Comparison of amlodipine and enalapril in the treatment of isolated systolic hypertension in the elderly: an open-label, randomized, parallel-group study

Background: The benefits of treating isolated systolic hypertension (ISH) are well established, but the most appropriate drug choice is still uncertain.Objective: The purpose of this study was to compare amlodipine, a calcium channel blocker, with enalapril, an angiotensin-converting enzyme inhibitor, in the treatment of ISH in a cohort of elderly patients (≥60 years of age).Methods: Ambulatory patients with ISH (seated systolic blood pressure [SBP] >160 mm Hg and <220 mm Hg; diastolic blood pressure [DBP] <95 mm Hg) who had not been treated previously or who had stopped their medication at least 4 weeks before the study were enrolled. Patients were randomized to receive amlodipine 5 mg/d or enalapril 10 mg/d. After 4 weeks of treatment, the dose was doubled for those patients whose sitting SBP had not decreased to <150 mm Hg or by >20 mm Hg, and treatment was continued for an additional 4 weeks.Results: A total of 89 patients were randomized to treatment, 46 to amlodipine and 43 to enalapril; 1 patient in the enalapril group died due to ischemic stroke despite adequate blood pressure control. The absolute reductions in seated and standing SBP/DBP were similar with both drugs after 8 weeks: 27 mm Hg/4.6 mm Hg with amlodipine and 23.9 mm Hg/3.9 mm Hg with enalapril (sitting) and 25.1 mm Hg/4.1 mm Hg and 21.3 mm Hg/4.2 mm Hg (standing) with amlodipine and enalapril, respectively (P = NS). At 4 weeks, 24 patients (52.2%) in the amlodipine group and 33 patients (76.7%) in the enalapril group had their medication dose doubled because their SBP was not adequately controlled with the initial dose (P < 0.01). At the end of the study, 24 patients were taking 10 mg amlodipine and 22 patients were taking 5 mg (mean dose 7.6 ± 2.5 mg); 33 patients were taking 20 mg enalapril and 10 patients were taking 10 mg (mean dose 17.8 ± 4.1 mg). Side effects occurred significantly more frequently in the amlodipine group (P = 0.01).Conclusion: The results of this study suggest that amlodipine and enalapril are similarly effective in treating ISH in elderly patients, with few side effects.     

Effects of barnidipine on blood pressure and left ventricular diastolic function in patients with hypertension and metabolic syndrome: A 12-week, open-label noncomparison study

Background: Barnidipine is one of a new generation of dihydropyridine calcium-channel blockers. Despite evidence of favorable effects on blood pressure (BP) and insulin sensitivity, this drug has rarely been tested in hypertensive patients with metabolic syndrome (MS).Objective: The aim of this study was to evaluate the effects of barnidipine on BP and left ventricular (LV) diastolic function in patients with hypertension and MS.Methods: Consecutive subjects aged 18 to 75 years with systolic BP (SBP) of 140 to 179 mm Hg and/or diastolic BP (DBP) of 90 to 109 mm Hg and MS (based on Adult Treatment Panel III criteria) were assessed for inclusion in the study. Lifestyle changes according to current guidelines were recommended and barnidipine monotherapy 10 mg daily was initiated. All patients entered a 2-week run-in period. After a 6-week treatment period, the daily dosage was doubled for the remainder of the study in patients whose BP remained uncontrolled (≥140/≥90 mm Hg). We assessed the glycolipidic profile and LV structure and function using standard Doppler and tissue Doppler imaging (TDI) echocardiography before and after 12 weeks of treatment. Ambulatory BP records and electrocardiographic and echocardiographic tracings were coded and shipped to a central laboratory for blinded analysis. Possible adverse events (AEs) were recorded at predetermined intervals throughout the follow-up period and at unplanned intervals whenever an AE became known to the investigators.Results: Thirty-four consecutive patients were assessed for inclusion. Thirty consecutive patients (20 men, 10 women; mean {SD| age, 55.9 {10.3| years; 5 current smokers) were included in the study. At study entry, mean office SBP was 146 mm Hg, DBP was 87 mm Hg, and heart rate was 72 beats/min. At the study end, mean office SBP/DBP was <140/90 mm Hg in 20 patients (66.7%). From baseline to study end, 24-hour ambulatory BP decreased significantly by 12 and 8 mm Hg for SBP and DBP, respectively (both, P = 0.001). The smoothness index was 0.92 for SBP and 0.82 for DBP. Fasting plasma glucose concentration decreased significantly from 110 to 104 mg/dL (P = 0.001). Total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol concentrations did not change significantly. From baseline to study end, there were no significant changes in LV structure or systolic function (LV mass, 50.7 vs 50.6 g/ht^2.7; LV diastolic/systolic diameters, 47.50/29.80 vs 48.40/30.76 mm; wall motion score index, 1.0 vs 1.0; ejection fraction, 61% vs 60%), while the peak E/A velocity ratio on TDI increased from 1.078 to 1.245 (P = 0.009). No AEs (including AEs reflected by chemistry values) either unrelated or related to treatment were noted during the 12-week duration of the study.Conclusions: In these hypertensive patients with MS, a 12-week treatment period with barnidipine in addition to lifestyle modifications was associated with significant reductions in 24-hour BP and BP variability, reduction in plasma glucose concentration, and improvement in LV diastolic relaxation. No significant changes in lipid concentrations, LV structure, or systolic function were found.     

Poster 22: Comparison between the cardiovascular responses of the 6-minute walk test and that of treadmill testing in patients undergoing cardiac rehabilitation

Objective: To compare the cardiovascular responses between the 6-minute walk test (6MWT) and treadmill exercise test (TET) in patients undergoing a phase 2 cardiac rehabilitation program. Design: Prospective cross-sectional study. Setting: Tertiary care general hospital. Participants: 25 patients with coronary artery disease, functional class 1 based on New York Heart Association classification, who will undergo phase 2 cardiac rehabilitation. Interventions: Patients underwent the 6MWT and the treadmill stress test. Cardiovascular parameters were tabulated, compared, and analyzed. Main Outcome Measures: Peak heart rate, systolic (SBP) and diastolic (DBP) blood pressures, and mean arterial blood pressure. Results: The cardiovascular responses to the 6MWT were significantly of lower magnitude compared with those of the treadmill stress test. Paired t test revealed significant differences between the means ± SD of the heart rate (6MWT, 89±13; TET, 132±30; P<.00), SBP (6MWT, 134±13; TET, 161±21; P<.05) and DBP (6MWT, 82±9; TET, 94±8; P<.00), and mean arterial blood pressure (6MWT, 117±10; TET, 142±20; P<.01). Conclusion: Care should be taken when interpreting the results of the 6MWT because it may underestimate the true functional capacity of patients with coronary artery disease.     

