Olmesartan Medoxomil-Based Antihypertensive Therapy Evaluated by Ambulatory Blood Pressure Monitoring

Hypertension affects approximately 26% of the world’s adult population and is a recognized major risk factor for morbidity and mortality associated with cardiovascular, cerebrovascular, and renal diseases. However, despite the availability of a range of effective antihypertensive agents and a growing awareness of the consequences of high blood pressure (BP), the treatment and control of hypertension remains sub-optimal. A number of patient subgroups are categorized as ‘high risk’ and may have hypertension that is more difficult to treat, including obese individuals, patients with stage 2 hypertension, those with type 2 diabetes mellitus (T2DM), patients with coronary artery disease or a history of stroke, and Black patients. As the benefits of lowering BP in patients with hypertension are unequivocal, particularly in high-risk patients, treating high-risk patients with hypertension to BP goals and maintaining 24-hour BP control is important to help reduce cardiovascular risk and improve outcomes. Although the BP goals recommended in current consensus guidelines for the management of patients with hypertension are based on cuff BP measurements, ambulatory BP monitoring (ABPM) provides a valuable diagnostic tool and allows a more accurate assessment of BP levels throughout the 24-hour dosing period. ABPM is a better predictor of prognosis than office BP measurement and is also useful for assessing whether antihypertensive therapy remains effective in the critical last few hours of the dosing period, which usually coincides with the morning BP surge associated with arousal and arising. ABPM has been adopted by new evidence-based guidelines in the United Kingdom to confirm a suspected diagnosis of hypertension, which is an indication of the growing importance of ABPM in the management of hypertension. This review provides an overview of the efficacy and safety of anti-hypertensive therapy based on olmesartan medoxomil ± hydrochlorothiazide and amlodipine/olmesartan medoxomil in high-risk patient populations enrolled in studies that reported ambulatory BP endpoints. The studies identified in this review showed that a titrate-to-BP goal strategy using olmesartan medoxomil- or amlodipine/olmesartan medoxomil-based antihypertensive therapy was an effective and well-tolerated approach for maintaining BP control throughout the full 24-hour dosing period in high-risk patients with difficult-to-treat hypertension.     

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.     

Management of antihypertensive treatment with Lisinopril: a chronotherapeutic approach

Risk for cardiovascular events seems to be higher in the early morning, also as consequence of a rise in blood pressure (BP) values due to the characteristic circadian pattern of BP variability. Therefore, a suitable therapeutic BP control should be tightest during the early morning. On the basis of the ambulatory blood pressure monitoring (ABPM) studies, it has been previously demonstrated that the antihypertensive effect of once daily drug, generally administrated in the morning, decreases at the end of the dosing period. A chronotherapeutic approach to the management of hypertension (this field has been pourly investigated so far) would allow the assessment of the optimum timing of drug dosing, according to the circadian BP rhythm and to the chronorisk maps, in hypertensive patients affected by associated vascular pathologies. This would increase the therapeutic effects. The aim of this study was to assess BP changes due to ACE-inhibitor (Lisinopril 20 mg/die) once daily administration at three different times (8.00 AM, 4.00 PM, 10.00 PM), in order to optimise the dosing time. 40 subjects (mean age +/- SD: 45 +/- 10) affected by primary mild to moderate hypertension were submitted to ABPM for 24 hours, by means of Spacelabs 90207, before and after pharmacological treatment. Patients were randomised to take the drug at 8.00 AM, 4.00 PM or 10.00 PM, and they repeated ABPM every two months, by changing the dosing time. The chronobiological analysis showed: 1) a sensible decrease both in Systolic (S)BP and Diastolic (D)BP without affecting the circadian rhythm, in all evaluations; 2) a greater reduction of SBP and DBP from 6.00 AM to 11.00 AM, period in which cardiovascular risk is higher, after 10.00 PM dosing; 3) no other sensible reduction in SBP and DBP occurred after night administration as compared to that caused by other dosing times. Lisinopril administration at 10.00 PM. has been shown to be much more useful since, although BP circadian rhythm was unmodified, it protects hypertensive patients from both vascular chronorisk and Cruickshank effect (J-curve). Therefore, a chronobiologist antihypertensive treatment in order to increase the therapeutic effect already obtained with the traditional statistic methods.     

