Manidipine-delapril combination in the management of hypertension

High blood pressure (BP) is the major cardiovascular risk factor and the main cause of death around the world. Control of blood pressure reduces the high mortality associated with hypertension and the most recent guidelines recommend reducing arterial BP values below 140/90 mmHg for all hypertensive patients (130/80 in diabetics) as a necessary step to reduce global cardiovascular risk, which is the fundamental objective of the treatment. To achieve these target BP goals frequently requires combination therapy with two or more antihypertensive agents. Although the combination of a diuretic and an angiotensin converting enzyme inhibitor (ACEI) is the most commonly used in the clinical practice, the combination of an ACEI and a calcium channel blocker may have an additive antihypertensive effect, a favorable effect on the metabolic profile, and an increased target organ damage protection. The new oral fixed combination manidipine 10 mg/delapril 30 mg has a greater antihypertensive effect than both components of the combination separately, and in non-responders to monotherapy with manidipine or delapril the average reduction of systolic and diastolic BP is 16/10 mmHg. The combination is well tolerated and the observed adverse effects are of the same nature as those observed in patients treated with the components as monotherapy. However, combination therapy reduces the incidence of ankle edema in patients treated with manidipine.     

Trandolapril/verapamil combination in hypertensive diabetic patients

Cardiovascular diseases are directly affected by arterial hypertension. When associated with diabetes mellitus, the potential deleterious effects are well amplified. Both conditions play a central role in the pathogenesis of coronary artery disease, heart failure, stroke, and renal insufficiency. Prevalence of hypertension is much higher among diabetic than non-diabetic patients, and the hypertensive patient is more likely to develop type 2 diabetes. Current international guidelines recommend aggressive reductions in blood pressure (BP) in hypertensive patients with additional risk factors, including cardiovascular risk factors, and emphasize the relevance of intensive reduction in patients with diabetes mellitus; a goal of 130/80 mm Hg is required. To achieve BP target a combination of antihypertensives will be needed, and the use of long-acting drugs that are able to provide 24-hour efficacy with a once-daily dosing confers the noteworthy advantages of compliance improvement and BP variation lessening. Lower dosages of the individual treatments of the combination therapy can be administered for the same antihypertensive efficiency as that attained with high dosages of monotherapy. Angiotensin-converting enzyme inhibitors and calcium-channel blockers as a combination have theoretically compelling advantages for vessel homeostasis. Trandolapril/verapamil sustained release combination has showed beneficial effects on cardiac and renal systems as well as its antihypertensive efficacy, with no metabolic disturbances. This combination can be considered as an effective therapy for the diabetic hypertensive population.     

Olmesartan medoxomil combined with hydrochlorothiazide for the treatment of hypertension

In most patients with hypertension, especially Stage 2 hypertension, adequate control of blood pressure (BP) is only achieved with combination drug therapy. When using combination therapy, antihypertensive agents with complementary mechanisms of action are recommended, for example, an angiotensin receptor blocker (ARB) in combination with hydrochlorothiazide (HCTZ), a beta-blocker + HCTZ, an ACE inhibitor + HCTZ, or a calcium channel blocker + an ACE inhibitor. One such combination is olmesartan medoxomil + HCTZ, which is available as fixed-dose, single-tablet combinations for once-daily administration. In clinical trials, olmesartan medoxomil/HCTZ reduced systolic BP (SBP) and diastolic BP (DBP) to a greater extent than either component as monotherapy. A clinical study in patients with Stage 1 or 2 hypertension showed that olmesartan medoxomil/HCTZ achieved a similar mean reduction in DBP, but a significantly greater mean reduction in SBP and higher rate of BP control (< 140/90 mmHg) than observed with losartan/HCTZ, at US/European-approved starting doses. In a non-inferiority trial, the antihypertensive efficacy of olmesartan medoxomil/HCTZ was comparable to that of atenolol/HCTZ. Furthermore, indirect comparisons have shown that olmesartan medoxomil/HCTZ compares favorably with other antihypertensive combination therapies, including other ARB/HCTZ combinations and amlodipine besylate/ benazepril. Olmesartan medoxomil/HCTZ is generally well tolerated. In conclusion, olmesartan medoxomil/HCTZ is an effective and well-tolerated combination antihypertensive therapy that results in significant BP reductions and BP control in many patients.     

