Differential time effect profiles of amlodipine, as compared to valsartan, revealed by ambulatory blood pressure monitoring, self blood pressure measurements and dose omission protocol

Amlodipine and valsartan are once-daily antihypertensive agents. To date, no comparison between these agents given as monotherapies was reported. This study was aimed to evaluate the therapeutic coverage and safety of amlodipine and valsartan in mild-to-moderate hypertensive patients. Multicenter, double-blind, randomized, comparative study. After a 4-week placebo wash-out period, 246 outpatients with office diastolic blood pressure 95 < or = DBP < or =110 mmHg and systolic blood pressure (SBP) < 180 mmHg, in addition to a mean daytime SBP and/or DBP > 135/85 mmHg on 24-h ambulatory blood pressure monitoring (ABPM), were randomly allocated to once-daily amlodipine 5-10 mg or valsartan 40-80 mg, for 12 weeks. In a subgroup of patients, 48-h ABPM were performed at the end of the treatment period. Dose omission was simulated by a single-blind placebo dosing. The primary efficacy end-point was the 24-h trough office BP after 12 weeks of active therapy. The reductions in 24-h trough BP were more pronounced in amlodipine compared with valsartan group as well in office [SBP: -17.8 +/- 10.9 vs. -14.6 +/- 11.2, P = 0.025, DBP: -12.7 +/- 7.2 vs. -10.9 +/- 7.8 mmHg, P = 0.06) as in ambulatory BP (SBP/DBP: -13.0 +/- 13.7/-10.8 +/- 9.1 vs. -7.2 +/- 19.4/-4.9 +/- 13.4 mmHg, P < 0.05). Forty-eight hours after the last active dose, the slope of the morning BP surge (4-9 h) was less steep with amlodipine vs. valsartan [DBP (P < 0.04), SBP (n.s.)]. Ankle edema were more often reported in amlodipine group. These results suggest a superior BP lowering and a longer duration of action with amlodipine compared with valsartan.     

An 18-week, prospective, randomized, double-blind, multicenter study of amlodipine/ramipril combination versus amlodipine monotherapy in the treatment of hypertension: the assessment of combination therapy of amlodipine/ramipril (ATAR) study

BACKGROUND: A combination of antihypertensive agents of different drug classes in a fixed-dose combination (FDC) may offer advantages in terms of efficacy, tolerability, and treatment compliance. Combination of a calcium channel blocker with an angiotensin-converting enzyme inhibitor may act synergistically to reduce blood pressure (BP). OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of an amlodipine/ramipril FDC with those of amlodipine monotherapy. METHODS: This 18-week, prospective, randomized, double-blind study was conducted at 8 centers across Brazil. Patients with stage 1 or 2 essential hypertension were enrolled. After a 2-week placebo run-in phase, patients received amlodipine/ramipril 2.5/2.5 mg or amlodipine 2.5 mg, after which the doses were titrated, based on BP, to 5/5 then 10/10 mg (amlodipine/ramipril) and 5 then 10 mg (amlodipine). The primary end point was BP measured in the intent-to-treat (ITT) population. Hematology and serum biochemistry were assessed at baseline and study end. Tolerability was assessed using patient interview, laboratory analysis, and physical examination, including measurement of ankle circumference to assess peripheral edema. RESULTS: A total of 222 patients completed the study (age range, 40-79 years; FDC group, 117 patients [mean dose, 7.60/7.60 mg]; monotherapy, 105 patients [mean dose, 7.97 mg]). The mean (SD) changes in systolic BP (SBP) and diastolic BP (DBP), as measured using 24-hour ambulatory blood pressure monitoring (ABPM) and in the physician's office, were significantly greater with combination therapy than monotherapy, with the exception of office DBP (ABPM, -20.76 [1.25] vs -15.80 [1.18] mm Hg and -11.71 [0.78] vs -8.61 [0.74] mm Hg, respectively [both, P = 0.004]; office, -27.51 [1.40] vs -22.84 [1.33] mm Hg [P = 0.012] and -16.41 [0.79] vs -14.64 [0.75] mm Hg [P = NS], respectively). In the ITT analysis, the mean changes in ambulatory, but not office-based, BP were statistically significant (ABPM: SBP, -20.21 [1.14] vs -15.31 [1.12] mm Hg and DBP, -11.61 [0.72] vs -8.42 [0.70] mm Hg, respectively [both, P = 0.002]; office: SBP, -26.60 [1.34] vs -22.97 [1.30] mm Hg and DBP, -16.48 [0.78] vs -14.48 [0.75] mm Hg [both, P = NS]). Twenty-nine patients (22.1%) treated with combination therapy and 41 patients (30.6%) treated with monotherapy experienced > or =1 adverse event considered possibly related to study drug. The combination-therapy group had lower prevalence of edema (7.6% vs 18.7%; P = 0.011) and a similar prevalence of dry cough (3.8% vs 0.8%; P = NS). No clinically significant changes in laboratory values were found in either group. CONCLUSIONS: In this population of patients with essential hypertension, the amlodipine/ramipril FDC was associated with significantly reduced ambulatory and office-measured BP compared with amlodipine monotherapy, with the exception of office DBP. Both treatments were well tolerated.     