Use of 24-Hour Ambulatory Blood Pressure Monitoring to Assess Antihypertensive Efficacy

INTRODUCTION: Goal rates, the percentage of patients with hypertension achieving recommended SBP/DBP, are a clinically important assessment of an antihypertensive agent's efficacy. Twenty-four-hour ambulatory blood pressure monitoring (ABPM) allows accurate assessment of a patient's hypertension and risk for cardiovascular events, and provides the most accurate measure of an antihypertensive agent's efficacy throughout a 24-hour dosing interval. METHODS: A 12-week (4-week single-blind placebo run-in phase followed by an 8-week double-blind active treatment phase) randomized, parallel-group study reported that the recommended starting dose of the angiotensin II receptor antagonist (angiotensin receptor blocker; ARB) olmesartan medoxomil (Benicar(trade mark)) 20 mg/day was more effective than starting doses of losartan potassium (Cozaar) 50 mg/day, valsartan (Diovan) 80 mg/day, or irbesartan (Avapro) 150 mg/day in reducing cuff DBP in patients with essential hypertension. The present report includes analyses of secondary efficacy variables from this 12-week trial. RESULTS: The mean reduction in blood pressure from baseline to week 8 (end of treatment) was significantly greater with olmesartan medoxomil than with valsartan for all ABPM times analyzed (24 hours, daytime, night-time, and last 2 and 4 hours of monitoring). Statistical significance was reached for comparisons of olmesartan medoxomil with losartan potassium for a majority of times analyzed and with irbesartan for SBP in the last 4 hours of monitoring. Goal rates for accepted critical ambulatory blood pressure (ABP) values of <130/80 mm Hg for mean 24-hour ABP, <135/85 mm Hg for mean daytime ABP, and <120/75 mm Hg for mean night-time ABP were significantly greater for patients receiving olmesartan medoxomil than for those receiving losartan potassium or valsartan. Goal rates were numerically superior, but not statistically significant, to those achieved with irbesartan. Compared with losartan potassium or valsartan recipients, a significantly higher percentage of patients treated with olmesartan medoxomil achieved the 24-hour ABP goal of <130/85 mm Hg. The last 2 and 4 hours of ABPM indicated that olmesartan medoxomil maintained larger mean decreases in blood pressure through the morning surge. DISCUSSION/CONCLUSION: ABP goal rates are a meaningful measure of antihypertensive efficacy. The effects on mean change from baseline in ABP and ABP goal rates after 8 weeks of treatment were numerically better, but not statistically significant, for olmesartan medoxomil than for irbesartan. However, olmesartan medoxomil was significantly more effective than losartan potassium or valsartan.     

ACE Inhibition in Hypertension

Ongoing developments in our understanding of cardiovascular disease, together with the introduction of new drugs to treat these conditions, has led to much debate over the optimal management of hypertension. The ALLHAT study showed no major differences in cardiovascular outcome among three major classes of antihypertensive drugs. Indeed, large meta-analyses have substantiated this view, and most experts would agree that BP reduction matters more than the choice of antihypertensive agent. However, recently published data from the ASCOT-BPLA trial for hypertensive patients at moderate risk of cardiac events have caused some experts to re-evaluate this view. The recent Blood Pressure Lowering Treatment Trialists' Collaboration publication confirmed this change. In the ASCOT-BPLA trial, antihypertensive therapy based on amlodipine+perindopril significantly reduced total and cardiovascular mortality as well as other clinically relevant outcomes in comparison with a traditional strategy based on atenolol and a thiazide diuretic, despite both regimens producing nonsignificantly different reductions in brachial BP. These findings suggest that amlodipine/perindopril may exert a beneficial effect by acting on other parameters such as central BP or BP variability. ACE inhibitors have been shown to have antiatherosclerotic and antithrombogenic effects, to improve endothelial dysfunction, and to prevent cardiac remodeling in patients with coronary heart disease. In this regard, perindopril, which has relatively high affinity for ACE and true 24-hour duration of action, is one of the most extensively studied ACE inhibitors. More recent data suggest that ACE inhibitors reduce arterial stiffness, an independent risk factor for cardiovascular events, and have a beneficial effect on central aortic BP, thus providing a possible explanation for the findings of ASCOT-BPLA and confirming that ACE inhibitors are an appropriate first choice for patients with hypertension.     

