Beneficial cardiometabolic actions of telmisartan plus amlodipine therapy in elderly patients with poorly controlled hypertension

Background

There is a growing body of evidence that blood pressure (BP) level is one of the major determinants of cardiovascular morbidity and mortality in individuals, including elderly people. However, to achieve a target BP level in the elderly is more difficult compared with patients aged <65 years. Current guidelines recommend combination drug therapy with different modes of action for the treatment of elderly patients with moderate hypertension (HT). However, the optimal combination regimen is not well established in elderly HT.

Hypothesis

We hypothesized that combination therapy of telmisartan plus amlodipine would exert favorable cardiometabolic actions in elderly HT.

Methods

Seventeen elderly patients with essential HT who failed to achieve a target home BP level with treatment of 5 mg amlodipine plus 80 mg valsartan or 8 mg candesartan for at least 2 months were enrolled. Then the patients were assigned to replace their valsartan or candesartan with 40 mg telmisartan. The subjects were instructed to measure their own BP at home every day during the study periods.

Results

Replacement of valsartan or candesartan by telmisartan in amlodipine‐treated elderly hypertensive patients showed a significant reduction in morning home systolic BP and evening home systolic and diastolic BP at 12 weeks. Switching to telmisartan significantly increased serum adiponectin level.

Conclusions

Our present study suggests that combination therapy with telmisartan plus amlodipine may exert more beneficial cardiometabolic effects in elderly patients with HT compared with valsartan or candesartan plus amlodipine treatment. © 2011 Wiley Periodicals, Inc. This work was supported in part by Grants of Collaboration with Venture Companies Project from the Ministry of Education, Culture, Sports, Science and Technology, Japan (to S.Y.). The authors have no other funding, financial relationships, or conflicts of interest to disclose.     

替米沙坦对高血压合并糖尿病患者血清脂联素的影响

目的观察替米沙坦治疗前、后高血压合并糖尿病患者血清脂联素水平的变化。方法将50名门诊高血压合并糖尿病病人分为替米沙坦和氨氯地平两组。观察治疗前及治疗10周后患者血压、脂联素及血糖、胰岛素变化。结果与治疗前相比,替米沙坦组与氨氯地平组收缩压和舒张压均显著降低(P<0.01),替米沙坦组血清脂联素水平较治疗前显著升高(P<0.01),血糖、胰岛素和胰岛素抵抗较治疗前显著降低(P<0.01);氨氯地平组治疗前后血清脂联素、血糖、胰岛素和胰岛素抵抗无明显改变(P>0.05)。结论与氨氯地平相比,替米沙坦在降压的同时,显著增高了血清脂联素水平并显著改善胰岛素抵抗,显示其具有降压外良好的代谢效应。     

Effects of bedtime vs. morning administration of the long-acting lipophilic angiotensin-converting enzyme inhibitor trandolapril on morning blood pressure in hypertensive patients.

Cardiovascular events occur most frequently in the morning. To study the effects of the long-acting lipophilic angiotensin-converting enzyme (ACE) inhibitor trandolapril on morning blood pressure (BP), we performed ambulatory BP monitoring (ABPM) before and after administration of trandolapril just before going to bed (bedtime-administered group: n=17) or in the morning (morning-administered group: n=20) in 37 hypertensive patients. Both sets of ABPM data were available in 30 patients. The 24-h systolic BP (SBP) levels were significantly decreased by 7.2 mmHg in the morning-administered group (p=0.02) and by 5.2 mmHg in the bedtime-administered group (p=0.04). In the bedtime-administered group, prewaking SBP (the average of the 2-h SBP values just before waking) and morning SBP (the average of the 2-h SBP values just after waking) were significantly decreased by 11 mmHg (p=0.005) and by 8.4 mmHg (p=0.03), respectively. On the other hand, in the morning-administered group, the reduction of prewaking SBP (3.9 mmHg, n.s.) and morning SBP (6.6 mmHg, n.s.) did not reach the level of statistical significance. However, the differences in the reductions of prewaking and morning SBPs between the two groups were not statistically significant. There was no additional reduction of the nighttime lowest BP in either administration group. In conclusion, bedtime administration of the long-acting ACE inhibitor trandolapril seems to be a safe and effective means of controlling morning BP in hypertensive patients without an excessive fall in nocturnal BP.     

