The prospective, randomized investigation of the safety and efficacy of telmisartan versus ramipril using ambulatory blood pressure monitoring (PRISMA I)

OBJECTIVE: To compare the efficacy and safety of once-daily telmisartan and ramipril on blood pressure (BP) reductions during the last 6 h of the dosing interval. PATIENTS AND METHODS: In a prospective, randomized, open-label, blinded-endpoint study using ambulatory BP monitoring, 801 patients with mild-to-moderate hypertension were randomly assigned to once-daily treatment with telmisartan 80 mg for 14 weeks or ramipril 5 mg for 8 weeks and then force titrated to ramipril 10 mg for the last 6 weeks. Primary endpoints were the reduction from baseline in the last 6-h mean ambulatory systolic BP (SBP) and diastolic BP (DBP). Secondary endpoints included changes in 24-h, morning, daytime and night-time mean ambulatory BP and ambulatory BP response rates. RESULTS: Telmisartan 80 mg produced greater reductions in the last 6-h mean ambulatory SBP and DBP compared with ramipril 5 mg (P < 0.0001) and 10 mg (P < 0.0001), and was superior to ramipril for all secondary ambulatory SBP and DBP endpoints (P < 0.05). Ambulatory BP response rates (24-h mean ambulatory SBP/DBP < 130/80 mmHg or reduction from baseline > or = 10 mmHg) were greater with telmisartan 80 mg (P < 0.01) than with ramipril 5 and 10 mg. Ramipril was associated with a higher incidence of treatment-related cough (5.7 versus 0.5% for telmisartan). CONCLUSIONS: Telmisartan was significantly more effective than ramipril in reducing BP throughout the 24-h dosing interval and particularly during the last 6 h, a time when patients appear to be at greatest risk of cerebro- and cardiovascular events. Both drugs were well tolerated, although ramipril was associated with a higher incidence of cough.     

A multicenter, 14-week study of telmisartan and ramipril in patients with mild-to-moderate hypertension using ambulatory blood pressure monitoring

BACKGROUND: Blood pressure (BP) has a circadian pattern with a morning surge that is associated with an increased risk of acute coronary and cerebrovascular events. In a prospective, randomized, open-label, blinded-endpoint, parallel-group, multicenter, forced-titration study of telmisartan and ramipril, the efficacy of both drugs on mean ambulatory diastolic BP (DBP) and systolic BP (SBP) during the last 6 h of a 24-h dosing interval was evaluated. METHODS: After screening and a single-blind run-in phase, 812 adults with mild-to-moderate hypertension (defined as a mean seated DBP > or =95 mm Hg and < or =109 mm Hg and a 24-h ABPM mean DBP 7 > or = 85 mm Hg) were randomized to the open-label, 14-week, forced-titration, active-treatment phase as follows: telmisartan 40 mg/80 mg/80 mg (n = 405) or ramipril 2.5 mg/5 mg/10 mg (n = 407), once daily in the morning. The primary efficacy variable was change from baseline in the last 6-h mean DBP and SBP at 8 and 14 weeks as assessed by ambulatory BP monitoring (ABPM). Secondary efficacy variables were changes from baseline in BP control during each of the 24-h periods and in-clinic trough cuff BP. RESULTS: Telmisartan 80 mg was superior to ramipril 5 mg and 10 mg in change from baseline in the last 6-h ABPM mean DBP and SBP at both 8 and 14 weeks (both P < .0001), respectively. At 14 weeks, the adjusted mean change from baseline in DBP for telmisartan 80 mg was -8.8 mm Hg compared with that for ramipril 10 mg of -5.4 mm Hg (P < .0001). For SBP, the adjusted mean change from baseline for telmisartan 80 mg was -12.7 mm Hg compared with that for ramipril 10 mg of -7.9 mm Hg (P < .0001). At 14 weeks, telmisartan 80 mg also yielded superior reductions from baseline in trough cuff BP compared with ramipril 10 mg (DBP: -11.0 mm Hg v -7.8 mm Hg, respectively; SBP: -14.3 mm Hg v -9.1 mm Hg, respectively; both P < .0001). Measures of 24-h BP control favored telmisartan 80 mg versus ramipril 10 mg (P < .0001), as did other secondary ABPM endpoints during the daytime, night-time, and morning periods. Treatment-related adverse events were uncommon; patients treated with ramipril had a higher incidence of cough than those treated with telmisartan (10.1% v 1.5%, respectively). CONCLUSIONS: Telmisartan 80 mg was consistently more effective than ramipril 10 mg in reducing both DBP and SBP during the last 6 h of the dosing interval, a measure of the early morning period when patients are at greatest risk of life-threatening cardiovascular and cerebrovascular events. Telmisartan 80 mg was also more effective than ramipril 10 mg in reducing BP throughout the entire 24-h dosing interval. Both drugs were well tolerated.     

