The efficacy of telmisartan compared with perindopril in patients with mild-to-moderate hypertension

In this study, efficacy of the angiotensin II type 1 receptor blocker telmisartan given as monotherapy was compared with that of perindopril monotherapy in patients with mild-to-moderate hypertension. After a 2-week, single-blind, placebo run-in period, 60 patients were randomised to double-blind, once-daily treatment with telmisartan 80 mg or perindopril 4 mg for 6 weeks. Clinic and ambulatory blood pressure measurements and clinical laboratory evaluation were performed at the end of the placebo run-in and active treatment phases. Both telmisartan and perindopril significantly (p < 0.0001) reduced clinic systolic blood pressure (SBP) and diastolic blood pressure (DBP) compared with baseline values. Also, both drugs significantly (p < 0.0001) reduced 24-h mean ambulatory SBP and DBP compared with baseline. Comparison of the mean hourly antihypertensive activities showed that the reduction in mean ambulatory DBP for the last 8 h of the dosing interval was significantly greater (p < 0.05) in telmisartan-treated patients. A 24-h mean DBP of <85 mmHg was observed in 66.6% of the telmisartan-treated patients but in only 46.6% of the perindopril-treated patients (p < 0.05). It is concluded that telmisartan and perindopril both produce significant reductions in clinic SBP and DBP, but the mean reduction in ambulatory DBP during the last 8 h of the dosing interval is greater in patients treated with telmisartan.     

Fixed combinations of delapril plus indapamide vs fosinopril plus hydrochlorothiazide in mild to moderate essential hypertension

This 12-week randomized, parallel-group, multicenter study compared fixed combinations of delapril (D) 30 mg plus indapamide (I) 2.5 mg and fosinopril (F) 20 mg plus hydrochlorothiazide (H) 12.5 mg in 171 adult patients with mild to moderate essential hypertension. After a 2-week placebo run-in, sitting and standing systolic (SBP) and diastolic blood pressure (DBP) was measured by conventional sphygmomanometry. The primary efficacy endpoint was the percentage of normalized (sitting DBP ≤90 mm Hg) and responder (sitting DBP reduction of ≥10 mm Hg or DBP ≤90 mm Hg) patients. Treatment effects were analyzed in the intention-to-treat (ITT; n = 171) and the per-protocol (PP; n = 167) populations. The percentage of normalized and responder patients did not differ significantly between the D + I (87.4% and 92%) and the F + H (81% and 86.9%) ITT groups. Similar results were seen in the PP population. In ITT and PP patients, sitting and standing SBP and DBP values were comparable at baseline in the two groups and were significantly (P<.01) and similarly reduced at weeks 4, 8, and 12. Neither treatment induced reflex tachycardia, and both regimens were well tolerated. Four patients in the F + H group dropped out because of adverse events. In this study, the efficacy and safety of D + I were comparable to those of F + H in patients with mild to moderate essential hypertension.     

Clinic blood pressure responses to two amlodipine salt formulations, adipate and besylate, in adult Korean patients with mild to moderate hypertension: a multicenter, randomized, double-blind, parallel-group, 8-week comparison

BACKGROUND: The commercially available formulation of amlodipine is conjugated with besylate salt to increase water solubility. Recently, a new amlodipine salt formulation has been developed in which the free base of amlodipine is conjugated with a chemically different salt, adipate. OBJECTIVE: The goal of this study was to compare the antihypertensive effect and tolerability of amlodipine adipate with those of amlodipine besylate in patients with mild to moderate hypertension. METHODS: This was a multicenter, randomized, doubleblind, parallel-group study in which patients received 8 weeks of treatment with either amlodipine adipate or amlodipine besylate. The primary efficacy variable was noninferiority of the difference in mean changes from baseline in trough diastolic blood pressure (DBP) after 8 weeks of treatment. Secondary efficacy variables included mean changes in DBP, systolic blood pressure (SBP), and response rate (defined as the proportion of patients whose DBP was <90 mm Hg or whose DBP had decreased from baseline by > or =10 mm Hg). The incidence of adverse events (AEs) was also assessed. RESULTS: Two hundred eleven patients were randomly assigned to receive amlodipine adipate (n = 106) or amlodipine besylate (n = 105). Study patients were primarily female (54.5%), with a mean (SD) age of 52.2 (9.6) years and a mean body weight of 67.1 (10.2) kg; there were no between-group differences in demographic profiles. After 4 weeks of randomized treatment, 58 (27.5%) patients (29 [27.4%] amlodipine adipate, 29 [27.6%] amlodipine besylate) had not achieved a mean DBP <90 mm Hg, and their dose was doubled. Mean DBP changes at 8 weeks were -15.2 (7.3) mm Hg in the amlodipine adipate group and -14.2 (7.4) mm Hg in the amlodipine besylate group (P = NS). Because the 95% CI for the difference in mean DBP changes between groups (-0.53 to 2.55) was within the prespecified lower limit (-4 mm Hg), amlodipine adipate was considered noninferior to amlodipine besylate. Mean SBP changes were -24.9 (12.1) mm Hg in the amlodipine adipate group and -22.0 (14.7) mm Hg in the amlodipine besylate group (P = NS). The response rates were 92.0% for amlodipine adipate and 95.4% for amlodipine besylate (P = NS). The overall incidence of clinical AEs was 20.8% in the amlodipine adipate group and 25.7% in the amlodipine besylate group (P = NS). Drug-related clinical AEs occurred in 5.7% and 12.4% of patients in the respective treatment groups (P = NS). Serum uric acid levels decreased significantly from base-line in both groups (P < 0.001). CONCLUSIONS: Eight weeks of treatment with amlodipine adipate produced significant reductions from baseline in blood pressure in these patients with mild to moderate hypertension. The efficacy of amlodipine adipate was not inferior to that of amlodipine besylate. Tolerability was comparable between the 2 treatment groups.     

