Antihypertensive therapeutic effect. Comparison of their evaluation using clinical and ambulatory measurements of arterial pressure. Preliminary study

The aim of this preliminary report is to compare the evaluation of the antihypertensive drug effect, during a controlled trial, using casual measurements and 24 hr B.P. monitoring. 20 patients (16 males, 4 females 55 +/- 10 years old) with primary hypertension (WHO stage I or II) were included with a diastolic blood pressure greater than or equal to 100 mmHg (mean blood pressure from three clinical readings). Casual B.P. and B.P. monitoring (Spacelabs - 4 measurements per hour during a 24 hr period) were established before and after the end of the placebo run in period (one placebo tablet given once daily at 8 h-8 h 30 a.m. for 15 days). Overall sample data: The clinical B.P. decrease (167 +/- 16-109 +/- 7 before and 147 +/- 17-97 +/- 11 after treatment) is higher that the ambulatory B.P. decrease (148 +/- 15-101 +/- 8 before and 138 +/- 21-94 +/- 14 after treatment). Individual patient data: A clinical B.P. decrease (of at least 10 mmHg) was found in 17 patients for systolic B.P. and in 15 patients for diastolic B.P. A significant ambulatory B. P. drop decrease (p less than 0.05) was found in 11 patients for 24 hr systolic and diastolic B.P. The clinical and ambulatory responses to the treatment are in line in 14 patients, but differ in 3 instances. There is a little correlation (for the diastolic B.P.) and no correlation (for the systolic B.P.) between the clinical and the ambulatory B.P. decreases after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ambulatory blood pressure monitoring during antihypertensive treatment: the case of non-responder patients

OBJECTIVE: To analyse the discrepancies between casual and ambulatory blood pressure in hypertensive patients during treatment. PATIENTS AND METHODS: Patients were gathered intio two groups according to casual diastolic blood pressure (DBP) and antihypertensive treatment: group A (responders) with casual DBP < 90 mmHg administered one or more antihypertensive drugs and group B (non-responders) with DBP >/= 95 mmHg taking two or more antihypertensive drugs, maintained during three consecutive visits at 2-week intervals. For all of them casual blood pressure measurements, 24 h ambulatory blood pressure monitoring and assessment of end-organ damage were performed. RESULTS: The difference between casual blood pressure and average 24 h ambulatory blood pressure were significantly higher for group B than those observed for group A (26 versus 7 mmHg systolic, 16 versus 5 mmHg diastolic). Thirty per cent of the patients in group B and 16% in group A had casual blood pressure more than 20 mmHg higher than awake ambulatory blood pressure, whereas 8% in group B and 20% in group A had higher values for ambulatory than for casual blood pressure. In group A 8% of patients had awake DBP higher than 95 mmHg and 8% had awake DBP 85-95 mmHg. Patients of group A with awake DBP >/= 85 mmHg were younger than those with awake DBP < 85 mmHg (41.4+/-8.8 and 52.1+/-13.4 years, respectively). In patients of group B, there was less end-organ damage in the patients with awake DBP < 85 mmHg than there was in patients with awake DBP >/= 95 mmHg (World Health Organization grade I/II-III, 6/10 and 3/20, respectively). CONCLUSION: The differences between casual and ambulatory blood pressures were higher in the 'non-responder' patients. In group A the small percentage of patients who had persistently higher ambulatory blood pressure were younger. In group B one-quarter of the patients had 'normal' ambulatory blood pressure and less end-organ damage. Ambulatory blood pressure monitoring will be useful for better assessment of hypertension control in a subset of hypertensive patients.     

Ambulatory recording of blood pressure. Study of the reproducibility of findings in 25 subjects

The reproducibility of a novel ambulatory blood pressure (B.P.) monitoring was tested, for clinical trial in hypertension. The spacelabs apparatus is based on standard auscultatory and oscillometric blood pressure measurements. Ten normotensive patients and 15 hypertensive patients were investigated as follows: their blood pressure was monitored twice over a 24 hr period at an interval of 30 and 15 days respectively. The monitoring data were expressed as the mean of the average blood pressure over day-time (7 hr-22 hr) and 24 hr as well as 24 hr. B.P. profiles (means of 4 measurements per hour). The statistical analysis of the two subpopulations of patients showed a satisfaction reproducibility of both the 24 hr B.P. curves (normotensive patients: PAS: r = 0.94; PAD: r = 0.92; Hypertensive patients PAS: r = 0.82; PAD: r = 0.64 p less than 0.001). and blood pressure levels (normotensive patients: J1: 113 +/- 10/70 +/- 6 mmHg; J30: 110 +/- 10/68 +/- 6 mmHg. Hypertensive patients: J1: 150 +/- 10/98 +/- 9 mmHg; J15: 155 +/- 15/96 +/- 8 mmHg). In contrast, analyzing each patient individually exhibited a correct reproducibility of the B.P. levels but the 24 hr--profiles of either the diastolic or systolic blood pressure could not be correlated with sufficient reliability (normotensive patients: 7 times out of 10 for PAS, and 4 times out of 10 for PAD; hypertensive patients: 5 times out of 15 for PAS, and 3 times out of 15 for PAD). In addition, the patient activity, should be carefully controlled during ambulatory blood pressure measurements.(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment of the anti-hypertensive effect of diltiazem in delayed-action capsules by ambulatory monitoring of arterial pressure]