Effect of telmisartan on paroxysmal atrial fibrillation recurrence in hypertensive patients with normal or increased left atrial size

Background:

Hypertension is the most prevalent and potentially modifiable risk factor for atrial fibrillation (AF). In a previous secondary prevention study, the authors observed that the angiotensin II receptor blocker telmisartan was more effective than the calcium channel blocker amlodipine in preventing AF relapse in hypertensive patients with normal atrial size.

Hypothesis:

Telmisartan may be more effective than amlodipine in preventing AF recurrence in hypertensive patients with paroxysmal AF and normal or increased left atrial dimension (LAD).

Methods:

The authors assigned 378 mild hypertensive outpatients in sinus rhythm, but with ≥2 episodes of AF in the previous 6 months, to 1 of 2 groups. Group 1 comprised patients with LAD <40 mm in females and <45 mm in males. Group 2 comprised patients with LAD >40 mm and <45 mm in females and >45 mm and <50 mm in males. In both groups, patients were randomly treated with telmisartan or amlodipine for 1 year.

Results:

Systolic and diastolic blood pressure were similarly reduced by telmisartan and amlodipine in both groups. The AF recurrence rate was significantly lower in the telmisartan‐treated patients than in the amlodipine‐treated patients in both group 1 (12 vs 39, P < 0.01) and group 2 (40 vs 59, P < 0.05). Under telmisartan, the AF recurrence rate was significantly lower in group 1 than in group 2 (12.9% vs 42.1%, P < 0.05). Time to a first AF relapse was significantly longer with telmisartan than with amlodipine in both group 1 (176 ± 94 days vs 74 ± 61 days, P < 0.05) and group 2 (119 ± 65 days vs 38 ± 35 days, P < 0.05).

Conclusions:

Telmisartan was more effective than amlodipine in preventing AF recurrences in hypertensive patients with paroxysmal AF. Clin. Cardiol. 2012 DOI: 10.1002/clc.21994 The authors have no funding, financial relationships, or conflicts of interest to disclose.     

Effect of telmisartan and amlodipine on home blood pressure by monitoring newly developed telemedicine system: monitoring test by using telemedicine. Telmisartan's effect on home blood pressure (TelTelbosu)

We have developed a new home blood pressure (BP) monitoring system by using cellular telephone and the Internet. All data of home BP and pulse rate were directly collected by I-converter date collecting system and sent online to a main server constructed in a central data center. The home doctor can monitor the exercise data of each patient by using this system. This home BP monitoring system was directly connected to the Internet by using application service provider technology (ASP). Anytime and anywhere, each patient can check the changes of these parameters by themselves by using cellular telephone and/or the Internet. The average of the data was calculated and demonstrated online. In real time, all data were monitored and sent to the home doctor's office. In the present study, we tried to use this monitoring system to compare the effect of some antihypertensive drugs on home BP. To compare the effects of telmisartan (TEL) and amlodipine (AM) on home BP, home BP was monitored for eight weeks using this telemedicine system. The target point of office BP was 140/90 mmHg or less. After two weeks control period, telmisartan (TEL group: 20-80 mg/day, n = 21) or amlodipine (AM group: 2.5-10 mg/day, n = 19) was orally administrated once a day in the morning. There was no significant difference of office BP between these two groups. Systolic home BP was significantly decreased from 144 +/- 4 to 134 +/- 3 mmHg (TEL group) and from 143 +/- 4 to 135 +/- 3 mmHg (AM group), respectively. There was no significant difference in the changes of home BP in the morning between groups (eight weeks home systolic BP reduction, TEL: 15 +/- 2 mmHg, AM: 13 +/- 2 mmHg). However the reduction of home BP in the evening in TEL group was significantly bigger than AM group (eight weeks home systolic BP reduction, TEL: 13 +/- 3 vs. AM: 6 +/- 3 mmHg). From these data, we concluded that there is a big difference on the effects of antihypertensive agents on diurnal variation and 24hr overall BP variability in home BP. TEL has a good effect on home BP for 24 hours compared to AM. This telemedicine system has a great advantage in monitoriong home BP correctly in hypertensive patients.     