Efficacy and tolerability of oral stevioside in patients with mild essential hypertension: a two-year, randomized, placebo-controlled study

BACKGROUND: Stevioside, a natural glycoside isolated from the plant Stevia rebaudiana Bertoni, has been used as a commercial sweetening agent in Japan and Brazil for >20 years. Previous animal and human studies have indicated that stevioside has an antihypertensive effect. OBJECTIVES: This study was undertaken to investigate the long-term (2-year) efficacy and tolerability of stevioside in patients with mild essential hypertension. Secondary objectives were to determine the effects of stevioside on left ventricular mass index (LVMI) and quality of life (QOL). METHODS: This was a multicenter, randomized, double-blind, placebo-controlled trial in Chinese men and women aged between 20 and 75 years with mild essential hypertension (systolic blood pressure [SBP] 140-159 mm Hg and diastolic blood pressure [DBP] 90-99 mm Hg). Patients took capsules containing 500 mg stevioside powder or placebo 3 times daily for 2 years. Blood pressure was measured at monthly clinic visits; patients were also encouraged to monitor blood pressure at home using an automated device. LVMI was determined by 2-dimensional echocardiography at baseline and after 1 and 2 years of treatment. QOL was assessed using the Medical Outcomes Study 36-Item Short-Form Health Survey. Electrocardiographic, laboratory, and QOL parameters were assessed at the beginning of treatment, and at 6 months, 1 year, and 2 years. RESULTS: One hundred seventy-four patients (87 men, 87 women) were enrolled in the study, and 168 completed it: 82 (42 men, 40 women; mean [SD] age, 52 [7] years) in the stevioside group and 86 (44 women, 42 men; mean age, 53 [7] years) in the placebo group. After 2 years, the stevioside group had significant decreases in mean (SD) SBP and DBP compared with baseline (SBP, from 150 [7.3] to 140 [6.8] mm Hg; DBP, from 95 [4.2] to 89 [3.2] mm Hg; P < 0.05) and compared with placebo (P < 0.05). Based on patients' records of self-monitored blood pressure, these effects were noted beginning approximately 1 week after the start of treatment and persisted throughout the study. There were no significant changes in body mass index or blood biochemistry, and the results of laboratory tests were similar in the 2 groups throughout the study. No significant difference in the incidence of adverse effects was noted between groups, and QOL scores were significantly improved overall with stevioside compared with placebo (P < 0.001). Neither group had a significant change in mean LVMI. However, after 2 years, 6 of 52 patients (11.5%) in the stevioside group had left ventricular hypertrophy (LVH), compared with 17 of 50 patients (34.0%) in the placebo group (P < 0.001). Of those who did not have LVH at baseline, 3 of 46 patients (6.5%) in the stevioside group had developed LVH after 2 years, compared with 9 of 37 patients (24.3%) in the placebo group (P < 0.001). CONCLUSIONS: In this 2-year study in Chinese patients with mild hypertension, oral stevioside significantly decreased SBP and DBP compared with placebo. QOL was improved, and no significant adverse effects were noted.     