The aim of this parallel controlled-placebo study was to assess the antihypertensive effect of diltiazem in a slow release formulation in monotherapy by the ambulatory blood pressure monitoring (ABPM). Twenty patients with moderate essential hypertension entered the trial. Whole day ambulatory blood pressure (BP) monitoring, with a COLIN ABPM 630, was done after a wash-out period, after placebo administration and 60 days of therapy with diltiazem in a 120 or 180 mg once or twice daily administration. We verified by ABPM that placebo administration did not have an antihypertensive effect (146 +/- 10 mmHg/87 +/- 7 mmHg at base line to 145 +/- 8 mmHg/84 +/- 6 mmHg with placebo p = ns). Eithy four percent of the patients showed a significant systolic and diastolic BP decrease after 60 days of therapy (from 146 +/- 10 mmHg/87 +/- 7 mmHg at base line to 132 +/- 7/77 +/- 6 mmHg - p less than 0.025). In 56% of the patients this was achieved with 180 mg/day and this effect was sustained throughout the 24 hours. We did not find a significant decrease on heart rate. The ABPM is a valuable technique to assess the effect of antihypertensive drugs and demonstrated that diltiazem in a slow release formulation was effective in decreasing systolic and diastolic BP, throughout the day even in patients with low doses, once daily.     

Repeated measurements of non-invasive ambulatory blood pressure: distinction between reproducibility and the proper effect of placebo

OBJECTIVE: To determine whether non-invasive ambulatory blood pressure is more reproducible and less affected by the placebo treatment than are clinic blood pressure measurements. METHOD: Thirty-four essential hypertensive outpatients were randomly allocated after a 4-week preselection period in two groups in a cross-over study design. One group received placebo for 4 weeks while the other formed the control group (reproducibility), then the treatments were exchanged for another 4 weeks. Clinic and ambulatory blood pressures were measured at three different times for each patient, namely bnefore the random allocation to groups and at the end of each period, using a mercury sphygmomanometer and 24 h non-invasive ambulatory blood pressure monitoring. RESULTS: Administration of placebo was accompanied by a significant reduction in systolic and diastolic clinic blood pressures (by 3.4+/-13 and 3.6+/-8 mmHg, respectively), but not in 24 h, daytime and night-time blood pressures. Circadian hourly blood pressure and heart rate curves were virtually superimposable. In the 13 placebo responder patients selected on the basis of clinic blood pressure, placebo decreased the clinic blood pressure and also reduced systolic and diastolic ambulatory blood pressures, mainly during the day period (by 5.2+/-6.2 and 4.89+/-7.8 mmHg, respectively). This effect is specific and related to the placebo administration because repetition of the measurements without any treatment showed no significant difference. To characterize at baseline the placebo responder patients, comparison with the non-placebo responders showed lower baseline values of ambulatory systolic blood pressure recorded during 24 h daytime and night-time in the placebo responder group. CONCLUSION: The 24 h ambulatory blood pressure average is not affected by placebo in the present group of patients but that a placebo effect occurs mainly during the daytime in patients who decreased their clinic blood pressure under placebo (placebo responders); the placebo-induced reduction in blood pressure is related to a specific effect of placebo and is independent from any alerting reaction or reproducibility hypothesis. This study clearly indicates the necessity of including placebo and ambulatory blood pressure monitoring in the therapeutic and pharmacological trials of antihypertensive drugs.     

Amlodipine 2.5 mg once daily in older hypertensives: a Brazilian multi-centre study

OBJECTIVES: The use of low-dose amlodipine has not yet been well established in the elderly. This study therefore aimed to evaluate the efficacy and tolerability of low-dose amlodipine in elderly patients with Joint National Committee VI stage I or II hypertension. PATIENTS AND METHODS: Sixty-five hypertensive individuals (aged 66.3 +/- 5.3 years) received amlodipine 2.5 mg per day for 12 weeks before and after two periods of 4 weeks of placebo. At weeks 0, 12 and 16, patients were submitted to office, 24 h ambulatory blood pressure monitoring and home blood pressure measurement. RESULTS: Office systolic and diastolic blood pressure showed decreases at weeks 8 (153 +/- 17, 90 +/- 9 mmHg) and 12 (152 +/- 16, 90 +/- 9 mmHg) compared with weeks 0 (164 +/- 16, 99 +/- 6 mmHg) and 16 (162 +/- 19, 95 +/- 9 mmHg). During ambulatory monitoring, a decrease was observed in the average 24 h systolic and diastolic pressure at week 12 (143 +/- 13, 86 +/- 7 mmHg) compared with weeks 0 (155 +/- 15, 93 +/- 6 mmHg) and 16 (152 +/- 16, 92 +/- 8 mmHg). A daytime and night-time reduction in systolic and diastolic pressure was observed on home blood pressure monitoring at week 12 (146 +/- 16/88 +/- 8, 144 +/- 16/93 +/- 8 mmHg) compared with weeks 0 (159 +/- 17/94 +/- 8, 161 +/- 19/93 +/- 8 mmHg) and 16 (153 +/- 16/93 +/- 8, 154 +/- 17/92 +/- 8 mmHg). Adverse reactions were infrequent. CONCLUSIONS: Amlodipine at a dose of 2.5 mg per day showed efficacy and good tolerability in elderly hypertensives.     