Effects of the fixed combination of manidipine plus delapril in the treatment of hypertension inadequately controlled by monotherapy with either component: a phase III, multicenter, open-label, clinical trial

Background: Failure to achieve good blood pressure (BP) control is probably the most important reason for high rates of morbidity and mortality in patients with hypertension. Combination therapy has been shown to increase the percentage of patients in whom BP control is achieved. One combination is a calcium channel blocker (CCB) and an angiotensin-converting enzyme inhibitor (ACE-I).Objective: The aim of this study was to assess the effects of the fixed combination of the CCB manidipine and the ACE-I delapril in the treatment of hypertensive patients already given monotherapy with either component but with poor results (ie, insufficient BP control or adverse events [AEs]).Methods: In this Phase III, multicenter, open-label, clinical trial, patients with mild to moderate hypertension were assigned to 1 of 2 groups. Group 1 comprised patients whose diastolic BP (DBP) was >90 mm Hg or who experienced AEs with manidipine 20 mg once daily. Group 2 comprised patients who had a DBP >90 mm Hg or who experienced AEs with delapril 30 mg BID. In both groups, patients aged <65 years were to be treated with a fixed combination of manidipine 10 mg plus delapril 30 mg once daily for 12 weeks, whereas patients aged ≥65 years were to be treated with manidipine 5 mg plus delapril 15 mg once daily for 2 weeks and then manidipine 10 mg plus delapril 30 mg once daily for 10 weeks. Patients were assessed at baseline and at 2, 4, 8, and 12 weeks of treatment. At each visit, systolic blood pressure (SBP), DBP, and heart rate were measured 24 hours after dosing, and AEs were recorded.Results: Group 1 included 154 patients (80 men, 74 women; mean [SD] age, 55 [6] years); group 2 included 158 patients (79 men, 79 women; mean [SD] age, 56 [5] years). Mean BP decreased significantly in both groups (P<0.01). Compared with baseline values, mean SBP/DBP decreased 16.2 (3.8)/10.1 (1.9) mm Hg in group 1 and 15.8 (3.1)/11.0 (1.5) mm Hg in group 2 at the last visit. The success rate—rate of normalized DBP (≤90 mm Hg) and responder rate (DBP reduction ≥10 mm Hg)—was 79% in group 1 and 82% in group 2. The rates of treatment-related AEs were 11% in group 1 and 8% in group 2. In group 1, heart rate significantly increased from baseline only at 2 weeks (P<0.05); in group 2, at each visit (P<0.05) except at week 12. However, none of these differences were clinically significant.Conclusion: In this study population of patients whose BP was not adequately controlled by monotherapy, the fixed combination of manidipine 10 mg plus delapril 30 mg, once daily, was effective and well tolerated.     

Efficacy and tolerability of nebivolol monotherapy by baseline systolic blood pressure: A retrospective analysis of pooled data from two multicenter, 12-week,randomized, double-blind,placebo-controlled,parallel-group,dose-ranging studies in patients with mild to moderate essential hypertension

Background: In clinical studies, nebivolol at doses of 2.5 to 40 mg once daily was associated with significant decreases in systolic blood pressure (SBP) and diastolic BP (DBP) in patients with hypertension and was well tolerated.Objectives: This post hoc analysis of pooled data from 2 previously published registration studies was conducted to further evaluate the antihypertensive efficacy and tolerability of nebivolol in patients with mild to moderate (stage 1–2) hypertension.Methods: The 2 trials were similarly designed multicenter, 12-week, randomized, double-blind, placebocontrolled, parallel-group, dose-ranging studies in patients 18 years of age and older with stage 1 or 2 hypertension (SBP 140–159 mm Hg and/or DBP 90–99 mm Hg [stage 1] or SBP ≥ 160 mm Hg and/or DBP ≥ 100 mm Hg [stage 2]). The primary efficacy end point of the 2 studies was the change from baseline in mean trough SiDBP at week 12. A secondary end point was the change from baseline to week 12 in mean trough sitting SBP (SiSBP). The present analysis included only patients who received nebivolol 5, 10, or 20 mg (the doses were common to both studies) or placebo, including analyses stratified by baseline SBP, although DBP represented a criterion for entry into the studies. Baseline SBP stratification levels were 140 to 149 mm Hg, 150 to 159 mm Hg, 160 to 169 mm Hg, and 170 to 179 mm Hg. For the tolerability analysis, the prevalences of treatment-emergent adverse events (AEs) were compared between the 3 nebivolol dose groups and the placebo group.Results: Of the 1716 randomized patients who received study medication in the 2 trials, data from 1385 patients were included in this pooled analysis (759 men, 626 women; median age, ~54 years; 13.6% black). Mean (SD) baseline SiSBP and SiDBP values were 151.9 to 152.7 and 99.2 to 99.5 mm Hg, respectively. Reductions from baseline in trough SiSBP were ?10.8 (13.5), ?10.7 (14.7), and ?12.4 (15.5) mm Hg with nebivolol 5, 10, and 20 mg, respectively, compared with ?4.5 (13.4) mm Hg with placebo (all, P < 0.001). Reductions from baseline in trough SiDBP (the primary end point) were ?9.8 (7.9), ?10.5 (8.2), and ?11.1 (8.6) mm Hg with nebivolol 5, 10, and 20 mg, respectively, compared with ?5.1 (8.1) mm Hg with placebo (all, P < 0.001). In a subgroup of 1227 patients stratified by baseline SBP, the reductions in SBP and DBP were significantly greater (P < 0.03 and P < 0.001, respectively) with nebivolol at each dose compared with placebo in those with baseline SBP of 140 to 149 mm Hg and 150 to 159 mm Hg (the lowest 2 baseline strata); in the highest 2 baseline strata (SBP 160–169 and 170–179 mm Hg), the reductions in SBP with nebivolol 5 mg and nebivolol 20 mg in the 160 to 169-mm Hg baseline SBP stratum and in DBP with nebivolol 20 mg in the 170 to 179-mm Hg baseline stratum were significantly greater (P < 0.03) compared with placebo. The most common AE in the nebivolol 5?, 10?, and 20-mg groups and the placebo group was headache (36/409 [8.8%], 25/410 [6.1%], 27/410 [6.6%], and 10/156 [6.4], respectively), fol-lowed by fatigue (9/409 [2.2%], 10/410 [2.4%], 25/410 [6.1%], and 3/156 [1.9%]) and dizziness (6/409 [1.5%], 9/410 [2.2%], 15/410 [3.7%], and 4/156 [2.6%]).Conclusion: The present analysis of pooled data from 2 previously published registration studies found that nebivolol was associated with significant reductions in BP compared with placebo in these patients with stage 1 or 2 hypertension, with a tolerability similar to that of placebo.     

