Search

Background: Several studies have found that measurement of blood pressure (BP) in the clinical setting may lead to overestimation of hypertension and may yield inaccurate assessments of the efficacy of antihypertensive treatment., Objective: The aim of this study was to determine whether the use of clinic BP in the Valsartan and Amlodipine for the Treatment of Isolated Systolic Hypertension in the Elderly (Val-Syst) study accurately identified those elderly outpatients with systolic hypertension who had true 24-hour elevations in BP, as well as those who required dose increases in antihypertensive therapy during follow-up., Methods: In Val-Syst, patients aged between 60 and 80 years with a clinic sitting systolic BP (SBP) of 160 to 220 mm Hg and a diastolic BP <90 mm Hg after a 2-week placebo washout period were randomized to receive valsartan 80 mg or amlodipine 5 mg once daily (level 1). In those with a trough SBP > or =140 mm Hg after 8 weeks of double-blind treatment, doses were titrated upward to valsartan 160 mg or amlodipine 10 mg once daily (level 2). If clinic SBP was > or =140 mm Hg after a further 8 weeks, hydrochlorothiazide 12.5 mg was added for an additional 8 weeks (level 3). Clinical decisions during the active-treatment period were based on clinic BP measurements. Thirteen of the 35 participating centers assessed ambulatory BP as well as clinic BP at baseline and the end of the treatment, making it possible to compare the results of the 2 modes of measurement. The Student test was used to compare drug-induced changes in clinic and ambulatory BP in individual patients. Differences between the decreases in clinic and ambulatory BP at the 3 treatment levels were tested using repeated-measures analysis of covariance (ANCOVA), with baseline as the covariate., Results: One hundred sixty-four elderly patients (age range, 60-80 years; 85 men, 79 women) were included in the study (79 valsartan, 85 amlodipine), and valsartan and amlodipine were reported to have comparable effects on the level and rhythm of 24-hour BP In the present study, 22 of 164 patients had white-coat hypertension at baseline (clinic SBP > or =160 mm Hg and mean 24-hour SBP <130 mm Hg). For both treatments combined, the mean (SD) decreases in clinic SBP were inversely proportional to the treatment level (level 1 = -33.2 (7.9) mm Hg; level 2 = -31.6 (11.8) mm Hg; level 3 = -29.3 (11.6) mm Hg; P = 0.001, overall ANCOVA). In contrast, after adjusting for baseline values, the decreases in mean 24-hour SBP did not differ between treatment levels (level 1 = -10.8 [10.4] mm Hg; level 2 = -13.0 [11.2] mm Hg; level 3 = -16.4 [13.8] mm Hg). The decrease in clinic BP during therapy was similar in patients with white-coat hypertension and sustained hypertension (clinic SBP > or 160 mm Hg and mean 24-hour SBP > or =130 mm Hg), whereas 24-hour and 8- to 9-am SBP decreased significantly only in patients with sustained hypertension (P < 0.001). At the end of the study, mean 24-hour SBP continued to be uncontrolled (> or =130 mm Hg) in 16 of 53 patients (30.2%) at treatment level 1, 27 of 62 (43.5%) at level 2, and 19 of 49 (38.8%) at level 3 (P = NS)., Conclusion: Based on the findings in this population of elderly patients with systolic hypertension, the management of hypertension may vary depending on whether decisions concerning the selection of patients for clinical trials and treatment adjustments during follow-up are made using clinic or ambulatory BP measurement.