A comparison of the efficacies and duration of action of the angiotensin II receptor blockers telmisartan and amlodipine

OBJECTIVES: To compare the antihypertensive effects and duration of action of the angiotensin II receptor antagonist, telmisartan, amlodipine, and placebo in patients with mild-to-moderate hypertension using both conventional clinic blood pressures and ambulatory blood pressure monitoring (ABPM). METHODS: After a 4-week single-blind, placebo run-in period, qualifying patients were randomly allocated in double-blind manner to be administered 40 mg telmisartan (n = 73; increased to 80 and 120 mg as necessary for patients whose diastolic blood pressure (DBP) remained > 90 mmHg); 5 mg amlodipine (n = 78; titrated to 5 mg and titrated to 10 mg for patients whose DBP remained > 90 mmHg); or placebo (n = 81). ABPM was performed at the end of the baseline period and again at the end of 12 weeks of double-blind treatment. RESULTS: Telmisartan and amlodipine treatments significantly decreased trough supine systolic blood pressure and DBP (P < 0.001, measured conventionally) to a similar extent (by 13.1/7.1 and 14.0/7.1 mmHg, respectively, at the end of 12 weeks' treatment) compared with placebo. Both drugs also significantly reduced 24 h mean systolic blood pressures and DBP compared with placebo (P < 0.0001), measured using ABPM, maintaining control of blood pressure throughout the dosing period. Reductions in DBP with telmisartan were greater (P < 0.05) than those with amlodipine during the night-time interval and the last 4 h of the dosing period. Twenty-four-hour mean ABPM DBP < 85 mmHg were observed in 71% of telmisartan patients and in 55% of patients administered amlodipine. In addition, heart rates in patients treated with telmisartan were lower than heart rates in those treated with amlodipine during the final 4 h of the dosing period (P = 0.0003) and during the morning interval (P = 0.005). Generally, both telmisartan and amlodipine were well tolerated, however, drug-related edema occurred significantly more commonly (P < 0.05) among the patients administered amlodipine than it did among patients administered either telmisartan or placebo. CONCLUSIONS: Clinic blood pressure measurements detected no difference between the antihypertensive effects and durations of action of telmisartan and amlodipine, both agents producing statistically significant reductions compared with placebo. ABPM measurements, however, revealed differences between the efficacies at specific time points within the dosing periods. These findings highlight the potential importance of the use of ABPM for evaluating and comparing efficacies of antihypertensive agents.     

24-Hour and Nighttime Blood Pressures in Type 2 Diabetic Hypertensive Patients Following Morning or Evening Administration of Olmesartan

Ambulatory blood pressure monitoring (ABPM) allows determining of the nocturnal blood pressure fall (NBPF). An NBPF below 10% (nondipper pattern) has been related to increased cardiovascular risk, and it is a common finding in type 2 diabetic hypertensive patients. The authors evaluated the impact on 24-hour blood pressure, NBPF, and albuminuria of olmesartan 40 mg, administered in a morning- vs a nocturnal-based dosing scheme, in type 2 diabetic patients with newly diagnosed hypertension. Using a crossover design, 40 patients (42.1% men) received olmesartan 40 mg once daily at wake up or bedtime for 8 weeks. Patients underwent 24-hour ABPM at baseline and at weeks 8 and 16, and albumin to creatinine ratio was measured at baseline and 8 weeks. Night systolic blood pressure (BP) ( P =.007) and mean BP ( P =.012) were significantly reduced following the bedtime dose, compared with morning dosing. Night BP fall (%) was significantly reduced by bedtime dosing, compared with morning dosing ( P =.0001). No differences were seen for urinary albumin excretion between both arms at week 8. Without affecting 24-hour BP control, night dosing of olmesartan increases nocturnal BP fall significantly more than conventional morning dosing, increasing the number of dipper diabetic hypertensive patients.     