Epidemiology and Management of Hypertension in the Hispanic Population

Hispanics are the fastest growing ethnic minority in the USA. Among Hispanics, lack of hypertension awareness and lack of effective blood pressure (BP) control are problematic, as are higher incidence rates of hypertension-related co-morbidities compared with non-Hispanic populations. Moreover, there are currently no hypertension treatment guidelines that address the unique characteristics of this ethnic group. This article discusses ethnic differences in hypertension and cardiovascular risk factors and reviews the literature on the efficacy of antihypertensive agents in Hispanic patients, with a focus on the role of renin-angiotensin-aldosterone system (RAAS) inhibition in the management of hypertension in these patients. Hypertension in Hispanic patients can be challenging to manage, in part because this population has a higher prevalence of obesity, diabetes, and metabolic syndrome compared with non-Hispanic whites. The presence of these co-morbidities suggests that RAAS-inhibitor-based therapies may be particularly beneficial in this population. However, few studies have evaluated the efficacy of antihypertensive treatments in Hispanic patients. Two outcomes studies in hypertensive patients have shown the benefits of treating Hispanic patients with antihypertensive therapy and included RAAS inhibitors as part of the treatment regimen. In addition, BP-lowering trials have shown the antihypertensive efficacy of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and direct renin inhibitors, although data on the latter are more limited. Additional studies are needed to more thoroughly evaluate the effects of RAAS inhibitors (and other drug classes) on outcomes and BP lowering in the Hispanic hypertensive population.     

珍菊降压片早、中二次投药的降压效果

目的以24h动态血压监测（ABPM）评价珍菊降压片早、中二次投药治疗轻中度原发性高血压患者的疗效。方法80例轻中度高血压患者随机分为试验组40例和对照组40例。试验组口服珍菊降压片早晨2片,中午1片;对照组口服珍菊降压片1片,每天3次。治疗8周。分别于治疗前后行24hABPM。结果2组24hABPM参数均较用药前显著下降（P〈0.01）;降压总有效率试验组为90.0%,对照组87.5%,2组比较差异无统计学意义（P〉0.05）。3例夜间血压最低值均出现在对照组。结论珍菊降压片降压效果良好。早、中2次投药,可防止夜间靶器官缺血。     

Telmisartan: a review of its use in the management of hypertension

Telmisartan (Micardis, Pritor), a highly selective angiotensin II (AII) type 1 (AT1) receptor antagonist, is approved for the treatment of hypertension, either as monotherapy or in combination with other antihypertensive agents. The long elimination half-life of telmisartan ensures the drug provides effective reductions in blood pressure (BP) across the entire 24-hour dosage interval. Extensive evidence from well designed clinical trials and the clinical practice setting indicates that telmisartan, either as monotherapy or in combination with other antihypertensive agents, provides long-term antihypertensive efficacy and is well tolerated in a broad spectrum of hypertensive patients, including the elderly and those with coexisting type 2 diabetes mellitus, metabolic syndrome and/or renal impairment. Notably, BP control is sustained throughout the 24-hour dosage interval, including during the last 6 hours of this period. Independent of its effect on BP, telmisartan displays favourable effects on insulin resistance, lipid levels, left ventricular hypertrophy (LVH) and renal function. The consistent antihypertensive efficacy during the entire 24-hour dosage interval and sustained BP-lowering effect in the long term, combined with its favourable tolerability profile, mean that telmisartan is a valuable first-line treatment option for the management of essential hypertension.     

