Effects of slow-release nifedipine on nighttime blood pressure

With the advent of long-acting or slow-release antihypertensive drugs, we should be aware of a fall in nighttime blood pressure (BP) as well as daytime blood pressure. In the present study, casual BPs at the physician's office as well as ambulatory BP was recorded every hour throughout 24 hours with a noninvasive automated BP monitoring device in 24 essential hypertensives treated with slow-release nifedipine. Administration of slow-release nifedipine (20-40 mg, b.i.d.) decreased not only casual BPs but also ambulatory mean BP during the whole day or daytime (6 am to 10 pm). Slow-release nifedipine at 10 mg in the morning did not affect casual BPs at the office. However, mean BP obtained by ambulatory BP monitoring during the daytime was significantly attenuated. In addition, a profound fall in mean BP amounting to more than 20 mmHg during the night in some of the patients was observed during treatment with slow-release nifedipine not only at 20-40 mg (b.i.d.) but also at 10 mg once a day. These results suggest that we have to take into consideration the possibility that long-acting hypotensive agents may cause a great fall in nighttime BP during sleep, especially in the elderly.     

Clinical significance of ambulatory blood pressure monitoring. Evaluation of severity of hypertension, efficacy of treatment and effects on nighttime blood pressure

Blood pressure (BP) obtained by the physician in his office and ambulatory BP recorded every hour throughout 24 hours with a noninvasive automated BP monitoring device were compared in 10 normotensives and 162 hypertensives. Casual BPs significantly correlated with averages in ambulatory BPs (ABPs) throughout the whole day, day (7 am - 10 pm) and night (0-5 am). However, it was noted that 6 of 10 normotensives and all of the moderate to severe hypertensives had ABPs of more than 150/90 mmHg at least once during the 24-hour period. The incidence of ABPs greater than 150/90 mmHg among all readings was higher in untreated and treated hypertensives with diastolic BPs in the office of more than 105 mmHg, and, when checked along with the clock time, higher not only in the morning but also in the evening. On the other hand, one-third or one-fifth of treated hypertensives with diastolic office BPs less than 90 mmHg or between 90 and 105 mmHg respectively had ABPs less than 150/90 mmHg throughout the whole day. When the effect of nicardipine (60 mg, t.i.d.) or slow-release nifedipine (27.3 +/- 3.0 mg, b.i.d.) on minimum BP during the night was analyzed, long-acting nifedipine decreased BP throughout the night to levels not significantly different from normotensive controls, whereas short-acting nicardipine did not affect nighttime BPs. These results suggest that simple ABP monitoring throughout the day gives us useful information to evaluate the severity of hypertension and the efficacy of antihypertensive medication as well as to avoid overtreatment with long-acting hypotensive agents resulting in a great fall in BP during sleep.     

Comparison of atenolol, amlodipine, enalapril, hydrochlorothiazide, and losartan for antihypertensive treatment in patients with obstructive sleep apnea

We compared the effects of atenolol (50 mg), amlodipine (5 mg), enalapril (20 mg), hydrochlorothiazide (25 mg), and losartan (50 mg) given in once-daily oral doses on office and ambulatory blood pressures (BPs) in patients with hypertension and obstructive sleep apnea (OSA). Each of 40 randomized patients was treated in sequence with two of the five agents (balanced incomplete block design). Treatment periods lasted 6 wk and were separated by a 3-wk washout period. Changes in BP from baseline with the study substances were compared through analysis of variance. Office diastolic BP, our primary outcome variable, was most effectively lowered by atenolol, with all four post hoc differences between atenolol and the remaining substances being statistically significant. Reductions in office systolic and daytime ambulatory BP were not significantly different among the five compounds. However, atenolol reduced mean nighttime ambulatory diastolic and systolic BP more effectively than did amlodipine, enalapril, or losartan (but not hydrochlorothiazide). Severity of sleep-disordered breathing and well-being during the day were not significantly influenced by any of the study compounds. Our findings are in accordance with the hypothesis that an overactivity of the sympathetic nervous system is an important mechanism behind the development or maintenance of hypertension in patients with OSA.     

