Influence of two doses of irbesartan on non-dipper circadian blood pressure rhythm in salt-sensitive black hypertensives under high salt diet

The authors examined whether the blockage of angiotensin II receptors by irbesartan (IRB) can reverse the "non-dipper" circadian rhythm of blood pressure (BP) to a "dipper" pattern in black salt-sensitive hypertensive patients submitted to a high-sodium loading. Twelve black salt-sensitive hypertensive patients (seven men; age, 35-58 years) on a high-sodium diet (300 mmol Na+ per day) were followed for 8 weeks. A placebo was given during the first 2 weeks, followed by 2 weeks on IRB 150 mg/d, 2 weeks on placebo, and 2 weeks on IRB 300 mg/d. On the last day of placebo, IRB 150 mg/d, and IRB 300 mg/d treatments, 24-hour BP and urinary 24-hour excretion of Na+ and potassium were measured. On placebo, ambulatory mean arterial pressure (MAP) was 112 mm Hg+/-2 (24 h), 112 mm Hg+/-2 (daytime), and 111 mm Hg+/-2 (nighttime), showing a clear circadian non-dipper profile. Versus placebo, IRB 150 mg/d reduced MAP by 4.2 mm Hg+/-1.1 (24 h), 2.6 mm Hg+/-0.8 (daytime) and 6.0 mm Hg+/-1.3 (nighttime; P<0.05 vs. placebo) and IRB 300 mg/d reduced MAP by 7.8 mm Hg+/-1.4 (24 h), 3.9 mm Hg+/-1.1 (daytime), and 11.8 mm Hg+/-2.1 mm Hg (all P<0.02 vs. placebo); nighttime/daytime MAP decrease was 0.7+/-0.8% on placebo, 3.5+/-2.1% on IRB 150 mg/d, and 7.0+/-1.2% on IRB 300 mg/d (P<0.02 for trend). Compared with placebo, IRB significantly increased serum potassium and plasma renin activity and reduced fractional excretion of potassium and plasma aldosterone levels in a dose-dependent manner. Body weight and urinary sodium excretion did not change throughout the study. It was concluded that the angiotensin receptor blocker IRB can reverse the BP non-dipper profile in salt-sensitive hypertensive patients on a high-salt diet, restoring nocturnal BP decline by a predominantly dose-dependent reduction of nighttime BP. Although the increment of potassium balance and reduction of aldosterone may account for this effect, it occurs independently of increased natriuresis. It is speculated that blunting of nighttime BP decrease in black salt-sensitive hypertensive patients may be related to a deficient suppression of the renin-angiotensin system during the night.     

Blood pressure- and pulse pressure-lowering effects, trough:peak ratio and smoothness index of telmisartan compared with lisinopril

OBJECTIVE: To compare lisinopril with telmisartan, in regard to: 1) their effect on blood pressure (BP) and pulse pressure (PP), and 2) the duration and the homogeneity of their antihypertensive effect. PATIENTS AND METHODS: A randomized, open-label, crossover, comparative study of telmisartan 80 mg versus lisinopril 20 mg was conducted in 32 untreated hypertensive patients using clinic and 24-hour ambulatory BP measurements. Trough: peak ratio (TPR) and smoothness index (SI) were calculated for each drug. RESULTS: Using both measurement techniques no difference was detected between the 2 drugs in their effects either on BP (mean difference in 24-hour systolic BP 1.2 +/- 7.1 mm Hg, 95% confidence intervals -1.4, 3.8, and diastolic 0.7 +/- 5.1, -1.2, 2.5) or on PP (0.5 +/- 3.5, -0.7, 1.8). There was no difference between the TPR and the SI values of telmisartan (TPR 0.85/0.61 for systolic/diastolic BP and SI 1.46/1.2) and lisinopril (TPR 0.74/0.64 and SI 1.3/1.17). CONCLUSIONS: These data suggest that telmisartan is as effective as lisinopril in reducing BP and PP. Both drugs seem to provide smooth and sustained effects throughout the full 24-hour period.     