普伐他汀治疗老年单纯收缩期高血压的疗效与安全性

目的:研究普伐他汀治疗老年单纯收缩期高血压(ISH)的疗效和安全性.方法:选取老年ISH患者102例,随机分为对照组和治疗组,对照组给予苯磺酸氨氯地平5 mg,每日1次口服,治疗组在此基础上加用普伐他汀20 mg,每晚1次口服,疗程1年.分别在用药前后监测血压、脉压(PP)、血脂、心脑血管事件发生率和不良反应.结果:治疗1年后,两组收缩压(SBP)、舒张压(DBP)及PP与治疗前比较均下降,差异有统计学意义(P＜0.01),治疗组SBP及PP与对照组比较,差异有统计学意义(P＜0.05),DBP差异无统计学意义(P＞0.05);治疗后两组血脂指标比较,差异有统计学意义(P＜0.05);两组1年内心血管病因住院率比较差异有统计学意义(P＜0.05),脑血管病因住院率差异无统计学意义(P＞0.05),总心、脑血管事件发生率差异有统计学意义(P＜ 0.05);对照组出现1例轻微头痛,治疗组出现1例肝功能轻微异常,均未特殊处置.结论:普伐他汀对老年ISH患者有协同降压的作用,可缩小PP、降低血脂,减少心血管事件发生,且不良反应少,安全,可靠.     

Ambulatory monitoring of systolic hypertension in the elderly: Eprosartan/hydrochlorothiazide compared with losartan/hydrochlorothiazide (INSIST trial)

Introduction

Systolic hypertension is very common in the elderly and is strongly associated with the risk of cardiovascular and cerebrovascular events. The control of systolic hypertension is difficult and most patients require combination antihypertensive therapy. Few data are available regarding the efficacy of angiotensin II receptor antagonists on systolic hypertension of the elderly. The aim of this double-blind, double-dummy, randomized, parallel-group, multicenter study was to assess the efficacy of eprosartan 600 mg in combination with hydrochlorothiazide (HCTZ) 12.5 mg in comparison with losartan 50 mg in combination with HCTZ 12.5 mg, in reducing blood pressure in elderly patients with grade 2 systolic hypertension who did not optimally respond to eprosartan or losartan monotherapy.

Methods

After a 3-week placebo wash-out, 155 patients with an Office trough sitting systolic blood pressure (Office sitSBP) ≥160 mmHg and <180 mmHg were randomized to eprosartan 600 mg (n=78) or losartan 50 mg (n=77) once daily for 6 weeks. In patients not optimally responding to monotherapy (Office sitSBP≥130 mmHg) 12.5 mg HCTZ was added as fixed combination once daily for 6 weeks. A 24-hour ambulatory blood pressure monitoring (ABPM) was performed at the end of wash-out and at the end of the fixed-combination period.

Results

No statistically significant difference was found between eprosartan/HCTZ and losartan/HCTZ on the primary endpoint (24-hour ABPM SBP) with an adjusted mean difference between treatments of 3.1 mmHg (95% CI: ?0.32–6.59). However, the mean 24-hour ABPM SBP significantly decreased by 16.7 mmHg with eprosartan/HCTZ and 20.3 mmHg with losartan/HCTZ (P<0.001 vs. baseline). The mean Office sitSBP significantly decreased by 28.7 mmHg and 29.6 mmHg respectively, with eprosartan/HCTZ and losartan/HCTZ (P<0.001 vs.baseline and vs. monotherapy).