Spectral analysis of 24 h blood pressure monitoring in the assessment of trough: peak ratio. A randomized, placebo-controlled, cross-over comparison of ramipril and enalapril

BACKGROUND: The ratio between the magnitude of blood pressure reduction during the steady-state dosage interval (trough) and the maximum blood pressure reduction (peak) is an integrated in-vivo index both of the pharmacokinetic properties and of pharmacodynamic activity of an antihypertensive drug. Angiotensin converting enzyme inhibitors are often characterized by a low (often lower than 50%) trough: peak ratio but no direct drug comparisons are available. OBJECTIVE: To compare the absolute blood pressure reduction and the trough: peak ratio of daily doses of two angiotensin converting enzyme inhibitors, 5 mg ramipril and 10 mg enalapril. METHOD: After a 1-month wash-out and a 2-week placebo run-in, 25 mild hypertensives aged 47 +/- 4 years (17 men and eight women) were randomly assigned to treatments separated by a 2-week interval. Ambulatory blood pressure monitoring was performed and trough: peak ratio was calculated by the fast Fourier transform analysis of placebo-effect-subtracted data. RESULTS: After 1 month of ramipril treatment, 24 h blood pressure decreased from 139 +/- 10 to 129 +/- 11 mmHg for systolic (P < 0.05) and from 89 +/- 8 to 81 +/- 5 mmHg for diastolic blood pressure (P < 0.01). Also enalapril treatment caused a significant 24 h reduction in blood pressure both for systolic (to 132 +/- 7 mmHg, P < 0.05) and for diastolic blood pressure (to 84 +/- 5 mmHg, P < 0.05). Placebo caused a 24 h reduction in blood pressure (to 136 +/- 8 mmHg for systolic and 87 +/- 5 mmHg for diastolic blood pressure, NS, versus wash-out period). The two drugs were equally effective in reducing ambulatory blood pressure, but ramipril produced a trough: peak ratio significantly higher than that with enalapril both for systolic (48 +/- 11%, range 34-74%, versus 38 +/- 11%, range 21-67%, P < 0.005)and for diastolic blood pressure (47 +/- 11%, range 30-79 %, versus 37 +/- 12%, range 21-68%, P < 0.05). CONCLUSION: The low trough : peak ratios could have been due to the daily pattern of blood pressure of mild hypertensives, many of whom are normotensives at night-time, so that the main antihypertensive effect is exerted during daytime rather than during the night or early morning.     

Efficacy of a once-daily formulation of carvedilol for the treatment of hypertension

Beta-blockers with pharmacologic effects that differ from conventional agents might add to antihypertensive treatment options. This study evaluated a new once-daily formulation of the beta-/alpha1-blocker, carvedilol controlled-release (CR), in hypertensive patients off treatment or while still taking up to 2 (non-beta-blocker) agents. After a 4-week run-in phase, patients were randomized either to placebo (n=76) or carvedilol CR 20 mg (n=82), 40 mg (n=76), or 80 mg (n=86) once daily. After 6 weeks of treatment, ambulatory blood pressure monitoring was repeated to measure the primary end point of changes in mean 24-hour diastolic blood pressure. During treatment, 24-hour diastolic blood pressure fell in the placebo and carvedilol CR 20-mg, 40-mg, and 80-mg groups by (mean +/- SE) 0.4+/-0.9, 4.4+/-0.9, 7.9+/-0.9, and 9.6+/-0.9 mm Hg, respectively (P< or =.001, trend test for all carvedilol CR doses with placebo). Corresponding 24-hour systolic blood pressure changes were 0.6+/-1.4, 6.8+/-1.3, 10.1+/-1.4, and 12.5+/-1.3 mm Hg, respectively (P< or =.001, trend test). Diastolic blood pressure trough-to-peak ratios (placebo-corrected) based on ambulatory blood pressure monitoring (trough = mean of 20- to 24-hour post-dose readings; peak = mean of 3- to 7-hour post-dose readings) for 20-mg, 40-mg, and 80-mg doses were 0.73, 0.64, and 0.65, respectively. Adverse events, including clinical chemistry values, were similar in the drug-treated and placebo groups. Carvedilol CR has a clinically meaningful defined dose-dependent antihypertensive effect that persists throughout a 24-hour period.     