The bedtime administration of doxazosin controls morning hypertension and albuminuria in patients with type-2 diabetes: evaluation using home-based blood pressure measurements

The control of high blood pressure (BP) after awakening in the morning (morning hypertension) as determined by home BP (HBP), as well as BP control throughout the day, may prevent diabetic vascular complications. We examined the effect of an alpha-adrenergic blocker (doxazosin) on BP measurements taken by HBP after awakening and during clinic visits (CBP) in 50 patients with type-2 diabetes and morning hypertension. We evaluated the urinary albumin excretion rate as an indicator of nephropathy. Doxazosin was taken orally once at bedtime for 1 to 3 months. The mean (+/- SD) dose was 2.9 +/- 2.1 mg/day (1 to 8 mg/day). The BP was measured monthly at the clinic during the day and at home after awakening in the morning. In this short-term trial (2.8 +/- 0.4 months), the systolic HBP decreased significantly from 164 +/- 17 mmHg before treatment to 146 +/- 19 mmHg after treatment, and the diastolic HBP decreased significantly from 85 +/- 14 mmHg before treatment to 80 +/- 9 mmHg after treatment. The systolic, but not the diastolic CBP, decreased significantly after treatment. There was no significant difference in the systolic or diastolic values between the HBP and the CBP after treatment. The percentage change in the systolic HBP after treatment was three times greater than for the systolic CBP. The median (interquartile) urinary albumin excretion rate decreased significantly (P < 0.001) from 62 (25-203) mg/g creatinine before treatment to 19 (9-76) mg/g creatinine after treatment. On multiple regression analysis, the decrease in the systolic HBP with treatment positively correlated with the reduction in urinary excretion of albumin. The control of morning hypertension reduced the albuminuria found in both untreated and treated hypertensive patients with type-2 diabetes. Bedtime administration of doxazosin appears to be safe and effective in reducing morning hypertension as measured by HBP. This finding also demonstrates that HBP taken in the morning has a stronger predictive power for the albuminuria level than does CBP.     

Exponential–Exponential Cosine Fitting of Blood Pressure Decay Induced by a Long‐Acting Calcium Blocker,Amlodipine, Using Home Blood Pressure Measurement

Blood pressure (BP) decay data obtained from home BP measurements in six patients with uncomplicated essential hypertension treated with a calcium blocker, amlodipine, were fitted to an exponential–exponential cosine function to determine the characteristic BP‐lowering effects of amlodipine. An exponential–exponential cosine function fitted the morning and night systolic BP (sBP) decay data better than a simple exponential function. From the coefficients of the equation, the estimated BP lowering, time constant for BP decay and BP oscillation induced by amlodipine for morning and night sBP were approximately 23 and 25 mmHg, 10 and 6 days, and 12 and 12 mmHg, respectively. Diastolic BP showed a similar fitting though the fitting was weaker. The fitting results indicate that the BP decay, especially the sBP decay, induced by amlodipine occurred in an oscillative fashion, and the present analysis using home BP data may provide clinically useful information about the characteristic effects of amlodipine.     

The Bedtime Administration of Doxazosin Controls Morning Hypertension and Albuminuria in Patients with Type-2 Diabetes: Evaluation Using Home-Based Blood Pressure Measurements

The control of high blood pressure (BP) after awakening in the morning (morning hypertension) as determined by home BP (HBP), as well as BP control throughout the day, may prevent diabetic vascular complications. We examined the effect of an α-adrenergic blocker (doxazosin) on BP measurements taken by HBP after awakening and during clinic visits (CBP) in 50 patients with type-2 diabetes and morning hypertension. We evaluated the urinary albumin excretion rate as an indicator of nephropathy. Doxazosin was taken orally once at bedtime for 1 to 3 months. The mean (± SD) dose was 2.9 ± 2.1 mg/day (1 to 8 mg/day). The BP was measured monthly at the clinic during the day and at home after awakening in the morning. In this short-term trial (2.8 ± 0.4 months), the systolic HBP decreased significantly from 164 ± 17 mmHg before treatment to 146 ± 19 mmHg after treatment, and the diastolic HBP decreased significantly from 85 ± 14 mmHg before treatment to 80 ± 9 mmHg after treatment. The systolic, but not the diastolic CBP, decreased significantly after treatment. There was no significant difference in the systolic or diastolic values between the HBP and the CBP after treatment. The percentage change in the systolic HBP after treatment was three times greater than for the systolic CBP. The median (interquartile) urinary albumin excretion rate decreased significantly (P < 0.001) from 62 (25–203) mg/g creatinine before treatment to 19 (9–76) mg/g creatinine after treatment. On multiple regression analysis, the decrease in the systolic HBP with treatment positively correlated with the reduction in urinary excretion of albumin. The control of morning hypertension reduced the albuminuria found in both untreated and treated hypertensive patients with type-2 diabetes. Bedtime administration of doxazosin appears to be safe and effective in reducing morning hypertension as measured by HBP. This finding also demonstrates that HBP taken in the morning has a stronger predictive power for the albuminuria level than does CBP.     

