Effects of graded-release diltiazem versus ramipril, dosed at bedtime, on early morning blood pressure, heart rate, and the rate-pressure product

Background

Therapeutic agents for the treatment of hypertension may differ in their efficacy during the early morning period, a time when both morbid and mortal cardiovascular events are increased compared to other times of the day.

Methods

We studied the effects of a graded-release delivery system of diltiazem (diltiazem HCL extended release tablets) versus ramipril, both dosed at bedtime, on blood pressure (BP), heart rate, and the heart rate-systolic BP product during the first 4 hours after awakening in a double-blind, titration-to-effect trial. There were 261 men and women enrolled in the trial with an untreated sitting diastolic BP of 90 to 109 mm Hg and ambulatory daytime diastolic BP of 85 to 109 mm Hg. Patients were randomized to either diltiazem extended release (ER) tablets each evening (240 mg titrated to 360 mg and to 540 mg) or ramipril each evening (5 mg titrated to 10 mg and to 20 mg). Early morning assessments of BP, heart rate, and the heart rate-systolic BP product were performed using 24-hour ambulatory recordings after 10 weeks of therapy.

Results

In each therapeutic group, 76% of patients were titrated to the highest possible dose. After 10 weeks of treatment, reductions in early morning BP by diltiazem ER tablets were significantly greater (−18/−15 mm Hg) than reductions by ramipril (−13/−8 mmHg , P < .005 for systolic BP and P < .001 for diastolic BP). Diltiazem ER tablets also led to greater reductions in morning heart rate and the heart rate-pressure product compared to ramipril. Reductions in mean 24-hour diastolic BP, heart rate, and the rate-pressure product were greater in patients treated with diltiazem ER tablets compared to ramipril, while reductions in 24-hour systolic BP were similar in each group. The observed adverse effects were not serious and incidences were similar for the 2 treatment groups.

Conclusions

These data demonstrate that bedtime administration of diltiazem ER, an agent designed to parallel the circadian rhythm of BP and heart rate, led to significantly greater early morning hemodynamic effects compared to the angiotensin-converting enzyme inhibitor ramipril, also dosed in the evening.     

Effects of metoprolol succinate extended release vs. amlodipine besylate on the blood pressure,heart rate,and the rate-pressure product in patients with hypertension

Ambulatory monitoring of the blood pressure (BP) and heart rate allows for the assessment of the 24-hour rate-pressure product (RPP), a close correlate of myocardial oxygen demand, both in the untreated state and while on antihypertensive therapy. To evaluate the clinical effects of metoprolol succinate extended release (ER) tablets (100 mg titrated to 200 mg for clinic BP >140/90 mm Hg) vs. amlodipine (5 mg titrated to 10 mg for clinic BP >140/90 mm Hg) on the 24-hour and early morning hemodynamic parameters, we performed a double-blind crossover trial that included 8 weeks of active treatment, 4 weeks of placebo washout, and 8 weeks of active crossover treatment using 24-hour ambulatory blood pressure (ABP) measurements. Patients were included if they were untreated, had hypertension based on both clinic (140 to 179/90 to 109 mm Hg) and ABP recordings (>135/85 mm Hg while awake), and were 18 to 65 years of age. Patients enrolled in the trial (n = 35) had a mean age of 55 ± 7 years, 24-hour mean BP of 148/91 ± 11/7 mm Hg, heart rate (HR) of 76 ± 10 beats/minute, and a RPP of 11,230 ± 1717 mm Hg·beats·minute). In the early morning period (6 am to 10 am), baseline BP was 155/98 ± 11/7 mm Hg and the RPP was 12,084 ± 1752 mm Hg·beats·minute. The 24-hour diastolic blood pressure (DBP), HR, and RPP were lowered to a greater extent by metoprolol succinate compared with amlodipine. Additionally, changes from baseline in early morning DBP, HF, and RPP were lowered to a significantly greater extent by metoprolol (mean dose, 124 ± 44 mg daily) compared with amlodipine (mean dose, 7.2 ± 2.5 mg daily) (P = .02 for DBP and P < .0001 for HR and the RPP). The incident rates of adverse events were low and similar for the two treatment groups. These data demonstrate that metoprolol succinate ER induced greater reductions in early morning BP, HR, and FPP than amlodipine in middle-aged patients with Stages 1 and 2 hypertension. These findings have clinical implications for patients with hypertension and coronary heart disease.     