Telmisartan vs losartan plus hydrochlorothiazide in the treatment of mild-to-moderate essential hypertension--a randomised ABPM study

The objective of this prospective, randomised, open-label, blinded-end point parallel-group, multicentre study was to show that telmisartan 80 mg is not inferior to a fixed-dose combination of losartan 50 mg/hydrochlorothiazide (HCTZ) 12.5 mg in patients with mild-to-moderate hypertension. The criterion for noninferiority was a treatment difference of < or =3.0 mmHg in the reduction of 24-h mean ambulatory diastolic blood pressure (DBP) from the end of the 4-week placebo washout period to the end of the 6-week active treatment period. In the intent-to-treat analysis, the mean reduction in 24-h DBP was 8.3+/-6.7 mmHg among telmisartan-treated patients (n=332) and 10.3+/-6.3 mmHg among losartan/HCTZ-treated patients (n=350). The mean adjusted difference in 24-h DBP between the two treatment groups was 1.9 mmHg, allowing rejection of the a priori null hypothesis of a treatment difference of >3 mmHg. The reduction in mean 24-h systolic blood pressure was 13.2+/-10.2 mmHg with telmisartan and 17.1+/-10.3 mmHg with losartan/HCTZ. Both drugs provided effective control over the 24-h dosing interval. Analyses of morning (0600-1159) ambulatory blood pressure monitoring DBP means and trough cuff DBP confirmed the noninferiority hypothesis of the protocol for telmisartan 80 mg vs losartan 50 mg/HCTZ 12.5 mg. The reductions in office blood pressures measured at trough in patients treated with telmisartan were -16.3/-9.6 and -18.5/-11.1 mmHg in the patients treated with losartan/HCTZ (difference -2.4/-1.2 mmHg). There were no differences between the side-effect profiles of the two treatments.     

Telmisartan/Hydrochlorothiazide in comparison with losartan/hydrochlorothiazide in managing patients with mild-to-moderate hypertension.

Hypertension is risk factor for cardiovascular morbidity and mortality, and stroke. A critical surge in blood pressure occurs during the early morning hours coincident with increased incidences of myocardial infarction, unstable angina, stroke and sudden cardiac death. This suggests that, in patients with hypertension, it may be important to maintain the efficacy of antihypertensive medication over the 24-h dosing interval, especially in the risky early morning hours. In order to evaluate the antihypertensive efficacies of fixed-dose combinations of angiotensin II receptor blockers with hydrochlorothiazide (HCTZ) 12.5 mg, a multicenter, randomized, prospective, open-label, blinded-endpoint study was performed in 805 patients with mild-to-moderate hypertension randomized to once-daily treatment with telmisartan 40 mg plus HCTZ (T40/H12.5), losartan 50 mg plus HCTZ (L50/H12.5), or telmisartan 80 mg plus HCTZ (T80/H12.5), with the primary objective of comparing T40/H12.5 with L50/H12.5 and evaluating the additional response of T80/H12.5. Efficacy was assessed by ambulatory blood pressure monitoring (ABPM), clinic seated cuff sphygmomanometry and calculated responder rates after 6 weeks' active treatment. The primary endpoint was reduction from baseline in the last 6-h mean (relative to dosing) diastolic blood pressure (DBP) measured using 24-h ABPM. Compared with the L50/H12.5 group, the mean reductions in the last 6-h mean DBP for the T40/H12.5 and T80/H12.5 groups were significantly greater: -2.0 mmHg (p=0.0031) and -2.8 mmHg (p=0.0003), respectively. We conclude that T40/H12.5 provided clinically and statistically significantly superior blood pressure reductions compared with L50/H12.5 during the last 6 h of the 24-h dosing interval, which corresponds to the high-risk early-morning hours, and that T80/H12.5 provided additional blood pressure reductions.     

