Evaluation of the antihypertensive effect of celiprolol by ambulatory blood pressure monitoring

The use of ambulatory blood pressure monitoring has gained popularity because it is not subject to those limitations associated with traditional sphygmomanometry (inaccuracy of blood pressure readings, low number of readings, and failure to represent daytime blood pressure readings). In the present study, we provide evidence that the 24-hour mean blood pressure obtained through intraarterial blood pressure measurements in ambulatory patients provides a more accurate diagnosis (and perhaps a prognosis) of hypertension than that provided by cuff-obtained casual blood pressure measurement. Furthermore, despite a reduction in the amount and in the accuracy of the information obtained, blood pressure data provided by noninvasive blood pressure monitoring are also more accurate diagnostically than cuff-obtained casual blood pressure measurements. In 15 essential hypertensive patients in whom celiprolol, 400 mg once daily, was compared with placebo in a randomized double-blind crossover study, the use of noninvasive 24-hour automatic blood pressure monitoring showed that in responsive patients, celiprolol induced a sustained reduction in systolic and diastolic blood pressure throughout the 24 hours. The blood pressure reduction was also apparent during the night, despite the concomitant occurrence of a slight tachycardia. These findings demonstrate that once-daily administration of celiprolol provides an effective lowering of the 24-hour blood pressure profile. This dosing schedule can therefore be regarded as appropriate for antihypertensive therapy.     

24小时动态血压监测厄贝沙坦降压效果

目的　评价24小时动态血压监测(ABPM)厄贝沙坦降压效果。　方法　选择1级至2级原发性高血压患者45例给予厄贝沙坦150mg每日一次,早晨7∶00口服,共4周。ABPM用药前后24小时血压变化情况。　结果　厄贝沙坦治疗后24小时血压显著下降(P<005),总有效率为82%,白天与夜间血压下降幅度大致相同,保持正常血压昼夜节律变化。　结论　厄贝沙坦对1~2级高血压是较为理想的药物。     

动态血压监测评价吲哒帕胺新型缓释片的降压作用

目的　评价吲哒帕胺 (商品名纳催离 ,法国施维雅药厂生产 ) 1 5mg缓释片的长效降压效果及安全性。方法　 3个中心收治的 10 8例轻、中度高血压病患者 [男 5 9例 ,女 4 9例 ,平均年龄 (5 1± 11)岁 ]服安慰剂 2周后及服吲哒帕胺 1 5mg缓释片 8周后 ,分别于早晨 8:0 0来医院佩带 2 4h动态血压监测仪 ,进行连续 30h动态血压测定 ,计算谷峰比值 (T/P)及每小时平均血压 ,同时在服吲哒帕胺1 5mg缓释片的第 2、4、8周在诊所测坐位血压。药物安全性主要观察血钾及血尿酸。结果　 10 8例轻、中度高血压患者服药后通过诊所测坐位血压评价 ,降压总有效率为 6 7 6 % ;2 4h动态血压监测结果按全部患者计算或有效病例计算 ,T/P比值结果相近。全组计算收缩压 (SBP)与舒张压 (DBP)的T/P比值分别为 0 80和 0 79。服缓释片与服安慰剂后第 2 5～ 30h动态血压监测发现 ,血压分别为 (134± 12 ) /(89± 9)mmHg (1mmHg =0 133kPa)及 (14 2± 12 ) / (92± 7)mmHg(P <0 0 1)。对 2 4h动态血压最大降压幅度≥ 2 0 / 10mmHg的 33例有反应者 ,分析其最大降压时间 ,93%在 8～ 19h,其中 14～ 17h为最高峰。服药后出现轻度低血钾 8例 (7 4 % ) ,仅 1例血钾 <3 0mmol/L(2 94mmol/L) ;血尿酸轻度升高者 18例(16 7% )。结论　吲哒     

Assessment of antihypertensive efficacy by non-invasive ambulatory blood pressure monitoring

The session devoted to the usefulness of non-invasive ambulatory blood pressure monitoring (ABPM) in the evaluation of antihypertensive therapy allowed us to discuss a number of important issues. ABPM emerged as a widely accepted technique to measure blood pressure in clinical trials. Actually, it was generally considered to provide more valuable information than do conventional blood pressure readings obtained sporadically by a doctor. However, still debated was the way of analysing ABPM recordings. This was particularly true with respect to the proposal of considering separately responders and non-responders when assessing the quality of blood pressure control achieved during treatment.     