动态血压评价不同时间服用氨氯地平的降压效应

目的：研究服药时间对氨氯地平降压效应的影响。方法：采用随机、开放、自身对照的研究方法。高血压患者经二周安慰剂导入期,服安慰剂末诊室血压在９５￣１１５ｍｍＨｇ者入选,随机于７：００或２１：００予５ｍｇ氨氯地平治疗,二周后降压不满意者加至１０ｍｇ,服用氨氯地平六周后,交换服药时间再服六周。服安慰剂末、早晨给药六周、睡前给药六周后分别行动态血压监测,分析其Ｔ／Ｐ、收缩压峰值,舒张压峰值,夜间收缩压和舒张     

Clinical assessment of early morning blood pressure in patients with hypertension

In most individuals with hypertension, blood pressure (BP) shows a moderate to marked increase around the time of awakening, which has been linked to increases in cardiovascular complications occurring at this time of day. Many antihypertensive agents do not adequately control early morning BP, particularly when administered once daily in the morning. Points to consider in selecting an effective antihypertensive drug include pharmacokinetics and formulation of the agent and timing of administration. Agents with long pharmacologic half-lives, such as the angiotensin II receptor blocker telmisartan, the calcium antagonist amlodipine, and the beta-blocker bisoprolol, are examples of antihypertensive drugs with demonstrated efficacy in controlling early morning BP. Bedtime administration of chronotherapeutic preparations is also effective for controlling early morning BP. Given the association between early morning BP and cardiovascular risk, future clinical trials should focus on the efficacy of antihypertensive drugs during this important period of risk.     

Differing Effects of Aliskiren/Amlodipine Combination and High‐Dose Amlodipine Monotherapy on Ambulatory Blood Pressure and Target Organ Protection

The aim of this study was to compare an aliskiren/amlodipine combination with high‐dose amlodipine monotherapy on ambulatory blood pressure monitoring (ABPM) and organ protection. The study was a prospective, randomized, multicenter, open‐label trial in elderly essential hypertensive patients. A total of 105 patients with clinic BP (CBP) ≥140/90 mm Hg with amlodipine 5 mg were randomly allocated to aliskiren (150–300 mg)/amlodipine (5 mg) (ALI/AML group, n=53) or high‐dose amlodipine (10 mg) (h‐dAML group, n=52) and treated for 16 weeks. Each patient's CBP, ABPM, urine albumin‐to‐creatinine ratio (UACR), and brachial‐ankle pulse wave velocity (baPWV) were measured at baseline and at the end of the study. The ALI/AML and h‐dAML groups showed similarly reduced mean 24‐hour SBP, daytime SBP, nighttime SBP, and baPWV. However, UACR reduction was significantly greater in the ALI/AML group (P=.02). ALI/AML was significantly less effective in reducing early‐morning BP (P=.002) and morning BP surge (P=.001) compared with h‐dAML.     

Is ambulatory blood pressure monitoring reliable in hypertensive patients with atrial fibrillation?]