Effect of enalapril at rest, during tilt, static and dynamic exercise in systemic hypertension

Using the “Oxford system” for ambulatory monitoring of direct arterial blood pressure (BP), the hypotensive effect of enalapril (20 to 40 mg/day), was assessed in 15 patients with essential hypertension. BP was reduced by enalapril throughout the 24 hours of study. A within-patient comparison of corresponding mean hourly systolic and diastolic BP values showed a reduction from (p <0.05 to p <0.001) for 18 of the 24 hours. Four patients had an increase in BP during treatment with enalapril. There was a significant decrease in systolic BP in response to 60° head-up tilt. During isometric and dynamic exercise there was a smaller increase in systolic BP but a less marked effect on diastolic BP. Heart rate was unaffected either during free ambulation or during physiologic testing. The incidence of side effects was low. These results indicate that enalapril administered once daily may be an effective form of antihypertensive therapy. However, there is a group of patients who are unresponsive to treatment with converting enzyme inhibitors.     

Crossover comparison of atenolol, enalapril, hydrochlorothiazide and isradipine for isolated systolic systemic hypertension.

The benefit of antihypertensive therapy in reducing cardiovascular morbidity and mortality associated with isolated systolic hypertension has now been established by the Systolic Hypertension in the Elderly Program. However, there is little information about the relative effectiveness of different drug regimens in this condition. This study compared the efficacy and tolerability of 50 mg of atenolol, 10 mg of enalapril, 25 mg of hydrochlorothiazide and 2.5 mg of isradipine in the treatment of isolated systolic hypertension. After a 3-week placebo run-in phase, 24 subjects were randomized into a 4-period double-blind crossover study by use of an orthogonal latin square design. Treatment periods were of 6 weeks' duration with titration to a higher dose after 4 weeks in those not reaching goal blood pressure (BP). Each active treatment was followed by a 3-week placebo washout. Casual clinic and 24-hour ambulatory BP (Accutracker II) were measured at the end of each treatment phase. Routine biochemistry was also performed after the placebo run-in, at the end of each active treatment phase, and after the placebo run-out. Of the 24 subjects entered (mean age 72.3 years, 38% men) 20 completed the whole study. Mean +/- standard deviation of supine clinic and daytime ambulatory BP on entry were 181/79 +/- 21/9 mm Hg and 165/82 +/- 23/15 mm Hg, respectively. All drugs reduced mean casual and ambulatory BP significantly relative to placebo but only hydrochlorothiazide and enalapril produced a consistent hypotensive effect throughout the entire 24-hour period. Isradipine and enalapril exhibited a relatively greater effect on reducing systolic BP than either hydrochlorothiazide or atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)     

A randomised, placebo-controlled, double-blind, crossover study of losartan and enalapril in patients with essential hypertension

The primary objective of this randomised, placebo- controlled, double-blind, crossover study, was to evaluate and compare the longer term effects of the angiotensin II type 1 receptor antagonist losartan and the converting enzyme inhibitor enalapril on 24-h ambulatory blood pressure (BP). After a 4-week placebo run-in period, nine patients with essential hypertension entered the double-blind phase of the study, which consisted of three 6-week periods during which patients were treated with placebo, enalapril 20 mg o.d. or losartan 50 mg o.d. Losartan and enalapril, taken between 07.00 and 08.00, reduced ambulatory BP throughout the 24-h period. Average night time BP was reduced from 133/85 mm Hg on placebo to 124/78 mm Hg on enalapril and to 126/77 mm Hg on losartan. Daytime BP averaged 157/101 mm Hg on placebo, and was significantly lower during enalapril (142/91 mm Hg) than during losartan treatment (147/95 mm Hg). Clinic BP, measured 2 to 4 hours after drug intake, was reduced to the same extent by both drugs. The losartan-induced BP changes were significantly related to those obtained with enalapril (0.63 < r < 0.93). Ambulatory BP monitoring was repeated after 4 weeks of combined therapy in six patients. The BP lowering effect of the combination was not significantly better than that achieved with enalapril alone. In conclusion, losartan 50 mg o.d. and enalapril 20 mg o.d. lower BP to approximately the same extent, except for a more pronounced effect of enalapril on daytime ambulatory BP. The current study does not provide convincing evidence that addition of losartan to enalapril in the doses used further reduces BP.     