Perindopril/Hydrochlorothiazide Combination in Hypertensive Patients Unresponsive to Hydrochlorothiazide Alone: A Double-Blind, Multicenter Study

This study evaluated the efficacy and tolerability of perindopril erbumine, a long-acting ACE inhibitor, added to continuing hydrochlorothiazide (HCTZ) therapy in hypertensive patients (DBP of 95 to 114 mmHg) whose blood pressure did not normalize (supine DBP <90 mmHg) with HCTZ therapy alone. In this multicenter study, 252 patients received HCTZ 25 mg/day for 4 weeks; the 208 whose blood pressure did not normalize entered a 12-week, double-blind segment. These patients continued to receive HCTZ and were randomly assigned to perindopril (2, 4, or 8 mg) or placebo once daily. Mean supine SBP/DBP reductions from baseline for all HCTZ plus perindopril groups were significantly (p less-than-or-equal 0.05) greater than for HCTZ plus placebo. At the start of double-blind treatment, mean supine SBP/DBP readings were 146.1/97.0, 145.4/98.2 and 146.4/98.2 mmHg for the HCTZ plus perindopril 2-, 4-, and 8-mg groups, respectively, and 143.9/96.9 mmHg for HCTZ plus placebo group. At the final visit, mean reductions in supine SBP/DBP were 10.3/6.7, 9.6/8.0, and 9.3/6.3 mmHg for HCTZ plus perindopril 2, 4, and 8 mg, respectively, and 1.6/2.0 mmHg for HCTZ plus placebo. Significantly (p less-than-or-equal 0.05) more HCTZ plus perindopril patients (53.2%) than HCTZ plus placebo patients (24.5%) achieved an adequate response to therapy (supine DBP <90 mmHg or decrease by >10 mmHg). Incidences of adverse experiences were similar among treatment groups. There were no reports of first-dose hypotension. In patients unresponsive to HCTZ alone, the addition of perindopril at doses of 2--8 mg once daily provided safe and effective blood pressure reduction with no added side-effect liability.     

Blood pressure and heart rate effects following a single dose of bitter orange

BACKGROUND: The ingredients of numerous "ephedra-free" dietary supplements used for weight loss include bitter orange, which contains sympathomimetic alkaloids such as synephrine. Due to the similarity in chemical structure to ephedrine and the potential sympathomimetic effects of synephrine, it is hypothesized that bitter orange may increase blood pressure (BP) and heart rate (HR). OBJECTIVE: To determine the effects on BP and HR after a single dose of bitter orange in healthy adults. METHODS: In a prospective, randomized, double-blind, placebo-controlled, crossover study, 15 young, healthy, adult subjects received either a single dose of Nature's Way Bitter Orange--a 900 mg dietary supplement extract standardized to 6% synephrine--or matching placebo, with a one week washout period. Systolic BP (SBP), diastolic BP (DBP), and HR were measured at baseline and every hour for 6 hours after administration. RESULTS: SBP after bitter orange was significantly increased versus placebo at hours 1-5 (p < 0.0001); the peak difference was 7.3 +/- 4.6 mm Hg. Although the baseline DBP was higher than after administration of both placebo and bitter orange, DBP after bitter orange was significantly increased versus placebo at hours 4 and 5 (p < or = 0.02); the peak difference was 2.6 +/- 3.8 mm Hg. HR was significantly increased after bitter orange versus placebo for hours 2-5 (p < 0.01); the peak difference was 4.2 +/- 4.5 beats/min. CONCLUSIONS: SBP, DBP, and HR were higher for up to 5 hours after a single dose of bitter orange versus placebo in young, healthy adults.     

Effect of acute and long-term administration of ramipril on circadian rhythm of blood pressure in essential hypertension

Ambulatory monitoring was used to evaluate the antihypertensive efficacy and effect on circadian rhythms of blood pressure and heart rate of a single dose and long-term administration of ramipril in 20 patients with mild to moderate essential hypertension. Patients initially were randomized to receive either placebo or a single 5-mg dose of ramipril, followed 1 week later by 5 mg of ramipril daily for 6 months. Systolic (SBP) and diastolic blood pressure (DBP) and heart rate were measured every 20 minutes for 24 hours. Single-dose ramipril reduced both SBP and DBP (P < .001) without affecting heart rate. Long-term treatment produced a small additional antihypertensive effect, again without modifying heart rate. Cosinor analysis demonstrated that both administrations of ramipril effectively lowered SBP and DBP mesors (P < .001), compared to placebo; circadian rhythms remained undisturbed. Heart rate also was not modified on any circadian parameter. A significant reduction (P < .001) of blood pressure amplitude, however, occurred after long-term treatment and may have importance in terms of preventing cardiac damage.     

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.     