Gender and age effects on the ambulatory blood pressure and heart rate responses to antihypertensive therapy

BACKGROUND: The aim of this study was to assess potential differences in the 24-h antihypertensive response to treatment with the controlled-onset, extended-release (COER) calcium antagonist, verapamil in men versus women and older versus younger patients with hypertension. METHODS: Meta-analyses were performed of three prospective randomized, double-blind, placebo-controlled trials with COER-verapamil in patients with mid-stage I to stage III essential hypertension. The trials were conducted at medical clinics in the US and Canada in patients with a mean office diastolic blood pressure (BP) of 95 to 115 mm Hg on 2 consecutive weeks and a mean daytime diastolic BP >90 mm Hg. Patients were randomized to treatment with 180 to 540 mg/day of COER-verapamil (N = 273) or placebo (N = 125). Changes from baseline in ambulatory BP and heart rate after COER-verapamil were compared in men versus women and in older versus younger patients. RESULTS: Treatment with COER-verapamil caused significant reductions in 24-h and early-morning systolic and diastolic BP in all of the subpopulations as compared with placebo (P < .001). COER-verapamil induced a greater reduction in both 24-h systolic (-15.1 v -10.0 mm Hg; P < .001) and diastolic (-10.4 v -8.2 mm Hg; P = .003) BP in women compared with men. Older patients showed a greater mean reduction in 24-h diastolic BP (-10.2 v -8.2 mm Hg; P < .05) and heart rate (-5.7 v -4.4 beats/min; P < .05) compared with younger patients. Side effects were similar in all of the COER-verapamil treatment groups. CONCLUSIONS: Both gender and age were significant determinants of the response to COER-verapamil. The antihypertensive effect of verapamil is greater in women than in men and in older patients compared with younger patients.     

Antihypertensive efficacy of night-time graded-release diltiazem versus morning amlodipine in African Americans

BACKGROUND: The effect of a once daily night-time (10 pm) graded-release diltiazem (GRD) on early morning blood pressure (BP), heart rate (HR), and rate-pressure product (RPP) were compared with the effect of morning (8 am) amlodipine in 262 African American individuals with hypertension. METHODS: The multicenter, randomized, double-blind, parallel-group, dose-to-effect trial evaluated changes from baseline in BP, HR, and RPP (HR x systolic BP) by ambulatory BP monitoring during the first 4 h after awakening (diastolic BP = primary), between 6 am and 12 noon, and over a 24-h period. Patients were randomized to night-time GRD 360 mg (n = 132) or morning amlodipine 5 mg (n = 130) for 6 weeks, and were titrated to GRD 540 mg or amlodipine 10 mg after 6 weeks if clinic systolic BP/diastolic BP (SBP/DBP) was > or = 130/85 mm Hg. RESULTS: Compared with amlodipine, GRD showed significantly greater DBP reductions of 3.5 mm Hg (P < .0049) and 3.2 mm Hg (P < .0019) during the first 4 h after awakening and between 6 am and 12 noon respectively, as well as comparable reduction for the 24-h mean DBP. The SBP reductions during the morning periods were comparable, but the reduction in the 24-h mean SBP was 3.4 mm Hg greater (P < .0022) for amlodipine. Mean reductions in HR and RPP were significantly greater (P < or = .0008) for GRD during all intervals; amlodipine increased whereas diltiazem reduced HR with mean differences of 6.7 to 9.3 beats/min. Both treatments were well tolerated. CONCLUSIONS: Night-time GRD was more effective than morning amlodipine in reducing early morning DBP, HR, and RPP, as well as 24-h HR and RPP in African American individuals with hypertension. Amlodipine was more effective in reducing SBP over the 24-h period.     

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.     