Conclusion

In this study, eprosartan/HCTZ did not demonstrate to be superior to losartan/HCTZ in reducing ABPM systolic hypertension in the elderly.     

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.     

Time-effect profile of antihypertensive agents assessed with trough/peak ratio,smoothness index and dose omission: an ambulatory blood pressure monitoring study with trandolapril vs. quinapril

The duration of action of antihypertensive drugs may be assessed by several methods using ambulatory blood pressure monitoring (ABPM). The aim of this double-blind, randomized study was to compare the time-effect profile of once daily Trandolapril (Tra) 2 mg vs. Quinapril (Qui) 20 mg in 92 patients with mild-to-moderate hypertension. All patients received placebo during a 30-day run-in period followed by 2 months of active therapy and 1-day medication omission. ABPM was conducted on each period. 24 h antihypertensive coverage was assessed by trough:peak ratio (T/P) and smoothness index (SI) methods. Residual lowering of blood pressure after single-blind, 1 day medication omission was investigated as the SBP/DBP 48-h trough effect. There were no statistically significant differences between treatment groups in the mean SBP/DBP peak or trough effect. Individual T/P were not normally distributed and had very large variations explained by BP random- and activity-related fluctuations. Group T/P were 0.85 for Tra and 0.62 for Qui. The SI values were normally distributed and not statistically different between the two treatment groups. After dose omission, Qui was ineffective at 48-h trough while Tra retained a significant effect (SBP/DBP = -3.4/-4.3 mmHg) and this difference was even greater in ABPM-responders. Comparison of the trough:peak ratios and smoothness indexes of Tra and Qui failed to show any statistically significant difference on 24-h antihypertensive coverage. Nevertheless, residual lowering of blood pressure at 48-h trough suggests that Tra had a longer duration of action than Qui.     

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.     

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.     

Ambulatory versus clinic blood pressure for the assessment of anti hypertensive efficacy in clinical trials: insights from the Val-Syst Study

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.     

Antihypertensive effect of barnidipine 10 mg or amlodipine 5 to 10 mg once daily in treatment-naive patients with essential hypertension: A 24-week, randomized, open-label, pilot study

Background: Dihydropyridine calcium antagonists are largely employed for the treatment of hypertension, coronary heart disease, and heart failure.Objective: The aim of our study was to compare the antihypertensive effect of the dihydropyridine calcium antagonists barnidipine and amlodipine.Methods: This was a 24-week, randomized, open-label, pilot study. Consecutive treatment-naive patients with grade I or II essential hypertension (office sitting systolic blood pressure [BP] of 140-179 mm Hg and diastolic BP of 90-109 mm Hg) were enrolled. The primary end points were the effect of treatment with either barnidipine 10 mg or amlodipine 5 mg once daily on office and ambulatory BP, left ventricular mass index (LVMI), and markers of cardiac damage, serum procollagen type I C-terminal propeptide, and plasma amino-terminal pro-B-type natriuretic peptide concentrations. Patients were assessed at enrollment, and 12 and 24 weeks. During each visit, the prevalence of adverse events (AEs) was also monitored using spontaneous reporting, patient interview, and physical examination, the relationship to study drug being determined by the investigators. Compliance with treatment was assessed at each study visit by counting returned tablets.Results: Thirty eligible patients (20 men, 10 women; mean [SD] age, 47 [12] years) were included in the study; all patients completed the 24 weeks of study treatment. Twelve weeks after randomization, 6 patients in the amlodipine group had their dose doubled to 10 mg due to inadequate BP control. Mean BP reductions at study end were not significantly different between the barnidipine and amlodipine groups (office BP, −10.3/−9.4 vs −16.6/−9.1 mm Hg; ambulatory BP, 9.4/6.4 vs 8.1/5.1 mm Hg). Reductions in LVMI and markers of cardiac damage were not significantly different between the 2 groups. Significantly more patients in the amlodipine group reported drug-related AEs compared with those in the barnidipine group (9 [60%] vs 2 [13%]; P < 0.05).Conclusion: In this small sample of treatment-naive hypertensive patients, the antihypertensive effect of barnidipine 10 mg once daily was not significantly different from that of amlodipine 5 to 10 mg once daily.     