Telmisartan/Hydrochlorothiazide: a review of its use as fixed-dose combinations in essential hypertension

Fixed-dose combinations of telmisartan and hydrochlorothiazide (HCTZ) [Micardis Plus((R)), Micardis((R)) HCT, PritorPlus((R))] are available in many countries for the treatment of patients with essential hypertension. Combining the angiotensin II receptor antagonist (angiotensin II receptor blocker [ARB]) telmisartan with the thiazide diuretic HCTZ provides antihypertensive therapy with complementary mechanisms of action. In the US and EU, telmisartan/HCTZ is approved for patients whose hypertension is not adequately controlled with telmisartan monotherapy; US labelling for the fixed-dose combination also includes inadequate control of blood pressure (BP) with HCTZ monotherapy.The antihypertensive efficacy of once-daily telmisartan/HCTZ has been demonstrated in several large, randomized trials in patients with stages 1 and 2 hypertension. The addition of HCTZ to telmisartan achieved significant reductions in BP in nonresponders to telmisartan monotherapy, and the antihypertensive efficacy of telmisartan/HCTZ was similar to or significantly greater than that of various comparator agents. Moreover, in studies that used ambulatory BP monitoring, telmisartan/HCTZ provided consistent 24-hour BP reductions throughout morning, daytime and night-time periods. The BP-lowering efficacy over the entire 24-hour dose administration interval is consistent with the pharmacokinetic profile of telmisartan, which has the longest elimination half-life among currently available ARBs and a unique chemical structure. Adverse events with telmisartan/HCTZ in clinical trials were typically mild and transient, and no unexpected events occurred that had not been previously reported with either telmisartan or HCTZ. Extensive tolerability data are available for telmisartan, in particular from the ONTARGET study, the largest clinical outcomes trial with an ARB. As such, fixed-dose combinations of telmisartan/HCTZ provide an effective, rational and generally well tolerated treatment option for the management of patients with hypertension.     

Chronotherapy of hypertension: administration-time-dependent effects of treatment on the circadian pattern of blood pressure

Some specific features of the 24-hour blood pressure (BP) pattern are linked to the progressive injury of target tissues and the triggering of cardiac and cerebrovascular events. Thus, there is growing interest in how to best tailor the treatment of hypertensive patients according to the circadian BP pattern of each individual. Significant administration-time differences in the kinetics (i.e., chronokinetics) plus beneficial and adverse effects (i.e., chronodynamics) of antihypertensive medications are well known. Thus, bedtime dosing with nifedipine GITS is more effective than morning dosing, while also significantly reducing adverse effects. The dose-response curve, therapeutic coverage, and efficacy of doxazosin GITS are all markedly dependent on the circadian time of drug administration. Moreover, valsartan administration at bedtime, as opposed to upon wakening, results in an improved diurnal/nocturnal BP ratio, increased percentage of controlled patients, and significant reduction in urinary albumin excretion in hypertensive patients. Chronotherapy provides a means of individualizing the treatment of hypertension according to the circadian BP profile of each patient, and constitutes a new option to optimize BP control and to reduce the risk of cardiovascular disease (myocardial infarction and stroke) and of end-organ injury of the blood vessels and tissue of the heart, brain, kidney, eye, and other organs.     

Noninvasive 24-hour ambulatory blood pressure monitoring: overview of technology and clinical applications

During the last 25 years, 24-hour noninvasive ambulatory blood pressure monitoring (ABPM) has evolved from a research tool of limited clinical use into an important tool for stratifying cardiovascular risk and guiding therapeutic decisions. Until recently, clinical use of ABPM focused on identifying patients with white-coat hypertension, but accumulated evidence now points to greater prognostic significance of ABPM in determining risk for target-organ damage compared with that of office blood pressure measurements. Clinicians involved in the care of patients with hypertension should familiarize themselves with the role of this technology and how to use it in an appropriate and cost-effective manner.     

Cardioprotective effects of telmisartan in uncomplicated and complicated hypertension

The development of angiotensin II receptor blockers (ARB) as a new class of drugs for the management of hypertension has elicited the attention of many clinicians worldwide with the aim of improving blood pressure (BP) control as well as cardiovascular protection. Among ARB telmisartan has been shown to be characterised by an antihypertensive efficacy fully covering the 24-hour period, thereby allowing to antagonise the adverse effects of early morning BP rise on cardiovascular risk. Other specific effects of the drug are represented by its favourable metabolic profile (particularly on insulin sensitivity) and neutral effects on sympathetic cardiovascular function. These properties are coupled with cardioprotective effects, documented by the evidence that the drug: 1) is effective in favouring the regression of cardiac and vascular organ damage, 2) reduces arterial stiffness and improves vascular distensibility and 3) reverses the endothelial dysfunction typical of the hypertensive state particularly when complicated by renal failure, diabetes, obesity or metabolic syndrome. Several of these properties can account for the results of the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET), documenting the beneficial effects on the drug on cardiovascular morbidity and mortality.     