我院门诊抗高血压药物的处方分析

目的 探讨我院门诊处方抗高血压药物使用情况以及发展趋势.方法 抽取我院门诊高血压药物处方进行统计分析.结果 年龄越大,就医高血压的患者越多;抽取处方中,我院门诊抗高血压药应用方式最多的为单一用药;使用频率最高的依次为钙离子拮抗剂(CCB)、血管紧张素Ⅱ受体拮抗剂(ARB)和β受体阻断剂;使用频率最高的品种依次是硝苯地平控释片、琥珀酸美托洛尔缓释片、非洛地平缓释片;联合用药中以CCB+其他等两药联用为主,3种或4种联用的较少.结论 我院抗高血压药物的使用情况基本合理.     

Fixed combination of zofenopril plus hydrochlorothiazide in the management of hypertension: a review of available data

Angiotensin-converting enzyme (ACE) inhibitors effectively interfere with the renin-angiotensin system and exert various beneficial actions on vascular structure and function beyond their blood pressure-lowering effects. Zofenopril, a potent sulphydryl ACE inhibitor, is characterized by high lipophilicity, sustained cardiac ACE inhibition, and antioxidant and tissue protective activities. Its ancillary properties, such as antioxidant activity and cardiovascular (CV) protection, make this drug potentially suitable for the treatment and prevention of certain CV diseases. The Survival of Myocardial Infarction Long term Evaluation trials have demonstrated that the early administration of zofenopril to patients with acute myocardial infarction is associated with a significant reduction in the 6-week occurrence of major CV events in high-risk patients with anterior non-thrombolyzed myocardial infarction. The fixed combination of zofenopril-hydrochlorothiazide (HCTZ) 30/12.5 mg/day is approved for the management of mild-to-moderate hypertension in different European countries. In clinical trials comparing zofenopril-HCTZ with each agent administered as monotherapy, combination therapy was clearly more effective in normalizing blood pressure (BP). In addition, combination therapy provided sustained and consistent BP control over the entire 24 hour dosing interval. The efficacy and safety profile of zofenopril-HCTZ highlights that this combination is a potentially useful addition to currently available therapy for patients with BP inadequately controlled by monotherapy, as well as for patients who require more rapid and intensive BP control.     

Multiple risk factor intervention trial (MRFIT).: VI. Intervention on blood pressure

The MRFIT blood pressure data derived from the Special Intervention (SI) group of men over the first 4 years are presented, and the results of the hypertension treatment program are reviewed. A therapeutic goal diastolic blood pressure (DBP) was established for each man determined to be hypertensive which included men with DBP ?90 mm Hg and men who were already taking antihypertensive drugs. A stepped care protocol was used to guide the drug treatment. At the fourth annual examination, 63.8% of the 5,790 SI men seen had been previously declared hypertensive. The mean baseline blood pressure (BP) for the hypertensive group was 140.3 mm Hg, systolic, and 94.5 mm Hg, diastolic, and at the 48-month visit, the mean BP was 120.7 mm Hg, systolic, and 82.5 mm Hg, diastolic. Of the hypertensive men seen at 48 months, 87.3% were taking antihypertensive drugs, 65.4% were at or below their goal pressure, and 83.5% had a DBP <90 mm Hg. Most men on antihypertensive drug therapy were at protocol Step 1 or Step 2, receiving a diuretic agent alone (32.9%), or in combination with an antiadrenergic drug (40.4%). Data for specific drug regimens are presented. Older men and men with higher BP levels at entry had a better response. The MRFIT BP results, achieved within a context of a multiple-risk-factor intervention program, compare favorably with the results from recently reported trials that focused solely on the treatment of mild hypertension.     