Comparison of the blood pressure-lowering effects and tolerability of Losartan- and Amlodipine-based regimens in patients with isolated systolic hypertension

BACKGROUND: Elevated systolic blood pressure is a more important risk factor for cardiovascular and renal disease than elevated diastolic blood pressure. Isolated systolic hypertension (ISH) is the predominant form of hypertension in the elderly. Effects of angiotensin II on the vascular wall and endothelium may contribute to development of ISH. OBJECTIVE: The primary objective of this study was to compare the effects on trough sitting systolic blood pressure (SiSBP) of a regimen of losartan, a selective angiotensin II-receptor antagonist, and an amlodipine-based regimen in patients with ISH. METHODS: This multicenter, prospective, randomized, double-blind, parallel-group study consisted of a 4-week placebo phase and an 18-week active-treatment phase. The losartan-based regimen consisted of losartan 50 mg, increased as needed to losartan 50 mg/hydrochlorothiazide (HCTZ) 12.5 mg at week 6 and to losartan 100 mg/HCTZ 25 mg at week 12 to achieve a target SiSBP <140 mm Hg. the amlodipine-based regimen consisted of amlodipine 5 mg, increased as needed to amlodipine 10 mg at week 6 and to amlodipine 10 mg/HCTZ 25 mg at week 12. The primary efficacy measure was change in trough SiSBP from baseline to week 18. Information on the tolerability of study treatments was collected at each visit, including the investigator's and patient's observations of clinical adverse experiences (CAEs), laboratory adverse experiences, and responses to a symptom questionnaire. RESULTS: Eight hundred fifty-seven patients (65.6% female) were randomized to treatment, 432 in the losartan group and 425 in the amlodipine group. Their mean age was 67.6 years, and they had a mean duration of hypertension of 6.7 years at baseline. The losartan and amlodipine groups (intent-to-treat population) had baseline mean SiSBP values of 171.2 and 171.9 mm Hg, respectively. At week 18 (the primary end point), the mean change from baseline in SiSBP was -27.4 mm Hg for 426 patients who received losartan and -28.1 mm Hg for 419 patients who received amlodipine (estimated least-square mean difference, 0.3 mm Hg; 95% CI, -1.4 to 2.0), indicating that losartan's effect on systolic blood pressure was noninferior to that of amlodipine. The proportion of patients who responded (SiSBP <140 mm Hg or a > or =20-mm Hg decrease in SiSBP from baseline) was comparable between groups (73.9% losartan, 75.4% amlodipine). The incidence of CAEs and drug-related CAEs was significantly greater in the amlodipine group (amlodipine, 79.8% and 43.8%, respectively; losartan, 67.8% and 25.5%; P < or = 0.001). In addition, more patients in the amlodipine group discontinued therapy due to a drug-related CAE compared with patients in the losartan group (12.9% vs 4.4%, respectively; P < or = 0.001). Lower-extremity edema was the most common drug-related CAE in the amlodipine group (24.0% amlodipine, 2.5% losartan; P < or = 0.001); dizziness was the most common drug-related CAE in the losartan group (6.0% losartan, 4.0% amlodipine). CONCLUSIONS: In these patients with ISH, losartan and amlodipine produced comparable clinically relevant reductions in SiSBP; however, losartan was better tolerated, as evidenced by fewer CAEs and discontinuations compared with amlodipine. Losartan may be considered for the initial treatment of ISH.     

老年高血压患者动态血压监测特点及其预测意义

目的：探讨老年高血压患者动态血压监测特点、正常值及其预测意义。方法：使用英国产MEDILOG ABP monitoring system无创伤性动态血压监测仪对80例老年高血压患者进行24h动态血压监测，包括采用固定日间和夜间时间段，日间每15min、夜间每30min记录1次。包括24h、日间和夜间收缩压及舒张压，24h、日间和夜间血压负荷值。结果：80 例患者24h平均压及平均脉压等常用参数值明显高于正常参考值，其中白大衣高血压占15％。结论：动态血压监测参数值比随测血压能更准确预测心脑血管并发症状发生。 单独诊断白大衣高血压与传统方式有高度一致性。     