Effects of progressive muscular relaxation and stretching exercises combination on blood pressure among farmers in rural areas of Indonesia: a randomized study

Objective: Maintaining blood pressure (BP) could improve the quality of life among farmers in agricultural health. The study aims to evaluate the effects of progressive muscular relaxation and stretching exercises (SEs) for BP in farmer subjects in rural areas.Methods: A randomized controlled design was applied for this study. We performed a method, which is the combination of progressive muscle relaxation (PMR) and SEs for participants (30 in the control group and 60 in the intervention group). The intervention group self-practiced PMR and SEs through a video that providing instructions for 15 min. PMR practiced before going to sleeping in the night,and SEs practiced before going to farms in the morning per day for 3-months. Wilcoxon signed-rank test was performed to measure the difference between systolic blood pressure (SBP) and diastolic blood pressure (DBP) as one pre- and post-test comparison of baseline and 3 months data in control and intervention groups.Results: There were no significant differences between SBP and DBP pre- and post-test in control group (P > 0.050). Meanwhile, there were significant differences in reducing SBP (M = 126.67; SD = 18.07; 95％ CI = 120–147.5 mmHg) and DBP (M = 80.67; SD = 6.91;95％ CI = 80–90 mmHg) pre- and post-test combination of PMR and SEs in intervention group (P < 0.001). After 3-months of followup data, number type SBP and DBP still remained at the same levels of baseline and 3-month data in control group. While, there was an increased number of normal and prehypertension for SBP and DBP (10％ vs. 10％ and 20％ vs. 31.6％) and reduced of hypertension stage I for SBP and DBP (30％ vs. 41.6％).Conclusions: This pilot study demonstrated effectively to reduce SBP and DBP among farmers using the combination of PMR and SEs in the agricultural health setting.     

Assessment of the antihypertensive efficacy of various doses of delapril by office and ambulatory blood pressure measurement: The DEFIND study

This study was undertaken to compare and verify the antihypertensive effects of various delapril doses versus placebo on office and ambulatory blood pressure (BP). After a 2-wk placebo period, 303 patients with mild to moderate essential hypertension were randomized in a double-blind study to 8 wk of treatment with placebo, or delapril 7.5 mg twice daily, delapril 15 mg twice daily, delapril 30 mg twice daily, or delapril 30 mg once daily. BP changes versus baseline and rates of normalized office systolic blood pressure (SBP) > 140 mm Hg and diastolic blood pressure (DBP) > 90 mm Hg, as well as responder office SBP > 140 mm Hg or reduction ≥20 mm Hg and office DBP > 90 mm Hg or reduction ≥10 mm Hg, were calculated. In the intention-to-treat population (n=296), office SBP and DBP reductions were more notable with 30 mg twice daily (15.6/11.5 mm Hg) and 15 mg twice daily (14.8/12.5 mm Hg) than with other delapril regimens (30 mg once daily: 11.8/10.5 mm Hg; 7.5 mg twice daily: 12.9/10.1 mm Hg) and placebo (P< .05 for DBP;P< .01 for SBP). The same was true for frequency of responders (63.8% and 60.3%; P≤.05 vs placebo) and normalized patients (58.6% and 53.4%;P< .05 vs placebo). Analysis of ambulatory BPs confirmed the accuracy of office BPs. Drug-related adverse events occurred in 3.4% to 6.7% of patients given delapril and in 6.5% of those given placebo. The lowest effective dose of delapril, 15 mg twice daily, may be recommended as the initial dose for patients who begin treatment with this agent.     

Manidipine versus enalapril monotherapy in patients with hypertension and type 2 diabetes mellitus: a multicenter, randomized, double-blind, 24-week study