Irbesartan monotherapy in systemic hypertension: An open-label, uncontrolled trial

Background: Irbesartan is an orally active, specific blocker of the AT₁ receptor of angiotensin II that produces insurmountable antagonism. Irbesartan's plasma half-life of 11 to 15 hours and higher affinity for the AT₁ receptor versus other angiotensin II receptor subtypes may make it a suitable choice for once-daily treatment of hypertension. Few studies have examined the efficacy of this agent in Asian patients.Objective: The purpose of this open-label, uncontrolled study was to assess the 24-hour efficacy of irbesartan once-daily monotherapy in Chinese outpatients with mild to moderate hypertension.Methods: Patients with stage I or stage II hypertension (as defined by the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) were treated with irbesartan once daily for 6 to 8 weeks. The dose of irbesartan was titrated from an initial dose of 150 mg to 275 mg or 300 mg if adequate blood pressure (BP) control was not achieved by week 3 or 4; doses were taken once daily between 8 am and 9 am. For each patient, 24-hour ambulatory BP monitoring was performed twice, once before and once after 6 to 8 weeks of treatment.Results: A total of 25 patients (mean age, 54 years) were enrolled; 24 completed the study. Mean 24-hour systolic/diastolic BP after irbesartan treatment was significantly decreased compared with baseline values (128 ± 14 mm Hg/82 ± 8 mm Hg vs 143 ± 12 mm Hg/91 ± 7 mm Hg, P < 0.05 for both). The mean final dose of irbesartan was 243.8 ± 63.5 mg daily after a 7-week titration period. Mean daytime (6 am to 6 pm) BP decreased from 146 ± 11 mm Hg/94 ± 7 mm Hg to 130 ± 14 mm Hg/84 ± 8 mm Hg (P < 0.05), and nighttime (6 pm to 6 am) BP decreased from 139 ± 14 mm Hg/88 ± 7 mm Hg to 127 ± 15 mm Hg/81 ± 9 mm Hg (P < 0.05). The BP decrease was more pronounced during the day. Before treatment, the circadian variation showed a peak BP at 11 am and a nadir at 4 am. After treatment, significant BP reductions versus baseline (P < 0.05 for both diastolic and systolic BP) were observed for 23 of the 24 hourly mean points. The circadian rhythm of BP cycles was preserved. Mean heart rate did not change after treatment. Two patients reported dizziness and 1 reported heartburn.Conclusions: Irbesartan administered as once-daily monotherapy provided effective BP control during 23 of the 24 hourly mean points while preserving the circadian rhythm of BP cycles, and was well tolerated.     

Poster 20: Community integration after traumatic brain injury

Objective: To determine the level of community integration after traumatic brain injury (TBI) and its association with clinical inpatient outcome measures. Design: The Community Integration Questionnaire (CIQ) was used to conduct telephone interviews with either the patient or a proxy who lived with the patient. Setting: Community. Participants: 77 patients with TBI who were 5 to 34 months postdischarge from an acute rehabilitation hospital. Interventions: Not applicable. Main Outcome Measure: The CIQ. Results: The CIQ total score had an inverse correlation with age (r=−.300, P<.008) and length of stay (r=−.290, P<.011). There were low but statistically significant correlations with discharge cognitive skills on the FIM™ instrument (r=.451, P<.0001), discharge FIM total score (r=.366, P<.001), and FIM efficiency (r=.367, P<.001). There were significant differences between subjects who were not currently working or attending school versus those who were. The latter group scored higher on home integration (5.6±3.0 vs 3.6±2.9), social integration (8.9±2.1 vs 6.6±2.8), productivity (5.4±0.8 vs 1.5±1.1), and CIQ total scores (20.0±3.7 vs 11.8±5.8). Conclusion: Consistent with previous findings, community integration correlated with functional outcome at discharge from rehabilitation. Patients who return to work or school exhibit better social and home integration.     

Effects of valsartan treatment on indicators of cardiovascular damage in newly diagnosed hypertensive patients: A prospective, twelve-month, open-label, pilot study

