Antihypertensive efficacy of olmesartan medoxomil alone and in combination with hydrochlorothiazide

Angiotensin receptor blockers (ARBs) are highly effective antihypertensive agents with excellent safety profiles. ARBs have been shown to improve cardiovascular morbidity and mortality in hypertensive patients with heart failure or diabetic nephropathy. For this later class of patients, the American Diabetes Association recommends ARBs as the primary treatment option. The ARBs function by blocking the binding of angiotensin-II (A-II) to its receptor, thereby inhibiting the action of A-II. Unlike the angiotensin-converting enzyme (ACE) inhibitors, which block the production of A-II through the ACE pathway, the ARBs effectively inhibit A-II regardless of whether it is produced through ACE or some alternate enzyme pathway. This difference in action offers a distinct advantage of ARBs over ACE inhibitors. Olmesartan medoxomil, the latest addition to the ARB class, is a long-acting, safe and well-tolerated antihypertensive drug. The combination of olmesartan medoxomil with a low-dose diuretic, potentiates the blood pressure lowering effect of either agent alone and is highly effective in achieving the recommended blood pressure goals in the majority of patients treated.     

Beating the clock: reducing cardiovascular risk by rapid blood pressure reduction with olmesartan

Importance of the field: Hypertension is a major cardiovascular risk factor, and treatment guidelines acknowledge the value not only of reducing elevated blood pressure (BP) to target levels (< 140/90 mmHg and < 130/80 mmHg in patients with diabetes or those at high cardiovascular risk) but also of doing this rapidly.

Areas covered in this review: The importance of rapid BP control has been demonstrated by trials like the Valsartan Antihypertensive Long-term Use Evaluation trial. Combination therapy provides greater efficacy than monotherapy and reduces BP more rapidly. Combining angiotensin receptor blockers (ARBs) with agents from other classes, like calcium channel blockers or diuretics, is an established way to provide effective, rapid and well-tolerated BP reduction.

What the reader will gain: Although ARBs are widely used as mono- and combination therapy, it is not widely appreciated that there are differences between these drugs in efficacy and speed of action. The ARB olmesartan medoxomil provides rapid reductions in BP as monotherapy and combination therapy, with large BP reductions observed within the first few weeks of treatment.

Take home message: In addition to controlling BP, speed of onset of action is an important factor in the management of hypertensive patients and treatments that lower BP rapidly should help to reduce cardiovascular risk.     

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。     

Telmisartan/hydrochlorothiazide combination therapy in the treatment of essential hypertension

Telmisartan is an angiotensin-II receptor blocker that has demonstrated efficacy in the reduction of blood pressure in patients with hypertension. Patients with hypertension commonly require two or more antihypertensives to reduce their blood pressure to safe levels, and the choice of combination therapy should be informed by clinical trial data. Telmisartan is available in fixed-dose combination with hydrochlorothiazide (telmisartan/HCTZ) in doses of 40 mg/12.5 mg and 80 mg/12.5 mg. Telmisartan/HCTZ has been studied in a number of clinical trials in essential hypertension, for the most part using ambulatory blood pressure monitoring. It has been compared with monotherapy in full patient populations and in non-responders, and has been compared with other drug combinations. Telmisartan/HCTZ provides significantly greater reductions in blood pressure than monotherapy, and significantly increases the percentage of patients who achieve target blood pressure. The reduction in blood pressure achieved by adding HCTZ to telmisartan is greater than that achieved by adding HCTZ to atenolol, despite the fact that telmisartan and atenolol monotherapy had similar efficacy. Telmisartan/HCTZ provides significantly greater reductions than losartan plus HCTZ in 24-h mean blood pressure, primarily due to a significantly greater effect in the risky, early morning hours. Telmisartan/HCTZ is effective and well-tolerated in the elderly, diabetics and African-American patients. Ongoing studies are comparing the efficacy of telmisartan/HCTZ with valsartan plus HCTZ and amlodipine plus HCTZ in overweight, hypertensive diabetics and in patients with isolated systolic hypertension – two patient groups who are particularly at risk of target organ damage.     

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)...     

Olmesartan medoxomil-based therapy for the management of hypertension

Contemporary practice guidelines for hypertension recommend a goal systolic/diastolic blood pressure (BP) of less than 140/90 mmHg for patients with hypertension and less than 130/80 mmHg for patients with diabetes mellitus or chronic kidney disease. Current guidelines recognize that most patients will require combination therapy to achieve these BP goals and recommend that the agents used in such therapy should have complementary mechanisms of action. Olmesartan medoxomil is an angiotensin receptor blocker approved for the treatment of hypertension as monotherapy or in combination with antihypertensive agents. It is also approved in a fixed-dose combination with hydrochlorothiazide or amlodipine. Olmesartan medoxomil-based therapy can manage hypertension across a range of patient types and has demonstrated good BP-lowering efficacy and goal attainment in individuals with stage 1 or stage 2 hypertension. The comparative antihypertensive efficacy and safety of olmesartan medoxomil, as monotherapy and as part of combination therapy, has been established in several large, randomized clinical trials. This review evaluates the chemistry, efficacy and safety of olmesartan medoxomil-based therapy and its expanding role in hypertension management.     