Population trends in antihypertensive drug use: results from the MONICA Augsburg Project 1984 to 1995.

Trends in antihypertensive drug use were assessed among 25- to 64-year-old participants of three independent surveys of the MONICA Augsburg region in 1984/85, 1989/90, and in 1994/95. Despite constant prevalences of hypertension, the percentage of hypertensives taking medication increased over the study period. The latter was mainly due to significant rises in antihypertensive monotherapy. By contrast, the use of combination treatments with two or more agents remained constant; however, although combinations composed of only two drugs were taken more often in 1995, those with three or more agents and fixed-dose preparations decreased substantially. Beta-blockers were most frequently, and with a rising tendency, taken as antihypertensive monotherapy. Newer drug classes like calcium channel blockers and ACE-inhibitors were introduced as monotherapy more hesitantly. Diuretics persisted as the basis of antihypertensive combination therapy. The use of combination therapies containing obsolete drugs, like reserpine, declined significantly with corresponding increases in drug combinations of, in particular, calcium channel blockers or ACE-inhibitors. We conclude that monotherapies account for most of the rising antihypertensive treatment rates and probably reflect intensified therapy of borderline hypertensives. The trends in antihypertensive drug classes and treatment regimens reflect a less rapid adoption of novel therapeutic concepts but a fairly close adherence to national and international guidelines.     

Antihypertensive Mechanism of Orally Administered Acetylcholine in Spontaneously Hypertensive Rats

Acetylcholine (ACh) acts as a neurotransmitter and neuromodulator. A small dose of eggplant powder rich in ACh (equivalent to 22 g fresh eggplant/d) has been shown to reduce blood pressure (BP) in individuals with higher BP. Here, we investigated the mechanisms underlying the antihypertensive effects of low-dose orally administered ACh in spontaneously hypertensive rats (SHRs). The effects of ACh on BP and sympathetic nervous activity (SNA), including lumbar SNA (LSNA) and renal SNA (RSNA), were evaluated by subjecting conscious SHRs to a telemetry method. Single oral administration of ACh decreased LSNA and lowered BP. Repeated oral administration of ACh for 30 d decreased RSNA and suppressed the elevated BP. Noradrenaline levels in the urine also decreased. However, vagotomy and co-administration of M3 muscarinic ACh receptor antagonist reversed the BP-lowering effect; the dynamics of non-absorbable orally administered ACh was revealed using stable isotope-labeled ACh. In conclusion, ACh acts on the gastrointestinal M3 muscarinic ACh receptor to increase afferent vagal nerve activity, which decreases SNA by autonomic reflex, suppressing noradrenaline release and lowering BP. This study suggests the use of exogenous ACh as an antihypertensive food supplement for controlling the autonomic nervous system, without absorption into the blood.     

盐酸羟考酮控释片联合加巴喷丁治疗癌性神经性疼痛疗效分析

目的：观察盐酸羟考酮控释片联合加巴喷丁治疗癌症神经病理性疼痛的疗效及不良反应。方法：单药组盐酸羟考酮控释20 mg/片，口服每12 h 1次。联合组盐酸羟考酮控释20 mg/片，口服每12 h 1次；加巴喷丁胶囊300 mg/片，口服每12 h 1次。治疗2周后评价疗效。结果：单药组和联合组总有效率分别为70.83%（17/24）、91.67%（22/24），比较差异有统计学意义（P〈0.05）。患者不良反应主要是便秘，恶心呕吐。结论：盐酸羟考酮控释片联合加巴喷丁治疗癌症神经病理性疼痛明显优于单药盐酸羟考酮控释片方案，两种药物联合使用相互取长补短，止痛效果好，安全有效并且不良反应无明显增加，值得进一步深入研究和临床推广使用。     

Evaluating the interaction between the therapy and the treatment in clinical trials by the propensity score weighting method