Background: The goal of antihypertensive therapy is to provide good blood pressure (BP) control without eliciting adverse effects., Objective: This study compared the risk-benefit profile of the angiotensin II receptor blocker valsartan with that of the angiotensin-converting enzyme inhibitor lisinopril in patients with mild to severe hypertension. The primary objective was to show that the equipotent BP-lowering effect of the valsartan-based treatment is accompanied by a better tolerability profile., Methods: This 16-week, randomized, double-blind, parallel-group study was conducted at 88 outpatient centers across Italy. After a 2-week placebo run-in period, patients aged > or = 18 years with mild to severe hypertension (systolic BP [SBP], 160-220 mm Hg; diastolic BP [DBP], 95-110 mm Hg) were eligible. Patients were randomized to receive once-daily, oral, self-administered treatment with valsartan 160-mg capsules or lisinopril 20-mg capsules under double-blind conditions for 4 weeks. Responders continued monotherapy, whereas nonresponders had hydrochlorothiazide 12.5 mg added for the final 12 weeks of the study. The 2 primary variables used to assess the equivalence of therapeutic efficacy of the 2 regimens were sitting SBP and sitting DBP, which were measured at weeks 0 (baseline), 4, 8, and 16. The rate of drug-related adverse events (AEs) was used to assess whether 1 treatment had a better tolerability profile than the other. Tolerability was assessed by collecting information about AEs by means of questioning the patient or physical examination at each visit., Results: A total of 1213 patients were enrolled (635 men, 578 women; mean [SD] age, 54.5 [10.1] years [range, 28-78 years]). The study was completed by 1100 patients (553 receiving valsartan and 547 receiving lisinopril). Fifty-one patients (8.4%) treated with valsartan and 62 (10.2%) [corrected] treated with lisinopril withdrew, mainly because of AEs (9 [1.5%] and 23 patients [3.8%], respectively). The valsartan- and lisinopril-based treatments were similarly effective in reducing sitting BP, with mean SBP/DBP reductions of 31.2/15.9 mm Hg and 31.4/15.9 mm Hg, respectively. At the end of the study, BP was controlled in 82.6% [corrected] of the patients receiving valsartan and 81.6% of those receiving lisinopril. AEs were experienced by 5.1% of the patients treated with valsartan and 10.7% of those treated with lisinopril (P=.0001), with dry cough observed in 1.0% and 7.2% of patients, respectively (P<0.001)., Conclusions: Valsartan and lisinopril were both highly effective in controlling BP in these patients with mild to severe hypertension, but valsartan was associated with a significantly reduced risk for AEs, especially cough.

Objective: To compare the efficacy and tolerability of benazepril 10 mg + amlodipine 5 mg combination (BZ+AM) versus captopril 50 mg + hydrochlorothiazide 25 mg (CP+HT) combination., Material: 405 outpatients with mild-to-moderate arterial hypertension not adequately controlled by a monotherapy with ACE inhibitors or calcium channel blockers or diuretics entered this multicenter, double-blind, randomized, parallel-group study., Method: After a 2-week placebo run-in, 397 patients with sitting diastolic (D) blood pressure (BP) > 95 mmHg and/or sitting systolic (S) BP > 160 mmHg were randomized to receive either BZ+AM (201 patients) or CP+HT (196 patients) once daily for 12 weeks. Main outcome measure was sitting DBP and SBP values at the end of active treatment. The response rate was defined as the proportion of patients with either a final sitting DBP < 90 mmHg or decreased by at least 10 mmHg or a sitting SBP < 150 mmHg or decreased by at least 20 mmHg from baseline., Results: The DBP and SBP values obtained with BZ+AM were, respectively, 2.7 and 3.7 mmHg lower than those obtained with CP+HT (both p < 0.001 vs. CP+HT). The response rate in the BZ+AM group (94.8%) was better than that observed in the CP+HT group (86.0%, p = 0.004). The incidence of adverse events was similar with the 2 treatment regimens (17.9% for both)., Conclusions: These data suggest a higher antihypertensive efficacy of the fixed combination BZ 10 mg+AM 5 mg as compared with CP 50 mg+HT 25 mg.