Antihypertensive efficacy and safety of olmesartan medoxomil compared with amlodipine for mild-to-moderate hypertension

The antihypertensive efficacy of the angiotensin II receptor blocker olmesartan medoxomil has been shown to compare favourably with that of other antihypertensive agents. This randomized, double-blind study compared the antihypertensive efficacy of the starting dose of olmesartan medoxomil with that of the calcium channel blocker amlodipine besylate (amlodipine) in subjects with mild-to-moderate hypertension. Following a 4-week, single-blind, placebo run-in period, 440 subjects aged >/=18 years were randomized to the starting dose of olmesartan medoxomil (20 mg/day), amlodipine (5 mg/day), or placebo for 8 weeks. Subjects were evaluated by 24-h ambulatory blood pressure monitoring (ABPM) and by seated cuff blood pressure (BP) measurements at trough. The primary end point was the change from baseline in mean 24-h diastolic blood pressure (DBP) by ABPM at Week 8. Secondary end points included change from baseline in mean 24-h ambulatory systolic blood pressure (SBP) at 8 weeks, change from baseline in mean seated trough cuff DBP and SBP measurements, and response and control rates for DBP <90 and <85 mmHg. Control rates for SBP <140 and <130 mmHg were also calculated. Olmesartan medoxomil and amlodipine produced significantly greater reductions in ambulatory and seated DBP and SBP compared with placebo. Mean reductions in ambulatory and seated BP were similar between the two active agents; however, in the olmesartan medoxomil group, significantly more patients achieved the SBP goal of <130 mmHg and the DBP goal of <85 mmHg. Both drugs were well tolerated at the recommended starting dose. Although amlodipine was associated with a higher incidence of oedema, this did not reach statistical significance. Olmesartan medoxomil is an effective antihypertensive agent, with BP-lowering efficacy at the starting dose similar to that of amlodipine, and is associated with more patients achieving the rigorous BP goals of SBP <130 mmHg and DBP <85 mmHg.     

ABPM comparison of the antihypertensive profiles of the selective angiotensin II receptor antagonists telmisartan and losartan in patients with mild-to-moderate hypertension.

The antihypertensive efficacy and tolerability profiles of the selective AT1 receptor antagonists telmisartan and losartan were compared with placebo in a 6-week, multinational, multicentre, randomised, double-blind, double-dummy, parallel-group study of 223 patients with mild-to-moderate hypertension, defined as clinic diastolic blood pressure (DBP) >/=95 and /=140 and /=85 mm Hg. After a 4-week single-blind placebo run-in, eligible patients were randomised to receive telmisartan 40 mg, telmisartan 80 mg, losartan 50 mg, or placebo. Ambulatory blood pressure monitoring (ABPM) after 6 weeks of double-blind therapy showed that all active treatments produced significant (P < 0.01) reductions from baseline in 24-h mean SBP and DBP compared with placebo. During the 18-to-24 h period after dosing, the reductions in SBP/DBP with telmisartan 40 mg (10.7/6.8 mm Hg) and 80 mg (12.2/7. 1 mm Hg) were each significantly (P <0.05) greater than those observed for losartan 50 mg (6.0/3.7 mm Hg), and losartan was no better than placebo. Also for the 24-h mean blood pressure, telmisartan 40 mg and 80 mg were significantly (P< 0.05) better than losartan 50 mg. Compared with losartan, telmisartan 80 mg produced significantly (P < 0.05) greater reductions in both SBP and DBP during all monitored periods of the 24-h period, while telmisartan 40 mg produced significantly greater reductions in SBP and DBP in the night-time period (10.01 pm to 5.59 am) (P < 0.05) and in DBP in the morning period (6.00 am to 11.59 am) (P < 0.05). All treatments were comparably well tolerated. Telmisartan 40 mg and 80 mg once daily were effective and well tolerated in the treatment of mild-to-moderate hypertension, producing sustained 24-h blood pressure control which compared favourably with losartan.     