In clinical trials for antihypertensive drugs, a combination therapy trial and a monotherapy trial are often conducted simultaneously. In this situation, it can be a clinical concern to know the difference of the safety or efficacy of the new drug between the two therapies, in other words, to investigate the interaction between the therapy (monotherapy or combination therapy) and the treatment (test or control). However, because patients are often registered in either of these trials on the basis of their background characteristics, specific patients may be selected to participate in the monotherapy trial or combination therapy trial and not chosen at random, whereas the treatment is assigned randomly in each trial after registration. If this fact is not considered, the statistical analysis of the interaction may be biased. In this paper, we aim to evaluate the interaction between the two aforementioned factors by adjusting for covariates that may affect registration in the two trials. For this purpose, we apply the propensity score weighting method to suit the problem. The propensity score in this case is decomposed into the usual propensity score for the registration and the assignment probability for the random treatment assignment on the basis of their two-stage structure. We also discuss the augmented estimator known as the doubly robust estimator. In addition, we apply this method to data of a clinical trial for an antihypertensive drug that was conducted in Japan and conduct a simulation study to evaluate the performance of our proposed method.     

Carvedilol in hypertension treatment

Although beta-blockers have been previously shown to effectively reduce blood pressure (BP) and have been used for hypertension treatment for over 40 years, their effect on cardiovascular morbidity and mortality in hypertensive patients remains controversial and its use in uncomplicated hypertension is currently under debate. However, data on the above field derive mainly from studies which were conducted with older agents, such as atenolol and metoprolol, while considerable pharamacokinetic and pharmacodynamic heterogeneity is present within the class of beta-blockers. Carvedilol, a vasodilating non-cardioselective beta-blocker, is a compound that seems to give the opportunity to the clinician to use a cardioprotective agent without the concerning hemodynamic and metabolic actions of traditional beta-blocker therapy. In contrast with conventional beta-blockers, carvedilol maintains cardiac output, has a less extended effect on heart rate and reduces BP by decreasing vascular resistance. Further, several studies has shown that carvedilol has a beneficial or at least neutral effect on metabolic parameters, such as glycemic control, insulin sensitivity, and lipid metabolism, suggesting that they could be used in subjects with the metabolic syndrome or diabetes without negative consequences. This article summarizes the distinct pharmacologic, hemodynamic, and metabolic properties of carvedilol in relation to conventional beta-blockers, attempting to examine the potential use of this agent for hypertension treatment.     

Cognitive impairment and nocturnal blood pressure fall in treated elderly hypertensives

Objectives We investigated the association between the fall of nocturnal blood pressure (BP) and cognitive impairment in elderly subjects. Methods The study was a cross-sectional survey of 204 elderly subjects who had no cerebrovasucular episodes. Ambulatory BP monitoring and assessments of cognitive functions using the Mini-Mental State Examination (MMSE) were performed at the subjects’ homes. We classified, the subjects treated with antihypertensive drugs into three groups: non-dippers (nocturnal fall<10% of the mean day diastolic BP; n=51), normal dippers (10% to less than 20%; n=58), and extreme dippers (20% or more; n=17). The subjects not treated with antihypertensive drugs were also classified as non-dippers (n=40), normal dippers (n=24), and extreme dippers (n=14). Results The mean age of participants was 75.2±7.2 years, and 126 (61.7%) were being treated with antihypertensive drugs. In the group of antihypertensive drug users, the number with MMSE≤23 was 30 and the adjusted odds ratio for cognitive impairment in those with an extreme dip in diastolic BP (DBP) was 4.18 (95% CI, 1.07–16.40) in reference to the normal dippers. In contrast, no association was observed between cognitive function and nocturnal BP fall in the group no using antihypertensive drugs. Conclusions Cognitive impairment was associated with an extreme dip in DBP in the antihypertensive drug users only. It remains to be seen whether careful monitoring of nighttime BP as well as daytime BP may reduce the risk of cognitive impairment in antihypertensive drug users.     