Objective: The aim of this study was to measure the time-effect profiles of a once-daily administered valsartan/hydrochlorothiazide combination and amlodipine on blood pressure using various indices derived from 24-h ambulatory blood pressure (BP) monitoring., Methods: Of the 310 randomized outpatients with uncomplicated mild-to-moderate primary hypertension, 259 (133 on valsartan/hydrochlorothiazide, 126 on amlodipine) were eligible for analysis. After a 2-week placebo wash-out period, the patients were randomly allocated to treatment with either valsartan 80 mg once daily (o.d.) or amlodipine 5 mg o.d. for 4 weeks; in the case of an unsatisfactory blood pressure response, the treatments could be respectively changed to the fixed combination of valsartan 80 mg plus hydrochlorothiazide 12.5 mg o.d. or amlodipine 10 mg o.d. for a further 8 weeks. The trough:peak ratio (global and individualized approaches) and smoothness index (i.e., the ratio between the average of the 24-hourly BP changes after treatment and the corresponding standard deviation) were calculated from 24-h ambulatory blood pressure recordings made after the placebo period and after 4 weeks and 12 weeks of active treatment., Results: Both regimens effectively lowered systolic and diastolic ambulatory pressures after 4 weeks and 12 weeks (all P<0.001) but, among the responders, the valsartan/hydrochlorothiazide combination had a greater antihypertensive effect during the night-time hours after 12 weeks (P=0.03/0.02). In the responders, the placebo-adjusted, mean trough:peak ratios were 0.76/0.74 in the valsartan/hydrochlorothiazide group (n = 111) and 0.66/0.62 in the amlodipine group (n = 101). The corresponding global trough:peak ratios were 0.61/0.57 for the valsartan/hydrochlorothiazide combination and 0.56/0.56 for amlodipine. However, the between-group differences in individual or global trough:peak ratios were not significant. The smoothness index was slightly, but insignificantly, greater for valsartan/hydrochlorothiazide than for amlodipine in the responders and the groups as a whole., Conclusion: Valsartan/hydrochlorothiazide and amlodipine were equally effective in reducing ambulatory BP, but the valsartan/hydrochlorothiazide combination led to more homogeneous BP control during the inter-dosing interval. Trough:peak ratio and smoothness index did not reflect this finding accurately.

Objective: To compare the antihypertensive efficacy and tolerability of a once-daily fixed valsartan/hydrochlorothiazide (HCTZ) combination and amlodipine in subjects with mild-to-moderate hypertension., Subjects and Setting: In this multicentre, double-blind, randomized, comparative trial, 690 patients with sitting systolic blood pressure (BP) > or = 160 mmHg and sitting diastolic BP > or = 95 mmHg at the end of a 2-week placebo wash-out period were randomized to valsartan-based treatment (n = 342) or amlodipine (n = 348)., Methods: The patients received valsartan 80 mg o.d. or amlodipine 5 mg o.d for 4 weeks; in the case of an unsatisfactory blood pressure response, the treatments could be respectively changed to the fixed combination of valsartan 80 mg + HCTZ 12.5 mg o.d. or amlodipine 10 mg o.d. for a further 8 weeks., Results: Both treatment approaches decreased systolic blood pressure and diastolic blood pressure to the same extent. The rate of responders to treatment at the end of fourth week (before up-titration) was 57.4% among the valsartan-treated patients and 61.9% among the amlodipine-treated patients (ns). At the end of the study, the rate of responders was not significantly different between the two groups (74.9 versus 72.1%). Valsartan-based treatment had a slightly lower incidence of adverse events (1.5 versus 5.5%; P = 0.006)., Conclusions: The results of this trial demonstrate that the valsartan/hydrochlorothiazide combination and amlodipine are equally effective in lowering BP, and that the combination is better tolerated.

Objective: This study compares the effects of an AT1 angiotensin II receptor antagonist (valsartan) with those of an ACE inhibitor (enalapril) on left ventricular (LV) diastolic function in patients with mild or moderate essential hypertension and no evidence of LV hypertrophy at echocardiography., Methods: A total of 24 patients (16 men, mean age 47 +/- 8 years) underwent radionuclide ambulatory monitoring (Vest) of LV function at rest and during upright bicycle exercise testing before and after two 4-week treatment periods with valsartan (80-160 mg/day orally) and enalapril (20-40 mg/day orally) according to a double-blind, crossover randomization scheme., Results: In the overall population no differences between the two treatments were found in LV peak filling rate (PFR) either at rest or at peak exercise. In a subgroup analysis it was found that baseline PFR was normal (= 2.5 EDV/sec) in 12 patients (subgroup A) and impaired (< 2.5 EDV/sec) in the remaining 12 (subgroup B). In both subgroups, valsartan and enalapril induced a significant and comparable reduction of systolic and diastolic blood pressure. In subgroup A, valsartan and enalapril did not induce significant changes in PFR. In subgroup B, valsartan increased PFR both at rest (from 2.0 +/- 0.3 to 2.4 +/- 0.3 EDV/sec, P < 0.01) and at peak exercise (from 4.1 +/- 1.1 to 4.4 +/- 1.0 EDV/s, P < 0.05), whereas enalapril did not change PFR either at rest (2.0 +/- 0.4 EDV/s, P < 0.01 versus valsartan) or at peak exercise (3.7 +/- 1.1 EDV/sec, P < 0.05 versus valsartan)., Conclusions: Valsartan-induced renin-angiotensin system blockade is able to improve LV filling in patients with mild or moderate essential hypertension and impaired diastolic function. These findings support the hypothesis of a contribution of the renin-angiotensin system in the control of LV diastolic function in these patients.