动态血压评价替米沙坦、氯沙坦治疗轻、中度高血压的临床疗效

目的　比较选择性血管紧张素Ⅱ受体拮抗剂替米沙坦、氯沙坦治疗轻、中度原发性高血压的疗效及安全性。方法　对 77例原发性高血压患者分成两组 ,分别予以替米沙坦 80mg,氯沙坦 5 0mg ,每日一次 ,6周后观察动态血压 (ABPM)评价降压效果。结果　替米沙坦和氯沙坦两组 2 4小时平均动态收缩压 (SBP)、舒张压 (DBP)均明显降低 ,替米沙坦 80mg的降压效果比氯沙坦 5 0mg更好 (P <0 .0 5 ) ,特别是在给药间期的最后 4～ 6小时 ,SBP/DBP替米沙坦降低了12 .3± 14 /7.2± 0 .9mmHg ,氯沙坦降低了 6.0± 1.6/3 .8± 0 .9mmHg(P <0 .0 5 )。结论　替米沙坦 80mg每日用药一次 ,可以保持正常的血压昼夜节律 ,提供 2 4小时血压控制的效果     

Freehand three-dimensional echocardiographic evaluation of the effect of telmisartan compared with hydrochlorothiazide on left ventricular mass in hypertensive patients with mild-to-moderate hypertension: a multicentre study

Antihypertensive efficacy, effects on left ventricular mass index (LVMI) and tolerability of telmisartan, an angiotensin II receptor blocker, were compared with those of hydrochlorothiazide (HCTZ). Adult patients with mild-to-moderate hypertension and an optimal acoustic window by two-dimensional echocardiography were randomised at baseline to 12 months' double-blind, once-daily treatment with telmisartan 80 mg or HCTZ 25 mg. Two-dimensional echocardiography and freehand precordial three-dimensional echocardiography and 24-h ambulatory blood pressure monitoring were performed at baseline and after treatment. Of the 41 telmisartan group patients and 28 HCTZ group patients, 40 and 25, respectively, completed the study. Following treatment, 24-h mean SBP (telmisartan 157 +/- 11 vs 133 +/- 7 mmHg, P<0.001; HCTZ 154 +/- 10 vs 144 +/- 11 mmHg, P<0.003) and DBP (telmisartan 96 +/- 6 vs 83 +/- 5 mmHg, P<0.001; HCTZ 95 +/- 7 vs 87 +/- 8 mmHg, P<0.003) were significantly reduced. Telmisartan produced significantly greater 24-h mean SBP and DBP reductions than HCTZ (P<0.001). LVMI was significantly reduced by telmisartan (141 +/- 16 vs 125 +/- 19 g/m2, P<0.001), but not by HCTZ (139 +/- 20 vs 135 +/- 22 g/m(2)). Incidences of adverse events in both the treatment groups were low; two cases of hypokalaemia occurred with HCTZ. In conclusion, telmisartan 80 mg was well tolerated and significantly reduced SBP, DBP and LVMI after 12 months' treatment compared with HCTZ.     

A comparison of the efficacies and duration of action of the angiotensin II receptor blockers telmisartan and amlodipine