Background: Myocardial fibrosis and dysfunction can be detected in the early phases of organ damage associated with hypertension. Valsartan, an angiotensin-II receptor blocker, is efficacious in lowering blood pressure (BP) and reducing left ventricular mass in patients with hypertension. Levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and procollagen type I carboxy-terminal propeptide (PICP) are correlated with organ damage in patients with overt congestive heart failure; however, few data are available in patients with hypertension.Objective: The aim of this study was to assess the effects of 12 months of valsartan treatment on echocardiographic measures and indices of organ damage (NT-proBNP and PICP) in newly diagnosed patients with hypertension.Methods: This was a prospective, open-label, single-center, exploratory study. Patients with newly diagnosed, previously untreated hypertension were treated for 12 months with valsartan 160 mg/d and compared with an equal number of healthy, untreated control subjects. Baseline and follow-up visits at 3, 6, and 12 months included physical examination, systolic BP (SBP) and diastolic BP (DBP) measurements, ECG, echocardiography, and NT-proBNP and PICP determination.Results: A total of 20 patients (mean [SD] age, 48.05 [7.29] years) were enrolled and compared with 20 healthy controls (age, 49-6 [6.95] years). Compared with baseline, valsartan was associated with reduced BP in the group with hypertension after 12 months of treatment (mean SBP, 150.05 [11.15] vs 120.00 [8.43] mm Hg, P < 0.001; DBP, 97.80 [8.36] vs 79-50 [4.26] mm Hg, P < 0.001). Compared with the control group, at baseline, the group with hypertension had significantly higher mean left ventricular mass index (LVMI) (119.88 [22.86] vs 87.31 [15.77] g/m²; P < 0.001), relative wall thickness (thickness/radius [h/r] ratio: 0.45 [0.08] vs 0.35 [0.07]; P = 0.001), and NT-proBNP (50.00 [32.01] vs 25.47 [9.69] pg/dL; P = 0.002). PICP was higher, but the difference was not statistically significant (46.10 [15.69] vs 37.50 [7.20] μg/L). After 12 months, treatment with valsartan was associated with significant reductions in all measured parameters compared with baseline (LVMI, 106.51 [17.12] g/m², P = 0.004; h/r, 0.41 [0.07], P = 0.026; NT-proBNP, 22.55 [13.52] pg/dL, P = 0.001; PICP, 35.20 [9-19] μg/L, P < 0.008). At 12 months, patients with hypertension treated with valsartan achieved NT-proBNP and PICP levels not statistically different from those of the healthy controls (NT-proBNP, 22.55 [13-52] vs 25.24 [8.43] pg/dL; PICP, 35.20 [9.19] vs 36.90 [6.41] μg/L).Conclusion: Patients treated with valsartan for 12 months had significant reductions in BP, LVMI, and indices of subclinical organ damage (NT-proBNP and PICP) compared with baseline.     

Comparison of the efficacy, tolerability, and smoothness indexes of two nifedipine formulations: a randomized, double-dummy, double-blind, controlled trial

Background: Nifedipine is an effective dihydropyridine calcium channel antagonist used in the treatment of high blood pressure (BP), although side effects related to its potency and short half-life have led to development of a sustained-release formulation, nifedipine gastrointestinal therapeutic system (N-GITS) with osmotic pump.Objective: This study compared the efficacy, tolerability, and smoothness indexes of 2 formulations of nifedipine—N-GITS and slow-release microgranules (N-MG)—in patients with hypertension.Methods: This was a randomized, double-dummy, double-blind, controlled trial in outpatients with mild to moderate essential hypertension (sitting diastolic BP [DBP] >90 and <115 mm Hg). Patients were randomized to receive either N-GITS 30 mg plus N-MG placebo or N-MG 30 mg plus N-GITS placebo once daily for 12 weeks. In patients who had not achieved adequate BP control (DBP <90 mm Hg or a decrease in DBP of >10 mm Hg compared with baseline) at week 3, the dose of the respective formulations was increased to 60 mg once daily for the remainder of the trial. The primary end point was change in mean BP over 24 hours. In addition, the smoothness indexes of both formulations were compared between groups to evaluate the homogeneity of their antihypertensive effects. Tolerability was assessed in terms of the incidence of adverse events.Results: Fifty-four outpatients (44 women, 10 men; mean age, 54 years) were enrolled, 26 in the N-GITS-treated group and 28 in the N-MG-treated group. A decrease in mean BP over 24 hours was observed in both groups, with no significant differences between groups. The N-GITS-treated group showed a slight but statistically significant increase in heart rate (HR) at 12 weeks (P = 0.017); the N-MG-treated group showed a slight but statistically significant decrease in HR (P = 0.03). Smoothness index values (mean ± SD) for active drug versus comparison-drug placebo in all patients (including nonresponders) were 0.466 ± 0.5 for the N-GITS—treated group and 0.459 ± 0.4 for the N-MG—treated group. The corresponding smoothness index values when nonresponders (N-GITS, 1 nonresponder, 25 responders; N-MG, 3 nonresponders, 25 responders) were excluded were 0.716 ± 0.5 and 0.707 ± 0.7, respectively. No statistically significant difference in smoothness index was found between the 2 groups.Conclusion: The results of this study suggest that N-GITS and N-MG have similar therapeutic effects and smoothness indexes.     

Effect of antihypertensive treatment on the prevalence of ventricular arrhythmias among patients with isolated systolic hypertension without left ventricular hypertrophy

Background: The high incidence of ventricular arrhythmias in patients with hypertension and left ventricular hypertrophy (LVH) is well documented. However, few studies have been conducted on the prevalence of ventricular arrhythmias in patients with isolated systolic hypertension without LVH.Objectives: The objectives of this study were to (1) determine the prevalence of ventricular arrhythmias in patients with systolic hypertension without LVH and (2) estimate the effect of a perindopril/indapamide combination, which does not have an antiarrhythmic effect, on the incidence of ventricular arrhythmias.Methods: Patients with newly diagnosed isolated systolic hypertension (systolic blood pressure [SBP] >160 mm Hg) and a control group of normotensive patients were enrolled. During the 2-week washout period, patients underwent physical examination (including blood pressure measurements), ambulatory electrocardiography monitoring, echocardiography, and laboratory urine and blood tests. Absence of LVH was confirmed by echocardiographic examination. The group of hypertensive patients received 1 tablet of 2 mg perindopril/0.625 mg indapamide per day for a total of 4 weeks. Physical examinations and ambulatory electrocardiographic monitoring were repeated after treatment.Results: A total of 60 hypertensive (mean age, 63.1 years; mean SBP, 176.8 ± 3.1 mm Hg; mean diastolic blood pressure, 82.6 ± 2.9 mm Hg) and 60 normotensive patients were enrolled. Ambulatory electrocardiographic monitoring indicated that 18 of the 60 hypertensive patients (30%) had ventricular arrhythmias: 17 had ventricular premature contractions (>100/24 h) and 1 had ventricular tachycardia plus ventricular premature contractions. In the control group, 7 of 60 subjects (11.7%) had ventricular premature contractions. The difference between the 2 groups in incidence of ventricular arrhythmias was significant (P < 0.01). After treatment, mean SBP decreased to 136.1 ± 3.2 mm Hg, and ventricular premature contractions were found in 9 of 60 hypertensive patients (15%) (P < 0.02 vs pretreatment).Conclusions: The results of this study suggest that in patients with isolated systolic hypertension without LVH, (1) the prevalence of ventricular arrhythmia is higher than in normotensive patients and (2) treatment with perindopril/indapamide decreases the incidence of ventricular arrhythmias.     