Cross-over comparison of nifedipine Oros and felodipine extended release with blind 24 h ambulatory blood pressure assessments

1. The aim of the present study was to compare the efficacy of nifedipine Oros and felodipine extended release (ER) in controlling 24 h ambulatory blood pressures (ABP) in hypertensive patients. 2. The study was a randomized cross-over design with a 2 week open placebo run-in phase and two observer-blind treatment periods. 3. Subjects were males and females, aged between 18 and 65 years, suffering from mild to moderate essential hypertension with a sitting mean diastolic blood pressure (DBP) within the range of 95-114 mmHg. Twenty-three subjects were randomized to treatment; 15 patients completed the study. 4. Treatment intervention was 2 weeks of placebo followed by either 30 mg nifedipine OROS once daily or 5 mg felodipine ER once daily for 6 weeks, which was titrated up to 60 mg nifedipine OROS daily or 10 mg felodipine ER daily after 2 weeks of treatment on the lower doses if the DBP was > 90 mmHg. The main outcome measure was 24 h ABP after 6 weeks of active treatment, evaluated by an independent observer blinded as to treatment allocation. 5. Compared with placebo, mean (+/- SD) 24 h DBP was reduced by 6.2 +/- 6.8 and 5.2 +/- 5.1 mmHg after nifedipine and felodipine, respectively. The 24 h mean systolic blood pressure (SBP) fell by 11.8 +/- 10.9 and 10.1 +/- 8.2 mmHg for nifedipine and felodipine, respectively, compared with placebo. There were no significant differences between the two active treatments in the reduction of DBP or SBP during the 24 h period, daytime or night-time. 6. Similar antihypertensive effects are achieved with nifedipine Oros and felodipine ER when doses are individually titrated, with no significant differences between the two treatments.     

Trough-to-peak ratio,smoothness index,and circadian blood pressure profile after treatment with once-daily fixed combination of losartan 100 and hydrochlorothiazide 25 in essential hypertension

The once-daily fixed combination of losartan 100 mg/hydrochlorothiazide 25 mg was evaluated for safety and efficacy in a multicenter open study by using 24-h ambulatory blood pressure monitoring in untreated patients with moderate-to-severe essential hypertension or patients with uncontrolled hypertension despite treatment with monotherapy or low-dose combination. After a 2-week washout period, 41 patients (22 men, 19 women) aged 34-74 years, showing a mean daytime blood pressure > 135/85 mm Hg, were treated with losartan 100 mg/hydrochlorothiazide 25 for 8 weeks. Ambulatory blood pressure was monitored at the end of the washout period and during the last week of treatment. A significant reduction in the average values of clinic blood pressure (from 169.9 +/- 13.5 mm Hg to 139.5 +/- 15.6 mm Hg, p < 0.001 for systolic blood pressure [SBP]; and from 102.2 +/- 7.1 mm Hg to 85.1 +/- 9.5 mm Hg, p < 0.001 for diastolic blood pressure [DBP]) was observed after treatment in the whole group of 41 patients. Likewise, average values of both 24-h SBP and 24-h DBP were significantly reduced (from 145.7 +/- 13.1 mm Hg to 128.3 +/- 14.6 mm Hg, p < 0.001 for 24-h SBP; and from 90.3 +/- 7.3 mm Hg to 79.2 +/- 8.6 mm Hg, p < 0.001 for 24-h DBP). The average lowering at peak was 20.2 +/- 11.8 mm Hg for 24-h SBP and 12.1 +/- 7.4 mm Hg for 24-h DBP, whereas the lowering at trough was 17.8 +/- 12.0 mm Hg and 10.4 +/- 8.1 mm Hg, respectively. The trough-to-peak ratio (T/P) was 0.88 for SBP and 0.86 for DBP, and the smoothness index was 7.36 for SBP and 6.37 for DBP. The response rate was 87.8% (blood pressure lowering > 5 mm Hg of either 24-h SBP or 24-h DBP average values). Among responders, T/P ratio was 0.89 for SBP and 0.87 for DBP, and the smoothness index was 8.09 for SBP and 7.15 for DBP. No side effects or changes in metabolic parameters were observed. The fixed combination of losartan 100 mg/hydrochlorothiazide 25 was very effective and well tolerated.     

Comparison of 24-hour blood pressure profiles in patients with hypertension who were switched from amlodipine to nisoldipine.