Comparison of labetalol versus enalapril as monotherapy in elderly patients with hypertension: results of 24-hour ambulatory blood pressure monitoring

PURPOSE: This study compared the safety and efficacy of labetalol and enalapril as antihypertensive therapy for elderly patients. PATIENTS AND METHODS: A randomized, open-label, parallel controlled trial was conducted. After completing a 4-week placebo phase, 79 elderly (65 years or older) patients with an average standing diastolic blood pressure (BP) 95 mm Hg or above and 114 mm Hg or less were randomized to receive a 12-week course of either labetalol or enalapril in an open-label design. The patients' BP and heart rate were evaluated biweekly by trained observers unaware of the treatment status, and drug dosage was titrated (up to 400 mg twice a day of labetalol or 40 mg daily of enalapril) to achieve a standing diastolic BP of less than 90 mm Hg and a decrease of 10 mm Hg from baseline. Patients underwent 24-hour ambulatory BP monitoring (ABPM) at the end of the placebo phase and again after 8 weeks of active treatment. RESULTS: The treatment groups were comparable in their reduction of supine diastolic BP, with no significant differences between the two treatments. Labetalol demonstrated a significantly greater reduction (p less than 0.05) in standing diastolic BP at the end of the titration period compared to enalapril, but this difference was not significant by the end of the study period. Based on 24-hour ABPM readings, labetalol reduced mean 24-hour diastolic BP (p less than 0.05) and mean heart rate (p less than 0.05) more than enalapril. The labetalol-treated patients were significantly less often above their diastolic BP goal throughout the 24-hour ABPM period (p less than 0.01). The two treatments were equally well tolerated. CONCLUSIONS: The results indicate that labetalol and enalapril are equally effective in lowering supine diastolic BP in the elderly, but labetalol is more effective in lowering ambulatory BP and heart rate throughout the day.     

Losartan/hydrochlorothiazide combination vs. high-dose losartan in patients with morning hypertension--a prospective, randomized, open-labeled, parallel-group, multicenter trial

The treatment of morning hypertension has not been established. We compared the efficacy and safety of a losartan/hydrochlorothiazide (HCTZ) combination and high-dose losartan in patients with morning hypertension. A prospective, randomized, open-labeled, parallel-group, multicenter trial enrolled 216 treated outpatients with morning hypertension evaluated by home blood pressure (BP) self-measurement. Patients were randomly assigned to receive a combination therapy of 50?mg losartan and 12.5?mg HCTZ (n=109) or a high-dose therapy with 100?mg losartan (n=107), each of which were administered once every morning. Primary efficacy end points were morning systolic BP (SBP) level and target BP achievement rate after 3 months of treatment. At baseline, BP levels were similar between the two therapy groups. Morning SBP was reduced from 150.3±10.1 to 131.5±11.5?mm?Hg by combination therapy (P<0.001) and from 151.0±9.3 to 142.5±13.6?mm?Hg by high-dose therapy (P<0.001). The morning SBP reduction was greater in the combination therapy group than in the high-dose therapy group (P<0.001). Combination therapy decreased evening SBP from 141.6±13.3 to 125.3±13.1?mm?Hg (P<0.001), and high-dose therapy decreased evening SBP from 138.9±9.9 to 131.4±13.2?mm?Hg (P<0.01). Although both therapies improved target BP achievement rates in the morning and evening (P<0.001 for both), combination therapy increased the achievement rates more than high-dose therapy (P<0.001 and P<0.05, respectively). In clinic measurements, combination therapy was superior to high-dose therapy in reducing SBP and improving the achievement rate (P<0.001 and P<0.01, respectively). Combination therapy decreased urine albumin excretion (P<0.05) whereas high-dose therapy reduced serum uric acid. Both therapies indicated strong adherence and few adverse effects (P<0.001). In conclusion, losartan/HCTZ combination therapy was more effective for controlling morning hypertension and reducing urine albumin than high-dose losartan.     

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

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

Comparison of two strategies for intensifying antihypertensive treatment: low-dose combination (enalapril + felodipine ER) versus increased dose of monotherapy (enalapril). LEVEL (Lexxel vs Enalapril) Study Group.