Antihypertensive effect of zofenopril plus hydrochlorothiazide versus zofenopril monotherapy in patients with essential hypertension according to their cardiovascular risk level: A post hoc analysis

Background: International guidelines recommend the use of angiotensin-converting enzyme inhibitors, possibly in combination with other antihypertensive drugs, to treat hypertension with associated risk factors.Objective: The aim of this study was to compare the antihypertensive effect of the combination of zofenopril plus hydrochlorothiazide versus zofenopril monotherapy in patients with essential hypertension, according to their cardiovascular risk level.Methods: This was a post hoc analysis of a previously published efficacy and tolerability study. After a 4-week placebo washout, patients with mild to moderate essential hypertension (diastolic blood pressure [DBP] 95-115 mm Hg), aged 18 to 75 years, were randomized at a ratio of 2:1:1 to treatment with zofenopril 30 mg plus hydrochlorothiazide 12.5 mg or monotherapy with zofenopril 30 mg or hydrochlorothiazide 12.5 mg for 12 weeks in an international, multicenter, double-blind study. This period was followed by 24 weeks of open-label treatment. Systolic BP [SBP] and DBP were measured by mercury sphygmomanometry, and changes associated with treatment were calculated. Patients' cardiovascular risk was computed using the Heart Score algorithm. Patients were classified in quartiles according to distribution of cardiovascular risk level, and comparisons were limited to the zofenopril plus hydrochlorothiazide and zofenopril monotherapy treatment groups. The primary end point was change in office DBP.Results: Two hundred forty-six patients (139 men, 107 women; mean [SD] age, 54 [11] years) were included in the analysis. Mean baseline cardiovascular risk was similar in the zofenopril plus hydrochlorothiazide group and the zofenopril monotherapy group (7% vs 9%). DBP and SBP reductions with treatment were significantly greater (both, P < 0.01) with combination treatment than with monotherapy for each quartile of cardiovascular risk. Cardiovascular risk reduction at the end of the 12 weeks of double-blind treatment was greater in the zofenopril plus hydrochlorothiazide group than in the zofenopril monotherapy group (1.9% vs 0.2%; P < 0.01), particularly in the group of patients with the highest cardiovascular risk at baseline (5.2% vs 2.0%). At the end of the 24-week open-label treatment period, the mean reduction in cardiovascular risk was also significantly greater in the combination treatment group than in the monotherapy group (1.4% vs 0.5%; P < 0.01).Conclusions: In these hypertensive patients, combination treatment with zofenopril plus hydrochlorothiazide was associated with a significantly greater decrease in BP compared with zofenopril monotherapy, regardless of the patient's cardiovascular risk. The difference between combination treatment and monotherapy was particularly evident for the group of patients at highest risk.     

Blood pressure-lowering effects of extended-release niacin alone and extended-release niacin/laropiprant combination: A post hoc analysis of a 24-week,placebo-controlled trial in dyslipidemic patients

Background: Dyslipidemia and high blood pressure are both major cardiovascular disease risk factors. Niacin is an effective lipid-altering agent that has been reported to reduce the risk of cardiovascular disease. However, the more widespread use of niacin is limited, mainly due to the occurrence of flushing. Laropiprant (LRPT) is a selective antagonist of prostaglandin D₂ receptor subtype 1 that reduces extended-release niacin (ERN)-induced flushing without affecting its beneficial lipid effects. While the lipid effects of ERN are well known, the blood pressure effects are unclear.Objective: The aim of this analysis was to examine the blood pressure effects of ERN and ERN/LRPT.Methods: This was a post hoc analysis of a 24-week, worldwide, multicenter, double-blind, randomized, placebo-controlled, parallel, Phase III, previously published study of dyslipidemic patients, which examined the effect of ERN and ERN/LRPT on systolic blood pressure (SBP) and diastolic blood pressure (DBP).Results: A total of 1613 men and women, aged 21 to 85 years, with primary hypercholesterolemia or mixed dyslipidemia (66% on statins), were included in the original analysis. ERN alone, or in combination with LRPT, was associated with significant reductions in SBP and DBP at 24 weeks from baseline. The placebo-adjusted mean changes from baseline at week 24 in SBP were ?2.2 and ?3.1 mm Hg for the ERN and ERN/LRPT groups, respectively (P < 0.05 and P < 0.001). Similar changes in DBP were observed; ?2.7 and ?2.5 mm Hg in the ERN and ERN/ LRPT groups, respectively (both, P < 0.001).Conclusion: This post hoc analysis of a 24-week trial found that ERN alone, or in combination with LRPT, was associated with significant placebo-adjusted reductions from baseline in blood pressure in these hyperlipidemic hypertensive or normotensive subjects.     

Efficacy and Tolerability of Nilvadipine in Combination with an Angiotensin II Receptor Antagonist in Patients with Essential Hypertension: A Multicenter, Open-Label, Uncontrolled Study