BACKGROUND: Blood pressure reduction is associated with a reduced risk for cardiovascular events and death, particularly in patients with both hypertension and type 2 diabetes mellitus. OBJECTIVE: The aim of this study was to compare the antihypertensive efficacy, tolerability, and effect on metabolic risk factors of manidipine, a new dihydropyridine calcium channel antagonist, and enalapril, a widely used angiotensin-converting enzyme inhibitor, in patients with mild to moderate essential hypertension and type 2 diabetes. METHODS: This multicenter, double-blind trial compared manidipine and enalapril in patients with type 2 diabetes and hypertension (diastolic blood pressure [DBP] 90-104 mm Hg, systolic blood pressure [SBP] < or =190 mm Hg). Following a 3-week, single-blind placebo run-in period, eligible patients were randomized to receive either manidipine 10 mg or enalapril 10 mg once daily for 24 weeks. The dose was doubled after 3 weeks in patients who had not responded to treatment (DBP > or =90 mm Hg). The primary efficacy end point was change in DBP from baseline to the end of the study. Secondary outcomes were the responder rate (DBP <90 mm Hg and/or a DBP reduction of > or =10 mm Hg) at the end of the study. Other secondary measures were changes from baseline to the end of the study in heart rate and in the following measures obtained by ambulatory blood pressure monitoring (ABPM): 24-hour, daytime, and nighttime mean DBP and SBP, and the trough:peak ratio. Blood glucose, glycosylated hemoglobin (HbA1c), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, uric acid, and creatinine were measured at the end of the placebo run-in period and the end of treatment. The study had 80% power to detect a between-treatment difference in mean sitting DBP of >3 mm Hg. RESULTS: One hundred twenty-four patients were enrolled in the study. After the placebo run-in period, 13 patients were excluded from the study: 4 for DBP values outside the specified limits, 7 at their request, and 2 for adverse events. Thus, 111 patients met the eligibility criteria and were randomized to treatment (53 manidipine, 58 enalapril). The population consisted of 61 men and 50 women with a mean (SD) age of 62 (11) years and a body mass index of 28.2 (2.4) kg/m2. Among patients who completed the study, drug doses were doubled in 67.6% (25/37) of patients in the manidipine group and 60.0% (24/40) of patients in the enalapril group (P = NS). Similar reductions in blood pressure were observed in both groups, from a mean (SD) of 164 (12)/97.5 (5) mm Hg at baseline to 141 (12)/84.5 (6) mm Hg at the end of the study in the manidipine group (P < 0.01), and from 159 (12)/98 (4) mm Hg to 139 (12)/86 (8) mm Hg in the enalapril group (P < 0.01). The proportion of responders was 66.7% (32/48) in the manidipine group and 60.0% (30/50) in the enalapril group; the difference between groups was not significant. Twenty-four-hour ABPM revealed significant (P < 0.01) and similar reductions in blood pressure in both groups, with a trough:peak ratio of approximately -50%. Neither drug affected heart rate. Among the statistically significant changes in metabolic parameters, significant reductions in HbA(1c) (from 6.7% [1.4%] to 6.2% [1.1%]) and blood glucose concentrations (from 152 [44] to 143 [44] mg/dL) were observed only in the manidipine group (P < 0.05). The incidence of adverse events was similar between groups. CONCLUSIONS: In the present study, manidipine was as metabolically neutral and as effective as enalapril in reducing blood pressure in hypertensive patients with type 2 diabetes, providing a sustained 24-hour antihypertensive effect.     

A randomized,placebo-controlled,phase 2 study of the efficacy and safety of droxidopa in patients with intradialytic hypotension

Introduction: Intradialytic hypotension (IDH) is the most common complication of hemodialysis (HD), and it plays a significant role in the morbidity and mortality associated with maintenance HD. Methods: This was a placebo-controlled, parallel-group study evaluating efficacy and safety of droxidopa in improving intradialytic blood pressure (BP) responses in 85 adults with end-stage renal disease (ESRD) and prone to IDH. Following screening and baseline periods, patients received 400 mg or 600 mg droxidopa, or placebo, orally 1 hour before HD for 4 weeks. Primary outcome endpoint was the change between baseline and last 2 treatment weeks in average mean arterial pressure (MAP) during HD. Also assessed were changes from baseline in systolic BP (SBP) and diastolic BP (DBP) during and after HD; number of hypotension-induced interventions and symptoms; and adverse events. Results: Increase in droxidopa intra-HD MAP were not significantly different from placebo, although droxidopa groups showed significant improvements in mean SBP after HD of +4.8 ± 11.6 mm Hg (600-mg) and +3.4 ± 13.1 (400-mg) compared with –4.4 ± 17.9 mm Hg in placebo, and the drop seen in mean nadir SBP pre- to intra-HD was also reduced. Changes in mean DBP pre- and post-HD, changes in mean nadir SBP post-HD, or intra-HD SBP were not significant over the treatment period. HD terminations decreased 5-fold in the 600-mg group and 2-fold in the 400-mg group, whereas the number of discontinuations stayed unchanged in the placebo group. Overall, treatment with 600-mg or 400-mg droxidopa was well tolerated in this population. Conclusion: These data suggest that droxidopa may have a role in reducing IDH complications in patients with ESRD on chronic HD.     