Evaluation of borderline arterial hypertension in young adults by ambulatory arterial pressure measurements

Casual measurements of blood pressure (BP) with a mercury manometer and ambulatory BP recordings with the Spacelabs apparatus at the rate of one measurement every 15 minutes during 24 hours were carried out in two groups of young male adults of the same age. One group consisted of 105 normotensive controls (age 21.2 +/- 1.5 years, weight 69 +/- 8 kg, height 177 +/- 8 cm, casual BP 129/75 mmHg). The other group comprised 104 subjects with borderline hypertension (BHT) as defined by the WHO criteria (age 21.2 +/- 1.6 years, weight 74 +/- 12 kg, height 177 +/- 7 cm, casual BP 148/83 mmHg). Mean levels of recorded BP in controls were: 24 hours 122/70 mmHg, active periods (9 a.m. to 8.30 p.m.) 128/74 mmHg, night 111/64 mmHg. The corresponding values in BHT subjects were: 24 hours 132/83 mmHg, active periods 137/79 mmHg, night 118/67 mmHg. There was no difference between mean casual BP measurements and mean BP recordings during periods of activity in controls, whereas BP recordings during periods of activity were lower in BHT subjects. Results of the two measurement methods showed important individual variations. BP variability (variation coefficient = VC) in BHT subjects was more pronounced in respect of systolic arterial pressure than in controls: Syst VC 24 h: Contr. 12 p. 100, BHT 13 p. 100, p less than 0.001; Diast VC 24 h: Contr. 17 p. 100, BHT 18 p. 100, p less than 0.05. In both populations there was no difference in VC between night and day.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of atenolol and diltiazem-SR on exercise and pressure load in hypertensive patients

The effects of monotherapy with atenolol or diltiazem-SR on blood pressure, 24-h blood pressure (BP) load, and exercise capacity were tested in patients with mild to moderate (stages I and II) essential hypertension. After 3-week single blind placebo therapy, patients with sitting diastolic blood pressure (SDBP) of 94-114 mmHg were randomized to atenolol 50 mg/day (62 patients) or diltiazem-SR 90 mg b.i.d. (60 patients) in a double-blind parallel study. Depending on SDBP response, the dose was increased to 100 mg/day for atenolol and 180 mg b.i.d. for diltiazem-SR. Twenty-four-hour ambulatory blood pressure measurements and exercise tolerance lest by the Bruce protocol were done at the end of placebo and active treatment. Compared with placebo, both atenolol and diltiazem-SR significantly decreased heart rate (HR), sitting systolic blood pressure (SSBP), SDBP, ambulatory BP, BP load for waking and sleeping hours, area under the BP curve, rate-pressure product (p < 0.001), and exercise time (NS). Atenolol exerted a greater effect on ambulatory BP, HR, rate-pressure product, waking diastolic BP load, and area under the 24-h BP curve. The drugs were well tolerated and caused no serious side effects necessitating discontinuation of treatment. These findings indicate that (1) monotherapy for hypertension with atenolol or diltiazem SR is effective and well tolerated, (2) it decreases the 24-h BP load, (3) it does not interfere with exercise capacity.     