Twenty-four-hour ambulatory blood pressure monitoring in the evaluation of antihypertensive drugs: methodological aspects

Ambulatory blood pressure monitoring (ABPM) provides reproducible measurements over 24 h, avoiding the alerting reaction. However, the reproducibility of mean hourly ambulatory values is poorer by far than the whole day average. In phases II and III clinical triams ABPM seems to evaluate the time-course of the antihypertensive effect and helps to determine the trough: peak ratio. The potential advantage of the method could be an increase in statistical power of the trial, with regard to the number of patients to include, according to the study design. ABPM led to the identification of 'white-coat' hypertension with elevated clinic blood pressure measurements and persistently normal ABPM over time. No epidemiological evidence to include patients in trials according to ABPM criteria has been provided to date, but a subsequent stratification on the initial ABPM data has to be performed. Although an insignificant effect on the 24 h mean blood pressure values in short-term trials, the use of placebo seems to be necessary to supply reference blood pressure values for dosing and trough: peak ratio determination. Whether ABPM is able to decrease the number of patients to include remains debated. It has been noted that an increasing number of readings could lead to a decrease in SD and that a decrease in the number of patients required can be expected both in parallel and in cross-over design trials. However, it has been reported that the advantage of the higher reproducibility of ABPM could be lost in parallel design trials and that analysis of the antihypertensive effect of the drug throughout the 24 h could then require more patients. In order to conduct multicentre trials using ABPM, a consensus among investigators is needed for the presentation and analysis of the results. We have to overcome these difficulties in order to avoid a 'centre effect' and to allow for the expected increase in power of the trial. In such a trial the comparability of parallel groups could be jeopardized by a misadherence to the ABPM protocol. How can ABPM modify the doctor-patient relationship?. A pedagogical approach seems necessary, namely to inform the patients concerning technical and medical prerequisites of the method, in order to conform to the 'guidelines'. ABPM might constitute a new determinant of compliance with treatment; but its influence, beneficial or not, remains to be assessed. Compliance evaluation could be combined with ABPM, in order to provide a better evaluation of the antihypertensive effect of the drugs.     

动态血压监测评价复方厄贝沙坦的降压作用

目的评价厄贝沙坦/氢氯噻嗪(复方厄贝沙坦,商品名安博诺)降压谷/峰比值及降压效果. 方法开放试验.28例轻中度高血压患者日服一次复方厄贝沙坦(厄贝沙坦150mg/氢氯噻嗪12.5mg)、共8周,治疗前后行24h动态血压监测. 结果收缩压、舒张压谷/峰比值分别为56.1%、55.3%,24h、昼、夜平均血压分别下降22.2/13.3mmHg、23.8/14.1mmHg、15.0/9.1mmHg.结论复方厄贝沙坦日服一次,降压作用可维持24h.     

Usefulness of ambulatory blood pressure monitoring in detecting the additional antihypertensive effect of non-pharmacologic treatment

OBJECTIVE: The present study was designed to investigate whether a non-pharmacologic intervention program (NPIP) consisting of a weight-lowering diet, a reduction in alcohol consumption and physical training at 50% peak aerobic capacity could enhance the blood-pressure-lowering effect of calcium antagonists in obese sedentary, hypertensive patients. METHODS: Fifty-nine subjects were treatred with 5-10 mg isradipine once daily for 8 weeks and were then randomly allocated to either isradipine monotherapy or isradipine plus NPIP for 20 weeks. Clinic and ambulatory blood pressure were used for assessing the antihypertensive effect obtained in both treatment groups. RESULTS: Clinic and ambulatory systolic and diastolic blood pressures decreased significantly after 8 weeks of isradipine monotherapy. At week 28, the group treated with isradipine combined with NPIP and in which significant modifications in body weight (P < 0.0001), alcohol intake (P < 0.0001) and peak oxygen uptake (P <0.01) were observed, had significant (P < 0.05) additional decrements in ambulatory but not clinic blood pressure. CONCLUSIONS: These results demonstrate that the addition of lifestyle modifications in obese sedentary hypertensive patients already receiving pharmacological therapy can induce further blood pressure decrements. Because significant decrements were noticed only with ambulatory blood pressure monitoring, the results of the present study advocate this technique for assessing the magnitude of blood pressure reduction with non-pharmacological therapy.     