Effect of a polyphenol-rich dietary supplement containing Pinus massoniana bark extract on blood pressure in healthy adults: A parallel,randomized placebo-controlled trial

ObjectivesHigh blood pressure (BP) is a major risk factor for cardiovascular disease and prevalence rates continue to rise with ageing populations. Polypharmacy remains a burden among the ageing, thus alternative effective strategies are warranted. This study investigated the effects of a polyphenols rich dietary supplement containing Pinus massoniana bark extract (PMBE) for modulating BP in healthy Australian adults.DesignThis study is a secondary analysis of data from a double-blinded, placebo-controlled clinical trial.MethodsSixty-two healthy adults aged 55–75 years were randomized to receive 50 mL dietary supplement containing placebo (0 mg PMBE) or PMBE (1322 mg PMBE) daily for 12 weeks. Seated systolic BP (SBP) and diastolic (DBP) were measured at baseline, 6 weeks and 12 weeks. Effects of PMBE on modulating BP was also explored in this study stratified for SBP status (optimal v high) as well as by SBP medication status. Mixed effect regression modelling was employed involving fixed categorical effects for elapsed time, treatment assignment and their interaction as well as random subject-level intercept to account for within-subject correlations resulting from repeated measurements. Significant models were further examined by addition of covariates and power calculations were performed since this study was a secondary analysis.ResultsSBP significantly reduced (−3.29 mmHg, p = 0.028) after PMBE at 12 weeks compared to baseline. SBP in individuals with normal-high SBP (>120 mmHg) in the PMBE group reduced by − 6.46 mmHg (p = 0.001) at 12 weeks compared to baseline. No significant changes were reported for individuals with optimal (≤120 mmHg) SBP nor did DBP significantly change in either study groups. In individuals with non-medicated normal-high SBP, SBP significantly reduced by − 7.49 mmHg (p = 0.001) and DBP by − 3.06 mmHg (p = 0.011) at 12 weeks compared to baseline after PMBE. Cross-group comparisons were not statistically different.ConclusionsA polyphenol-rich dietary supplement derived from PMBE led to a clinically and statistically significant reduction in SBP in adults. Future studies to investigate the effects of PMBE-polyphenol supplementation on BP are warranted to confirm and explore optimal dose and impact on hypertension.     

The adjunctive effect of telmisartan in patients with hypertension uncontrolled on current antihypertensive therapy

This prospective, double-blind, randomised, parallel-group, multicentre study assessed the adjunctive effect of telmisartan monotherapy versus placebo in controlling blood pressure during the last six hours of the 24-hour dosing period. After a two-week run-in phase, 375 patients with essential hypertension uncontrolled on existing therapy were randomised to either placebo or telmisartan (40 mg uptitrated to 80 mg after four weeks, if needed) for eight weeks. Ambulatory blood pressure monitoring (ABPM) was conducted at randomisation (baseline) and treatment end. The change from baseline in diastolic blood pressure (DBP) over the last six hours (primary endpoint) was significantly greater with telmisartan than placebo (adjusted mean treatment difference in favour of telmisartan: -3.7 mmHg, 95% confidence interval (CI) -5.5, -1.9 mmHg, p < or = 0.001, n = 350), as was the reduction in 24-hour DBP (adjusted mean treatment difference: -5.0 mmHg, 95% CI -6.5, -3.5 mmHg, p < or = 0.001). Telmisartan also reduced mean systolic blood pressure significantly more than placebo over the last six hours and the entire 24-hour dosing interval. Responder rates (ABPM DBP, seated DBP, and overall [seated SBP/DBP]) at 8 weeks were significantly higher with telmisartan than with placebo (p < or = 0.01). All treatments were well tolerated. When added to existing antihypertensive regimens, telmisartan offers additional effectiveness while maintaining placebo-like tolerability.     

不同剂量艾司洛尔预防双腔支气管内插管时心血管反应的临床研究

目的观察不同剂量的艾司洛尔对预防双腔支气管内插管时心血管反应的临床效果及合适剂量。方法选择ASAⅠ～Ⅱ级开胸手术患者60例,随机分为三组,每组20人。A组：注射生理盐水10ml（对照组）,B组：静脉注射艾司洛尔0．5mg／kg,C组：静脉注射艾司洛尔1mg／kg,记录麻醉诱导前（基础值）、诱导后2min、插管后即刻、插管后2min、5min、10min的收缩压（SBP）、舒张压（DBP）、心率（HR）,计算各对应时点HR和收缩压（SBP）的乘积（RPP）。结果与基础值相比,诱导后2min三组SBP、DBP、HR和RPP均较基础值显著降低（P〈0．05）,B组降低的程度比A组更甚,但不及c组低;气管插管后即刻,A组、B组的SBP、DBP、HR和RPP显著升高（P〈0．05）,但B组增高的程度明显低于A组（P〈0．05）,而C组保持稳定;插管后2min、5min、10min三组SBP、DBP、HR和RPP随时间逐渐趋于基础值,但B、C组仍低于A组（P〈0．05）。结论应用0．5mg／kg和1mg／kg两种剂量的艾司洛尔均能有效抑制双腔支气管内插管引起的心血管反应,但1mg／kg艾司洛尔为合适剂量,且血流动力学稳定。     