100例高血压患者24小时动态血压测定

１００例高血压得的２４小时动态血压测定（ＡＢＰＭ）研究发现：白大衣性高血压在全组、未用药和用药组中的发生率占２０％左右，说明偶测血压的白大衣效应可引起高血压的过多诊断和低估了药物的降压效果。２８％高血压者ＡＢＰＭ血压大于偶测血压。用药组中，偶测血压判断为满意控制者中有４０％ＡＢＰＭ血压仍高于正常水平。这种由于正常活动的应激影响致使偶测血压高估了药物的降压效果。     

Fixed-Dose Combination Antihypertensives and Reduction in Target Organ Damage

Hypertension is a multifactorial disorder leading to pathophysiologic changes in target organs over time through diverse mechanisms. In addition, hypertension frequently resists control with monotherapy, necessitating combination therapy with two or more antihypertensive agents. Many currently available fixed-dose antihypertensive combinations combine drugs with different, but complementary, mechanisms of action to improve overall efficacy and tolerability. In addition, it is possible to select drug combinations whereby one drug offsets the negative effects of the other drug. Fixed-dose antihypertensive combinations may provide significant advantages over high-dose monotherapy, such as improved BP-lowering efficacy, reduced adverse event frequency, improved patient compliance, potentially lower treatment costs, and shorter time to BP control. Combination therapy has been recommended as potential first-line therapy in recent consensus guideline statements, especially for higher-risk patients, such as those with stage 2 hypertension. The combination of a renin-angiotensin-aldosterone system-targeting agent, such as an ACE inhibitor or angiotensin II receptor antagonist (ARB), and a diuretic or calcium channel antagonist appears to provide synergy with regard to BP lowering. In addition, ACE inhibitors and ARBs have demonstrated beneficial effects beyond BP reduction, reducing cardiovascular morbidity and mortality, inhibiting development and progression of type 2 diabetes mellitus and the progression of renal disease. Preliminary studies of fixed-dose combinations have shown reductions in left ventricular hypertrophy and improvements in markers of renal function. Additional studies currently underway will compare the effects of available fixed-dose combinations on cardiovascular morbidity and mortality, and markers of renal dysfunction.     

福辛普利与卡托普利治疗老年高血压病的疗效比较

目的:比较福辛普利与卡托普利治疗老年高血压病的疗效.方法:应用动态血压监测30例老年高血压病患者po福辛普利(10～20 mg)4wk后的降压疗效,并与卡托普利组相对比.结果:服药前后两组偶测血压及24h白昼平均压、24h最高血压均明显降低(P<0.05).福辛普利对夜间血压呈一致性下降,降压谷/峰比值收缩压与舒张压均>50%.且无严重不良反应.结论:福辛普利治疗老年高血压病安全而有效.     

厄贝沙坦单用及合用治疗轻、中度原发性高血压60例

目的 :比较国产厄贝沙坦单用以及与非洛地平或雷米普利合用对轻、中度原发性高血压的降压疗效。方法 :6 0例轻、中度高血压病人 ,经 2wk安慰剂导入期后 ,单服厄贝沙坦 15 0mg ,qd。 4wk后随机分 2组 ,分别联合服用非洛地平 5mg ,qd ,或雷米普利 5mg ,qd ,均为 4wk。治疗前及治疗后 4wk和 8wk行 2 4h动态血压监测 ,并测治疗前后坐位血压。结果 :厄贝沙坦单用 4wk后 ,坐位血压和2 4h动态血压均下降 (P <0 .0 5或P <0 .0 1) ,收缩压和舒张压的谷峰比值为 0 .82和 0 .86。厄贝沙坦与非洛地平或雷米普利合用 4wk后 ,坐位血压总有效率从 4 0 %增加为 89%和 70 % ;动态血压显示联合用药降压作用较明显。结论 :厄贝沙坦单用有长效的降压作用 ,与非洛地平或雷米普利联合用药有叠加降压作用     