To compare two popular strategies for intensifying treatment for hypertension, a double-blind, randomized, prospective, parallel-group, and partial crossover study was done. After 2 weeks of placebo run-in (baseline) and 3 weeks of 5 mg enalapril once daily, 217 patients were randomized to 6 weeks of treatment with either a low-dose combination therapy (5 mg enalapril + 5 mg felodipine ER once daily, Lexxel, Astra Merck, Inc.), or a higher dose of monotherapy (10 mg enalapril once daily, Vasotec, Merck & Co., Inc.). The group randomized to the combination had significantly greater reductions in sitting systolic/diastolic blood pressure (BP)--14.2/10.6 mm Hg compared with baseline versus 9.6/7.4 mm Hg (P < .05/.01)--as well as a greater percentage of patients having achieved either diastolic BP < 90 mm Hg or a decline of at least 10 mm Hg (responders), 59% v 41% (P < .01). When patients originally taking 10 mg enalapril were crossed over to the combination therapy for a further 6 weeks, there was a further BP reduction and increase in response rate, with loss of significant differences compared with those treated continuously with the combination for the entire 12 weeks. The greater BP-lowering efficacy of the combination was independent of age, gender, and race. There were no significant differences in tolerability between the regimens. These data support the hypothesis that in patients who do not achieve goal BP reduction with a low dose of an antihypertensive agent, a combination of two drugs with complementary mechanisms of action is more effective than increasing the dose of the first agent.     

Angiotensin II type 1 (AT1) receptor blockade in hypertensive women: benefits of candesartan cilexetil versus enalapril or hydrochlorothiazide

The aim of this large, randomized, double-blind, parallel-group study in hypertensive women was to compare the antihypertensive efficacy and effects on subjective symptoms and quality of life of the new angiotensin II type 1 (AT₁) receptor blocker candesartan cilexetil, the angiotensin-converting enzyme inhibitor enalapril, and the diuretic hydrochlorothiazide (HCTZ). Women, aged 40 to 69 years, with a seated diastolic blood pressure (DBP) of 95 to 115 mm Hg, were randomized to candesartan cilexetil, 8 to 16 mg (n = 140), enalapril, 10 to 20 mg (n = 146), or HCTZ, 12.5 to 25 mg (n = 143), for 12 weeks; the higher doses were used if DBP was greater than 90 mm Hg after 6 weeks. Candesartan cilexetil lowered seated blood pressure by 17/11 and 19/11 mm Hg after 6 and 12 weeks of treatment, respectively. This reduction was greater (P < .01) than with enalapril (12/8 and 13/9 mm Hg) or HCTZ (12/7 and 13/8 mm Hg). The proportions of patients with controlled DBP (< 90 mm Hg) after 12 weeks of treatment with candesartan cilexetil, enalapril, or HCTZ were 60%, 51%, and 43%, respectively. Patients experienced less dry cough (P < 0.001) with candesartan cilexetil or HCTZ than with enalapril. No treatment differences were found in the incidence of dizziness and quality of life was well maintained in all groups. Compared with candesartan cilexetil and enalapril, HCTZ increased uric acid and decreased serum potassium (P < .001). In conclusion, candesartan cilexetil reduced blood pressure more effectively and was better tolerated than enalapril or HCTZ in women with mild to moderate hypertension.     

The effects of amlodipine compared to losartan in patients with mild to moderately severe hypertension

The calcium channel blocker amlodipine and angiotensin II receptor blocker losartan, with or without hydrochlorothiazide (HCTZ), were compared for the treatment of mild to moderate hypertension in a multicenter, double-blind, parallel-group clinical trial. Following a 2-week placebo run-in, 440 adults (45-80 years old) were randomized to receive either amlodipine 5 mg once daily or losartan 50 mg once daily. Patients who failed to meet the sitting diastolic blood pressure (BP) reduction goal of 相似文献   

Diltiazem and captopril alone or in combination for treatment of mild to moderate systemic hypertension