Atrial fibrillation (AF) is commonly seen in patients (pts) with systemic hypertension. They are usually excluded from ambulatory blood pressure monitoring (ABPM) because its accuracy is unknown. The aim of our study was to determine if ABPM can be used to assess 24 hour BP in pts with AF. We included hypertensive pts with chronic (> 6 months) AF, controlled heart rate (60-100 c.p.m), under therapy and also hypertensive pts in sinus rhythm (control group--CG). They were submitted to 24 hour ABPM (Spacelabs 90207). Manual BP with a standard mercury sphygmomanometer was taken during 3 visits (office BP) and on the day of ambulatory monitoring. Simultaneous measurements with a T-Tube were also performed. Thirty pts with chronic AF (63% males), mean age 73 +/- 8 years (52-85) and 18 pts in sinus rhythm (CG) were studied. The age, gender, office BP, ambulatory BP and proportion of successful measurements was similar in the 2 groups. In CG systolic and diastolic office BP did not differ from day ambulatory BP (148 +/- 14/84 +/- 7 vs 138 +/- 18/76 +/- 11 mmHg) and the same was seen in pts in AF (table). In this group, only the systolic BP taken immediately before the ambulatory device was put on, was significantly different from day ambulatory BP (148 +/- 21 vs 137 +/- 19 mmHg, p = 0.04). The proportion of successful measurements in AF group was 94 +/- 8 (65-98) with 93% > 80%. In 64 simultaneous measurements the differences were 6 +/- 5 and 5 +/- 5 mmHg for systolic and diastolic BP. Casual and ambulatory heart rate was also similar in the two groups (76 +/- 7/76 +/- 12--AF group; 78 +/- 10/78 +/- 8--control group). In conclusion, this study demonstrates that ABPM can be used to assess BP in patients with atrial fibrillation. There was a high percentage of successful recordings (93%). As in patients in sinus rhythm, there was no significantly difference in mean office blood pressure and daytime ambulatory blood pressure.     

Therapeutic effects of evening administration of guanabenz and clonidine on morning hypertension: evaluation using home-based blood pressure measurements

OBJECTIVE: To clarify the effects of bedtime administration of the centrally acting alpha(2)-agonists, guanabenz and clonidine, on morning hypertension. METHODS: Patients with morning hypertension were assigned to receive once-daily evening administration of guanabenz (2 mg/day, n = 81; 4 mg/day, n = 2) or clonidine (75 microg/day, n = 40; 150 microg/day, n = 10) for 4 weeks, and the blood pressure (BP)-lowering effects of these drugs in the morning and evening were evaluated by assessing self-monitored BP in the home environment. The subjects were then subdivided into different groups according to their evening BP, and the effects of guanabenz and clonidine on evening BP were evaluated further for each group. In addition, as a substitute for the trough/peak ratio, the evening/morning (E/M) ratio was calculated to assess the duration of action of the two alpha(2)-agonists. RESULTS: Evening dosing with guanabenz or clonidine lowered morning BP significantly. Both drugs decreased evening BP in the subgroup of subjects with a high evening BP, but not in those with a normal evening BP. The individual E/M ratios for guanabenz, but not for clonidine, were significantly greater in those with a high evening BP than in those with a normal evening BP. In the early treatment period, treatment with guanabenz resulted in a higher diastolic E/M ratio in those subjects with a high evening diastolic BP than did treatment with clonidine. CONCLUSION: The results suggest that evening administration of the central alpha(2)-agonists guanabenz and clonidine effectively suppresses the morning BP elevation in treated hypertensive patients.     

Comparison of valsartan and amlodipine on ambulatory and morning blood pressure in hypertensive patients

BACKGROUND: Cardiovascular events occur most frequently in the morning. We aimed to study the effects of monotherapy with the long-acting angiotensin II receptor blocker valsartan compared with the long-acting calcium antagonist amlodipine on ambulatory and morning blood pressure (BP). METHODS: We performed ambulatory BP monitoring before and after once-daily dose of valsartan (valsartan group, n = 38) and amlodipine (amlodipine group, n = 38) therapy in 76 hypertensive patients. To achieve the target BP of < or =140/90 mm Hg, valsartan was titrated from 40 mg/day to 160 mg/day (mean dose 124 mg/day) and amlodipine was titrated from 2.5 mg/day to 10 mg/day (mean dose 6.4 mg/day). RESULTS: Both drugs significantly reduced clinic and 24-h systolic BP (SBP) and diastolic BP (DBP) (P <.002). However, the antihypertensive effect of amlodipine was superior to that of valsartan in clinical SBP (-26 mm Hg v -13 mm Hg, P =.001) and 24-h SBP (-14 mm Hg v -7 mm Hg, P =.008). In addition, morning SBP was significantly reduced by amlodipine from 156 to 142 mm Hg (P <.001) but not by valsartan. Both agents reduced lowest night SBP to a similar extent (amlodipine 121 to 112 mm Hg, P <.001; valsartan 123 to 114 mm Hg, P <.002). Reduction in morning SBP surge (morning SBP minus lowest night SBP) was significantly greater in patients treated with amlodipine compared with those treated with valsartan (-6.1 mm Hg v +4.5 mm Hg, P <.02). CONCLUSIONS: Amlodipine monotherapy was more effective than valsartan monotherapy in controlling 24-h ambulatory BP and morning BP in hypertensive patients.     