Fixed-dose combination enalapril/nitrendipine: a review of its use in mild-to-moderate hypertension

The fixed-dose combination of enalapril 10mg with nitrendipine 20mg combines an ACE inhibitor with a calcium channel antagonist (CCA) and is indicated for the treatment of patients with mild-to-moderate hypertension whose blood pressure (BP) is inadequately controlled with enalapril or nitrendipine monotherapy. In randomised, double-blind clinical trials, enalapril/nitrendipine 10/20 mg/day was significantly more effective than its individual components in reducing diastolic BP (DBP) in patients with mild-to-moderate hypertension inadequately controlled with enalapril 10 mg/day or nitrendipine 20 mg/day. The fixed-dose combination was similar in efficacy at reducing DBP to amlodipine 10 mg/day in patients who failed to achieve BP control with amlodipine 5 mg/day, and to losartan/hydrochlorothiazide 50/12.5 mg/day in patients who received the combinations as first-line therapy. Enalapril/nitrendipine 10/20 mg produced a consistent antihypertensive effect that persisted for the entire 24-hour dosage interval as shown by ambulatory BP monitoring. Enalapril/nitrendipine 10/20 mg was well tolerated in clinical trials where it was administered to patients with mild-to-moderate hypertension for up to 12 weeks. The adverse events were those expected of ACE inhibitors and CCAs and included cough, headache and flushing. Evidence from clinical trials, including a pooled analysis, suggests that the incidence of oedema may be significantly lower with the fixed-dose combination than with CCA monotherapy.In conclusion, enalapril/nitrendipine 10/20 mg is a well tolerated fixed-dose combination of two established antihypertensive agents administered once daily that effectively lowers BP throughout the 24-hour dosage interval. Importantly, the fixed-dose combination may have a lower incidence of oedema than CCA monotherapy. Enalapril/nitrendipine 10/20 mg provides an additional treatment option for patients with mild-to-moderate hypertension for whom combination therapy is appropriate.     

国产厄贝沙坦复方制剂对高血压患者动态血压的影响

目的 应用动态血压监测评价厄贝沙坦氢氯噻嗪复方制剂(商品名依伦平)的降压疗效.方法 原发性高血压患者口服安慰剂2周后,改服依伦平片1片/d,于药物治疗前和治疗4周末各行动态血压监测1次.结果 治疗4周后24 h、日间、夜间的收缩压/舒张压分别下降(15.59±8.21/9.55±6.31),(17.53±9.64/10.90±6.77),(14.17±9.85/7.13±5.91)mm Hg,收缩压和舒张压的24 h降压疗效谷/峰比值分别为75.9%和73.6%.结论 每日口服1片国产厄贝沙坦氢氯噻嗪片,降压效果可以维持24 h,疗效确切,安全性和患者耐受性好.     

A cyclic fluctuation model for 24-h ambulatory blood pressure monitoring in Chinese patients with mild to moderate hypertension

Aim:

The conventional method for analyzing 24-h ambulatory blood pressure monitoring (24-h ABPM) is insufficient to deal with the large amount of data collected. The aim of this study was to develop a novel cyclic fluctuation model for 24-h ABPM in Chinese patients with mild to moderate hypertension.

Methods:

The data were obtained from 4 independent antihypertensive drug clinical trials in Chinese patients with mild to moderate hypertension. The measurements of 24-h ABPM at the end of the placebo run-in period in study 1 were used to develop the cyclic fluctuation model. After evaluated, the structural model was used to analyze the measurements in the other 3 studies. Models were fitted using NONMEM software.

Results:

The cyclic fluctuation model, which consisted of 2 cosine functions with fixed-effect parameters for rhythm-adjusted 24-h mean blood pressure, amplitude and phase shift, successfully described the blood pressure measurements of study 1. Model robustness was validated by the bootstrap method. The measurements in the other 3 studies were well described by the same structural model. Moreover, the parameters from all the 4 studies were very similar. Visual predictive checks demonstrated that the cyclic fluctuation model could predict the blood pressure fluctuations in the 4 studies.

Conclusion:

The cyclic fluctuation model for 24-h ABPM deepens our understanding of blood pressure variability, which will be beneficial for drug development and individual therapy in hypertensive patients.