Clinical value of ambulatory blood pressure monitoring in the assessment of antihypertensive therapy.

Non-invasive ambulatory blood pressure monitoring (ABPM) is particularly useful for assessing the efficacy of antihypertensive drugs. It provides a large number of blood pressure readings during daytime as well as night-time, which results in a more precise assessment of prevailing blood pressure than can be obtained from sporadic measurements taken by a doctor. Because of this greater precision ABPM reduces the number of patients required in clinical trials to demonstrate differences. It also allows one to define precisely the profile of the blood-pressure-lowering effect of a given drug. Placebo has little effect on ABPM. Thus, a placebo phase is not absolutely necessary. ABPM makes it possible to evaluate the efficacy of an antihypertensive medication by analysing data for patients with a placebo effect separately from data for true responders to the medication. In everyday practice ABPM helps one to detect among patients with hypertension refractory to treatment those who exhibit controlled blood pressures outside the medical environment, thus permitting one to avoid an unnecessary step-up of treatment. In addition ABPM can also help one to identify symptoms occurring during antihypertensive treatment that are related to excessive drug-induced changes in blood pressure.     

Evaluation of antihypertensive therapy by ambulatory blood pressure monitoring and establishment of the level of antihypertensive goal on the circadian rhythm of blood pressure

We have developed a new method for the evaluation of antihypertensive therapy on the circadian rhythm of blood pressure and attempted to determine the indications for antihypertensive therapy and the level of antihypertensive goal. Blood pressures were measured for 24 hours by the use of ambulatory blood pressure monitoring using 630 (ABPM-630) in 50 normotensives, 50 untreated hypertensives and 50 hypertensives undertreatment with various antihypertensive drugs (110 males and 40 females, with a mean age of 53.4 +/- 13.3 yrs). Blood pressure profiles were prepared for determination of the hyperbaric and hypobaric indexes. According to the WHO's definitions for blood pressure, the hyperbaric index was defined as the area above 140 mmHg in systolic blood pressure or 90 mmHg in diastolic blood pressure, and the hypobaric index, as the area below 100 mmHg or 60 mmHg, respectively. The criteria of the hypobaric index was obtained from the mean basal blood pressure (the lowest blood pressure during sleep) of the 50 normotensives. The mean hyperbaric index of the 50 normotensives was 20.4 +/- 40.2/5.5 +/- 15.3 (systole/diastole) mmHg.hour/day and the mean hypobaric index, 12.2 +/- 22.5/9.0 +/- 24.0 mmHg.hour/day. The 50 untreated hypertensives showed a mean hyperbaric index of 281.8 +/- 197.0/156.0 +/- 126.1 mmHg.hour/day and a mean hypobaric index of 0.1 +/- 0.6/0.3 +/- 1.5 mmHg.hour/day. Comparison of the indexes before and after treatment with various antihypertensives showed that a decrease in the hyperbaric index without an increase in the hypobaric index was the most optimal reduction of blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Limited reproducibility of hourly blood pressure values obtained by ambulatory blood pressure monitoring: implications for studies on antihypertensive drugs.

OBJECTIVE: To assess the reproducibility of average hourly blood pressure values obtained by 24-h non-invasive ambulatory monitoring. PATIENTS: Fifteen outpatients with essential hypertension. In all subjects antihypertensive treatment was withdrawn for 4 weeks before and during the 4 weeks of the study. METHODS: The 24-h blood pressure was monitored by a SpaceLabs 5300 device (four readings per hour during the day and three readings per hour during the night) twice, at a 4-week interval. Systolic (SBP) and diastolic blood pressure (DBP) were averaged for each hour and for the whole 24-h period, and hourly and 24-h reproducibility was quantified by the standard deviation of the mean difference (SDD) between the values obtained in the two recordings. RESULTS: The SDD of hourly SBP and DBP was much greater than that of the 24-h values and ranged widely between the hours of recording. The SDD of hourly SBP and DBP were also variably greater than the SDD of the 24-h value in another 14 untreated essential hypertensives in whom 24-h ambulatory blood pressure was monitored intra-arterially twice at a 4-week interval to calculate hourly average blood pressure on thousands rather than on three or four values per hour. CONCLUSION: Reproducibility is less for hourly than for 24-h average blood pressure. This feature (which probably depends on behavioural differences between two recordings) suggests that ambulatory blood pressure measurement partly loses its advantages for reproducibility and reduction in trial size if the results are analysed over hourly periods.     