STUDY OBJECTIVE: To compare 24-hour blood pressure control and adverse effects in patients with essential hypertension who were switched from amlodipine to nisoldipine. DESIGN: Open-label, one-way crossover study. SETTING: Cardiac clinic and patients' homes. PATIENTS: Twenty-five patients with stage I or II essential hypertension stabilized with amlodipine for at least 3 months, of whom 21 patients completed the study. INTERVENTION: All patients underwent 24-hour ambulatory blood pressure monitoring while receiving amlodipine 5 or 10 mg/day. Patients then were switched to nisoldipine 10 mg/day (> or = 65 yrs old) or 20 mg/day (< 65 yrs old) and returned to the clinic at 2-week intervals to assess cuff blood pressure, heart rate, adverse effects, and compliance. No adverse effects were experienced in 15 of the 25 patients. Lower extremity edema was the most commonly reported adverse effect (four patients). Two patients discontinued treatment because of pulmonary edema in one and chest pain in the other. Two patients were lost to follow-up. After a mean of 10.6 weeks, repeat 24-hour ambulatory monitoring was performed to evaluate blood pressure control with nisoldipine. Systolic and diastolic ambulatory results for daytime, nighttime, and total 24 hours were calculated. For amlodipine versus nisoldipine, no significant differences existed in any of the blood pressure parameters (p>0.05) in the 21 patients who completed the study, except for 24-hour diastolic pressure (p<0.05); however, this latter difference was only 2 mm Hg (nisoldipine 77 mm Hg, amlodipine 75 mm Hg). CONCLUSION: Both amlodipine and nisoldipine have similar 24-hour ambulatory blood pressure profiles. The frequency of lower extremity edema was no different after the switch to nisoldipine than when the patients were taking amlodipine.     

Felodipine ER formulation in the treatment of mild hypertension: efficacy and tolerability vs placebo.

1. Felodipine is a new calcium-antagonist dihydropyridine derivative with a high degree of selectivity for smooth muscle of arteriolar resistance vessels, as opposed to cardiac cells. 2. In this double-blind, cross-over study the antihypertensive efficacy and tolerability of the new extended release (ER) formulation of felodipine 10 mg, once daily, in patients with mild essential hypertension was evaluated. After a 4-week single-blind placebo period 28 patients (15 males; mean age 48 +/- 12 years) were randomized to receive felodipine 10 mg ER once daily or placebo for 4 weeks and the alternative treatment for a further 4 weeks. Supine blood pressure and heart rate were measured in the out-patients department every 2 weeks, 22-24 h after the last drug administration. 3. Felodipine 10 mg ER induced a significant reduction in blood pressure in comparison with placebo (from 149 +/- 16/97 +/- 6 to 140 +/- 12/89 +/- 6 mm Hg). Heart rate remained unchanged. Seven patients dropped-out; five during felodipine ER administration and two during placebo. 4. A once daily dose of felodipine ER significantly reduces blood pressure in mild hypertensive patients 22-24 h after administration. It is well tolerated and the adverse events are related to its pharmacodynamic effects.     

A placebo-controlled dose-response study of felodipine extended release in hypertensive patients

This placebo-controlled study assessed antihypertensive effect and tolerability of two dose levels of an extended release (ER) formulation of felodipine (Plendil), given once daily to patients in primary health care. The patients had mild to moderate hypertension and were randomized to receive felodipine ER (FER) 20 mg (n = 50), FER 10 mg (n = 50), or placebo (n = 51) in a 4-week, double-blind, parallel-group multicenter study. After 4 weeks, the 24-h reduction in supine diastolic BP (DBP) was greater (p less than 0.01) in both FER groups (7 +/- 6 and 8 +/- 5 mm Hg) than in the placebo group (4 +/- 6 mm Hg). The 24-h reduction in supine systolic BP (SBP) was greater (p less than 0.01) in the FER 20-mg group (14 +/- 11 mm Hg), but not in the FER 10-mg group, than in the placebo group (8 +/- 11 mm Hg). No significant difference in blood pressure (BP) was found between FER 10 and 20 mg. Heart rate (HR) did not differ between any of the groups, nor did body weight or routine laboratory parameters. During felodipine treatment, 17 patients (12 receiving FER 20 mg) were withdrawn mostly because of vasodilatory side effects such as headache and ankle edema. We conclude that FER 10 mg and 20 mg once daily had an antihypertensive 24-h effect and that FER 10 mg may be more suitable as initial dose.     