氨氯地平加替米沙坦对轻、中度高血压的疗效及与AVP和NO的关系

目的 观察氨氯地平加替米沙坦对轻、中度高血压的疗效，探讨高血压患者血管加压素(AVP)和一氧化氮（NO）的变化与疗效的关系。方法 将60例轻、中度高血压病患者（包括:正在服用降压药的高血压病患者和新发病例没有服用降压药的患者）随机分为:氨氯地平组，替米沙坦组和氨氯地平＋替米沙坦组（氨+替组）,每组各20例。测定各组治疗前后血压的变化。采用放免法、比色法测定各组患者治疗前后血浆AVP和NO的含量。结果 ①氨氯地平组、替米沙坦组及氨＋替组治疗前收缩压（SBP）分别为:(146.31±3.15)mmHg、(145.92±2.71)mmHg及(146.00±2.42)mmHg；舒张压(DBP)分别为:(93.77±2.39)mmHg、(92.54±2.68)mmHg及(94.93±1.15)mmHg。在治疗6个月后，SBP分别为:(126.69±1.74)mmHg、(126.08±1.52)mmHg及(102.71±2.20)mmHg；DBP分别为:(80.76±1.13)mmHg、(81.00±0.80)mmHg和(76.11±1.36)mmHg，与治疗前比较明显降低（P<0.05）。氨+替组患者的SBP和DBP均明显低于氨氯地平组和替米沙坦组（P<0.05）；氨氯地平组与替米沙坦组比较无显著差异。②治疗1月、2月末，氨+替组患者的血压达标率均明显高于氨氯地平组和替米沙坦组（P<0.05）；氨氯地平组和替米沙坦组比较无显著差异。③氨氯地平组、替米沙坦组及氨＋替组治疗前血浆NO的含量分别为:(12.77±0.23)μmol/L、(11.68±0.35)μmol/L及(10.09±1.04)μmol/L；治疗6个月后其含量分别为:(18.50±2.14)μmol/L、(19.07±1.96)μmol/L及(25.47±1.84)μmol/L，与治疗前比较差异显著（P<0.05）。氨+替组患者NO的含量明显高于氨氯地平组和替米沙坦组（P<0.05）；氨氯地平组和替米沙坦组比较无显著差异。④氨氯地平组、替米沙坦组及氨＋替组患者治疗前血浆AVP的含量分别为:(34.71±4.36)ng/L、(33.07±3.77)ng/L及(35.06±4.12)ng/L；治疗6个月后分别为:(22.35±2.71)ng/L、(24.12±3.11)ng/L及(17.98±1.79)ng/L,与治疗前比较差异显著（P<0.05）。氨+替组血浆AVP的含量低于氨氯地平组和替米沙坦组（P<0.05），氨氯地平组和替米沙坦组组间比较无显著差异。结论 ①3个组均能有效控制血压，但氨+替组的降压效果更佳。②3个组在显著降低血压的同时，均伴有血浆AVP含量降低和血浆NO含量增高，氨+替组的效果更明显，提示AVP和NO参与了高血压的发生发展，可作为观察高血压疗效的指标。     

Effectiveness of using long-acting angiotensin II type 1 receptor blocker in Japanese obese patients with metabolic syndrome on morning hypertension monitoring by using telemedicine system (FUJIYAMA Study)

Aim: Recently, obesity patients have been diagnosed as metabolic syndrome. The aim of this study was to evaluate which angiotensin type 1 receptor blockers (ARBs), telmisartan or candesartan, is superior for the control of home blood pressure (BP) in the morning when the outpatient clinic BP was well controlled in the patients with metabolic syndrome.

Methods: The patients with metabolic syndrome were enrolled. Home BP was monitored by using a telemedicine system. After a 2- to 4-week control period to establish baseline home BP values, these patients were randomly divided into telmisartan (20–80?mg) and candesartan (4–12?mg) groups. These end points were evaluated by using the telemedicine system during steady-state active therapy. A total of 356 patients attending 60 outpatient Japanese centers were recruited.