Comparison of daily anti-hypertensive effects of amlodipine and nifedipine coat-core using ambulatory blood pressure monitoring - utility of "hypobaric curve" and "hypobaric area"

When selecting anti-hypertensives, most physicians do not consider daily blood pressure (BP) variation. To evaluate the effectiveness of anti-hypertensives on the temporal profile of BP, we proposed three new parameters obtained by ambulatory BP monitoring and evaluated these parameters by comparing 5 mg of amlodipine and 40 mg of nifedipine coat-core. Hypobaric values were determined by subtracting BP data collected before administration of the drug from those collected after drug treatment at the corresponding time of day. The hypobaric curve was drawn by plotting the hypobaric values in chronological order, with the time at which the drug was taken set as the starting point. The hypobaric area was the area encircled between the 0 mmHg level line and the hypobaric curve. For amlodipine, the hypobaric areas of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were -19,110 mmHg/min and -10,695 mmHg/min, respectively. Systolic BP decreased -13.3 mmHg, and DBP BP -7.4 mmHg as daily averages. For nifedipine coat-core, the hypobaric areas of SBP and DBP were -32,235 mmHg/min and -18,150 mmHg/min, respectively. Systolic BP decreased -22.3 mmHg and DBP -12.6 mmHg as daily averages. From the hypobaric curves, the trough-to-peak ratios of amlodipine and nifedipine coat-core were measured as 0.67 and 0.60, respectively. The total anti-hypertensive power of nifedipine coat-core, measured by the hypobaric area, was 1.69 times more potent than that of amlodipine. These parameters seem to be useful for evaluating the daily temporal profile of the BP-lowering effects of anti-hypertensive drugs.     

Evaluation of the antihypertensive effect of once-a-day trandolapril by 24-hour ambulatory blood pressure monitoring. The Italian Trandolapril Study Group.

The aim of this study was to evaluate the effects of trandolapril on 24-hour blood pressure in patients with mild-to-moderate essential hypertension. After a washout period of 4 weeks, 42 patients were randomized to receive 2 mg of trandolapril once daily and 20 to receive placebo in a double-blind fashion for 6 weeks. This was followed by a second washout period of 4 weeks. At the end of each period, clinic blood pressure was assessed at 24 hours after the last dose and 24-hour ambulatory blood pressure was measured noninvasively, taking blood pressure readings every 15 minutes during the day and every 20 minutes during the night. Two patients were dropped out before any blood pressure evaluation under treatment. Analysis of ambulatory blood pressure was performed in 48 patients who met the criteria for the minimal number of ambulatory blood pressure data (2 values per hour during the day and 1 value per hour in the night). In the trandolapril-treated group (n = 41) clinic systolic/diastolic blood pressures were 159.8 +/- 2.0/102.4 +/- 0.8, 146.8 +/- 2.3/94.8 +/- 1.1, and 155.7 +/- 2.0/99.2 +/- 0.7 mm Hg in the pretreatment, treatment, and post-treatment periods, respectively. The corresponding values for 24-hour mean blood pressure (n = 31) were 139.5 +/- 1.9/91.2 +/- 1.5, 131.0 +/- 2.0/84.3 +/- 1.2, and 139.7 +/- 1.8/90.9 +/- 1.1 mmHg. The differences between the lower treatment, versus the higher pre- and post-treatment, values were all statistically significant (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Benefits of ambulatory blood pressure monitoring in the design of antihypertensive drug trials

REVIEW IN DEPTH: Ambulatory blood pressure monitoring (ABPM) offers substantial advantages over conventional clinic measurement in the assessment of antihypertensive agents. There is a greater reproducibility of an average blood pressure taken from multiple readings,s and in the setting of a clinical trial this translates into increased precision of the assessment of mean antihypertensive effect. The temporal profile of blood pressure and the antihypertensive effect of an agent can be studied directly, and times of the day of particular clinical importance, such as the end of the dosing period and the early morning period, can be studied more easily than for conventional blood pressure measurement. ABPM reduces the size of any placebo effect on blood pressure to very low values, and it can be used to exclude white-coat hypertensives from clinical trials, thereby reducing the noise in a clinical trial. The role of ABPM in drug evaluation looks set to increase further with new developments in blood pressure measurement technology.     