Comparison of once daily felodipine 10 mg ER and hydrochlorothiazide 25 mg in the treatment of mild to moderate hypertension

Summary The efficacy of extended release felodipine 10 mg (ER) o.d., a new dihydropyridine calcium antagonist, and 25 mg hydrochlorothiazide (HCTZ) o.d. have been compared in a randomized, double-blind, crossover trial in 28 mildly to moderately hypertensive subjects (supine diastolic blood pressure, BP, 95 mm Hg and 110 mm Hg on three separate occasions).Both drugs significantly reduced systolic and diastolic BP in the sitting position felodipine from 157.1/93.8 mm Hg at baseline to 133/78.9 mm Hg 2.5 h after medication and to 138/82.7 mm Hg after 2 weeks of treatment, and HCTZ from 156/95.6 mm Hg to 147/88.4 mm Hg 2.5 h after medication and to 149/89.5 mm Hg also after 2 weeks.A decrease of the same magnitude in standing systolic and diastolic BP was observed after both treatment regimens with the exception of diastolic BP 2.5 h after dosing with HCTZ, which was not significantly lower. At all times (2.5 h and 2 weeks), the reduction in systolic and diastolic BP was greater after felodipine compared to HCTZ. Heart rate was significantly increased after felodipine in both the sitting and standing positions, and both 2.5 h following medication and after 2 weeks of treatment. The difference between the regimens was significant only 2.5 h after dosing. Overall, felodipine 10 mg ER o.d. was superior to 25 mg HCTZ o.d. in lowering BP.Presented in part at the Vth Scientific Meeting of the American Society of Hypertension, 17–20 May 1990, New York     

Plasma concentration-effect relationships of intravenous and extended-release oral felodipine in hypertensive patients.

Felodipine, a dihydropyridine calcium antagonist, was given double-blind in a crossover design comparing once-daily doses of 20 mg felodipine extended-release (ER) tablets with placebo in 12 hypertensive patients. A 2-h intravenous infusion was given after a placebo washout. After oral felodipine, blood pressure (BP) was significantly lower than after placebo, both after the first dose and after 2 weeks of treatment. Supine BP 24 h after the first dose of placebo and felodipine was 159/97 and 153/92 mm Hg (p less than 0.01/0.05), respectively. Corresponding BPs at 2 weeks were 158/99 and 144/89 mm Hg (p less than 0.01/0.01). Approximately 75% of the maximal and 60% of the trough effect at steady state were obtained already after the first dose. The plasma concentration (CpF) vs. time curve after felodipine ER was relatively flat. After oral felodipine, a linear correlation was found between BP reduction and logarithmic CpF. After intravenous administration, CpF correlated well with a hyperbolic function. These data indicate that there is an almost linear relation between BP reduction and log CpF in the range from 2-20 nmol/L, and that little additional effect is to be expected above approximately 20 nmol/L. No hysteresis was found for the relationship between CpF and BP reduction. The absolute bioavailability of felodipine ER was 22%.     

Combination of lisinopril and nifedipine GITS increases blood pressure control compared with single drugs in essential hypertensive patients

The present study was designed to evaluate the effect of combination therapy using the angiotensin-converting enzyme-inhibitor lisinopril and the dihydropyridine calcium antagonist nifedipine GITS on the degree and homogeneity of 24-hour blood pressure reduction in essential hypertensive patients. After a 4-week placebo run-in period, 51 patients (mean age, 54.4 +/- 9.4 years) with essential hypertension and clinic diastolic blood pressure between 105 and 115 mm Hg were randomized to 4-week treatment with lisinopril (20 mg), nifedipine GITS (30 mg), or their combination according to a multicenter, randomized, double-blind, crossover study. Trough clinic blood pressure and 24-hour ambulatory blood pressure were measured at the end of the run-in period and after 4 weeks of treatment. In addition to clinic and 24-hour average blood pressure reduction, the trough-to-peak ratio and the smoothness index, a new measure for the homogeneity of blood pressure reduction, were also calculated. Although both lisinopril and nifedipine GITS produced a significant reduction in clinic and 24-hour average blood pressure values, the reduction obtained with the combination was significantly (P < 0.001) greater. Moreover, the combination therapy increased (P < 0.01) the smoothness index as compared with each single drug for both systolic (lisinopril, 1.02; nifedipine GITS, 1.1; combination, 1.76) and diastolic (lisinopril, 0.98; nifedipine GITS, 0.87; combination, 1.54) blood pressure values, whereas trough-to-peak ratio values (expressed as median) for systolic (lisinopril, 0.41; nifedipine GITS, 0.52; combination, 0.55) and diastolic (lisinopril, 0.35; nifedipine GITS, 0.40; combination, 0.49) blood pressure values were not significantly increased by the combination therapy. Thus, antihypertensive treatment with the combination of lisinopril and nifedipine GITS is more effective and balanced over the 24 hours than the combination components administered alone, confirming that the smoothness index is superior to the trough-to-peak ratio in assessing homogeneity of pharmacologic blood pressure reduction.     