Arterial hypertension difficult to control in the elderly patient. The significance of the "white coat effect"]

OBJECTIVE: Previous studies have revealed a high prevalence of white coat effect among treated hypertensive patients. The difference between clinic and ambulatory blood pressure seems to be more pronounced in older patients. This abnormal rise in blood pressure BP in treated hypertensive patients can lead to a misdiagnosis of refractory hypertension. Clinicians may increase the dosage of antihypertensive drugs or add further medication, increasing costs and producing harmful secondary effects. Our aim was to evaluate the discrepancy between clinic and ambulatory blood pressure in hypertensive patients on adequate antihypertensive treatment and to analyse the magnitude of the white coat effect and its relationship with age, gender, clinic blood pressure and cardiovascular or cerebrovascular events. POPULATION AND METHODS: We included 50 consecutive moderate/severe hypertensive patients, 58% female, mean age 68 +/- 10 years (48-88), clinic blood pressure (3 visits) > 160/90 mm Hg, on antihypertensive adequate treatment > 2 months with good compliance and without pseudohypertension. The patients were submitted to clinical evaluation (risk score), clinic blood pressure and heart rate, electrocardiogram and ambulatory blood pressure monitoring (Spacelabs 90,207). Systolic and diastolic 24 hour, daytime, night-time blood pressure and heart rate were recorded. We considered elderly patients above 60 years of age (80%). We defined white coat effect as the difference between systolic clinic blood pressure and daytime systolic blood pressure BP > 20 mm Hg or the difference between diastolic clinic blood pressure and daytime diastolic blood pressure > 10 mm Hg and severe white coat effect as systolic clinic blood pressure--daytime systolic blood pressure > 40 mm Hg or diastolic clinic blood pressure--daytime diastolic blood pressure > 20 mm Hg. The patients were asked to take blood pressure measurements out of hospital (at home or by a nurse). The majority of them performed an echocardiogram examination. RESULTS: Clinic blood pressure was significantly different from daytime ambulatory blood pressure (189 +/- 19/96 +/- 13 vs 139 +/- 18/78 +/- 10 mm Hg, p < 0.005). The magnitude of white coat effect was 50 +/- 17 (8-84) mm Hg for systolic blood pressure and 18 +/- 11 (-9 +/- 41) mm Hg for diastolic blood pressure. A marked white coat effect (> 40 mm Hg) was observed in 78% of our hypertensive patients. In elderly people (> 60 years), this difference was greater (50 +/- 15 vs 45 +/- 21 mm Hg) though not significantly. We did not find significant differences between sexes (males 54 +/- 16 mm Hg vs 48 +/- 17 mm Hg). In 66% of these patients, ambulatory blood pressure monitoring showed daytime blood pressure values < 140/90 mm Hg, therefore refractory hypertension was excluded. In 8 patients (18%) there was a previous history of ischemic cardiovascular or cerebrovascular disease and all of them had a marked difference between systolic clinic and daytime blood pressure (> 40 mm Hg). Blood pressure measurements performed out of hospital did not help clinicians to identify this phenomena as only 16% were similar (+/- 5 mm Hg) to ambulatory daytime values. CONCLUSIONS: Some hypertensive patients, on adequate antihypertensive treatment, have a significant difference between clinic blood pressure and ambulatory blood pressure measurements. This difference (White Coat Effect) is greater in elderly patients and in men (NS). Although clinic blood pressure values were significantly increased, the majority of these patients have controlled blood pressure on ambulatory monitoring. In this population, ambulatory blood pressure monitoring was of great value to identify a misdiagnosis of refractory hypertension, which could lead to improper decisions in the therapeutic management of elderly patients (increasing treatment) and compromise cerebrovascular or coronary circulation.     

Analysis of ambulatory blood pressure monitoring: the problem of 'white-coat' hypertension, responders and non-responders

OBJECTIVE: To analyse a randomized study undertaken to compare the antihypertensive efficacy of dihydropyridine calcium antagonists in patients with essential hypertension. METHOD: Blood pressure was measured both conventionally by a doctor and by non-invasive ambulatory monitoring. RESULTS: During amlodipine therapy (5 mg once a day for 4 weeks, n = 121), the mean daytime diastolic blood pressure was lowered by 8.2+/-7.1 and 0.9+/-7.4 mmHg (means +/- SD) in patients with a pretreatment daytime diastolic blood pressure >/= 90 (n = 89) and < 90 mmHg (n = 32), respectively. In 60 (67%) among the 89 patients who had an initial daytime diastolic blood pressure >/= 90 mmHg the daytime diastolic blood pressure was lowered by >/= 5 mmHg, with a mean fall of 12.0+/- 5.2 mmHg. The decrease in daytime diastolic blood pressure averaged 0.6+/- 3.5 mmHg in the remaining non-responder patients (n = 29). CONCLUSION:It seems important to evaluate the efficacy of a given antihypertensive drug by analysing patients with white-coat hypertension separately from responders to the medication. This allows one to gain maximum information concerning the effect of therapy in the individual hypertensive patients.     