The efficacy and safety of sustained-release diltiazem, 60 to 180 mg twice daily, was compared with that of captopril, 25 to 75 mg twice daily, alone and in combination, in 132 patients with mild to moderate essential hypertension (supine diastolic blood pressure [BP] 95 to 114 mm Hg). All patients received placebo for 4 to 6 weeks, followed by randomization to diltiazem or captopril during the double-blind monotherapy phase. Either study drug was titrated over 6 weeks to achieve a goal supine diastolic BP reduction of at least 10 mm Hg and a diastolic BP of less than 90 mm Hg. Patients achieving the goal BP reduction were maintained on monotherapy for an additional 8 weeks. Patients not achieving the treatment goal after 8 weeks with either drug alone received the other drug in combination, titrated to achieve goal BP response. Both drugs lowered BP significantly and, at the doses used, diltiazem had a greater effect on diastolic BP than did captopril. The mean changes from baseline at week 8 were -10.6 and -7.3 mm Hg, respectively, (p = 0.01). Goal BP was achieved in 38% of patients taking diltiazem monotherapy and in 34% of patients taking captopril monotherapy. There were no significant differences between diltiazem and captopril in diastolic or systolic BP reductions by race or age. The addition of alternate therapy for non-goal achievers at week 8 resulted in significant reductions in diastolic and systolic BP by week 16.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential effects of morning and evening dosing of nisoldipine ER on circadian blood pressure and heart rate

The time of administration of once-daily antihypertensive agents may have a significant impact on blood pressure control during awake and sleep periods. Using 24-h ambulatory monitoring, we compared the effects of morning and evening dosing of the long-acting dihydropyridine calcium channel blocker, nisoldipine extended-release (ER), on circadian blood pressure (BP) and heart rate in patients with mild-to-moderate hypertension. After completing a 3-week placebo run-in period, 85 patients were randomized to morning versus evening nisoldipine ER treatment at a fixed 20-mg dose. Patients were treated for 4 weeks, followed by crossover to the alternate dosing regimen for 4 additional weeks. Twenty-four–hour ambulatory monitoring was performed at baseline and at 4 and 8 weeks after randomization. Awake and sleep times were determined by electronic activity recorders (Actigraphy). Similar least-squares (±SE) mean changes from baseline in 24-h BP (systolic BP/diastolic BP: −11.9/−7.4 ± 0.6/0.5 v −11.6/−6.5 ± 0.6/0.5 mm Hg) and heart rate (1.0/1.7 ± 0.4/0.4 beats/min) occurred with morning and evening administration, respectively. A significantly greater effect on awake diastolic BP (systolic BP/diastolic BP: −12.6/−8.1 ± 0.7/0.4 v −11.3/−6.4 ± 0.7/0.4 mm Hg; P = .16/.01) was observed with morning dosing compared with evening dosing. In addition, small increases in sleep and early morning heart rate were seen with evening compared with morning administration of nisoldipine (sleep, 3.1 ± 0.4 v 0.4 ± 0.4 beats/min; P < .001; early morning, 3.5 ± 0.7 v 0.5 ± 0.7 beats/min; P = .002). These differential effects on awake BP and sleep heart rate were also observed in patients who had normal (dippers) and elevated (nondippers) BP values during sleep. Appropriate evaluation of the efficacy and safety of long-acting antihypertensive agents is essential when evening administration is being considered. In the present study, the timing of nisoldipine ER administration had no effect on mean changes in BP and heart rate over a 24-h period. However, nisoldipine ER had some differential effects during sleep and awake periods with morning relative to evening dosing.     

Acute blood pressure response to trandolapril and captopril in patients with left ventricular dysfunction after acute myocardial infarction