Randomized, double-blind, crossover comparison of amlodipine and valsartan in african-americans with hypertension using 24-hour ambulatory blood pressure monitoring

STUDY OBJECTIVE: To compare the efficacy of amlodipine and valsartan in African-American patients with hypertension using ambulatory blood pressure monitoring (ABPM). DESIGN: Prospective, randomized, double-blind, crossover comparison study. SETTING: University-affiliated cardiac center clinic. PATIENTS: Twenty African-Americans (12 men, 8 women), with a history of uncomplicated hypertension (blood pressure > 140/90 mm Hg). INTERVENTION: Patients were randomized to receive amlodipine 5 or 10 mg/day or valsartan 80 or 160 mg/day for 8-10 weeks, depending on response. Dosages were titrated to achieve a blood pressure of 140/90 mm Hg or below. For patients whose blood pressures were not controlled, hydrochlorothiazide 12.5 mg/day was added to their regimens. Patients then underwent 24-hour ABPM. After an intervening washout period during which baseline blood pressure was reestablished, patients received the other treatment. MEASUREMENTS AND MAIN RESULTS: Mean +/- SD baseline blood pressure before the two ABPM periods were 155 +/- 12/100 +/- 8 mm Hg and 156 +/- 11/101 +/- 9 mm Hg, respectively. Fifteen (75%) patients achieved goal blood pressure with amlodipine and 14 (70%) with valsartan (p=0.62). Final daily dosages were as follows: amlodipine 5 mg in nine patients, 10 mg in five patients, and 10 mg plus hydrochlorothiazide in six patients; valsartan 80 mg in nine patients, 160 mg in four patients, and 160 mg plus hydrochlorothiazide in seven patients. Ambulatory blood pressure monitoring was not completed in three patients due to adverse effects: headache and dizziness (one patient each, amlodipine and valsartan) and hyperkalemia (one patient, valsartan). Four patients (20%) in each treatment group had drug-related adverse effects. Results of ABPM including averages for 24-hour, daytime, nighttime, first 4 hours, and last 8 hours, and trough:peak ratios were not significantly different between the amlodipine- and valsartan-based treatments. CONCLUSION: Based on both clinic blood pressure measurements and ABPM data, amlodipine and valsartan produced similar reductions in blood pressure in African-American patients with uncomplicated hypertension.     

Additive hypotensive effect of angiotensin-converting enzyme inhibition and angiotensin-receptor antagonism in essential hypertension

The study was designed to assess the antihypertensive effect of combined angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 receptor (AT1) antagonism in patients with essential hypertension. Twenty patients with uncontrolled ambulatory diastolic blood pressure (BP) after 6 weeks of ACE inhibitor monotherapy (benazepril, 20 mg, o.d.) were randomized to receive double-blind valsartan, 80 mg, o.d. (AT1 antagonist) or matching placebo for 5 weeks while continuing to receive background benazepril. Then patients crossed over to the alternative regimen for a second 5-week period. The 24-h ambulatory BP was monitored on the final day of the benazepril monotherapy period and on the final day of each double-blind treatment period. Valsartan added to benazepril produced a significant antihypertensive effect with a benefit over placebo of 6.5 +/- 12.6/4.5 +/- 8.0 mm Hg (systolic/diastolic) for average awake ambulatory BP (p < 0.05), 7.1 +/- 9.4/5.6 +/- 6.5 mm Hg for asleep BP (p < 0.01), and 6.8 +/- 9.7/4.9 +/- 6.8 mm Hg for average 24-h ambulatory BP (p < 0.01). Pulse rate was unaffected. Plasma active renin was higher on the benazepril-valsartan combination compared with benazepril-placebo (p < 0.05). There was no change in routine biochemical variables when valsartan was added to benazepril. Six patients reported mild dizziness or fatigue (three also with placebo). These data suggest that in hypertensive patients uncontrolled with an ACE inhibitor, the addition of an AT1 antagonist provides a powerful and safe antihypertensive drug combination.     