Background: Combination therapy with different classes of antihypertensive drugs often is needed to achieve controlled blood pressure (BP). The combination of an angiotensin II receptor antagonist (AIIA) and a calcium antagonist is a preferred option for reducing uncontrolled BP.Objective: The aim of this study was to assess the clinical efficacy and tolerability of nilvadipine, a dihydropyridine calcium antagonist, in combination with an AIIA.Methods: Patients with essential hypertension whose BP was not controlled by an AIIA alone were eligible for this multicenter, open-label, uncontrolled study. One of 3 AIIAs (candesartan cilexetil, losartan potassium, or valsartan) was given for at least 10 weeks before the addition of nilvadipine (daily dose, 4 or 8 mg orally). This combination therapy was given for 8 weeks. BP and heart rate were measured between 2 and 4 weeks before and 0, 4, and 8 weeks after the start of combination therapy. Adverse events were monitored at each visit.Results: Thirty-one patients (18 women [58.1%], 13 men [41.9%]; mean [SD] age, 58.5 [10.5] years) were enrolled. At weeks 4 and 8 of combination therapy, mean systolic BP (SBP) and diastolic BP (DBP) were significantly decreased (P<0.01) (at week 8, by 22.0 mm Hg and 12.5 mm Hg, respectively). The mean BP-lowering effect did not differ significantly between the 3 AIIAs tested. Pulse pressure also decreased significantly at week 8, by 9.6 mm Hg (P<0.01). The responder rate (ie, the percentage of patients with DBP <90 mm Hg or a decrease in DBP ≥10 mm Hg) was 72.0% at week 8. Three patients experienced a total of 4 adverse events: mild or severe flushing, mild headache, and mild palpitation. All of these symptoms resolved after nilvadipine treatment was discontinued.Conclusions: Nilvadipine in combination with an AIIA showed good antihypertensive efficacy and was well tolerated in the hypertensive patients in this study. This combination also significantly decreased pulse pressure, suggesting that this combination therapy also may have a beneficial effect in elderly patients with isolated systolic hypertension.     

Abstract 23: Selective serotonin reuptake inhibitors in acute ischemic stroke patients during inpatient rehabilitation

Objective: To examine the safety of selective serotonin reuptake inhibitor (SSRI) antidepressants after stroke and their effect on rehabilitation. Design: Chart review study. Setting: Community-based rehabilitation hospital. Participants: 147 ischemic stroke survivors admitted between August 1, 2001 and May 31, 2002. Interventions: Not applicable. Main Outcome Measures: Evidence of SSRI-related adverse events and FIM™ instrument score. Results: 85 patients received an SSRI for depressive symptoms. +SSRI and −SSRI patients did not differ in age, gender, length of stay (LOS) in the acute care hospital (9.5±7.6d vs 8.2±5.9d, P=.065), or change FIM score (22.1±13.2 vs 20.5±16.2, P=0.5). +SSRI patients had longer LOS in rehabilitation (20.1±9.1d vs 13.7±8.0d, P<.0001), lower FIM score at admission (55.6±20.7 vs 73.8±20.2, P<.0001), and lower FIM efficiency (1.2±1.0 vs 1.8±1.5, P=.01). 16 +SSRI (18.8%) and 6 −SSRI (9.7%) patients experienced 1 or more bleeding episodes, most commonly: gastrointestinal bleed (including occult bleeding), bleeding from a recently inserted gastrostomy tube or pacemaker, nose bleeds, hematuria, or easy bruising. Only 1 +SSRI and 1 −SSRI patient with bleeding required acute medical care. No hemorrhagic transformations of ischemic strokes were noted. Altered mental status occurred in 2 +SSRI and 6 −SSRI patients. Worsening neurologic symptoms occurred only in 4 −SSRI patients. All patients with abnormal bleeding received ≥1 anticoagulant or antiplatelet agents (n=21) or had recently undergone a surgical procedure (renal stent placement, n=1). Conclusions: Bleeding complications were more common in +SSRI patients despite equivalent anticoagulant and antiplatelet treatment, emphasizing the importance of monitoring for bleeding complications during SSRI treatment. +SSRI patients experienced a similar improvement in FIM score, but had lower FIM efficiency, possibly reflecting the underlying effect of depressive symptoms.     

A randomized,double-blind,controlled, parallel-group comparison of perindopril and candesartan in hypertensive patients with type 2 diabetes mellitus

BACKGROUND: When choosing an antihypertensive drug for patients with hypertension and diabetes mellitus (DM), the metabolic side effects, possibility of improving some metabolic parameters, and need for adequate blood pressure control must all be considered. OBJECTIVE: The goal of this study was to compare the impacts of perindopril and candesartan on blood pressure, glucose metabolism, serum lipid profile, and metabolic parameters in patients with mild hypertension and type 2 DM during therapy and after a 1-month washout period. METHODS: Type 2 DM patients with mild hypertension and good glucose control who were not taking hypercholesterolemic drugs were enrolled. Perindopril 4 mg QD or candesartan 16 mg QD was administered for 12 months in this randomized, double-blind, controlled, parallel-group clinical trial. Fasting plasma glucose (FPG), fasting plasma insulin (FPI), glycosylated hemoglobin, homeostasis model assessment (HOMA) index, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, lipoprotein(a) (Lp[a]), plasminogen activator inhibitor 1 (PAI-1), homocysteine, body mass index (BMI), and albumin excretion rate (AER) were assessed. RESULTS: Ninety-six patients (49 women and 47 men; mean [SD] ages, 53 [10] years [perindopril] and 55 [9] years [candesartan]) were enrolled. Mean (SD) body weight, height, and BMI were 78.2 (9.4) kg, 1.69 (0.05) m, and 27.2 (2.0) kg/m(2) in the perindopril group and 77.5 (8.6) kg, 1.70 (0.06) m, and 26.8 (2.5) kg/m(2) in the candesartan group. A significant change occurred from baseline to month 12 during treatment with perindopril in SBP and DBP (both P < 0.01), FPG (P < 0.05), FPI (P < 0.05), TC (P < 0.05), LDL-C (P < 0.05), Lp(a) (P < 0.05), PAM (P < 0.05), and AER (P < 0.05). Significant changes from baseline to month 12 occurred with candesartan in SBP and DBP (both P < 0.01) and AER (P < 0.05). The HOMA index was significantly lower at month 12 in the perindopril group than in the candesartan group (P < 0.05). When we interrupted perindopril and candesartan therapy for a 1-month washout period, changes in SBP and DBP values were significant compared with month 12 in both groups (all P < 0.05). Changes in TC and LDL-C from month 12 to the end of washout were significant only in the perindopril group (both P < 0.05). CONCLUSIONS: Perindopril and candesartan both effectively lowered blood pressure in this group of patients with mild hypertension and type 2 DM. Perindopril showed an improvement on some metabolic parameters compared with candesartan. However, the inclusion/exclusion criteria could limit the ability to extrapolate the results to a general population.     