To assess the comparative effects of benazepril and nitrendipine monotherapies on left ventricular mass index (LVMI) in hypertensive patients with echocardiographically determined left ventricular hypertrophy, patients with diastolic blood pressure (BP) > or = 100 mm Hg were randomized to benazepril, 10 mg, or nitrendipine, 20 mg, both given once or twice daily. After 4 weeks, only the responders (diastolic BP <90 mm Hg) entered a 5-month maintenance period. At baseline, and after 3 and 6 months, LVMI was blindly estimated by means of magnetic resonance imaging (MRI) and, for comparison, by means of echocardiography. Of the 50 randomized patients, three were excluded from the study as nonresponders after 4 weeks; moreover, two patients taking benazepril and one taking nitrendipine discontinued the treatment after 2 months for adverse effects. Both monotherapies reduced systolic and diastolic BP to a similar extent. After 3 months, MRI-estimated LVMI decreased by 21.5 g/m2 in the benazepril and 8.8 g/m2 in the nitrendipine group, with an adjusted mean difference between the two groups of 11.1 g/m2 (95% CI, 7.3-14.8 g/m2; p = 0.0001). After 6 months, it decreased by 23.6 g/m2 and 10.0 g/m2, respectively, with an adjusted mean difference of 11.3 g/m2 (95% CI, 7.5-15.5; p = 0.0001) in favor of benazepril. In conclusion, despite a similar antihypertensive effect, benazepril led to a greater reduction in MRI-measured LVMI than did nitrendipine (-16.2% vs. -7.2%) in hypertensive patients with left ventricular hypertrophy.

In a multicenter, randomized, double-blind, placebo-controlled study, we evaluated the efficacy and tolerability of the combination of benazepril, 10 mg, and amlodipine, 2.5 or 5 mg once daily, compared with benazepril, 10 mg, monotherapy in patients with hypertension inadequately controlled with angiotensin-converting enzyme (ACE)-inhibitor monotherapy. After a 2-week placebo and 4-week single-blind benazepril, 10 mg once daily, run-in period, 448 patients, 213 men and 235 women, aged 24-73 years (mean, 55 years), with mean diastolic blood pressure (DBP) > or =95 and < or =120 mm Hg at the end of the benazepril run-in period, were randomized to receive one of the following treatments once daily for 8 weeks: (a) benazepril, 10 mg, plus placebo (BZ10); (b) benazepril, 10 mg, plus amlodipine, 2.5 mg (BZ10/AML2.5); or (c) benazepril, 10 mg, plus amlodipine, 5 mg (BZ10/AML5). Before the patients were admitted to the trial, at the end of the placebo run-in and the benazepril run-in period and at the end of weeks 4 and 8 of the treatment period, sitting and standing blood pressure (BP), heart rate (HR), and body weight were measured 22-26 h after the intake of the trial medication. Both BZ10/AML2.5 and BZ10/AML5 combinations showed better antihypertensive activity than did BZ10 monotherapy at the terminal visit as demonstrated by (a) the 24-h postdosing sitting and standing systolic BP (SBP) and DBP values, which were statistically lower with combination therapy than with BZ10; (b) the success rate, which was statistically higher with both the combinations (69.2% in the BZ10/AML2.5 and 65.8% in the BZ10/AML5 group) compared with the BZ10 group (40.5%). The tolerability was good in the three treatment groups. No significant abnormal laboratory data were detected. There was no difference in efficacy and safety/tolerability between the BZ10/AML2.5 and BZ10/AML5 groups.