Objective Our purpose was to compare the blood pressure response to short-term treatment with captopril or trandolapril in patients with left ventricular (LV) dysfunction after acute myocardial infarction (AMI). Methods A multicenter, randomized, double-blind, double-dummy, parallel group study was performed. Treatment was initiated 3 to 10 days after the onset of symptoms. On day 1, patients received a single dose of captopril 6.25 mg, trandolapril 0.5 mg, or placebo in the morning. Treatment was then titrated upward over the next 5 days. Blood pressure was monitored with an automated device for the first 12 hours after dosing on day 1. Conventional blood pressure measurements were performed throughout the study. Results Of 205 patients treated in the study, 193 patients were evaluated for first-dose effects. In the captopril group, the maximum decrease in blood pressure occurred after 2 hours, and the magnitude of this decrease was significantly greater than in the other 2 groups: 8.8 ± 12/6.3 ± 8 mm Hg (captopril) versus 5.4 ± 10/3.1 ± 8 mm Hg (trandolapril) versus 2.4 ± 9/1.4 ± 7 mm Hg (placebo) (P < .01). In the trandolapril group, the maximum decrease occurred after 7 hours and the magnitude of this effect was similar in all 3 groups: 5.9 ± 11/3.6 ± 8 mm Hg (trandolapril) versus 4.3 ± 10/3.5 ± 8 mm Hg (captopril) versus 3.1 ± 11/2.8 ± 8 mm Hg (placebo) (not significant). Although there was a higher incidence of hypotension on day 1 in the captopril group, the overall incidence of hypotension during the study period was similar in both active treatment groups. Conclusion Because of differences in initial blood pressure response profiles, short-term treatment with trandolapril tended to be better tolerated than captopril in post-AMI patients with LV dysfunction. (Am Heart J 2002;143:313-8.)     

ABPM comparison of the antihypertensive profiles of the selective angiotensin II receptor antagonists telmisartan and losartan in patients with mild-to-moderate hypertension.

The antihypertensive efficacy and tolerability profiles of the selective AT1 receptor antagonists telmisartan and losartan were compared with placebo in a 6-week, multinational, multicentre, randomised, double-blind, double-dummy, parallel-group study of 223 patients with mild-to-moderate hypertension, defined as clinic diastolic blood pressure (DBP) >/=95 and /=140 and /=85 mm Hg. After a 4-week single-blind placebo run-in, eligible patients were randomised to receive telmisartan 40 mg, telmisartan 80 mg, losartan 50 mg, or placebo. Ambulatory blood pressure monitoring (ABPM) after 6 weeks of double-blind therapy showed that all active treatments produced significant (P < 0.01) reductions from baseline in 24-h mean SBP and DBP compared with placebo. During the 18-to-24 h period after dosing, the reductions in SBP/DBP with telmisartan 40 mg (10.7/6.8 mm Hg) and 80 mg (12.2/7. 1 mm Hg) were each significantly (P <0.05) greater than those observed for losartan 50 mg (6.0/3.7 mm Hg), and losartan was no better than placebo. Also for the 24-h mean blood pressure, telmisartan 40 mg and 80 mg were significantly (P< 0.05) better than losartan 50 mg. Compared with losartan, telmisartan 80 mg produced significantly (P < 0.05) greater reductions in both SBP and DBP during all monitored periods of the 24-h period, while telmisartan 40 mg produced significantly greater reductions in SBP and DBP in the night-time period (10.01 pm to 5.59 am) (P < 0.05) and in DBP in the morning period (6.00 am to 11.59 am) (P < 0.05). All treatments were comparably well tolerated. Telmisartan 40 mg and 80 mg once daily were effective and well tolerated in the treatment of mild-to-moderate hypertension, producing sustained 24-h blood pressure control which compared favourably with losartan.     

A home blood pressure monitoring study comparing the antihypertensive efficacy of two angiotensin II receptor antagonist fixed combinations