Antihypertensive efficacy of amlodipine and losartan after two 'missed' doses in patients with mild to moderate essential hypertension

We compared the effects of amlodipine (5-10 mg, n=94) and losartan (50-100 mg, n=94) on the lowering of blood pressure (BP) at steady state and after two missed doses, as well as on tolerability. This was a randomized, double-blind study of 12 weeks of active treatment followed by 2 days of placebo treatment. Twenty-four-hour ambulatory blood pressure monitoring and office BP measurements were performed at baseline, week 12 and after the 2-day drug holiday. After 12 weeks, amlodipine was significantly more effective than losartan in reducing both 24-h systolic blood pressure (SBP) (-18.0 versus -10.8 mmHg) and diastolic blood pressure (DBP) (-10.6 versus -8.0 mmHg). While mean SBP and DBP for both treatments increased comparably during the drug holiday, BP values remained significantly lower than baseline for both treatments. The superior BP-lowering effect of amlodipine compared with losartan was maintained during the drug holiday.     

A multicenter, randomized, double-blind study of the antihypertensive efficacy and tolerability of irbesartan in patients aged > or = 65 years with mild to moderate hypertension

BACKGROUND: Blockade of the renin-angiotensin-aldosterone system (RAAS) is the preferred mechanism of action for controlling hypertension in select groups of patients, including those with diabetic nephropathy and heart failure. Currently, 2 classes of drugs work by blocking the RAAS, albeit by differing mechanisms: angiotensin-converting enzyme (ACE) inhibitors and angiotensin II angiotensin type 1 receptor blockers (ARBs). OBJECTIVE: The goal of this study was to assess the comparative efficacy and tolerability of the ARB irbesartan and the ACE inhibitor enalapril in patients > or = 65 years of age with mild to moderate hypertension (sitting diastolic blood pressure [DBP], 95 to 110 mm Hg). METHODS: Elderly (> or = 65 years of age) patients were recruited from 26 Canadian study centers for a randomized, double-blind, 8-week clinical trial. Exclusion criteria included sitting DBP >110 mm Hg or sitting systolic blood pressure (SBP) >200 mm Hg, angina pectoris, myocardial infarction, cardiac procedure, stroke, or transient ischemic attack within 6 months of randomization, as well as other preexisting or present severe medical or psychologic conditions. Patients were randomly assigned to receive a single daily dose of irbesartan 150 mg (n = 70) or enalapril 10 mg (n = 71) with treatment doses of study drugs doubled at week 4 for sitting DBP > or = 90 mm Hg. Reductions from baseline blood pressure measurements at trough (24 +/- 3 hours after the last dose of medication) were assessed for sitting DBP and sitting SBP. Comparative tolerability to study drugs was also assessed. RESULTS: The intent-to-treat analysis demonstrated similar reductions at week 8 in both DBP and SBP for both groups. For the primary efficacy analysis of sitting DBP, there was a mean reduction from baseline of 9.6 mm Hg and 9.8 mm Hg for the irbesartan and enalapril groups, respectively (P = 0.93). The mean reduction from baseline in sitting SBP was 10.1 mm Hg and 11.6 mm Hg for the irbesartan and enalapril groups, respectively (P = 0.54). Normalization rates (sitting DBP <90 mm Hg) at week 8 did not differ between groups (52.9% in the irbesartan group and 54.9% in the enalapril group; P = 0.81). No statistical difference existed between the 2 groups with respect to serious adverse events or discontinuations due to adverse events. Irbesartan was associated with a significantly lower incidence of cough than was enalapril (4.3% vs 15.5%, respectively; P = 0.046). CONCLUSIONS: Irbesartan is an effective and well-tolerated antihypertensive for elderly patients with mild to moderate hypertension. This study establishes that irbesartan has better tolerability than enalapril with respect to cough and suggests that irbesartan is as effective at lowering blood pressure but better tolerated than an ACE inhibitor in hypertensive patients > or = 65 years of age.     