Objective: This double-blind, placebo-controlled randomized study was designed to compare the antihypertensive effect and tolerability of extended-release felodipine and slow-release nifedipine retard in elderly hypertensive patients., Methods: Thirty patients of both sexes (mean age 71 years) with mild to moderate essential hypertension were recruited from our hypertension outpatient clinic. After a 2-week placebo period, felodipine extended-release (felodipine ER), 10 mg once daily, nifedipine slow-release retard (nifedipine SR), 20 mg twice daily or placebo were administered to each patient for 2 weeks according to a 3 x 3 latin-square design. At the end of each treatment period, the patients underwent 24-h noninvasive blood pressure monitoring., Results: All of the patients completed the trial and no serious adverse experience was reported. In comparison with placebo, felodipine and nifedipine decreased mean 24-h diastolic blood pressure by 6.7 and 4.3 mmHg, respectively, with no significant difference between the two drugs. Mean 24-h systolic blood pressure also decreased after felodipine and nifedipine, with no difference between the two drugs. Both drugs reduced blood pressure variability, lowering the 24-h mean standard deviation of mean hourly blood pressure values. The trough:peak ratio for felodipine was 80% for systolic and 75% for diastolic blood pressure., Conclusion: Felodipine ER once daily lowers blood pressure in elderly hypertensives and is as effective as nifedipine SR twice daily. The high trough:peak ratio suggests that the dose and the between-dose interval of felodipine provides adequate therapeutic coverage.

Diabetic nephropathy is the most frequent cause of chronic renal failure. The onset of microalbuminuria in patients with diabetes mellitus, which seems to be related to blood pressure and the control of glycemia, is predictive of the development of true proteinuria. This multicenter, single-blind, randomized study examined the effects of benazepril and nicardipine on overnight microalbuminuria in 57 normotensive and 46 hypertensive diabetic patients. At the end of a 3-month placebo run-in period, the patients were stratified on the basis of the presence or absence of arterial hypertension and, within each stratum, randomized to receive one daily tablet of 10 mg benazepril or one tablet of 20 mg nicardipine twice daily for 6 months. Renal hemodynamics was investigated in 25 patients. Both drugs decreased overnight microalbuminuria throughout the study period, but benazepril was more effective than nicardipine (p = 0.025); in the patients with hypertension, both drugs led to a similar marked reduction in systolic and diastolic blood pressure. This study shows that benazepril was more effective than nicardipine in reducing overnight microalbuminuria in patients with diabetes mellitus, independently of their antihypertensive properties.

This was a double-blind, within-patient, crossover study to evaluate the effects of a new formulation of metoprolol on blood pressure (BP) and myocardial ischemia. Twenty outpatients with mild to moderate essential arterial hypertension, chronic stable angina pectoris and positive exercise test, after a 2-week baseline placebo period, were randomized to receive long-acting metoprolol (OROS) 14/190 mg o.d., nifedipine SR 20 mg b.i.d. or their combination in a sequence of a 3 x 3 Latin square design. Two patients withdrew from the study (1 for adverse event during metoprolol and 1 for rise of BP during nifedipine). Nifedipine, metoprolol and their combination significantly reduced the weekly number of angina attacks and nitroglycerin consumption with respect to baseline. The total number of ischemic events (at 24-hour ECG monitoring) significantly decreased after each treatment with respect to baseline. Twenty-four hours mean systolic and diastolic BP were reduced by both nifedipine alone and metoprolol alone; the combination of the two drugs led to a further decrease in both systolic and diastolic BP. The duration of silent ischemic episodes was significantly reduced by nifedipine and combination but not by metoprolol. On the other hand 24 hours symptomatic attacks/patient were significantly reduced by beta-blocker and combination, but not by nifedipine. Metoprolol alone and administered with nifedipine caused a decrease, with respect to placebo baseline, in 24-hour mean heart rate (HR) and reduced the increase of HR and systolic BP at the onset of ST depression during symptomatic ischemic episodes. The effort time and time to ST = -1 mm at treadmill were significantly increased by treatment with nifedipine alone, with metoprolol alone and with their combination, but the combination was more effective than the individual therapies. ST depression at peak exercise was significantly reduced by each treatment. The slopes of correlations between the ST-segment variation and systolic BP, HR and rate-pressure product during exercise, significantly decreased after all treatments with respect to placebo baseline, more with the combination therapy than with nifedipine alone and metoprolol alone. In conclusion, based on our results the favourable interaction of metoprolol OROS and nifedipine given concomitantly, is likely to be due to a better control, respect to each individual therapy, of the pathogenetic mechanism of myocardia ischemia: BP and HR increases during exercise and during symptomatic ischemic episodes are controlled by the beta-blocker and coronary vasoconstriction during silent ischemia is prevented by the calcium-antagonist.