Efficacy and Tolerability of Delapril Plus Indapamide Versus Lisinopril Plus Hydrochlorothiazide Combination Treatments in Mild to Moderate Hypertension: A Multicenter, Randomized Clinical Study

Background: Several studies have shown that antihypertensive monotherapy is commonly insufficient to control blood pressure (BP) in hypertensive patients and that concomitant use of ≥2 drugs is necessary in ∼50% of these patients. The combination of an angiotensin-converting enzyme (ACE) inhibitor and a diuretic, delapril plus indapamide (D + I), has been shown to be effective and tolerable, with no interaction between the 2 components. Another widely used combination of ACE inhibitor and diuretic is lisinopril plus hydrochlorothiazide (L + H).Objectives: The aims of this study were to confirm the antihypertensive efficacy and tolerability of the fixed combination of D + I in mild to moderate hypertension, and to compare its therapeutic efficacy and tolerability with that of L + H.Methods: The antihypertensive efficacy and tolerability of a fixed combination of D + I (30-mg + 2.5-mg tablets once daily) or L + H (20-mg + 12.5-mg tablets once daily) in patients with mild to moderate hypertension were compared in a multinational, multicenter, randomized, 2-armed, parallel-group study. Eligible patients were aged 18 to 75 years and had a diastolic blood pressure (DBP) 95 to 115 mm Hg and a systolic blood pressure (SBP) ≤180 mm Hg, both measured in the sitting position. After a single-blind, placebo run-in period of 2 weeks, patients were randomized to receive 1 of the 2 treatments for a 12-week period. The primary efficacy end point was the BP normalization rate (ie, the percentage of patients with a sitting DBP ≤90 mm Hg) after 12 weeks of treatment. Secondary end points were as follows: (1) the responder rate (ie, the percentage of patients whose sitting DBP was reduced by ≥10 mm Hg from baseline or had a DBP ≤90 mm Hg after 12 weeks of treatment), (2) the percentage of patients with a DBP ≤85 mm Hg, and (3) changes in sitting SBP and DBP after 4, 8, and 12 weeks of treatment.Results: A total of 159 hypertensive patients (88 women, 71 men) were randomized to receive D + I (44 women, 36 men; mean [SD] age, 53 [¹¹] years) or L + H (44 women, 35 men; mean [SD] age, 55 [¹⁰] years). No significant between-group differences were found in any of the primary or secondary end points of the study. Both combinations induced a significant reduction in sitting DBP and SBP from baseline (P<0.001 for both groups at week 12), without significant differences between the groups. Five mild to moderate adverse drug reactions (ADRs) occurred in each treatment group. No patient dropped out of the study because of an ADR.Conclusion: This study showed no difference between D + I and L + H interms of antihypertensive efficacy or tolerability in patients with mild to moderate hypertension.     

Effects of amlodipine and candesartan on arterial stiffness estimated by cardio-ankle vascular index in patients with essential hypertension: A 24-week study

Background: Aortic stiffness assessed by brachio-ankle pulse wave velocity (baPWV) can be used to predict cardiovascular events. However, baPWV is dependent on blood pressure. Antihypertensive drugs have been reported to reduce baPWV; but it is difficult to determine if this effect is associated with lowered blood pressure or reduced arterial stiffness.Objectives: The primary end point of this study was to assess whether antihypertensive drugs reduce arterial stiffness as estimated by cardio-ankle vascular index (CAVI). The secondary end point was to compare the effects of 2 widely used drugs, the calcium-channel blocker amlodipine and the angiotensin II receptor blocker candesartan, on arterial stiffness.Methods: Between October 2005 and September 2006, consecutive Japanese outpatients with essential hypertension (EHT) (defined as using antihypertensive drugs at screening, systolic blood pressure [SBP] > 140 mm Hg, or diastolic BP [DBP] >90 mm Hg) were assigned to treatment for 24 weeks with either amlodipine (5-10 mg/d) or candesartan (8-12 mg/d). Arterial stiffness was evaluated with CAVI before and after 24 weeks of treatment. Relative change in arterial stiffness from baseline was also compared. The evaluator was blinded to treatment.Results: Twenty patients (11 men, 9 women; mean [SD] age, 62 [10] years) were included in the study. There were no significant differences in clinical characteristics between the 2 groups. At baseline, mean (SD) CAVI was not significantly different in the amlodipine group compared with the candesartan group (8.93 [0.93] vs 8.46 [1.34], respectively). During the 24-week treatment period, mean SBP and DBP decreased significantly in both the amlodipine (14/10 mm Hg; P = 0.006 and P = 0.005) and the candesartan groups (13/11 mm Hg; P = 0.033 and P = 0.005). Amlodipine was associated with a significant change in CAVI from baseline (8.93 [0.93] vs 8.60 [1.50]; P = 0.017), whereas candesartan was not (8.46 [1.34] vs 8.81 [1.20]). The percentage change in CAVI was significantly different in the amlodipine group compared with the candesartan group (−7.14 [8.83] vs 5.85 [16.0], respectively; P = 0.038). After 24 weeks of treatment, the CAVI of the amlodipine group was still numerically larger than baseline CAVI of the candesartan group, although the difference was not statistically significant. Furthermore, there was no significant difference in absolute CAVI between the 2 groups after 24 weeks, but the relative change from baseline was significant in favor of amlodipine. Logistic regression analysis revealed that amlodipine improved CAVI independent of its antihypertensive effect.Conclusion: These data suggest that amlodipine and candesartan had different effects on aortic stiffness estimated by CAVI, despite similar effects on brachial blood pressure after 24 weeks of treatment in these Japanese patients with EHT.     