奥美沙坦酯对自发性高血压大鼠心室重构的影响

目的 研究奥美沙坦酯对自发性高血压大鼠(SHR)心室重构及过氧化物酶体增殖物激活受体α(PPARα)、过氧化物酶体增殖物激活受体γ(PPARγ)表达的影响.方法 将36只雄性SHR随机分为模型组与实验组,各18只;同时选择18只相应周龄的Wistar Kyoto(WKY)大鼠作为对照组.实验组大鼠灌胃给予奥美沙坦酯10...     

苯那普利与小剂量氢氯噻嗪合用治疗高血压疗效观察

目的：研究苯那普利与小剂量氢氯噻嗪合用对高血压患者的疗效。方法：采用随机分组法将60例原发性高血压病人分为两组,A组30例单用苯那普利10mg,每日一次;B组30例用苯那普利10mg,每日一次,加服氢氯噻嗪12．5mg,每日一次。两组治疗时间均为4周。观察治疗前后的基础血压及24h动态血压,并测定治疗前后的空腹血糖、血脂、血尿酸、尿素氮、肌酐。结果：苯那普利加小剂量氢氯噻嗪组的总有效率及24h动态血压的结果明显优于单用苯那普利组,两组治疗前后的代谢指标均无明显改变。结果：苯那普利与小剂氢氯噻嗪合作治疗高血压较单用苯那普利更有效,而且对代谢无明显影响。     

抗高血压新药选择性AT1亚型血管紧张素II受体拮抗剂——阿齐沙坦酯

阿齐沙坦酯为新一代选择性AT1血管紧张素II亚型1受体拮抗剂,临床前和临床研究证实其具有平稳持久的抗高血压作用。2011年2月25日,FDA批准阿齐沙坦酯(商品名为Edarbi)用于治疗成人高血压。本综述主要介绍其药物作用机制,药物代谢动力学、疗效、安全性及临床研究进展。     

抗高血压药物的联合应用

血压达标可明显降低心血管病发病率和死亡率;然而在我国,人群高血压的控制率仅为6.1%.联合降压治疗,如固定剂量复方制剂的联合治疗与单药降压治疗比较,可明显降低血压和减少药物不良反应的发生.由于联合降压治疗可能减少不良事件的发生、提高患者的依从性、降低治疗成本和改善血压的达标率,因此联合降压治疗对高危高血压患者是一项有价值的选择.     

The ROADMAP trial: olmesartan for the delay or prevention of microalbuminuria in type 2 diabetes

Microalbuminuria is a major target of the therapeutic interventions in clinical trials aimed at assessing whether and to what extent antihypertensive treatment can favor the regression and/or slow down the progression of renal dysfunction in cardiometabolic disease. The Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention (ROADMAP) trial has recently investigated the impact of an angiotensin II receptor blocker (olmesartan) on the new onset of microalbuminuria in type 2 diabetic patients, thus providing direct information on the ability of the drug to prevent the development of this marker of renal organ damage and, more generally, of cardiovascular risk. The results provide evidence that pharmacological blockade of angiotensin II receptors is highly effective in reducing the risk of developing microalbuminuria and that this effect can be achieved through blood-pressure-dependent and blood-pressure-independent effects. Despite the nephroprotective properties of olmesartan, the drug did not reduce the number of cardiovascular events and cardiovascular complications associated with the diabetic state.     

A randomized,comparative study evaluating the efficacy and tolerability of losartan-low dose chlorthalidone (6.25 mg) combination with losartan-hydrochlorothiazide (12.5 mg) combination in Indian patients with mild-to-moderate essential hypertension