Effect of amlodipine on systolic blood pressure

BACKGROUND: Systolic hypertension is the most common form of hypertension, particularly in people aged >60 years. Caused by decreased compliance of large arteries, systolic hypertension is an independent risk factor for cardiovascular disease. Recent studies have demonstrated that it is more important to control systolic blood pressure (SBP) than diastolic blood pressure (DBP). OBJECTIVE: The objective of this study was to perform a systematic literature review to examine the effectiveness of amlodipine in lowering SBP in a variety of patient subgroups and clinical settings. METHODS: The literature review methodology included identifying, selecting, appraising, extracting, and synthesizing primary research studies. Following an a priori protocol, published literature was searched from 1980 to 2001 using 3 electronic databases. A manual review of the reference lists of recent review articles and all accepted studies was performed. Parallel-group, randomized, controlled trials that included at least 10 adults with baseline hypertension (SBP>or=140 mm Hg, DBP>or=90 mm Hg, or both), included at least 1 arm randomized to initial treatment with amlodipine monotherapy, had a minimum treatment duration of 8 weeks, and reported baseline and end-point blood pressure were included. RESULTS: Of 696 citations identified, 85 primary studies met all inclusion criteria. Comparable treatment arms were pooled, and weightd mean SBP was calculated. In the amlodipine monotherapy arms, which included >5000 patients, SBP decreased by a mean of 17.5 mm Hg from baseline. The effect of amlodipine in reducing SBP was greater in elderly patients (age>or=60 years) and patients with author-defined isolated systolic hypertension. The dose was titrated to achieve the target blood pressure in 73 of 89 amlodipine treatment arms, whereas 16 treatment arms reported fixed doses. The median daily dose was 5 mg (range, 1.25-15 mg) in both the fixed-dose and dose-titration groups. CONCLUSIONS: In this review of the published literature, amlodipine monotherapy was effective in reducing SBP. Antihypertensive agents such as amlodipine warrant consideration for the management of patients with inadequately controlled SBP.     

Long‐term reproducibility of ambulatory blood pressure in unselected elderly subjects

The aim of this study was to evaluate the long‐term reproducibility and validity of 24‐h ambulatory blood pressure measurements (ABPM) in an unselected elderly population. In a rural Finnish community 503 randomly chosen invited persons over 65 years of age participated and went through 24‐h ABPM. As part of the validation of the methodology, the reproducibility study was conducted in 26 persons (age 65–76 years). Two identical sets of measurement were performed at 4–12 (median 8) month intervals. The agreement between measurements was assessed by correlation coefficients and standard deviation (SD) of the differences. There were no significant differences in 24‐h, daytime and night‐time average diastolic blood pressure (DBP) and daytime average systolic blood pressure (SBP) between the two measurements. During the second measurement, 24‐h SBP and night‐time average SBP were slightly higher than those obtained by the first monitoring. Average 24‐h SBP and DBP were 18 and 7 mmHg lower, respectively, than office blood pressure averages. The correlation coefficients were significantly higher for 24‐h ambulatory blood pressure than for office blood pressure. The SD of the mean difference between visits was significantly lower for 24‐h ambulatory blood pressure than for office blood pressure measurements. These findings show that the long‐term reproducibility of ambulatory blood pressure is good in an elderly unselected population and better than the office blood pressure reproducibility.     

A multicenter, randomized, double-blind comparison of the efficacy and safety of irbesartan and enalapril in adults with mild to moderate essential hypertension, as assessed by ambulatory blood pressure monitoring: the MAPAVEL Study (Monitorización Ambulatoria Presión Arterial APROVEL)