OBJECTIVES: To compare the antihypertensive effects and duration of action of the angiotensin II receptor antagonist, telmisartan, amlodipine, and placebo in patients with mild-to-moderate hypertension using both conventional clinic blood pressures and ambulatory blood pressure monitoring (ABPM). METHODS: After a 4-week single-blind, placebo run-in period, qualifying patients were randomly allocated in double-blind manner to be administered 40 mg telmisartan (n = 73; increased to 80 and 120 mg as necessary for patients whose diastolic blood pressure (DBP) remained > 90 mmHg); 5 mg amlodipine (n = 78; titrated to 5 mg and titrated to 10 mg for patients whose DBP remained > 90 mmHg); or placebo (n = 81). ABPM was performed at the end of the baseline period and again at the end of 12 weeks of double-blind treatment. RESULTS: Telmisartan and amlodipine treatments significantly decreased trough supine systolic blood pressure and DBP (P < 0.001, measured conventionally) to a similar extent (by 13.1/7.1 and 14.0/7.1 mmHg, respectively, at the end of 12 weeks' treatment) compared with placebo. Both drugs also significantly reduced 24 h mean systolic blood pressures and DBP compared with placebo (P < 0.0001), measured using ABPM, maintaining control of blood pressure throughout the dosing period. Reductions in DBP with telmisartan were greater (P < 0.05) than those with amlodipine during the night-time interval and the last 4 h of the dosing period. Twenty-four-hour mean ABPM DBP < 85 mmHg were observed in 71% of telmisartan patients and in 55% of patients administered amlodipine. In addition, heart rates in patients treated with telmisartan were lower than heart rates in those treated with amlodipine during the final 4 h of the dosing period (P = 0.0003) and during the morning interval (P = 0.005). Generally, both telmisartan and amlodipine were well tolerated, however, drug-related edema occurred significantly more commonly (P < 0.05) among the patients administered amlodipine than it did among patients administered either telmisartan or placebo. CONCLUSIONS: Clinic blood pressure measurements detected no difference between the antihypertensive effects and durations of action of telmisartan and amlodipine, both agents producing statistically significant reductions compared with placebo. ABPM measurements, however, revealed differences between the efficacies at specific time points within the dosing periods. These findings highlight the potential importance of the use of ABPM for evaluating and comparing efficacies of antihypertensive agents.     

An ambulatory blood pressure monitoring study of the comparative antihypertensive efficacy of two angiotensin II receptor antagonists,irbesartan and valsartan

BACKGROUND: The primary objective of this study was to compare the change from baseline in mean diastolic ambulatory blood pressure (ABP) at 24 h post dose (trough measurement) after 8 weeks of treatment with irbesartan or valsartan in subjects with mild-to-moderate hypertension. Secondary objectives included comparing the mean changes from baseline in systolic ABP at trough; 24-h ABP; morning and night-time ABP; self-measured systolic blood pressure (SBP) and diastolic blood pressure (DBP); and office-measured SBP and DBP at trough. DESIGN: After a 3-week, single blind, placebo lead-in period, 426 subjects were randomized to receive either irbesartan 150 mg or valsartan 80 mg for 8 weeks. METHODS: Ambulatory blood pressure measurements were obtained at baseline and at week 8. Self-measured morning and evening DBP and SBP readings were obtained at home over a 7-day period at baseline and at week 8. Office-measured seated DBP and SBP measurements were obtained at trough, at baseline, and at week 8. RESULTS: Irbesartan demonstrated significantly greater reductions than valsartan for mean change from baseline in diastolic ABP at trough (-6.73 versus -4.84 mmHg, respectively; P = 0.035). Irbesartan produced significantly greater reductions than valsartan for mean systolic ABP at trough (-11.62 versus -7.5 mmHg, respectively; P < 0.01) and for mean 24-h diastolic ABP (-6.38 versus -4.82 mmHg, respectively; P = 0.023) and systolic ABP (-10.24 versus -7.76 mmHg; P < 0.01). Irbesartan also produced significantly greater reductions than valsartan for office-measured seated DBP (-10.46 versus 7.28 mmHg, respectively; P < 0.01) and SBP (-16.23 versus -9.96 mmHg, respectively; P < 0.01) and for self-measured morning DBP (-6.28 versus -3.75 mmHg, respectively; P < 0.01) and SBP (-10.21 versus -6.97 mmHg, respectively; P < 0.01). Both drugs were well tolerated. CONCLUSION: Irbesartan was more effective than valsartan in reducing DBP and SBP at trough and in providing greater overall 24-h blood pressure-lowering efficacy.     