Ambulatory blood pressure monitoring after successful repair of coarctation of the aorta at mid-term follow-up

Variations of systolic and diastolic blood pressure in patients with normotension at rest after successful surgical repair of coarctation of the aorta were examined using 24 hour ambulatory monitoring at mid-term follow-up. Ambulatory blood pressure monitoring, m-mode measurements of left ventricle and transmitral Doppler spectrals in 18 patients aged 7.6 +/- 4.5 years after 9 months to 6.1 years (2.5 +/- 1.9 years) following operation were compared with the findings in 18 matched controls. Patients had significantly higher mean systolic blood pressures (24 hours: 115 +/- 10 mmHg, awake: 119 +/- 11 mmHg and asleep: 106 +/- 8 mmHg) than controls (24 hours: 108 +/- 6 mmHg, awake: 112 +/- 7 mmHg and asleep: 101 +/- 7 mmHg) (p = 0.04, 0.03 and 0.03, respectively). Patients had also more systolic blood pressure readings above the 95th percentile for age (24 hours: 28 +/- 20%, awake: 39 +/- 27% and asleep: 12 +/- 14%) than controls (24 hours: 10 +/- 9%, awake: 14 +/- 13% and asleep: 1 +/- 4%) (p = 0.03, 0.002 and 0.007, respectively). No significant difference was found in diastolic blood pressure profiles. There were no significant differences in left ventricular m-mode measurements and diastolic function parameters. Left ventricular mass index was significantly increased in patients (81.7 +/- 28.7 g/m2) compared with controls (64.5 +/- 20.9 g/m2) (p = 0.03). Operation age and post-surgical period did not affect ambulatory blood pressure profiles at mid-term follow-up. Patients who are normotensive at rest after successful surgical repair of coarctation of the aorta show higher systolic blood pressure profiles than healthy children with ambulatory blood pressure monitoring at mid-term follow-up. Ambulatory blood pressure monitoring in patients operated on for coarctation of the aorta despite their good clinical status is useful to detect and monitor subtle abnormalities of blood pressure.     

Double blind comparative trial of Abana and methyldopa for monotherapy of hypertension in Indian patients

Abana is a herbomineral medicinal preparation with a property of down-regulation of beta-adrenergic receptors. A double-blind, parallel group study was conducted in 43 Indian men and women suffering from hypertension to evaluate the antihypertensive effect of Abana and compare it with that of methyldopa (M-DOPA). Twenty-one patients received 800 mg tds of Abana and 22 patients received 250 mg tds of M-DOPA for 4 weeks. Blood pressure and pulse rate were recorded at weekly intervals. Relevant clinical and biochemical investigations were carried out before and after treatment. In patients treated with Abana, there was a significant fall both in systolic B.P. (from 167 +/- 3.73 to 145 +/- 6.11 mmHg) and in diastolic B.P. (from 110 +/- 1.86 to 91 +/- 3.04 mmHg) at the end of 4 weeks. Similarly in patients treated with M-DOPA, systolic blood pressure was significantly reduced from 165 +/- 4.92 to 146 +/- 4.9 mmHg and diastolic blood pressure was reduced from 106 +/- 2.74 to 96 +/- 2.67 mmHg after 4 weeks. The onset of antihypertensive effect was earlier and there was a higher percentage of responders (80%) in the Abana-treated group. None of the patients had clinically or biochemically significant side-effects. The results of this study suggest that therapy with Abana proved highly effective in hypertensive patients.     

Twenty-four hour ambulatory blood pressure in the Hypertension Optimal Treatment (HOT) study

BACKGROUND AND AIMS: The Hypertension Optimal Treatment (HOT) study showed that when antihypertensive treatment reduces diastolic blood pressure well below 90 mmHg, there can be a further reduction of cardiovascular events, particularly myocardial infarction, with no evidence of a J-shaped curve at lower pressures. Office measurement, however, gives no information about blood pressure outside the office. This paper describes a HOT substudy in which patients underwent both office measurement and 24 h ambulatory blood pressure monitoring. METHODS: The mean age of the substudy population was 62 +/- 7 years. Substudy patients were treated for a median period of 2 years. All received the dihydropyridine calcium antagonist felodipine, while some also received an ACE-inhibitor, a beta-blocker or a diuretic. Average 24 h, day and night ambulatory blood pressure values were computed at baseline (n = 277) and during treatment (n = 347): 112 patients had been randomized to a target office diastolic blood pressure 相似文献   

Persistence of the antihypertensive effect of low-dose combination therapy in mild hypertension