Objective: The relationship of blood pressure (BP) to cardiovascular risk is linear, positive, and continuous. Lowering elevated BP reduces the risk of cardiovascular events. The primary objective of this randomized, multicenter, comparative, 3-month, open-label study was to evaluate the antihypertensive efficacy of losartan/chlorthalidone versus losartan/hydrochlorothiazide in mild-to-moderate essential hypertension. Methods: A total of 137 eligible patients underwent a 2-week placebo washout period, following which 131 patients were randomized to losartan (L) 25mg/chlorthalidone (C) 6.25 mg (66/131) or to losartan 25 mg/hydrochlorothiazide (H) 12.5 mg (65/131) at three centers. Patients not responding after 4 weeks of therapy were escalated to losartan 25 mg/chlorthalidone 12.5 mg and losartan 50 mg/hydrochlorothiazide 12.5 mg, respectively. Results: Both treatment groups were similar with respect to demography and baseline characteristics. Altogether, 120 patients completed the study. After 4 weeks of therapy, both treatments showed a significant fall from baseline in systolic BP (SBP) and diastolic BP (DBP) (L/C: -20.17/-10.30; L/H: -17.63/-10.20). Both treatments were similar with respect to mean fall in SBP (p = 0.258), DBP (p = 0.934) and response rate (p = 0.769). Both step-up therapies were similar with respect to mean fall in SBP (p = 0.418), DBP (p = 0.389) from baseline and response rate (p = 0.769). All reported adverse events were of mild-to-moderate intensity, except for two serious AEs that occurred in patients who received L/H. Conclusions: The losartan/low-dose chlorthalidone (6.25 mg) combination is as effective as the widely used losartan/hydrochlorothiazide combination in lowering BP and is well tolerated, thus providing a useful therapeutic option for treating mild-to-moderate hypertension.     

Antihypertensive therapy: special focus on drug interactions

Today, the lifetime risk of patients aged 55 – 65 years to receive antihypertensive drugs approaches 60%. Yet, recent trials suggest that hypertension is not adequately controlled in the majority of patients. The prevalence of hypertension increases with advancing age, as does the prevalence of comorbid conditions and the total number of medications taken. Multi-drug therapy, advancing age and comorbid conditions are also key risk factors for adverse drug reactions and drug interactions. In this review, the authors evaluate the most frequently used antihypertensive drugs (diuretics, β-adrenergic blockers, angiotensin-converting enzyme inhibitors, calcium channel blockers, angiotensin II receptor Type 1 blockers and α-adrenergic blockers) with special reference to pharmacodynamic and pharmacokinetic drug interactions. As the spectrum of drugs prescribed is constantly changing, safety yesterday does not imply safety today and safety today does not imply safety tomorrow. Furthermore, therapeutic efficacy should not be neglected over concerns regarding drug interactions. Many patients are at risk of clinically relevant drug interactions involving antihypertensive drugs but, presently, even more patients may be at risk of suffering from the consequences of their inadequately treated hypertension. In this respect, the authors discuss controversial viewpoints on the overall clinical relevance of drug interactions occurring at the level of cytochrome P450 metabolism.     

Single-pill combination of amlodipine and valsartan in the management of hypertension

Combination therapy is increasingly recommended for selected patients with hypertension to facilitate prompt attainment and maintenance of goal blood pressure (BP). Single-pill combination therapy simplifies treatment and optimizes long-term compliance. Amlodipine, a dihydropyridine calcium antagonist, and valsartan, an angiotensin receptor blocker, are well-established antihypertensive agents with complementary mechanisms of action. This combination lowers BP significantly more than either of its components, and valsartan reduces the incidence of dose-related amlodipine-induced edema. Rigorous clinical trial data have proven the BP-lowering efficacy and high tolerability of the amlodipine/valsartan combination in patients with moderate to severe hypertension as well as other difficult-to-treat populations. Amlodipine/valsartan is indicated as initial therapy in patients who are unlikely to be controlled with a single drug and as second-line therapy in patients not responding adequately to monotherapy.     

Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: efficacy and safety compared to hydrochlorothiazide

Objective: To compare the antihypertensive efficacy of a new angiotensin II antagonist, valsartan, with a reference therapy, hydrochlorothiazide (HCTZ). Methods: In this double-blind study, 167 adult outpatients with mild-to-moderate essential hypertension were randomly allocated in equal number to receive valsartan 80 mg or HCTZ 25 mg for 12 weeks. In patients whose blood pressure (BP) remained uncontrolled after 8 weeks of monotherapy, atenolol 50 mg was added to the initial treatment. Patients were assessed at 4, 8 and 12 weeks. The primary efficacy variable was change from baseline in mean sitting diastolic BP (SDBP) at 8 weeks. Secondary variables included change in sitting systolic BP (SSBP) and responder rates (percentage of patients with SDBP <90 mmHg or drop ≥10 mmHg compared to baseline) at 8 weeks. Results: Valsartan and HCTZ were both effective at lowering diastolic and systolic blood pressure at all time points. Similar falls were seen in both groups with no significant differences between treatments. For the primary variable (decrease in SDBP) there was no significant difference between treatments. For SSBP there was also no significant difference observed. Responder rates at 8 weeks were 74% for valsartan and 62% for HCTZ (P = 0.10). Both treatments were well tolerated, both as monotherapy, and when combined with atenolol 50 mg per day. Conclusion: The data show valsartan 80 mg to be as effective as HCTZ in the treatment of mild-to-moderate hypertension. The results also show valsartan to be well tolerated when taken alone or in combination with atenolol. Received: 7 March 1996 / Accepted in revised form: 29 July 1996     