Effects of Verapamil Slow Release Plus Trandolapril Combination Therapy on Essential Hypertension

Background: Fixed-dose combination antihypertensive therapy has been recommended for patients with essential hypertension who are unresponsive to monotherapy or as a first-line treatment.Objective: We investigated the effects of a fixed-dose combination of the phenylalkylamine-type calcium channel blocker verapamil slow release (SR)plus the angiotensin-converting enzyme inhibitor trandolapril on blood pressure (BP), serum lipid profile, urinary albumin excretion (UAE), left ventricular mass (LVM), and LVM index (LVMI), as well as the adverse events associated with this treatment.Methods: Patients aged 30 to 65 years with mild to moderate essential hypertension were included in the study. All of the patients received capsules containing combination treatment with verapamil SR 180 mg plus trandolapril 2 mg orally, daily for 12 weeks. Mean arterial pressure (MAP), systolic BP (SBP), diastolic BP (DBP), and heart rate (HR) were measured at baseline and at 4, 8, and 12 weeks of treatment. Serum lipid profile, UAE, LVM, LVMI, and body mass index (BMI) were determined at baseline and at the end of the study period. All patients underwent electrocardiography and echocardiography at baseline and week 12. The primary end point of the study was to achieve an SBP/DBP ≤140/≤90 mm Hg (ie, normotensive) during week 12. All adverse events were assessed as mild, moderate, or severe at each visit. According to the response rate at week 12, patients were divided into 2 groups: those who became normotensive (responders) or those who remained hypertensive (SBP/DBP >140/>90 mm Hg; nonresponders).Results: Forty-one patients (29 women, 12 men; mean [SD] age, 47.7 [7.8] years; mean [SD] BMI, 29.4 [3.5] kg/m²) were enrolled. The median durationof hypertension prior to enrollment was 5 months. Mean MAP, SBP, DBP, UAE, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), LDL-C/highdensity lipoprotein cholesterol (HDL-C) ratio, LVM, LVMI, and BMI decreased significantly after 12 weeks of combination treatment; HR and triglyceride level did not change significantly. Treatment-related adverse events occurred in 31.7% of patients, and none were severe or caused any patient to withdraw from the study. The most common adverse events were cough, constipation, headache, and dryness in the throat. Microalbuminuria, which may be a marker of endothelial dysfunction, was found in 7 (17.1%) patients at baseline and regressed significantly after 12 weeks.Conclusions: In this study population, the fixed-dose combination of verapamil-trandolapril was an effective and well-tolerated antihypertensive therapy. This combination significantly reduced MAP, BP, TC, LDL-C, LDL-C/HDL-C ratio, UAE, LVM, and LVMI. Also, microalbuminuria decreased after this treatment. Verapamil-trandolapril may be useful in preventing microalbuminuria and left ventricular hypertrophy in patients with essential hypertension.     

Effectiveness of hydrochlorothiazide in combination with telmisartan and olmesartan in adults with moderate hypertension not controlled with monotherapy: a prospective, randomized, open-label, blinded end point (PROBE), parallel-arm study

Background:The potential combinations of antihypertensive agents are many, and making rational choices depends on the characteristics of each drug and on their complementary mechanisms of action.Objective: The aim of this study was to evaluate the effectiveness of adding hydrochlorothiazide (HCTZ) 12.5 mg to olmesartan 20 mg or telmisartan 80 mg on blood pressure (BP) in patients with moderate hypertension.Methods: Consecutive outpatients at the Centro per l'Ipertensione e la Fisiopatologia Cardiovascolare, University of Pavia, Pavia, Italy, of both sexes aged 39 to 75 years were considered eligible for enrollment if they had a sitting diastolic BP (DBP) ->99 mm Hg and <110 mm Hg at the end of an initial 2-week washout period. Patients were random- ized to olmesartan 20 mg QD or telmisartan 80 mg QD according to a prospective, open-label, blinded end point, parallel-arm design. After 8 weeks of monotherapy, patients whose BP was not controlled (DBP ->90 mm Hg) received HCTZ 12.5 mg QD for 8 additional weeks. Clinical and ambulatory BPs were measured at the end of the washout period and at the end of both treatment periods. Adverse events (AEs) were recorded from spontaneous reports and direct inquiry from investigators.Results: One hundred forty-five patients, all of whom were white, were recruited for the study. After the initial washout period, 13 patients did not meet the inclusion criteria and 6 refused to continue. A total of 126 white patients (69 men, 57 women; mean [SD] age, 60.2 [11.6] years) were randomized to receive monotherapy. Of these, 35 patients (56%) in the olmesartan group and 33 (52%) in the telmisartan group had previously received antihypertensive therapy. At the end of monotherapy, the 52 patients in the olmesartan group and the 49 patients in the telmisartan treatment group who were still in the study and had their BP inadequately controlled by treatment had HCTZ 12.5 mg QD added to their treatment regimen. Both combinations induced a greater ambulatory mean (SD) systolic BP (SBP) and DBP reduction than monothera- py (SBP: 145.3 [6.1] in the olmesartan group and 140.1 [6.4] in the telmisartan group, P < 0.05; DBP: 88.1 [5.1] in the olmesartan group and 84.9 [4.9] in the telmisartan group, P < 0.05). The mean (SD) reduction from baseline in the telmisartan/HCTZ-treated patients (21.5 [10.1]/14.6 [5.2] mm Hg for 24 hours, 21.8 [10.2]/14.9 [5.2] mm Hg for daytime, and 20.4 [10.3]/13.7 [5.9] mm Hg for nighttime; all, P < 0.001 vs baseline) was significantly greater than that observed in the olmesartan/HCTZ-treated patients (18.8 [9.8]/12.3 [4.9] mm Hg for 24 hours, 19.3 [9.8]/12.8 [4.9] mm Hg for daytime, and 17.4 [10.2]/10.6 [5.5] mm Hg for nighttime; all, P < 0.001 vs baseline), with a significant difference between the 2 treatment groups (P < 0.01). Compared with mono- therapy, the add-on effect of HCTZ 12.5 mg QD administration was significantly greater in the telmisartan group than in the olmesartan group (P < 0.05); the differ- ence being more evident for nighttime BP values (SBP, P 0.031; DBP, P 0.025). Reported AEs were similar in the olmesartan/HCTZ and the telmisartan/HCTZ groups (4 patients [7%] vs 3 patients [6%]).Conclusion: The addition of HCTZ 12.5 mg to telmisartan 80 mg monothera- py was associated with greater BP reduction than the addition of the same dose of HCTZ to olmesartan 20 nag monotherapy in these patients previously uncontrolled on monotherapy.