Use of ambulatory blood pressure monitoring to evaluate the selective angiotensin II receptor antagonist, telmisartan, and other antihypertensive drugs

Telmisartan (Micardis (R)) is a new, orally active, long-acting angio-tensin (Ang) II receptor antagonist that is effective in the treatment of hypertension. Ambulatory blood pressure monitoring (ABPM) has emerged as an important method for evaluating the consistency of the antihypertensive effects of a drug throughout the dosing interval. ABPM was used to evaluate the antihypertensive efficacy of telmisartan in several placebo-controlled, double-blind, multicenter studies. Patients with mild-to-moderate hypertension were allocated randomly to groups to receive telmisartan 40 or 80 mg, losartan 50 mg, or placebo, once daily in a 6-week, fixed-dose study, or telmisartan 40-120 mg, amlodipine 5-10 mg, or placebo, once daily in a 12-week, dose-titration study. Patients treated with telmisartan 40 and 80 mg or placebo in a separate 4-week, fixed-dose study were included in an additional analysis. Telmisartan 40 and 80 mg significantly decreased mean ambulatory systolic blood pressure (SBP) and diastolic blood pressure (DBP) relative to placebo for the entire 24 h period and in the following intervals: day (6 a.m. to 10 p.m.), morning (6 a.m. to noon), night (10 p.m. to 6 a.m), and the last 4 h of the dosing interval (P<0.01). Notably, telmisartan 40 or 80 mg was more effective than losartan, especially during the last 4-6 h of the dosing interval (P<0.05). Telmisartan 40- 120 mg tended to be more effective than amlodipine 5-10 mg in reducing SBP and DBP in each time interval, with significant differences between treatments noted for DBP in the last 4 h of the dosing interval and in the morning (P < 0.05). ABPM also revealed that the magnitude of the blood pressure decreasing effect with telmisartan was consistent throughout the dosing interval. These results demonstrate that telmisartan maintains a normal circadian blood pressure pattern and provides full 24 h blood pressure control with once-daily dosing.     

Angiotensin II receptor antagonist telmisartan in isolated systolic hypertension (ARAMIS) study: efficacy and safety of telmisartan 20, 40 or 80 mg versus hydrochlorothiazide 12.5 mg or placebo

OBJECTIVE: To identify telmisartan doses that are more effective than placebo and non-inferior to hydrochlorothiazide (HCTZ) 12.5 mg, and are well tolerated, in lowering systolic blood pressure (SBP) in patients with isolated systolic hypertension (ISH). PATIENTS AND METHODS: A 2-4-week single-blind placebo run-in was followed by randomization of 1039 patients (age 36-84 years) with ISH [seated SBP 150-179 mmHg and seated diastolic blood pressure (DBP) < 90 mmHg] to once-daily double-blind treatment with telmisartan 20, 40 or 80 mg, HCTZ 12.5 mg, or placebo. The change in seated trough SBP after 6 weeks compared with baseline was the primary end point. Secondary end points were the percentage achieving the target fall in SBP and the change from baseline in seated trough DBP. Incidence and severity of adverse events and physical examination and laboratory parameters were monitored for the safety evaluation. RESULTS: Baseline demographics in telmisartan 20 mg (n = 206), 40 mg (n = 210), 80 mg (n = 207), HCTZ 12.5 mg (n = 205) and placebo (n = 211) treatment groups were comparable: (mean +/- SD) age, 63.0 +/- 10.9 years; SBP, 162.9 +/- 8.1 mmHg; and DBP 83.4 +/- 5.0 mmHg. No previous antihypertensive therapy had been received by 66% of the patients. Mean reductions in seated trough SBP (adjusted for baseline and country) were: telmisartan 20 mg, 15.6 mmHg (n = 204); 40 mg, 17.9 mmHg (n = 209); and 80 mg, 16.9 mmHg (n = 205), compared with placebo, 11.4 mmHg (n = 208), and HCTZ 12.5 mg, 15.7 mmHg (n = 204). The target fall in seated trough SBP (< or =140 mmHg or reduction by > or =20 mmHg) was achieved in 46.6% (telmisartan 20 mg), 51.7% (telmisartan 40 mg), 53.9% (telmisartan 80 mg), 27.4% (placebo) and 42.7% (HCTZ 12.5 mg); the response rate was significantly higher for telmisartan 80 mg than for HCTZ 12.5 mg (P = 0.03). All-causality adverse events occurred in 19.9, 17.6 and 20.3% receiving telmisartan 20, 40 and 80 mg, respectively; 20.9% receiving placebo and 22.0% receiving HCTZ 12.5 mg. No drug-related serious adverse events occurred. CONCLUSIONS: All doses of telmisartan (20-80 mg) were significantly superior to placebo in reducing SBP in patients with ISH and clinically comparable to HCTZ 12.5 mg. Tolerability of telmisartan was similar to that of placebo.     