BACKGROUND: When blood pressure (BP)-lowering efficacy is assessed by measurements taken in a clinic setting, angiotensin II-receptor antagonists show similar efficacy to angiotensin-converting enzyme inhibitors and better tolerability. A search of MEDLINE to date, however, reveals no randomized, double-blind studies using ambulatory BP monitoring (ABPM) to compare the BP-lowering efficacy of irbesartan and enalapril in a large number of patients ( > 200) with essential hypertension. OBJECTIVE: This study compared 24-hour BP reduction and BP control, as assessed by ABPM, in patients with mild to moderate essential hypertension treated with irbesartan or enalapril. The relative tolerability of the 2 treatments was also evaluated. METHODS: This was a multicenter, randomized, double-blind study in patients with mild to moderate essential hypertension (office diastolic BP [DBP] 90-109 mm Hg or systolic BP [SBP] 140-179 mm Hg). After a 3-week, single-blind placebo washout phase, patients with a mean daytime DBP > or = 85 mm Hg, as measured by ABPM between 10 AM and 8 PM, were randomized to 12 weeks of active treatment with irbesartan or enalapril. Starting doses were 150 and 10 mg/d, respectively, with titration to 300 or 20 mg/d if clinic DBP was > or = 90 mm Hg at week 4 or 8. Based on clinic measurements, BP control was defined as a BP reading < 140/90 mm Hg after 12 weeks of treatment; patients achieving a reduction in DBP of > or = 10 mm Hg at 12 weeks were considered responders. The ABPM criterion for BP control, independent of clinic values, was achievement of a daytime BP < 130/85 mm Hg after 12 weeks of treatment; patients achieving a reduction in 24-hour DBP > or = 5 mm Hg at 12 weeks were considered responders, in dependent of clinic values. RESULTS: A total of 238 patients were randomized to treatment, 115 to irbesartan and 123 to enalapril. The study population was approximately 52.0% female and 48.0% male, with a mean ( +/- SD) age of 52.7 +/- 10.6 years. The study was completed by 111 patients in the irbesartan group (dose titrated to 300 mg/d in 72.0% of patients) and 115 patients in the enalapril group (dose titrated to 20 mg/d in 76.5% of patients). BP reductions were similar in the 2 groups, both as measured in the clinic (DBP, 12.7 +/- 8.8 mm Hg irbesartan vs 12.4 +/- 7.4 mm Hg enalapril; SBP, 19.0 +/- 14.1 mm Hg vs 17.5 +/- 14.0 mm Hg) and by 24-hour ABPM (DBP, 9.4 +/- 8.5 mm Hg vs 8.8 +/- 8.5 mm Hg: SBP, 14.7 +/- 14.7 mm Hg vs 12.6 +/- 13.1 mm Hg). As assessed by ABPM, rates of BP control were 40.5% (45/111) for irbesartan and 33.9% (39/115) for enalapril, and the response rates were a respective 71.2% (79/111) and 71.3% (82/115). The overall incidence of adverse events (40.0% irbesartan, 51.2% enalapril) was not statistically different between groups, although the incidence of adverse events considered probably related to antihypertensive treatment was significantly higher with enalapril than with irbesartan (24.6% vs 9.2%, respectively; P = 0.026), essentially because of the higher incidence of cough (8.1% vs 0.9%). CONCLUSIONS: As assessed by ABPM, irbesartan 150 to 300 mg/d was as effective in lowering BP and achieving BP control as enalapril 10 to 20 mg/d. Based on the number of treatment-related adverse events, irbesartan was better tolerated than enalapril.     

Ambulatory blood pressure profiles in patients treated with once-daily diltiazem extended-release or indapamide alone or in combination

This randomized, double-blind, placebo-controlled, parallel-group study evaluated the efficacy and safety of single daily dose diltiazem extended-release (XR) and indapamide, given alone and combined, in 255 male and 170 female patients with mild to moderate hypertension. Blood pressure was assessed both manually in the office and by 24-hour ambulatory blood pressure monitoring (ABPM) techniques. Between-treatment efficacy comparisons were based on ABPM plots and changes from baseline in supine systolic (SuSBP) and diastolic (SuDBP) blood pressure after 6 weeks of double-blind treatment. Periodic 12-lead electrocardiograms (ECG), clinical laboratory tests, and physical examinations were used to assess safety. Both diltiazem XR 180, 240, and 360 mg and indapamide 2.5 mg monotherapy reduced ambulatory blood pressure to a greater extent than placebo. The ABPM data demonstrate that 2.5 mg indapamide produces an additional reduction in diastolic blood pressure when combined with fixed doses of diltiazem XR (120, 180, and 240 mg). The reduction was consistent over the entire 24-hour recording period for all combinations. Compared with monotherapy groups, higher therapeutic response rates (SuDBP < or = 90 mm Hg or Delta SuDBP > or = 10 mm Hg decrease from baseline) were also observed with combination therapy. Office blood pressure data qualitatively and quantitatively supported the observations made from the ABPM data. There were no unexpected adverse events or side-effect trends and no dose-response or clinically significant laboratory, ECG, or physical examination adverse effects. The combination therapy regimens were well tolerated with safety profiles comparable with those of the individual therapies.     