BACKGROUND: The objective of this prospective, randomized, open-label, blinded-endpoint study was to compare the antihypertensive efficacy of valsartan 80 mg v irbesartan 150 mg when combined with hydrochlorothiazide (HCTZ) 12.5 mg. METHODS: Untreated or uncontrolled hypertensive adults (n = 800) were enrolled by primary care physicians. After a 5-week open-label lead-in phase in which all patients received 12.5 mg HCTZ once daily, subjects whose blood pressure (BP) remained uncontrolled were randomized (n = 464) to valsartan/HCTZ (80/12.5 mg) or irbesartan/HCTZ (150/12.5 mg) for 8 weeks. Home BP monitoring (HBPM) was performed in the morning and in the evening for 5 days, at baseline, and after 8 weeks. Office BP measurements were obtained at baseline and after 8 weeks. RESULTS: Irbesartan/HCTZ produced greater reductions in average systolic BP (SBP) and diastolic BP (DBP) measured by HBPM than valsartan/HCTZ (SBP: -13.0 v -10.6 mm Hg, P = .0094; DBP: -9.5 v -7.4 mm Hg, P = .0007). These differences were more pronounced in the morning (trough) than in the evening. Office BP measurements also showed greater reductions in trough seated SBP and DBP with irbesartan/HCTZ compared with valsartan/HCTZ. Normalization rates observed with HBPM (SBP <135 mm Hg and DBP <85 mm Hg) were significantly greater with irbesartan/HCTZ than with valsartan/HCTZ (50.2 v 33.2%; P = .0003). The overall safety was similar in the two groups. CONCLUSIONS: The superior BP-lowering potency of the fixed combination irbesartan/HCTZ (150/12.5 mg) over valsartan/HCTZ (80/12.5 mg), evidenced independently from the investigators by HBPM, supports the use of this technique in trials with prospective, randomized, open-label, blinded-endpoint designs.     

Effects of the hormone therapy,drospirenone and 17-beta estradiol,on early morning blood pressure in postmenopausal women with hypertension

Drospirenone (DRSP), is a unique progestin with antimineralocorticoid activity that has been combined with 17-β estradiol (E2) for the treatment of symptoms of the menopause in women with hypertension. We assessed the effects of DRSP/E2, E2 alone, and placebo on early morning systolic blood pressure (BP) as well as the rate of rise in systolic BP in 748 postmenopausal women with stage 1 and 2 hypertension at baseline and after 8 weeks of double-blind therapy. Patient characteristics (mean age, 56.5 years, 73% to 77% Caucasian; 13% to 17% African-American) and the clinic (152/95 mm Hg) and 24-hour BP (139/83 mm Hg) measurements were similar at baseline. The early morning systolic BP was reduced significantly on DRSP at 3 mg, 2 mg, and 1 mg with E2 compared with placebo, while E2 alone was similar to placebo. The reductions in early morning systolic BP were larger with increasing dose. Changes in the rate of rise in systolic BP between the lowest values during sleep and following a plateau period post-awakening was significant for the 3 mg DRSP group. In conclusion, DRSP/E2 induced significant reductions in early morning systolic BP in post-menopausal women. This attribute could play a potential role in reducing some of the untoward cardiac and cerebrovascular events that have been observed in studies of other progestins/estrogens in postmenopausal women.     

Postexercise hypotension differs between white and black women

Background Because data are lacking, we examined the acute effect of exercise on ambulatory blood pressure (BP) in premenopausal white women (n = 18) and black women (n = 15) with normal (n = 21) and high (n = 12) BP. Methods Women performed 40 minutes of control and moderate-intensity exercise. BP and hormones were measured before, during, and after the control and exercise periods. By means of RMANCOVA (repeated measures analysis of covarience), we tested whether BP and hormones differed with time and between ethnic, BP, and experimental groups. Multiple regression analysis was used to examine hormonal mediators of the postexercise BP response. Results Among white women with hypertension, average daytime systolic (S) and diastolic (D) BP decreased 11.0 ± 3.3 mm Hg (−2.9, −19.1; P = .017) and 8.2 ± 2.8 mm Hg (−1.2, −13.9; P = .000), from 142.6 ± 5.8 mm Hg and 96.1 ± 2.8 mm Hg, respectively, after exercise. Among black women with high BP, mean daytime SBP rose 12.5 ± 5.2 mm Hg (−2.0, 27.1; P = .000) after exercise, from 121.8 ± 6.1 mm Hg, whereas DBP was similar before and after exercise (81.4 ± 4.3 mm Hg and 82.8 ± 4.7 mm Hg, respectively). In white women without hypertension, daytime SBP and DBP were similar before and after exercise. In black women without hypertension, mean daytime SBP increased 6.3 ± 2.6 mm Hg (0.4, 12.1; P = .000) after exercise from 103.6 ± 1.4 mm Hg, and DBP did not change. In black women, hypertension (P = 0.000) and exercise-mediated insulin decreases (P = .005) explained 85.6% of the postexercise SBP response (P = .000). In white women, hypertension (P = .003) and baseline plasma renin (P = .049) accounted for 53.3% of the postexercise SBP response (P = .001). Exercise acutely reduced daytime BP in white women, but not in black women with high BP. Conclusion Endurance exercise may adversely affect the BP of black women. (Am Heart J 2003;145:364-70.)     