A prospective, randomized, open-label trial comparing telmisartan 80 mg with valsartan 80 mg in patients with mild to moderate hypertension using ambulatory blood pressure monitoring

OBJECTIVE: To compare the antihypertensive efficacy and tolerability of telmisartan 80 mg with valsartan 80 mg throughout a 24 h dosing interval. DESIGN: A prospective, randomized, open-label, blinded end point, parallel group study. Treatment efficacy was compared using ambulatory blood pressure monitoring (ABPM), cuff sphygmomanometry and calculated responder rates. Tolerability was assessed by physical examination, laboratory parameters, 12-lead electrocardiogram, blood pressure and heart rate monitoring, and evaluation of adverse events. SETTING: Thirty-five centres in the United States. PATIENTS: Four hundred and twenty-six patients with mild to moderate essential hypertension entered the study. Ninety-two per cent (n=393) completed the study. INTERVENTIONS: Patients underwent a four-week, single-blind, placebo run-in period before being randomly assigned to once-daily oral telmisartan 80 mg (n=214) or valsartan 80 mg (n=212) for an eight-week, open-label treatment period. RESULTS: Treatment with telmisartan was associated with a significantly greater mean reduction from baseline in the last 6 h ABPM mean for diastolic blood pressure compared with the valsartan-treated group (-7.5+/-0.6 mmHg versus -5.2+/-0.6 mmHg, respectively, P<0.01). Secondary analyses showed significantly greater efficacy with telmisartan 80 mg than with valsartan 80 mg, including greater mean reductions from baseline of ABPM (systolic blood pressure and diastolic blood pressure) during the daytime (06:00 to 21:59) and morning (06:00 to11:59) hours, and larger decreases in trough cuff blood pressure (P<0.01). Both treatments showed placebo-like tolerability profiles. CONCLUSIONS: Telmisartan 80 mg once daily was superior to valsartan 80 mg once daily in reducing diastolic blood pressure during the last 6 h of the 24 h dosing interval. These results may be due to telmisartan's longer plasma half-life or to a higher potency compared with valsartan, such that a higher dose of valsartan may produce effects similar to those of 80 mg telmisartan. These data confirm the long duration of action of telmisartan with consistent and sustained control of blood pressure over 24 h and during the last 6 h of the dosing interval. Both treatments were well tolerated; the adverse event data confirmed the excellent tolerability profiles of telmisartan and valsartan that have been reported previously.     

Effect of telmisartan on blood pressure control and kidney function in hypertensive, proteinuric patients with chronic kidney disease

OBJECTIVES: To assess the antihypertensive and antiproteinuric efficacy and safety of the angiotensin II type 1 receptor blocker telmisartan in patients with hypertension and chronic kidney disease. METHODS: A multicenter, prospective trial was performed in adults with hypertension [systolic blood pressure (SBP)/diastolic blood pressure (DBP) >130/85 mmHg), chronic renal insufficiency (serum creatinine <4.0 mg/dl), and proteinuria (>1 g/24 h). In addition to existing antihypertensive therapy, the nature and doses of which remained unchanged throughout the study, patients received once-daily telmisartan 40 mg for the first 3 months followed by forced titration to telmisartan 80 mg for the subsequent 3 months to achieve a target SBP/DBP of <130/85 mmHg. The rationale for using telmisartan was its long half-life efficacy, greater antihypertensive effect compared with valsartan or losartan, and newly discovered potential antidiabetic effect. RESULTS: The study was conducted in 92 patients (45 men, 47 women), of whom 60 had diabetes mellitus (54 patients with type 2 disease). Five patients discontinued prematurely: two because of hyperkalemia, two because of protocol violation, and one because of lack of efficacy. After 6 months' telmisartan treatment, office trough seated SBP was reduced by 19.6 mmHg (P<0.001) from 154.9+/-14.6 mmHg and DBP by 11.8 mmHg (P<0.001) from 91.7+/-8.1 mmHg. Seated trough SBP/DBP of <130/85 mmHg was achieved at 6 months in 34.8% of patients. Ambulatory blood pressure monitoring also demonstrated significant reductions in mean daytime SBP of 10.9 mmHg (P=0.01), night-time SBP of 12.1 mmHg (P=0.05), daytime DBP of 3.1 mmHg (P=0.05), and night-time DBP of 6.5 mmHg (P=0.05). Proteinuria decreased significantly from 3.6+/-3.4 to 2.8+/-2.8 g/24 h (P=0.01). A decrease in proteinuria depended significantly on a decrease in SBP at the end of the study (P=0.044). Each decrease in SBP of about 10 mmHg led to a decrease in proteinuria of about 0.79 g/24 h (95% CI 0.02-1.56 g/24 h). Serum creatinine increased from 1.96+/-0.79 to 2.08+/-0.89 mg/dl (P=0.01), whereas creatinine clearance did not change significantly. CONCLUSIONS: Telmisartan effectively and safely reduced blood pressure and brought about regression of proteinuria in diabetic and nondiabetic, hypertensive, proteinuric patients with chronic kidney disease, even in those with mild-to-moderate chronic renal failure.     