Combination therapy for type 2 diabetes: dapagliflozin plus metformin

Introduction: Type 2 diabetes (T2D) is a chronic and multifactorial metabolic disease, which brings great threats to public health. The morbidity of T2D keeps growing, and it is estimated that the population with T2D will rise to 552 million throughout the world by 2030. Effective glycemic control in patients is crucial for the treatment of T2D. However, with progressive deterioration of disease, most patients are usually unable to achieve glycemic targets receiving antidiabetic agent monotherapy. In such cases, combination therapy with different mechanisms of antidiabetic agents is highly desired. In addition, combination therapy can provide advantages beyond better glycemic improvement such as reduced incidence of hypoglycemia and cardiovascular events.

Areas covered: We reviewed all the published data regarding the fixed-dose combination therapy of dapagliflozin combined with metformin, including complementary mechanism of action, pharmacodynamics, pharmacokinetics, clinical efficacy and safety.

Expert opinion: The fixed-dose combination of dapagliflozin and metformin exerts synergistic effects based on two antidiabetic agents with complementary mechanisms of action. Rational co-administration of dapagliflozin and metformin provides better glycemic control with potential weight loss and the reduced incidence of hypoglycaemia.     

Amlodipine/benazepril: fixed dose combination therapy for hypertension

Myocardial infarction, stroke, heart failure and end-stage renal disease have all been linked to inadequate control of blood pressure. Despite overwhelming evidence that uncontrolled hypertension is responsible for a sizeable number of adverse health-related outcomes, control of the disease remains considerably suboptimal. Available data demonstrate that in order to achieve adequate blood pressure control, a large number of patients require therapy with more than one medication. Fixed dose combination antihypertensive therapy has many advantages over other treatment options. Positive effects on blood pressure control, rates of adherence, adverse effects and cost have been identified. Amlodipine/benazepril (Lotrel^®, Novartis) is a fixed dose combination product indicated for the treatment of hypertension. Although not currently recommended as first-line therapy, studies confirm that this combination of a long-acting calcium antagonist and an angiotensin-converting enzyme (ACE) inhibitor possesses substantial blood pressure lowering capabilities. Whereas adverse events tend to become more frequent with increasing doses of antihypertensive monotherapy, the rate of adverse events attributed to amlodipine/benazepril in clinical trials often correlates with rates ascribed to placebo. Amlodipine/benazepril is capable of sustaining blood pressure control over a 24 h period and appears to be minimally affected by an occasional dose omission. Unlike the older calcium antagonists, amlodipine is unlikely to cause alterations in myocardial contractility. Additionally, the amlodipine/benazepril combination product costs less than the same therapy administered as the individual components. It is, therefore, reasonable to consider therapy with amlodipine/benazepril in appropriate patients after an adequate trial of antihypertensive monotherapy.     

Renin and the (pro)renin receptor in the renal collecting duct: Role in the pathogenesis of hypertension

The intrarenal renin–angiotensin system (RAS) plays a critical role in the pathogenesis and progression of hypertension and kidney disease. In angiotensin (Ang) II‐dependent hypertension, collecting duct renin synthesis and secretion are stimulated despite suppression of juxtaglomerular (JG) renin. This effect is mediated by the AngII type I receptor (AT₁R), independent of blood pressure. Although the regulation of JG renin has been extensively studied, the mechanisms by which renin is regulated in the collecting duct remain unclear. The augmentation of renin synthesis and activity in the collecting duct may provide a pathway for additional generation of intrarenal and intratubular AngII formation due to the presence of angiotensinogen substrate and angiotensin‐converting enzyme in the nephron. The recently described (pro)renin receptor ((P)RR) binds renin or prorenin, enhancing renin activity and fully activating the biologically inactive prorenin peptide. Stimulation of (P)RR also activates intracellular pathways related to fibrosis. Renin and the (P)RR are augmented in renal tissues of AngII‐dependent hypertensive rats. However, the functional contribution of the (P)RR to enhanced renin activity in the collecting duct and its contribution to the development of hypertension and kidney disease have not been well elucidated. This review focuses on recent evidence demonstrating the mechanism of renin regulation in the collecting ducts and its interaction with the (P)RR. The data suggest that renin–(P)RR interactions may induce stimulation of intracellular pathways associated with the development of hypertension and kidney disease.