolled patients started antihypertensive treatment with irbesartan/hydrochlorothiazide 150 mg/12.5 mg once daily, with the possible addition of irbesartan 150 mg once daily and up-titration to irbesartan/hydrochlorothiazide 300 mg/25 mg once daily at 4 and 8 weeks of follow-up, respectively. The primary efficacy variable was the goal blood pressure-attaining rate at 12 weeks of follow-up (<140/90 mmHg, or <130/80 mmHg in patients with diabetes mellitus).

Results

In the intention-to-treat analysis (n = 501) at 12 weeks of follow-up, the goal blood pressure-attaining rate was 57.3 %, and the mean change in blood pressure from baseline was 27.8 mmHg [95 % confidence interval (CI) 26.4–29.1 mmHg; p < 0.001] systolic and 13.5 mmHg (95 % CI 12.6–14.4 mmHg; p < 0.001) diastolic. Similar findings were observed in the per-protocol analysis (n = 449). The prevalence of microalbuminuria and left ventricular hypertrophy significantly (p ≤ 0.01) decreased from 33.4 % (150/449) and 50.4 % (215/427) at baseline to 23.4 % (105/447) and 41.3 % (176/427) at the end of follow-up, respectively. Four patients (2.0 %) reported a serious adverse event.

Conclusion

The fixed irbesartan/hydrochlorothiazide combination may control blood pressure to the target level in about 60 % of Chinese patients with moderate to severe hypertension, with an acceptable safety profile.     

奥美沙坦酯对原发性轻中度高血压患者血压变异性及血管内皮功能的影响

目的:探讨奥美沙坦酯对原发性轻、中度高血压患者血压变异性及血管内皮功能的影响。方法:选取轻、中度原发性高血压患者60例作为研究组,同时选取60例健康志愿者作为对照组。研究组患者口服奥美沙坦酯20 mg,qd,服药4周后若收缩压(SBP)≤140mmHg、舒张压(DBP)<90mmHg,则继续原剂量服药至12周末;未达目标者,剂量加倍治疗至12周末。治疗前后测量研究组患者平均血压、血压变异性参数及动脉内皮依赖性血管扩张百分率(FMD)和肱动脉内径百分变化率(NMD),同时检测血清中24h一氧化氮(NO)、内皮素(ET)浓度变化,并与对照组比较。结果:与治疗前比较,研究组患者治疗后平均血压、血压变异性、血清ET水平显著降低,血清NO水平显著上升,FMD、NMD显著改善,差异均有统计学意义(P<0.05);与对照组比较,差异无统计学意义(P>0.05)。研究组患者中3例有轻度腹泻,2例有轻度干咳,均未予特殊处理,继续用药均自行缓解。结论:奥美沙坦酯有较好的降压作用且耐受性好,可显著改善患者血管内皮功能。