The persistence of the antihypertensive effect of perindopril 2 mg + indapamide 0.625 mg once daily for up to 72 h was evaluated using the "missed-dose" technique. After 4 weeks on perindopril 2 mg+indapamide 0.625 mg, 79 of 216 hypertensive patients at goal (diastolic blood pressure < 85 mmHg) continued on perindopril 2 mg+indapamide 0.625 mg for a further 8 weeks. During either week 9 or 11, placebo was substituted for perindopril 2 mg+indapamide 0.625 mg on either 1 day or on 2 consecutive days. Twenty-four-hour ambulatory blood pressure was recorded at baseline, after 9 or 11 weeks of perindopril 2 mg+indapamide 0.625 mg and during the simulated missed doses, 24-48 and 48-72 h after perindopril 2 mg+indapamide 0.625 mg. Significant (p < 0.001) reductions in mean (+/- SD) 24-h blood pressure (mmHg) during the first 24 h after perindopril 2 mg+indapamide 0.625 mg vs baseline were noted for the two sub-groups subsequently allocated to one missed dose (-13.5 +/- 10.4/-8.0 +/- 6.6) or two missed doses (-12.2 +/- 7.4/-6.9 +/- 4.2). The antihypertensive effect persisted (p < 0.001 to p < 0.05 vs baseline) on the days when placebo was substituted for perindopril 2 mg+indapamide 0.625 mg with reductions in mean 24-h blood pressure from 24-48 h and 48-72 h after dosing being -11.6 +/- 9.6/-6.3 +/- 6.4 and -6.4 +/- 6.0/-3.9 +/- 4.2, respectively. Use of the "missed-dose" technique demonstrated persistence of an antihypertensive effect for perindopril 2 mg + indapamide 0.625 mg for up to 72 h after dosing.     

Comparison of telmisartan versus losartan: meta-analysis of titration-to-response studies

OBJECTIVES: To compare the ability of telmisartan and losartan to reduce mean diastolic blood pressure (DBP) during the last 6 h of the 24-h dosing interval in a prospectively planned meta-analysis of ambulatory blood pressure monitoring (ABPM) data from two independent studies. METHODS: Data were from two independent randomized, double-blind, double-dummy, titration-to-response studies conducted in patients with mild-to-moderate hypertension (seated cuff DBP 95-109 mmHg, 24-h mean ambulatory DBP >or=85 mmHg). After a 4-week placebo run-in period, patients received once-daily telmisartan 40 mg or losartan 50 mg, with up-titration after 4 weeks to telmisartan 80 mg or losartan 100 mg, respectively, if seated trough cuff DBP >or=90 mmHg. Blood pressures were recorded using ABPM immediately before randomization and after 8 weeks of active treatment. In addition, seated trough cuff blood pressures were measured at baseline and after 4 and 8 weeks of active treatment. RESULTS: Titration to the higher dose was required in 60.1% of telmisartan patients and 69.5% of losartan patients (P=0.01). Reductions from baseline in the last 6 h mean ambulatory DBP with telmisartan and losartan were 6.6+/-0.4 and 5.1+/-0.4 mmHg, respectively (P<0.01, adjusted for baseline and study); the effects were homogeneous across the two studies. During the last 6 h of the 24-h dosing interval, telmisartan produced greater reductions in each of the observed hourly mean ambulatory DBP values. Telmisartan-induced reductions were also greater for the majority of the observed hourly mean ambulatory DBP values over the entire 24-h dosing interval. Reductions from baseline in the last 6 h adjusted mean ambulatory systolic blood pressure (SBP) for telmisartan and losartan were 9.9+/-0.6 and 7.8+/-0.6 mmHg, respectively (P=0.01). The 24-h profiles of ambulatory SBP hourly mean reductions were similar to those for DBP. Both telmisartan and losartan were found to be safe and well tolerated. CONCLUSIONS: Telmisartan 40/80 mg is superior to losartan 50/100 mg in controlling DBP and SBP during the last 6 h of the 24-h dosing interval.     

Myths and reality concerning hypertension in peritoneal dialysis patients: results of a multicenter study

OBJECTIVES: To evaluate the prevalence of hypertension, the average blood pressure level, the 24 h blood pressure profile, and the efficacy of antihypertensive therapy for a large population of peritoneal dialysis patients.DESIGN: A cross-sectional, observational multicenter study. METHODS: From 504 peritoneal dialysis patients (18% of the Italian peritoneal dialysis population) involved in a multicenter observational study, we selected 414 who had undergone successful ambulatory blood pressure monitoring (i.e. no hours with data absent, >/= 75% successful readings and monitoring duration >/= 24 h). Office blood pressure measurements and ambulatory blood pressure monitoring were performed for each patient on the same day with a standard mercury sphygmomanometer and a SpaceLabs 90207 device, respectively.RESULTS: According to World Health Organization/International Society of Hypertension criteria, 44 peritoneal dialysis patients (10.6%) were normotensive and 370 patients (89.4%) were hypertensive, 304 (82.1%) of whom were being administered antihypertensive therapy. Daytime systolic and diastolic blood pressures were both significantly lower than office systolic and diastolic blood pressures (140.7 +/- 19.7/72.1 +/-11.1 versus 148.3 +/- 23.6/85.6 +/- 12 mmHg; P < 0.001). The difference between office blood pressure and daytime blood pressure was significantly correlated to office blood pressure (P < 0.001 for systolic and P < 0.001 for diastolic). The diurnal blood pressure rhythm evaluated by visual inspection of hourly mean plots was not influenced by sex, age, antihypertensive treatment, and peritoneal dialysis modality. Systolic and diastolic blood pressures exhibited a day-night mean decreases of 8.6 +/- 11.7 and 7.7 +/- 6.9 mmHg, respectively, and daytime blood pressure values were significantly higher than night-time ones (P < 0.001). Two hundred and twenty patients (53.1%) were nondippers according to O'Brien's criteria, 247 patients (59.7%) were nondippers according to Verdecchia's criteria, and 269 patients (65.0%) were nondippers according to Staessen's criteria. Only 39 patients (9.4%) had a reversed circadian rhythm. The day-night differences of systolic and diastolic blood pressures were in a unimodal distribution. Among hypertensive patients not being administered antihypertensive therapy, only six patients ( five women and one man) had white-coat hypertension. Among hypertensive patients being administered antihypertensive therapy, 235 patients (77.3%) had 24 h blood pressure loads > 30%.CONCLUSION: There is a high prevalence of hypertension among peritoneal dialysis patients. White-coat hypertension is very rare in this population. Despite the extensive use of antihypertensive therapy, control of blood pressure is maintained in a large number of our peritoneal dialysis patients. Any classification of patients into dipers and nondippers must be interpreted cautiously.     