观察洛伐他汀对老年单纯收缩期高血压患者脉压及动脉弹性的影响

目的 观察他汀类药物对血脂正常的老年单纯收缩期高血压(ISH)患者脉压及动脉弹性的影响.方法 随机将68例ISH患者分成治疗组及对照组,对照组给予贝那普利口服,每次10 mg,1次/d;治疗组在对照组治疗基础上加用洛伐他汀,20 mg/次,每晚1次,观察两组患者治疗前后收缩压(SBP)、舒张压(DBP)、脉压(PP)、颈动脉-挠动脉脉博波速度(C-RPWV)及颈动脉-股动脉脉搏波速度(C-FPWV)的变化.结果 治疗后两组SBP、PP、C-RPW及CFPWV均有所下降,随着治疗时间的延长,治疗组较对照组PP、C-RPWV及C-FPWV显著降低(P<0.01).结论他汀类与血管紧张素转换酶抑制剂合用,有益于控制患者的脉压及脉搏波速度,改善动脉弹性.     

观察洛伐他汀对老年单纯收缩期高血压患者脉压及动脉弹性的影响

目的 观察他汀类药物对血脂正常的老年单纯收缩期高血压(ISH)患者脉压及动脉弹性的影响.方法 随机将68例ISH患者分成治疗组及对照组,对照组给予贝那普利口服,每次10 mg,1次/d;治疗组在对照组治疗基础上加用洛伐他汀,20 mg/次,每晚1次,观察两组患者治疗前后收缩压(SBP)、舒张压(DBP)、脉压(PP)、颈动脉-挠动脉脉博波速度(C-RPWV)及颈动脉-股动脉脉搏波速度(C-FPWV)的变化.结果 治疗后两组SBP、PP、C-RPW及CFPWV均有所下降,随着治疗时间的延长,治疗组较对照组PP、C-RPWV及C-FPWV显著降低(P<0.01).结论他汀类与血管紧张素转换酶抑制剂合用,有益于控制患者的脉压及脉搏波速度,改善动脉弹性.     

观察洛伐他汀对老年单纯收缩期高血压患者脉压及动脉弹性的影响

目的观察他汀类药物对血脂正常的老年单纯收缩期高血压（ISH）患者脉压及动脉弹性的影响。方法随机将68例ISH患者分成治疗组及对照组,对照组给予贝那普利口服,每次10mg,1次／d;治疗组在对照组治疗基础上加用洛伐他汀,20mg／次,每晚1次,观察两组患者治疗前后收缩压（SBP）、舒张压（DBP）、脉压（PP）、颈动脉一挠动脉脉博波速度（C-RPWV）及颈动脉．股动脉脉搏波速度（C-FPWV）的变化。结果治疗后两组SBP、PP、C—RPW及CFPWV均有所下降,随着治疗时间的延长,治疗组较对照组PP、C-RPWV及c-FPWV显著降低（P〈0．01）。结论他汀类与血管紧张素转换酶抑制剂合用,有益于控制患者的脉压及脉搏波速度,改善动脉弹性。     

Comparison of the efficacy and tolerability of telmisartan 40 mg vs. enalapril 10 mg in the treatment of mild-to-moderate hypertension: a multicentre, double-blind study in Taiwanese patients

The purpose of this randomised, double-blind, double-dummy, parallel-group study was to evaluate the efficacy and tolerability of telmisartan 40 mg once daily vs. enalapril 10 mg once daily in 147 Taiwanese patients with mild-to-moderate essential hypertension (diastolic blood pressure [DBP] 90-109 mmHg). After 6 weeks' treatment, telmisartan produced a significantly greater reduction from baseline in the primary endpoint of trough seated DBP compared with enalapril 10 mg (11.7 vs. 8.7 mmHg, respectively; p = 0.02). Numerically greater reductions compared with baseline in seated systolic blood pressure (SBP), standing DBP, and standing SBP were achieved with telmisartan compared with enalapril. Also, numerically greater proportions of patients achieved blood pressure control (DBP/systolic blood pressure [SBP] <90/140 mmHg) and responded to treatment (reduction from baseline in trough seated DBP > or = 10 mmHg and/or post-treatment DBP <90 mmHg; reduction from baseline in trough seated SBP > or = 10 mmHg and/or post-treatment SBP <140 mmHg) with telmisartan 40 mg compared with enalapril 10 mg. Although both treatments were well tolerated, the incidence of cough was markedly lower with telmisartan 40 mg (8.5%) than with enalapril 10 mg (18.4%) in this population of Taiwanese hypertensive patients.