Differential effects of once-daily antihypertensive drugs on blood pressure,left ventricular mass and sympathetic activity: Nifedipine-GITS versus felodipine-ER versus enalapril

BACKGROUND: Recent meta-analyses suggest that once-daily dihydropyridines and angiotensin-converting enzyme inhibitors cause similar decreases in left ventricular (LV) mass for comparable decreases in blood pressure (BP). However, some dihydropyridines, such as felodipine-extended release (ER), still increase sympathetic activity and may, therefore, be less effective in decreasing LV mass. OBJECTIVES: To evaluate the effects of long term antihypertensive treatment with nifedipine-gastrointestinal therapeutic system (GITS) and felodipine-ER compared with enalapril on LV mass relative to the extent of BP control (assessed by 24 h ambulatory BP monitoring) and sympathetic activity (assessed by plasma catecholamine concentrations). PATIENTS AND METHODS: Enalapril was started at 10 mg/day, felodipine-ER at 5 mg/day and nifedipine-GITS at 30 mg/day, all once daily. Doses were increased to 20 mg/day, 10 mg/day or 60 mg/day, respectively, if the office BP remained 160/90 mmHg or greater at the end of the dosing interval. Evaluable echocardiograms were obtained for 116 patients at the end of the study (30 weeks of treatment). RESULTS: On 24 h ambulatory BP monitoring, nifedipine-GITS caused a consistent decrease in BP throughout the 24 h dosing interval, whereas felodipine-ER caused a more marked fall in BP during the day, and enalapril's effects diminished during the night and had disappeared by the morning. Only felodipine-ER significantly increased supine and standing plasma noradrenaline by more than 50% similarly after six, 18, and 30 weeks of treatment. In BP responders (decrease in systolic BP 10 mmHg or greater), enalapril and nifedipine-GITS caused clear decreases in LV mass by 12 to 16 g/m2, whereas felodipine-ER was less effective (decrease by only 6 g/m2, P<0.01 versus enalapril). CONCLUSIONS: Once-daily dihydropyridines should not be regarded as one homogeneous class and, compared with felodipine-ER, nifedipine-GITS exhibits a better profile regarding 24 h BP control, sympathetic activation and regression of LV mass.     

The effect duration of candesartan cilexetil once daily, in comparison with enalapril once daily, in patients with mild to moderate hypertension

OBJECTIVE: To determine the antihypertensive efficacy, effect duration and safety of the angiotensin II type 1 receptor blocker candesartan cilexetil and the angiotensin converting enzyme inhibitor enalapril once daily in patients with mild to moderate hypertension. METHODS: A multicenter, randomised, double-blind parallel group study was performed in Finland, France, the Netherlands, Spain and Sweden. Three-hundred-and-ninety-five men and women in the age range 20-80 years with primary hypertension were randomised to an 8-week double-blind treatment period with either candesartan cilexetil 8-16 mg or enalapril 10-20 mg once daily, with forced dose titration after 4 weeks. Non-invasive ambulatory blood pressure was measured for 36 h at baseline and after 8 weeks. The primary efficacy variable was the change in mean diastolic and systolic ambulatory blood pressure 22-24 h post-dose. RESULTS: There was a significant difference in the adjusted mean difference for the change from baseline to week 8 between candesartan cilexetil and enalapril 22-24 h post-dose by -3.5 mmHg (95% confidence interval, CI: -6.8 to -0.3 mmHg; p < 0.032) in ambulatory systolic blood pressure and -3.0 mmHg (95% CI: -5.1 to -0.8 mmHg; p < 0.008) in ambulatory diastolic blood pressure. There was a significant difference in adjusted mean daytime ambulatory blood pressure 24-36 h post-dose by -4.2 mmHg (95% CI: -6.8 to -1.6 mmHg; p < 0.002)/-3.5 mmHg (95% CI: -5.1 to -1.8 mmHg; p < 0.001). Both drugs were generally well tolerated. CONCLUSION: The results of the present study suggest that advantages may be attributed to the use of candesartan cilexetil, as compared to enalapril in the treatment of patients with essential hypertension. In comparison with enalapril 20 mg, candesartan cilexetil 16 mg more effectively lowered blood pressure at trough and in particular on the day following the day after the last dose.     