Antihypertensive effect of valsartan 80 mg and hydrochlorothiazide 12.5 mg evaluated by ambulatory blood pressure monitoring

OBJECTIVE: The aim of the study was to evaluate by ambulatory blood pressure measurement (ABPM) the 24 hours antihypertensive efficacy of the fixed combination therapy, valsartan 80 mg + hydrochlorothiazide 12.5 mg (V + H), once daily, after 6 weeks of treatment, in patients with mild to moderate hypertension. STUDY DESIGN: It was a French, multicenter, double blind, randomized trial in parallel groups comparing V + H and placebo. After an initial two weeks placebo period, patients were assigned to receive either V + H or placebo for six weeks. Were eligible those with clinical arterial blood pressure, measured by sphygmomanometer, between 160/95 and 209/114 mmHg after monotherapy. A 26 hours ABPM, with Spacelabs 90,207, was done at J0 and J42 (one measurement every 15 minutes, in day time and at night). Responders were defined as a fall in day diastolic blood pressure > or = 5 mmHg and/or day diastolic blood pressure < 90 mmHg with ABPM. RESULTS: 123 of the 138 randomized patients had two interpretative measurements. Their average age was 59 + 10 years. 57% (78) of them were males and their average ABPM before treatment was 143 +/- 15/88 +/- 11 mmHg. With V + H, the reduction of the systolic and the diastolic blood pressure measured by ABPM, was significantly more important than with placebo (SBP: -15.4 +/- 10.9 mmHg versus -0.6 +/- 7.7 mmHg, p < 0.001; DBP: -9.1 +/- 7 mmHg versus -0.4 +/- 5.4 mmHg, p < 0.001). Pulse pressure (PP) was also significantly reduced with the combination therapy V + H, but it was not modified with placebo (-6.3 + 5.5 mmHg versus -0.2 + 4.1 mmHg, p < 0.001). ABPM responder rate was 73% with V + H versus 24% with placebo (p < 0.001). Trough/peak ratio was 80.3% for systolic blood pressure and 57.3% for diastolic blood pressure. The combination V + H was as well tolerated as placebo. CONCLUSION: The fixed combination V + H used for treatment of hypertension, after failure of monotherapy, is very effective in reducing pulse pressure, systolic and diastolic blood pressure, over 24 hours, homogeneously, and is as well tolerated as placebo.     

Persistence of the antihypertensive efficacy of amlodipine and nifedipine GITS after two 'missed doses': a randomised,double-blind comparative trial in Asian patients

Suboptimal management of hypertension is often a result of poor patient compliance in the form of missed doses of their antihypertensive medication. This multicentre, randomised, double-blind, parallel-group trial was designed to compare the persistence of the antihypertensive efficacy of the amlodipine and nifedipine gastrointestinal therapeutic system (GITS) after two 'missed doses', and also to compare the drugs' overall efficacy and safety in Asian patients with mild-to-moderate essential hypertension. Following a 2-week placebo run-in period, 222 patients were randomised to receive either amlodipine (5 mg daily, increased after 6 weeks if necessary to 10 mg daily, n=109) or nifedipine GITS (30 mg daily, increased after 6 weeks if necessary to 60 mg daily; n=113) for 12 weeks. A placebo was then substituted for further 2 days with continuous ambulatory blood pressure (BP) monitoring. The increases in the last 9 h of mean ambulatory BP on day 2 after treatment withdrawal were significantly less with amlodipine than with nifedipine GITS: 4.4+/-7.0 vs 11.2+/-11.3 mmHg for systolic BP (P相似文献   

Superiority of home blood pressure measurements over office measurements for testing antihypertensive drugs