Antihypertensive therapy with once-daily administration of terazosin, a new alpha 1-adrenergic-receptor blocker

The antihypertensive activity of terazosin, an investigational alpha 1-adrenergic-receptor blocker, and its effect on blood lipids were compared with placebo in a double-blind study. After a 3-week placebo baseline period, patients were randomized to receive terazosin (n = 22) or placebo (n = 16). The dose of terazosin was titrated over 2 weeks to a maintenance dosage of 10 mg once daily for 4 weeks. Antihypertensive efficacy was assessed: (1) at the end of the 24-hour dosing interval by comparing the average blood pressure (BP) after 3 and 4 weeks of maintenance therapy to the average BP after 2 and 3 weeks of placebo therapy, and (2) for 3 hours after drug ingestion at the final visit in comparison to the predose BP at that visit. At the end of the 24-hour dosing interval, 10 mg of terazosin reduced the mean supine systolic BP from 155.6 to 152.2 mm Hg and mean supine diastolic BP from 101.9 to 99.0 mm Hg (p less than 0.05). During the 3 hours after drug ingestion, mean supine systolic and diastolic pressures decreased maximally from 151.8 to 142.7 mm Hg (p less than 0.05) and from 99.5 to 91.0 mm Hg (p less than 0.05) respectively. No supine BP reduction differed significantly from the placebo response. During terazosin therapy there was a nonsignificant increase in mean body weight of 1.4 +/- 2.9 kg and no change in blood lipids. Thus the drug demonstrated greater antihypertensive activity 1-3 hours after ingestion than at the end of the 24-hour dosing interval.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of rilmenidine and lisinopril on ambulatory blood pressure and plasma lipid and glucose levels in hypertensive women with metabolic syndrome

OBJECTIVE: In previous studies, the I1 imidazoline specific agonist rilmenidine effectively lowered office blood pressure (BP) in patients with metabolic syndrome, improved glucose metabolism and did not demonstrate unfavourable effects on plasma lipids. The aim of the present study was to investigate the effects of 12weeks therapy with rilmenidine compared with the ACE inhibitor lisinopril on ambulatory BP, plasma lipid and fasting glucose levels in women with metabolic syndrome. RESEARCH DESIGN: Prospective randomised open-label, blinded end-points study. METHODS: Female patients (n = 51) with hypertension and other components of metabolic syndrome were treated with 1 mg rilmenidine (n = 24) or 10 mg lisinopril (n = 27), once- or twice-daily. Anthropometric measurements, office BP and heart rate (HR) measurements, ambulatory BP monitoring, lipid and fasting glucose assessment were performed before and after 12weeks of treatment MAIN OUTCOME MEASURES: Changes in ambulatory BP and HR, including 24-h, daytime and night-time values, and in lipids and glucose levels. All changes were adjusted for baseline values using the analysis of covariance method. RESULTS: Ambulatory 24-h systolic BP and diastolic BP were decreased significantly in the rilmenidine group (-11.9 +/- 1.9 and -7.7 +/- 0.8 mm Hg, p < 0.001) respectively and the lisinopril group (-11.0 +/- 1.8 and -6.7 +/- 0.7 mm Hg respectively, p < 0.001). There were no significant differences between the two groups. Rilmenidine reduced 24-h ambulatory HR (-3.6 +/- 0.8 bpm versus 0.3 +/- 0.8 bpm with lisinopril; p = 0.002). The reductions of day-time and night-time BP were also significant for both treatment groups, but the rilmenidine group demonstrated a greater decrease in night-time diastolic BP (p = 0.046). Rilmenidine significantly increased HDL cholesterol and decreased fasting glucose levels (p = 0.009 and p = 0.012, respectively). HDL cholesterol tended to increase and fasting glucose tended to decrease in the lisinopril group. However, differences between groups were not significant. Conclusion: Rilmenidine has similar effects on ambulatory BP patterns in hypertensive women with metabolic syndrome as lisinopril. Rilmenidine compared with lisinopril significantly reduces ambulatory HR. In this study, rilmenidine and lisinopril demonstrate similar effects on plasma lipid and fasting glucose levels.     

Antihypertensive effects of a new sustained-release formulation of nifedipine

The blood pressure response to a new sustained-release formulation of nifedipine was evaluated in an 8-week, double-blind, placebo-controlled study. Twenty-nine patients with mild essential hypertension were randomized to receive placebo (N = 9), 30 mg nifedipine (N = 10), or 60 mg nifedipine (N = 10). During treatment, 30-mg and 60-mg doses of nifedipine administered once daily decreased office blood pressures from 137/98 +/- 8/2 mm Hg and 141/98 +/- 15/2 mm Hg at baseline, respectively, to 126/89 +/- 9/7 mm Hg and 126/86 +/- 6/7 mm Hg (P less than .005). Noninvasive automatic ambulatory blood pressure monitoring demonstrated a marginally significant (P less than .10) reduction in the mean 24-hour blood pressure of 2/6 +/- 8/8 mm Hg and 5/6 +/- 9/9 mm Hg for patients taking 30 mg and 60 mg nifedipine once daily, respectively. Diastolic blood pressure load (the percentage of ambulatory diastolic blood pressure readings greater than 90 mm Hg) during 24 hours was decreased by 41% and 35%, with 30 mg and 60 mg nifedipine administered once daily, respectively. No significant dose response to nifedipine at these dose levels was observed. Although the once-daily formulation of nifedipine achieved effective control of office blood pressure, similar control was not observed in awake and 24-hour periods in all patients.     