Results: On a day of active therapy, telmisartan significantly lowered both systolic and diastolic home BP in the morning to a greater extent compared to candesartan. At the end of the study, reductions in systolic and diastolic home BP in the morning, in telmisartan group were significantly larger compared to the changes in the candesartan group (systolic; Tel: 12.0?±?8.9 versus Can: 8.1?±?17.1?mmHg, p?=?0.0292, diastolic; Tel: 7.4?±?6.1 versus Can: 3.7?±?6.8?mmHg, p?=?0.0053). Additionally in the telmisartan treated group, LDL-cholesterol showed significant reduction (p?=?0.037), but candesartan did not.

Conclusion: The present study by using the telemedicine system clearly demonstrated that telmisartan has a strong effect on reducing morning home BP, and a good effect on lipid metabolism in patients with metabolic syndrome.     

Comparison of the efficacy of morning versus evening administration of telmisartan in essential hypertension

Valsartan administration at bedtime as opposed to on wakening improves the sleep time-relative blood pressure decline toward a more dipper pattern without loss in 24-hour efficacy. Yet to be determined is whether this administration time-dependent efficacy is a class-related feature, characteristic of all angiotensin receptor blockers or specific only to valsartan. Terminal half-life is a major difference between angiotensin receptor blockers, being largest ( approximately 24 hours) for telmisartan. This trial investigated the administration time-dependent antihypertensive efficacy of telmisartan. We studied 215 patients with hypertension (114 men and 101 women), 46.4+/-12.0 years of age, randomly assigned to receive telmisartan (80 mg/d) as a monotherapy either on awakening or at bedtime. Blood pressure was measured for 48 hours before and after 12 weeks of treatment. The significant blood pressure reduction after treatment was similar for both groups. Bedtime administration of telmisartan, however, was more efficient than morning dosing in reducing the nocturnal blood pressure mean. The sleep time-relative blood pressure decline was slightly reduced after telmisartan on awakening but significantly increased with bedtime dosing, thus reducing the prevalence of nondipping from baseline by 76%. Telmisartan administered at bedtime, as opposed to morning dosing, improved the sleep time-relative blood pressure decline toward a more dipper pattern without loss in 24-hour efficacy. Nocturnal BP regulation is significantly better achieved with bedtime dosing of telmisartan. Results from this prospective trial suggest that these beneficial features of bedtime dosing may be class related for angiotensin receptor blockers. These results should be taken into account when prescribing this class of antihypertensive medication for treatment of essential hypertension.     

Chronotherapy with nifedipine GITS in hypertensive patients: improved efficacy and safety with bedtime dosing

BACKGROUND: Previous studies have shown that the circadian pattern of blood pressure (BP) remains unchanged after either morning or evening dosing of several calcium-channel blockers (CCBs), including amlodipine, isradipine, verapamil, nitrendipine, and cilnidipine. This trial investigated the administration-time dependent antihypertensive efficacy of the slow-release, once-a-day nifedipine gastrointestinal-therapeutic-system (GITS) formulation. METHODS: We studied 180 untreated hypertensives (86 men and 94 women), 52.5 +/- 10.7 years of age, randomly assigned to receive nifedipine (30 mg/day) as a monotherapy either upon awakening or at bedtime. BP was measured for 48 h before and after 8 weeks of treatment. RESULTS: The BP reduction after treatment was significantly larger with bedtime dosing mainly during night time sleep (P < 0.012). The number of patients with controlled ambulatory BP after treatment was greater with bedtime than morning treatment (P = 0.016). The baseline prevalence of nondipping was unaltered after ingestion of nifedipine on awakening, but reduced from 51 to 35% after bedtime dosing (P = 0.025). The morning surge of BP, a risk factor for stroke, was significantly reduced (P < 0.001) only after bedtime administration of nifedipine. Bedtime in comparison to awakening-time ingestion of nifedipine was also associated with a reduction in the incidence of edema from 13 to 1% (P < 0.001). CONCLUSIONS: The increased efficacy on ambulatory BP as well as the significantly reduced prevalence of edema after bedtime as compared to morning ingestion of nifedipine should be taken into account when prescribing this medication to patients with essential hypertension.