A pressure-time index' for assessing the severity of essential hypertension.

OBJECTIVE: A new derivative of 24 h ambulatory blood pressure monitoring (ABPM) is introduced and its association with left ventricular mass index (LVMI) in essential hypertension is examined. PATIENT: population One hundred and fifty-three previously untreated essential hypertension patients. METHODS: Patients underwent casual blood pressure (BP) readings, 24 h ABPM and left ventricular echocardiographic assessment The following 24 h awake and sleep ABP variables were calculated: mean systolic and diastolic BP, systolic and diastolic BP loads (percentage of systolic readings > 140/120 mmHg (day/ night) and diastolic readings > 90/80 mmHg (day/night)), standard deviation of systolic and diastolic ABP and nocturnal fall of systolic BP, as well as the integrated areas under the ABP curve. The area under the BP curve divided in horizontal slices was accurately modelled by a sigmoid curve. The parameters controlling the shape of the curve and in particular that regarding its 'slope' is hereafter called the 'pressure-time index'. RESULTS: 'Systolic pressure-time index 24 h' (SPTI24) is related to left ventricular mass index (multivariate analysis, P= 0.008). Using either partial correlation coefficients or a multivariate analysis, SPTI24 is related to left ventricular mass index, independently of age, casual blood pressure, mean systolic and diastolic ABP, systolic and diastolic BP loads, BP variability (standard deviation (SD), nocturnal fall of systolic BP) and integrated area under the curve (multivariate analysis, P= 0.004). CONCLUSIONS: In essential hypertension, the SPTI24 is related to LVMI independently of age, casual blood pressure, integrated area under the curve or any other derivative of 24 h ABPM, and might be used to assess the extent of hypertensive load.     

The effects of enalapril on basal arterial pressure at rest and during exercise and on cardiac performance in hypertensive athletes

A dose of 10 mg of enalapril was administered once a day to regularly trained hypertensive athletes (mean age 39 +/- 8.9 range 29-51) in order to evaluate the effect of the drug on ambulatory blood pressure and on blood pressure and physical performance during stress testing. STUDY DESIGN. This investigation was a randomized, double blind, cross-over versus placebo trial. At first, subjects whose blood pressure met the entry criteria (casual diastolic blood pressure greater than or equal to 95 mmHg), were subjected to 24-hour ambulatory blood pressure monitoring and maximal upright bicycle stress testing including measurement of O2 uptake. Then they were randomly assigned to treatment with placebo or enalapril. After one month they repeated stress testing and then they were crossed over. Stress testing was repeated in all subjects after two months. The 24-hour ambulatory blood pressure monitoring was repeated in all subjects during enalapril treatment only, by a non-blind investigator. RESULTS. Ambulatory blood pressure decreased significantly during enalapril and no changes in heart rate were observed during the monitoring. The results of bicycle stress testing, both in basal and during the placebo test were comparable as regards blood pressure response, maximal workload, effort duration, maximal heart rate and VO2 max. With enalapril systolic and diastolic blood pressure decreased significantly during stress testing both versus basal test and placebo test at each workload considered including maximal workload. No changes were observed during enalapril as regards maximal workload, effort duration, maximal heart rate and VO2 max. CONCLUSION. Our results suggest that enalapril could be effective in treating hypertensive athletes because it reduces blood pressure during physical effort without affecting physical performance. We conclude that enalapril could be considered a first-choice drug in hypertensive athletes doing aerobic sports.     