Control of blood pressure in hypertensive patients with felodipine extended release or nifedipine retard.

1. This multicentre hospital study compared the antihypertensive efficacy and the tolerability of once daily felodipine extended release (ER) with twice daily nifedipine retard (R) in hypertensive patients inadequately controlled on metoprolol monotherapy. 2. One hundred patients, aged 20-70 years, whose seated diastolic blood pressure was 100-115 mmHg after 4 to 6 weeks of metoprolol (200 mg day-1) monotherapy, were randomised, double-blind, to receive felodipine ER 10 mg once daily or nifedipine R 20 mg twice daily for 8 weeks. The dosage of felodipine or nifedipine was doubled if seated diastolic blood pressure exceeded 95 mmHg, 2 or 4 weeks after randomisation. Metoprolol 200 mg once daily was taken throughout the trial. 3. Fifty-one patients received felodipine ER and 49 nifedipine R; 46 and 45 respectively completed the 8 week trial. About half of patients on each treatment needed the higher dose. The baseline characteristics of the felodipine and nifedipine groups were generally well balanced. 4. Seated diastolic blood pressure was reduced by 17 mmHg for felodipine (24 h post-dose) and by 9 mmHg for nifedipine (12 h post-dose), a difference between treatments of 8 mmHg (95% confidence interval 5 to 12 mmHg, P less than 0.0001). The attained blood pressures at the end of the study (felodipine 90 +/- 10, mmHg, mean +/- s.d.; nifedipine 95 +/- 10) were also significantly different (95% confidence interval for the 5 mmHg difference, -9 to -1 mmHg, P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of new calcium channel blocker, azelnidipine, and amlodipine on baroreflex sensitivity and ambulatory blood pressure

The effect of dihydropyridine calcium channel blocker (CCB) on baroreflex sensitivity (BRS) is not well described. We studied the effect of a new CCB, azelnidipine, compared with amlodipine, on BRS and ambulatory blood pressure (BP) in newly diagnosed untreated hypertension. This study was a prospective, randomized, and open-label study. We randomized patients to either azelnidipine or amlodipine treatment. Azelnidipine 8 to 16 mg (average 14.5 mg) and amlodipine 2.5 to 7.5 mg (average 4.9 mg) were used to lower the clinical BP <140/90 mm Hg. BRS, evaluated by the spontaneous and the Valsalva methods, and clinical and ambulatory BP were evaluated at baseline and after 13 weeks of each treatment. A total of 47 patients (age 53.1 +/- 10.8 years, 51% male), 26 in the azelnidipine group and 21 in the amlodipine group, completed the study. For baseline and after therapy respectively, both Valsalva-BRS (4.8 +/- 1.7 vs. 8.4 +/- 3.1 msec/mm Hg, P = 0.001) and spontaneous-BRS (5.5 +/- 2.5 vs. 8.2 +/- 5.6 msec/mm Hg, P = 0.019) were increased by azelnidipine, but amlodipine did not change them. Clinical and awake BPs were similarly reduced by each drug therapy. In conclusion, BRS was increased by azelnidipine therapy, but not by amlodipine therapy. This differential effect may be important in cardiovascular risk reduction.     

A dose-finding, placebo-controlled study on extended-release felodipine once daily in treatment of hypertension