OBJECTIVE: To compare the effects on office blood pressure and home blood pressure of placebo and active drug administration. DESIGN: After a 2-week wash-out period, patients with mild-to-moderate hypertension entered a 2-week single-blind placebo period and then a 4-week double-blind period. Patients were randomly assigned to be administered either 2 mg trandolapril once daily or its placebo in a 2:1 proportion. Office blood pressure was measured by a physician at the end of each period, using a mercury sphygmomanometer (mean of three consecutive measurements). Home blood pressure was measured during the last week of each period according to standard procedure carefully taught to each patient by the physician. Compliance was checked by using electronic pill boxes. RESULTS: Data for 34 of the 44 patients who entered the study were eligible for analysis. Baseline systolic blood pressure/diastolic blood pressure were significantly (P = 0.0001/P = 0.0001) higher for office blood pressure (161/101 mmHg) than they were for home blood pressure (145/93 mmHg). There was no statistically significant difference between the placebo and active-treatment groups at baseline. During the single-blind period, blood pressures measured at the office and at home did not change significantly. Office blood pressure decreased by 2.7 +/- 10 mmHg for systolic blood pressure and by 0.5 +/- 4 mmHg for diastolic blood pressure whereas home blood pressure increased by 0.8 +/- 6 mmHg for systolic blood pressure and by 0.7 +/- 4 mmHg for diastolic blood pressure. During the double-blind period, office blood pressure fell significantly with trandolapril treatment (systolic by 10.2 +/- 12 mmHg, diastolic by 8.3 +/- 6 mmHg; P = 0.0005/0.0001, versus single-blind placebo period) but this decrease was not significantly different (P = 0.45/0.92) from the fall in members of the placebo group (systolic by 6.9 +/- 9 mmHg, diastolic by 8.0 +/-6 mmHg; P = 0.04/0.002, versus single-blind placebo period). Thus, no antihypertensive effect of trandolapril was demonstrated. The fall lin home blood pressure with trandolapril treatment was significant (systolic by 10.7 +/- 8 mmHg, diastolic by 5.8 +/- 5 mmHg; both P = 0.0001, versus single-blind placebo period) and was significantly greater (P = 0.0004/0.004) than the minimal change observed with placebo (systolic fell by 0.2 +/- 5mmHg, diastolic fell by 0.6 +/- 4 mmHg; P = 0.90/0.62, respectively, versus single-blind placebo period). The evening decrease in home blood pressure was similar to the morning decrease in home blood pressure in members of the trandolapril-treated group. The resulting morning:evening decrease in blood pressure ratio was 0.83 for diastolic blood pressure and 0.95 for systolic blood pressure. For the subgroup of responders, mean of individual ratios was 0.77 +/- 0.43 for diastolic blood pressure and 0.70 +/- 0.39 for systolic blood pressure. CONCLUSION: The placebo effect observed with office blood pressure measurements does not occur with home blood pressure measurements. Expected treatment effect can alter a physician's blood pressure readings. The precision of measurements is greater with home blood pressure (there is a lower SD). Use of home blood pressure measurements increases the power of comparative trials, allowing one either to study fewer subjects or to detect a smaller difference in blood pressure.     

Uncontrolled early morning blood pressure in medicated patients: the ACAMPA study. Analysis of the Control of Blood Pressure using Abulatory Blood Pressure Monitoring

BACKGROUND: A blood pressure surge during the early morning may help to precipitate cardiovascular events. The objective of this study was thus to assess the blood pressure behaviour profile of early morning blood pressure in patients receiving antihypertensive treatment. DESIGN: The ACAMPA study is a multi-center, open, prospective, observational study that was carried out by 24 investigators in Spain. METHODS: Two hundred and ninety patients with essential hypertension who had been receiving the same antihypertensive treatment for at least 2 months were included in the study. Office blood pressure was measured before taking medication in the morning, and 24-h ambulatory blood pressure monitoring was performed. In addition to the automatic measurements, patients were instructed to take a blood pressure measurement after waking. RESULTS: The group analysis used 240 patients (mean age 54 years, including 101 males). Good clinical control (a blood pressure of less than 140/90 mmHg) was found in 53 cases (22%). The differences between the clinical and ambulatory readings during the period of activity were minimal in the group with good control (127 +/- 9/81 +/- 7 versus 127 +/- 10/81 +/- 7 mmHg; non-significant) but were significant in the group with poor control (155 +/- 16/93 +/- 10 versus 138 +/- 14/86 +/- 11 mmHg; P < 0.001). The blood pressure values were synchronized according to the moment of awakening. In almost half of the patients with good control, systolic and diastolic blood pressure values were higher than normal (135/85 mmHg); in those patients with poor control, this fraction rose to over 70%. The proportion of patients presenting high blood pressure values became even greater during the second hour after waking (62% in patients with good blood pressure control and 82% in those with poor control). CONCLUSIONS: In a large number of antihypertensive patients receiving treatment, blood pressure values remain high during the early-morning hours. At least half of those patients with an apparently well-controlled office blood pressure do not have their blood pressure under control for the period shortly after waking.