Predicting the blood pressure response to atenolol

The fall in blood pressure in response to atenolol 50 mg per day has been estimated using ambulatory BP and heart rate monitoring during the day in 35 mild to moderate hypertensive patients. The fall in pressure for the group averaged 18.2 +/- 11.3/11.5 +/- 8.3 mmHg. The 95% confidence internals were 14.5-22.0 mmHg systolic and 8.8-14.3 mmHg diastolic with the individual responses in diastolic pressure being related to the pretreatment variability of diastolic pressure (r = 0.65 P less than 0.001) and to the initial heart rate (r = 0.35 P less than 0.05). With atenolol treatment the BP fall is greater in patients with a more unstable BP. Blood pressure reduction is achieved by reducing the level of cardiac activity.     

A Method to Define Reference Profiles for Ambulatory Blood Pressure,with Application to Blood Pressure Profiles in 158 Young Subject

ABSTRACT

Ambulatory blood pressures (systolic, SBP, diastolic, DBP) and heart rate were determined over 24h every 15min in the day and every 15min in the night in 72 normal subjects aged 21±1SEM with normal casual office pressures (WHO's criteria: officeDBP ≤ 90mmHg, officeSBP ≤ 140mmHg) and in 86 essential hypertensive subjects aged 21±1, with borderline office pressure (WHO's criteria: officeDBP ≤ 95mmHg, officeSBP ≤ 160mmHg). Complete 24-hour profiles (mean±SD) were reported. In the average, mean ambulatory DBP in the normal group was about 72.5mmHg in “day time” (9 a.m.-9 p.m.) and 63.5mmHg in “night time” (midnight-7 a.m.). Ambulatory SBP in the normal group were about 126mmHg and 110mmHg for the same time periods. In the borderline hypertensive group, the figures were 74mmHg (day-time) and 67mmHg (night time) for diastolic pressure and 140mmHg (day time) and 118mmHg (night time) for systolic pressure. However, when the normal and borderline groups were defined as above on the basis of office pressures, ambulatory blood pressure profiles in the two groups showed a large overlap. A method was proposed to reduce this overlap by partially reallocating the subjects on the basis of ambulatory blood pressure. First, a typical profile was defined for each group and a distance was defined between two arbitrary profiles. Then a subject in the normal (resp. hypertensive) group was reallocated to the hypertensive (normal) group if his profile was closer to the typical profile of the hypertensive (normal) group than the typical profile of his own group. Applied to ambulatory DBP profiles, this method reallocated 49 subjects (over the total of 158), significantly reduced the initial overlap of BP profiles between the two groups, and defined reference profiles for “normal” and “borderline” ambulatory blood pressures.     

Relation of regression of left ventricular hypertrophy to changes in ambulatory blood pressure after long-term therapy with perindopril versus nifedipine.

Casual as well as ambulatory 24-hour blood pressure (BP) and echocardiographic parameters were studied in 40 patients with untreated or insufficiently treated mild to moderate essential hypertension. Left ventricular (LV) hypertrophy was assessed before and after 24 weeks of therapy with either the converting enzyme inhibitor perindopril or the calcium antagonist nifedipine. The design was a double-blind parallel study with a placebo run-in period. Patients received a daily oral dosage of either 4 to 8 mg of perindopril or 40 to 80 mg of nifedipine in slow-release form. A diuretic (25 mg/day of hydrochlorothiazide) was added in nonresponders (greater than 90 mm Hg casual diastolic BP). Once-daily perindopril and twice-daily nifedipine comparably reduced both casual and ambulatory BP throughout 24 hours (p less than 0.01) without affecting 24-hour heart rate. Six subjects withdrew from the nifedipine group and 4 from the perindopril group. After 12 and 24 weeks of therapy, LV hypertrophy was significantly reduced by both agents. Before active treatment was begun, LV mass index was more closely correlated to 24-hour (p less than 0.001) than to casual BP. This correlation disappeared after treatment with both agents. The correlation between ambulatory systolic day-time BP and LV mass was only still present (r = 0.54; p less than 0.05) after 24 weeks of treatment with nifedipine. It is concluded that regression of LV hypertrophy during converting enzyme inhibition or calcium antagonism may be partly independent of dosage and magnitude of 24-hour BP decrease.     