Antihypertensive regimen and quality of life in a disadvantaged population

A sample of family practice patients with essential hypertension (N = 106) who were predominantly elderly, black, and disadvantaged were studied to determine psychosocial and physiological side effects from antihypertensive therapy regimens. Patients were assigned randomly to one of four monotherapy treatment groups: Hydrochlorothiazide-triamterene, metoprolol, captopril, and methyldopa. These medications have been reported to have contrasting effects on quality of life. Measurements of quality of life, physical symptoms, and depression taken at baseline and during therapy revealed few significant changes in these indicators. Changes in mean levels of diastolic and systolic hypertension over time were clinically and statistically significant. Findings raise issues regarding medication effectiveness and cost given the disadvantaged population studied.     

The practice guideline 'Hypertension' (third revision) from the Dutch College of General Practitioners; a response from the perspective of general practice

In the revised practice guideline on hypertension from the Dutch College of General Practitioners, some changes have been made in the areas of diagnosis and therapy in comparison to the previous edition. Finding people with hypertension is a major goal for the prevention of cardiovascular disease. A systolic blood pressure > 140 mmHg (> 160 mmHg in patients > 60 years) necessitates non-pharmaceutical advice and antihypertensive therapy with diuretics, beta-blockers, angiotensin-converting-enzyme (ACE) inhibitors or calcium antagonists, either as monotherapy or in combination. In view of the ever-increasing importance of ACE inhibitors in antihypertensive therapy, we expect that the next revision of the practice guideline will soon be necessary.     

Atenolol or metoprolol as beta-blocker in the treatment of hypertension

Recently the guideline committee of the Dutch College of General Practitioners advocated the use of metoprolol instead of atenolol in patients with an indication for beta-blockers. This recommendation was based on a recent meta-analysis in The Lancet in which no effect was observed in favour ofatenolol compared with placebo on all-cause mortality, cardiovascular mortality and myocardial infarction. Atenolol also had a higher total mortality and stroke risk compared with other antihypertensive agents. Apart from the presence of statistical heterogeneity and the inappropriate use of a fixed-effect model, the studies referred to in this meta-analysis were also clinically heterogeneous. Furthermore, in most studies, only older patients were included. In older patients with hypertension, it is known that beta-blockers are less effective than diuretics or calcium antagonists. Comparative trials between atenolol and metoprolol in the treatment of hypertension have not been performed with regard to cardiovascular endpoints. We conclude that there is no evidence that atenolol is better or worse than metoprolol in the treatment of the hypertensive patient. For the treatment of patients with heart failure, however, lipophilic beta-blockers such as metoprolol may be preferred, as these drugs have been more thoroughly evaluated for this indication.     

Managing hypertension in diabetic patients--focus on trandolapril/verapamil combination

Hypertensive diabetes individuals are at higher risk for cardiovascular events and progression to end stage renal disease. Several well conducted clinical trials indicate that aggressive treatment of hypertension in individual with diabetes reduces these complications. Combinations of two or more antihypertensive drugs are frequently required to reach the target blood pressure and to improve the cardiovascular and renal outcomes in these patients. There are physiological and clinical rationales for renin-angiotensin system blockade in hypertensive diabetics. Trandolapril/verapamil sustained released (SR) is a fixed-dose combination of trandolapril and a sustained release formulation of verapamil and indicated in treatment of hypertension in patients who require more than one drug to reach target blood pressure. The antihypertensive efficacy of trandolapril/verapamil SR has been evaluated extensively in large trials. In the INVEST trial, a verapamil SR-based treatment strategy that included trandolapril in most patients was effective in reducing the primary outcome in hypertensive patients with coronary artery disease. The new onset of diabetes was also significantly lower in the verapamil SR/trandolapril treatment group in comparison with those on the atenolol/hydroclorothiazide treatment group. The BErgamo NEphrologic Diabetes Complications Trial (BENEDICT) documented that in hypertensive diabetes and normoalbuminuria, trandolapril plus verapamil or trandolapril alone delayed the onset of microalbuminuria independent of their blood pressure-reducing effect. Thus, trandolapril/verapamil is an effective option for treatment of hypertensive diabetes patients requiring more than one agent to achieve target blood pressure.     