Clinical efficacy and safety of telmisartan 80 mg once daily compared with enalapril 20 mg once daily in patients with mild-to-moderate hypertension: results of a multicentre study

The efficacy and safety of once-daily telmisartan 80 mg vs. once-daily enalapril 20 mg in the treatment of essential hypertension were evaluated in a multicentre, single-blind, placebo-controlled, randomised trial. In total, 68 patients (49 females, 19 males) with mild-to-moderate hypertension, defined as morning supine systolic blood pressure (SBP) 141-149 mmHg, diastolic blood pressure (DBP) 95-114 mmHg, were enrolled. After a 4-week placebo run-in phase, patients were randomly assigned to treatment with telmisartan or enalapril administered once daily in the morning for 8 weeks. No statistically significant differences were found in the baseline characteristics of patients in either group. Both SBP and DBP were decreased in both treatment groups, but the reductions were statistically different in favour of telmisartan (SBP, p = 0.013; DBP, p = 0.002). The incidence of adverse effects was lower in the telmisartan group, with the absence of cough. In conclusion, telmisartan is more effective and better tolerated than enalapril for the treatment of hypertension and has the advantage that it does not cause cough.     

不同剂量右美托咪啶对冠心病患者气管插管血流动力学的影响

目的研究不同剂量右美托咪啶对冠心病患者气管插管血流动力学的影响。方法择期气管内插管全身麻醉行腹部外科手术冠心病患者75例,随机将其分成L组(右美托咪啶0.5μg/kg)、M组(右美托咪啶1.0μg/kg)、C组(咪唑安定对照组),每组25例。麻醉诱导前静脉泵注用生理盐水稀释成50 ml右旋美托咪啶,L组0.5μg/kg,M组1.0μg/kg,输注时间为20 min;C组全麻诱导时先静脉注射咪唑安定0.03～0.05 mg/kg。记录入室后基础值(T1)、全麻诱导前(T2)、插管前(T3),插管后即刻(T4),插管后3 min(T5)各时点的心率(HR)、有创血压值[收缩压(SBP)、舒张压(DBP)]、心电图(ECG)变化。结果与基础值相比较,输注右美托嘧啶后全麻诱导前L组、M组患者HR、SBP、DBP均下降(P<0.05),但两组之间差异无统计学意义(P>0.05)。气管插管前,三组患者的SBP、DBP、HR均降至最低(与基础值比较,P<0.05);三组间差异均无统计学意义(P>0.05)。气管插管前M组出现4例窦性心动过缓(<52次/min),3例低血压(SBP下降>40%);L组出现1例窦性心动过缓;C组出现1例低血压,2例窦性心动过速。气管插管后即刻三组患者血压、心率有不同程度上升;C组HR、SBP、DBP与插管前L组、M组相比明显上升(P<0.05)。L组、M组与插管前相比差异无统计学意义(P>0.05)。气管插管后3 min,C组血压、心率与气管插管后即刻比较有明显下降(P<0.05);与插管前相比仍明显升高(P<0.05)。L组、M组血压、心率与插管后即刻、插管前比较差异无统计学意义(P>0.05)。结论冠心病患者术前输注右美托咪啶可减少气管插管血流动力学变化;0.5μg/kg右美托咪啶可能更适合冠心病患者。     

Metoclopramide enhances labetalol-induced antihypertensive effect during handgrip in hypertensive patients

The effects of metoclopramide, labetalol, and metoclopramide plus labetalol treatments on baseline cardiovascular parameters and isometric handgrip-induced changes were evaluated in 11 hypertensive subjects. Although all treatments were effective in reducing resting systolic (SBP) and diastolic (DBP) blood pressures, the combination of metoclopramide and labetalol appeared to provide a greater decrease (changes in SBP/DBP: 15/11 mm Hg, P < 0.05; from 149 +/- 4/95 +/- 4 mm Hg to 134 +/- 5/84 +/- 3 mm Hg) than did labetalol alone (changes in SBP/DBP: 10/9 mm Hg, P < 0.05; from 149 +/- 4/95 +/- 4 to 139 +/- 4/86 +/- 3 mm Hg). At 2 minutes, handgrip increased blood pressure on placebo (changes in SBP/DBP: 34/7 mm Hg, P < 0. 001). In the presence of metoclopramide and metoclopramide plus labetalol, however, handgrip induced lesser increases in blood pressure (changes in SBP/DBP: 23/7 mm Hg, P < 0.01, and 18/4 mm Hg, P < 0.01, for metoclopramide and metoclopramide plus labetalol treatments). We conclude that (1) metoclopramide lowers blood pressure in hypertensive patients; (2) metoclopramide attenuates blood pressure response to isometric handgrip; and (3) both compounds, labetalol and metoclopramide, seem to have a pharmacologic interaction concerning blood pressure decrease. A clinical significance is suggested for the metoclopramide effect.