A forced titration study of antihypertensive efficacy of candesartan cilexetil in comparison to losartan: CLAIM Study II.

An 8-week, multicentre (72 sites in the US), double-blind, randomised, parallel group, forced titration study compared the antihypertensive efficacy of candesartan cilexetil and losartan. A total of 611 patients with essential hypertension (diastolic blood pressure 95 to 114 mm Hg) were randomised initially to candesartan cilexetil 16 mg once daily or losartan 50 mg once daily. After 2 weeks of randomised treatment, the doses of candesartan cilexetil and losartan were doubled to 32 mg and 100 mg once daily and continued respectively for 6 weeks. At week 8, candesartan cilexetil lowered the blood pressure (BP) at 24 h (trough), 6 h (peak) and 48 h post dose to a significantly greater extent (P < 0.05) than losartan: candesartan cilexetil lowered trough BP by 13.4/10.5 mm Hg, peak BP by 15.5/12.9 mm Hg and 48-h BP by 10.5/9.9 mm Hg compared to a reduction of trough BP by 10.1/9.1 mm Hg, peak BP by 12.0/9.5 mm Hg, and 48-h BP by 5.9/7.0 mm Hg by losartan. The responder and control rates were numerically higher in the candesartan cilexetil group, but the differences did not reach statistical significance; the responder rates were 58.8% for the candesartan cilexetil group and 52.1% for the losartan group and control rates were 49.0% for the candesartan cilexetil group and 44.6% for the losartan group. Overall, both treatment regimens were well tolerated. A total of 15 of the 611 (2.5%) patients withdrew from the study due to an adverse event, including nine (2.9%) in the candesartan cilexetil group and six (2.0%) in the losartan group. In conclusion, this forced titration study confirms that candesartan cilexetil is more effective in lowering BP than losartan when compared at once daily maximum doses.     

Comparative efficacy of olmesartan, losartan, valsartan, and irbesartan in the control of essential hypertension

In a multicenter, randomized, double-blind trial, the authors compared the antihypertensive efficacy of once-daily treatment with the new angiotensin II type 1 receptor blocker (ARB) olmesartan (20 mg) with recommended starting doses of losartan (50 mg), valsartan (80 mg), and irbesartan (150 mg) in 588 patients with a cuff diastolic blood pressure (DBP) of ≥100 and ≥115 mm Hg and a mean daytime DBP of ≥90 mm Hg and <120 mm Hg, as measured by ambulatory blood pressure monitoring. Cuff and ambulatory blood pressures were monitored at baseline and after 8 weeks of treatment. All groups were predominantly white and approximately 62% male, and their mean age was approximately 52 years. In all groups, mean baseline DBP and systolic blood pressure (SBP) were approximately 104 and 157 mm Hg, respectively. The reduction of sitting cuff DBP with olmesartan (11.5 mm Hg), the primary efficacy variable of this study, was significantly greater than with losartan, valsartan, and irbesartan (8.2, 7.9, and 9.9 mm Hg, respectively). Reductions of cuff SBP with the four ARBs ranged from 8.4–11.3 mm Hg and were not significantly different. The reduction in mean 24-hour DBP with olmesartan (8.5 mm Hg) was significantly greater than reductions with losartan and valsartan (6.2 and 5.6 mm Hg, respectively) and showed a trend toward significance when compared to the reduction in DBP with irbesartan (7.4 mm Hg; p=0.087). The reduction in mean 24-hour SBP with olmesartan (12.5 mm Hg) was significantly greater than the reductions with losartan and valsartan (9.0 and 8.1 mm Hg, respectively) and equivalent to the reduction with irbesartan (11.3 mm Hg). All drugs were well tolerated. The authors conclude that olmesartan, at its starting dose, is more effective than the starting doses of the other ARBs tested in reducing cuff DBP in patients with essential hypertension.