Recognition of illness associated with exposure to chemical agents--United States, 2003

Since September 11, 2001, concern has increased about potential terrorist attacks involving the use of chemical agents. In addition, recent cases involving intentional or inadvertent contamination of food with chemicals have highlighted the need for health-care providers and public health officials to be alert for patients in their communities who have signs and symptoms consistent with chemical exposures. For example, in February 2003, a Michigan supermarket worker was charged with intentionally contaminating 200 lbs. of meat with a nicotine-containing insecticide. Although intentional release of chemical agents might be an overt event (i.e., one whose nature reveals itself), such as release of a nerve agent in a subway or a large explosion of a chemical container, a chemical release might instead be a covert event (i.e., an unrecognized release in which the presence of ill persons might be the first sign of an exposure), such as deliberate contamination of food, water, or a consumer product. To increase the likelihood that health-care providers will recognize a chemical-release-related illness and that public health authorities will implement the appropriate emergency response and public health actions, CDC identified examples of chemical-induced illness and created appropriate guidance for health-care providers and public health personnel. This report summarizes the epidemiologic clues and clinical signs or patterns of illness that might suggest covert release of a chemical agent. CDC is working to develop national surveillance capabilities for detecting chemical-release-related illnesses.     

降压0号治疗老年单纯收缩期高血压的疗效和安全性评价

[目的]评价降压0号治疗老年单纯收缩期高血压的疗效与安全性。[方法]采用干预研究的方法,将510例轻中度老年单纯收缩期高血压患者分为0号组319例,服用降压0号控制血压;常规组191例,根据医生建议及自身需求选择降压药物。两组均随访观察12个月,记录血压水平、不良反应及实验室检查结果。[结果]随访12个月后服用降压0号者降压有效率为99.1%,常规组为96.8%,两组差异无统计学意义(χ2=1.038,P=0.308)。服用降压0号者血压达标率为92.0%,常规组为78.7%,两组差异有统计学意义(χ2=15.096,P﹤0.001)。0号组有14人报告不良反应,不良反应率为4.4%,未发生严重不良反应。服用降压0号对患者血脂、血糖、血清尿酸、血清钾水平无明显影响。[结论]应用降压0号治疗轻中度老年单纯收缩期高血压效果较好,无严重不良反应。     

Serum 25-hydroxyvitamin D3, parathyroid hormone and blood pressure in an elderly cohort from Germany: a cross-sectional study

Background

Although several studies indicate a link between vitamin D status and blood pressure (BP), the results are inconsistent. The purpose of this study is to investigate whether in predominantly non-obese elderly people without vitamin D deficiency or very high intact parathyroid hormone (iPTH) levels serum 25-hydroxyvitamin D₃ [25(OH)D₃] and iPTH are independently associated with BP.

Methods

Cross-sectional data of 132 non-institutionalised subjects (90 women and 42 men, aged 66- 96 years) from Giessen, Germany, were analysed. Serum 25(OH)D₃ and iPTH were measured by an electrochemiluminescence immunoassay and BP was determined with a sphygmomanometer. We performed univariate and multiple regression analyses to examine the influence of 25(OH)D₃ and iPTH on BP with adjustments for age, body composition and lifestyle factors.

Results

While iPTH had no impact on BP, 25(OH)D₃ was negatively associated with systolic BP in men, but not in women. After splitting the cohort into antihypertensive medication users and non-users, 25(OH)D₃ was a significant predictor for systolic and diastolic BP only in men not receiving antihypertensive medicine, even after multiple adjustment. Adjustment for 25(OH)D₃ resulted in an inverse association of iPTH with diastolic BP also only in men without intake of antihypertensive medicine.

Conclusions

In elderly men without vitamin D deficiency and not taking antihypertensive medicine, 25(OH)D₃ may be a negative determinant of BP, independent of iPTH, body composition and lifestyle factors. Furthermore, iPTH may be an independent negative determinant of diastolic BP in men not taking antihypertensive medicine.