Twenty-four hour blood pressure effect of once-daily lisinopril, enalapril, and placebo in patients with mild to moderate hypertension.

This multicentre, double-blind, parallel-group, placebo-controlled study compared the antihypertensive effects of equal doses of two long-acting angiotensin converting enzyme (ACE) inhibitors. After a two-week, placebo run-in phase, 110 patients with mild to moderate hypertension were randomised to receive 10 mg lisinopril or enalapril, or placebo for 4 weeks. Office BPs were measured at regular intervals throughout the study. Twenty-four hour ambulatory blood pressure (ABP) was measured at baseline and after the first and final doses of study drug. Serum ACE activity and aldosterone were obtained concomitantly with each ABP monitoring. Office BP differences from placebo reached (P less than 0.05) or approached (P less than 0.10) statistical significance at all observations for the lisinopril group but were not significant for any observation in the enalapril group and approached significance on two occasions. After four weeks of treatment, ABP analysis revealed that the lisinopril and enalapril groups, when compared with placebo, had similar and significant systolic and diastolic AUC reductions (P less than 0.01) from baseline over the 24 h dosing interval. During the second half of the dosing interval, 13-24 h post drug administration, the lisinopril group was significantly different from placebo (systolic BP, P = 0.002; diastolic BP, P = 0.005) while the enalapril group was not. Both drugs were well tolerated. The results indicate that monotherapy with 10 mg of lisinopril is as effective as with 10 mg of enalapril, and that ABP monitoring is useful in more precisely depicting the clinical effect of the known pharmacokinetic properties of these two agents.     

Ambulatory Blood Pressure Monitoring in Patients with Essential Hypertension Treated with a New Calcium Antagonist, Cilnidipine

Cilnidipine (FRC-8653), a new dihydropyridine calcium antagonist, was given to 14 hospitalized patients with essential hypertension, and 24-hour ambulatory blood pressure (BP) monitoring was performed. Once-daily administration of cilnidipine (5–20 mg) for 1–3 weeks decreased the 24-hour average BP significantly from 149 ± 4/88 ± 2 mmHg to 141 ± 3/82 ± 2 mmHg without any change in the pulse rate. The decrease in ambulatory BP by cilnidipine was evident during the daytime (156 ± 4/93 ± 2 mmHg to 143 ± 5/84 ± 2 mmHg, p > 0.01 for systolic BP and p > 0.01 for diastolic BP), while it was mild during nighttime (141 ± 4/80 ± 2 mmHg to 133 ± 4/76 ± 3 mmHg, p > 0.05 for systolic and ns for diastolic BP). The decrease in the ambulatory BP over the whole day and during the nighttime was significantly correlated with the basal ambulatory BP levels. When the subjects were divided into the high ambulatory BP (n = 7) and low ambulatory BP (n = 7) groups, the BP reduction by cilnidipine was evident throughout 24 hours in the high ambulatory BP group, while it was mild and significant only during daytime in the low ambulatory BP group. In summary, once-daily cilnidipine exerts a sufficient and prolonged reduction of BP without an increase in the pulse rate in patients with hypertension. The potency of cilnidipine to decrease ambulatory BP may depend on the basal ambulatory BP level. Cilnidipine is thus a useful antihypertensive drug that may not cause an excessive decrease in BP or a reflex tachycardia.     