Hypertensive patients received a beta-blocker plus placebo once daily for 4 weeks. If their diastolic blood pressure (DBP) was then 95-115 mm Hg, they were randomized to receive, in addition to the beta-blocker, placebo (n = 36), felodipine-extended release (ER) 10 mg (n = 36), or felodipine-ER 20 mg (n = 37) in a 4-week double-blind parallel-group trial. All medication was administered once daily and, when BP was measured 24 h after the last dose, felodipine-ER 10 mg reduced DBP by 14 +/- 9 mm Hg (mean +/- SD) from a mean of 103 mm Hg and felodipine-ER 20 mg reduced DBP by 18 +/- 9 mm Gg from 101 mm Hg. The reductions in DBP with both doses of felodipine were greater than reductions with placebo (5 +/- 8 mm Hg, from 102 mm Hg--both p less than 0.001). At the end of the study, 21% of patients receiving placebo had a DBP less than or equal to 90 mm Hg. In contrast, 69% of patients receiving felodipine-ER 10 mg and 82% receiving 20 mg attained this level. More than 90% of patients receiving 10 mg felodipine-ER once daily had a reduction in DBP greater than 5 mm Hg 24 h postdose. Felodipine-ER was well tolerated. Felodipine-ER once daily is an effective antihypertensive drug for patients who require therapy in addition to a beta-blocker; the tolerability in this study was good, and a starting dose greater than 10 mg once daily is not indicated.     

Antihypertensive efficacy of the calcium-antagonist felodipine in patients with persisting hypertension on beta-adrenoceptor blocker therapy. The Canadian Felodipine Study Group.

1. The antihypertensive efficacy of two different doses of the calcium antagonist felodipine was evaluated in patients with hypertension persisting despite beta-adrenoceptor blocker therapy. Following a single-blind placebo period of 4 weeks, patients were randomized to placebo (n = 36), felodipine 5 mg twice daily (n = 39) and felodipine 10 mg twice daily (n = 35) for another 4 weeks. beta-adrenoceptor blocker therapy remained unchanged throughout the study. 2. Effects on blood pressure (BP) were evaluated after the first dose and after chronic dosing at 2 h after dosing and the end of the dosing interval (12 h). 3. Felodipine decreased systolic and diastolic BP by 30-35/20-25 mm Hg at 2 h. These decreases were similar after acute and chronic treatment. Twelve hours after dosing, decreases of 15-20/10-15 mm Hg were observed compared to 10/5 mm Hg on placebo, and half of the patients still had a controlled BP (supine diastolic BP less than 90 mm Hg). BP responses were rather similar for both doses of felodipine at 2 and 12 h. 4. Multiple regression analysis showed that both initial BP level and plasma felodipine concentrations were significant predictors of the BP response to felodipine, but age was not. 5. Adverse effects attributed to felodipine were mainly related to vascular symptoms (primarily flushing and ankle swelling); these occurred in about 30% of patients, and were pronounced in three patients (4%). 6. Felodipine is therefore highly effective in lowering BP of hypertensive patients on chronic beta-adrenoceptor blocker therapy, with no evidence for a gradual lowering of the BP or for development of tolerance. Both initial BP level and plasma concentrations are better indicators of antihypertensive efficacy of this calcium antagonist than age.     

Antihypertensive effect of lisinopril assessed by 24-hour ambulatory monitoring: a double-blind, placebo-controlled, cross-over study.

The antihypertensive effect of the angiotensin-converting enzyme (ACE) inhibitor lisinopril administered in a single dose of 20 mg was evaluated by ambulatory blood pressure monitoring (ABPM) in a double-blind, placebo-controlled, cross-over study. Twenty-four patients (21 men and 3 women, mean age 52 +/- 6 years) with mild to moderate hypertension were included in the study and randomly assigned to two consecutive treatments with lisinopril 20 mg and placebo, each administered for 4 weeks. On the last day of each treatment, BP was assessed by noninvasive 24-h ABPM. BP was significantly lower after lisinopril than after placebo in a 24-h period (mean 24-h systolic BP (SBP) with lisinopril 120 +/- 7 mm Hg and with placebo 135 +/- 9 mm Hg; mean day SBP with lisinopril 125 +/- 3 mm Hg and with placebo 142 +/- 5 mm Hg; mean night SBP with lisinopril 112 +/- 4 mm Hg and with placebo 124 +/- 6 mm Hg; mean 24-h diastolic BP (DBP) with lisinopril 76 +/- 6 mm Hg, and with placebo 87 +/- 8 mm Hg; mean day DBP with lisinopril 80 +/- 3 mm Hg and with placebo 93 +/- 4 mm Hg; mean night DBP with lisinopril 69 +/- 2 mm Hg and with placebo 79 +/- 5 mm Hg, p less than 0.001). Mean 24-h, mean day, and mean night heart rate (HR) did not differ significantly between placebo and lisinopril treatments. Repeated-measures analysis of variance (ANOVA) showed a significant influence on SBP (p less than 0.001) and DBP (p less than 0.001) throughout the treatment.(ABSTRACT TRUNCATED AT 250 WORDS)