Methodological considerations in the evaluation of the duration of action of antihypertensive therapy using ambulatory blood pressure monitoring

We review the potential limitations of the two current methodologies for evaluating the duration of action of antihypertensive therapy: the smoothness index (SI) and the trough : peak ratio (TP). We propose a simple correction factor for the SI. The correction factor prevents the SI from reaching erroneous high values in situations in which the reduction in blood pressure (BP) is inadequate but very homogeneous. We refer to the corrected index as the SIn (normalized SI).     

The use of ambulatory blood pressure monitoring to evaluate antihypertensive drugs for drug approval

So far, the contribution of clinical studies using ambulatory blood pressure monitoring in the registration of a new antihypertensive agent for marketing authorization purposes has been limited. However, pre-registration studies can be particularly useful, especially to study dose and dose interval in relation to peak: trough ratio during phase II and to facilitate comparison with other antihypertensive agents during phase III of the development of a new antihypertensive agent. More attention should be paid to their design and implementation as high standards are recommended. If properly studied, ambulatory blood pressure monitoring could fulfil a major role in the registration process of a new antihypertensive agent.     

Results of antihypertensive treatment by primary and secondary care physicians as assessed by ambulatory blood pressure monitoring

BACKGROUND: We present data from a cross-sectional study on consecutive non-randomized drug-treated mild-to-moderate essential hypertensives, whose blood pressure was ambulatorily monitored for 24 h to evaluate the presence of adequate control. DESIGN: Primary and secondary care physicians were invited to send to our clinic drug-treated patients with essential hypertension (JNC VI stages 1-2) to undergo 24-h ambulatory blood pressure monitoring (ABPM) while continuing their prescribed medications. METHODS: The 436 enrolled patients (255 males, 181 females, age 61+/-11 years) were left on their therapeutic regime: monotherapy in 208 patients (47. 7%) and combination therapy in 228 patients (52.3%). All the patients were divided into two care groups: primary care, 238 patients (54.6%) and secondary care, 198 patients (45.4%). A mean daytime blood pressure < or =135/85 mmHg was chosen as a definition of adequate blood pressure control. RESULTS: Adequate blood pressure control was found in 196/436 total patients (45%); 112/238 patients in primary care (47%) and 84/198 patients in secondary care (42.4%) (P=NS); 94/208 patients (45.2%) in monotherapy and 102/228 patients (44.7%) in combination therapy (P=NS); 125/255 male patients (49%) and 71/181 female patients (39.2%) (P=0.0428). In the logistic regression model, female sex was associated with a higher risk of inadequate blood pressure control of about 50%. CONCLUSIONS: Adequate blood pressure control, as assessed by ABPM, is not different in the two settings of family doctor's office and specialist's clinic and is predicted by male gender. The figures of adequate blood pressure control remind us of the rule of halves, regardless of treatment regimes and medications.     

Discrepancy between clinic and ambulatory blood pressure measurement in the evaluation of two antihypertensive agents

Discrepancies between clinic and ambulatory BP measurements may be important in the assessment of antihypertensive drug efficacy. Trimazosin (50-200 mg twice daily) and propranolol (40-160 mg twice daily) were compared in 22 hypertensive subjects in a randomised double-blind cross-over study. Daytime ambulatory BP was measured with a non-invasive portable recorder (Remler M2000). Clinic BP measurements were made with a random zero sphygmomanometer. While both drugs reduced clinic supine BP (trimazosin by 16/10 mmHg, P less than 0.01/P less than 0.001; propranolol by 25/14 mmHg, P less than 0.001/P less than 0.001), equivalent decreases on ambulatory measurement occurred with propranolol (28/11 mm/Hg, P less than 0.001/P less than 0.001) but not trimazosin (8/3 mmHg, P less than 0.05/NS). This difference in drug efficacy persisted throughout the 12-hour dosing interval. We conclude that clinic BP measurements alone cannot be relied upon to reflect accurately changes in BP induced by antihypertensive drugs. Moreover this study confirms the necessity for ambulatory BP measurement in the evaluation of antihypertensive drugs.