Efficacy and safety of telmisartan, a selective AT1 receptor antagonist, compared with enalapril in elderly patients with primary hypertension. TEES Study Group

OBJECTIVE: To assess the antihypertensive efficacy and safety of the novel AT1 receptor antagonist, telmisartan, compared with that of enalapril in elderly patients with mild to moderate hypertension. DESIGN: A 26-week, multicenter, double-blind, parallel-group, dosage titration study. METHODS: A total of 278 patients aged > or = 65 years were randomized to eithertelmisartan or enalapril once a day. The telmisartan dosage was increased from 20 to 40-80 mg and that of enalapril from 5 to 10-20 mg at 4-week intervals until trough supine diastolic blood pressure was < 90 mmHg. After 12 weeks, hydrochlorothiazide at 12.5-25 mg once a day was added to the treatment regimen of those patients not controlled on monotherapy. RESULTS: Both treatments lowered blood pressure in a comparable and clinically meaningful manner. The adjusted mean changes from baseline in supine diastolic blood pressure at trough were -12.8 mmHg for telmisartan and -11.4 mmHg for enalapril (P = 0.074). Mean changes in supine systolic blood pressure were -22.1 mmHg for telmisartan and -20.1 mmHg for enalapril (P = 0.350). Overall, 63 and 62% of patients responded to telmisartan and enalapril, respectively, with a supine diastolic blood pressure of < 90 mmHg. Both regimens provided effective blood pressure lowering over the 24 h dosing interval, as determined by ambulatory blood pressure monitoring. Both regimens were well tolerated; however, patients on the enalapril regimen had more than double the incidence of treatment-related cough compared with those on the telmisartan regimen (16 versus 6.5%). CONCLUSIONS: These results demonstrate that telmisartan is well tolerated and is at least as effective as enalapril in treating elderly patients with mild to moderate hypertension.     

Antihypertensive effects of beta-blockers administered once daily: 24-hour measurements

Whole-day automated ambulatory blood pressure (BP) monitoring was used to assess the duration of the antihypertensive actions of the beta-blockers atenolol (50 to 100 mg; n = 20) and acebutolol (400 to 800 mg; n = 19) each given once daily at 9 AM. When compared with its pretreatment 24-hour average, atenolol decreased diastolic BP by 10 +/- 2 mm Hg (p less than 0.01) and systolic BP by 12 +/- 2 mm Hg (p less than 0.01). Acebutolol decreased the 24-hour diastolic BP by 11 +/- 1 mm Hg (p less than 0.01) and systolic BP by 13 +/- 2 mm Hg (p less than 0.01). More specifically, a comparison of the two drugs during the final 6 hours (3 AM to 9 AM) of the dosing interval showed that the mean decrease in diastolic BP of 10.2 +/- 1.5 mm Hg with acebutolol was greater (p less than 0.05) than the decrease of 6.2 +/- 1.3 mm Hg with atenolol. Moreover, this final 6-hour effect of atenolol was less (p less than 0.01) than that observed during the first 18 hours of the day. The late effects of acebutolol did not change significantly from its early effects. The two agents also differed in their trough (final 2-hour decrease in diastolic BP) and peak (maximum 2-hour decrease in diastolic BP) effects: for atenolol the peak-to-trough difference was 7.8 +/- 3.1 mm Hg (p less than 0.05), whereas for acebutolol it was 3.8 +/- 4.2 mm Hg (N.S.). This study confirms the efficacy of atenolol and acebutolol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Primary arterial hypertension. 24-hour recording or casual blood pressure measurement?]

In 134 patients with essential hypertension 24-hour blood pressure ambulatory monitoring (ABPM) as well as traditional blood pressure measurements (casual BP) were performed. Maximal and mean whole-day systolic and diastolic blood pressure values in ABPM were compared with casual BP (using test t). The casual BP was also compared with mean systolic and diastolic blood pressure values calculated separately in three eight-hours periods of day. Maximal BP values in ABPM were significantly higher and mean significantly lower than casual BP values. Blood pressure registered during work hours was closest to casual BP values. Blood pressure in the evening was similar to whole-day blood pressure mean. The results indicate, that automatic blood pressure monitoring performed in this period of day has the greatest diagnostic value because it could be free from "white coat hypertension" syndrome.