Comparative efficacy of olmesartan, losartan, valsartan, and irbesartan in the control of essential hypertension

In a multicenter, randomized, double-blind trial, the authors compared the antihypertensive efficacy of once-daily treatment with the new angiotensin II type 1 receptor blocker (ARB) olmesartan (20 mg) with recommended starting doses of losartan (50 mg), valsartan (80 mg), and irbesartan (150 mg) in 588 patients with a cuff diastolic blood pressure (DBP) of ≥100 and ≥115 mm Hg and a mean daytime DBP of ≥90 mm Hg and <120 mm Hg, as measured by ambulatory blood pressure monitoring. Cuff and ambulatory blood pressures were monitored at baseline and after 8 weeks of treatment. All groups were predominantly white and approximately 62% male, and their mean age was approximately 52 years. In all groups, mean baseline DBP and systolic blood pressure (SBP) were approximately 104 and 157 mm Hg, respectively. The reduction of sitting cuff DBP with olmesartan (11.5 mm Hg), the primary efficacy variable of this study, was significantly greater than with losartan, valsartan, and irbesartan (8.2, 7.9, and 9.9 mm Hg, respectively). Reductions of cuff SBP with the four ARBs ranged from 8.4–11.3 mm Hg and were not significantly different. The reduction in mean 24-hour DBP with olmesartan (8.5 mm Hg) was significantly greater than reductions with losartan and valsartan (6.2 and 5.6 mm Hg, respectively) and showed a trend toward significance when compared to the reduction in DBP with irbesartan (7.4 mm Hg; p=0.087). The reduction in mean 24-hour SBP with olmesartan (12.5 mm Hg) was significantly greater than the reductions with losartan and valsartan (9.0 and 8.1 mm Hg, respectively) and equivalent to the reduction with irbesartan (11.3 mm Hg). All drugs were well tolerated. The authors conclude that olmesartan, at its starting dose, is more effective than the starting doses of the other ARBs tested in reducing cuff DBP in patients with essential hypertension.     

Prospective,randomized, open-label,blinded-endpoint (PROBE) designed trials yield the same results as double-blind,placebo-controlled trials with respect to ABPM measurements

OBJECTIVE: This meta-analysis aimed to determine whether ambulatory blood pressure monitoring (ABPM) results from double-blind, placebo-controlled (DBPC) and prospective, randomized, open-label, blinded-endpoint (PROBE) hypertension trials are statistically comparable. METHODS: Two DBPC and three PROBE parallel-group studies were selected from an angiotensin II receptor blocker clinical programme. These were fixed-dose studies involving similar mild to moderate hypertensive patient populations. All used SpaceLabs 90207 ABPM devices, and each comprised a 4-week placebo period and a 4-8-week treatment period. Data from patients receiving telmisartan 80 mg were used to compare the results of DBPC (126 patients) and PROBE (734 patients) trials. The analysis had approximately 87% power to show equivalence between the two design types in terms of ruling out differences of >or= 3 mmHg in SBP and >or= 2 mmHg in DBP. Office blood pressure was also compared. RESULTS: The change from baseline in mean 24-h ambulatory SBP was -12.2 mmHg in DBPC trials and -12.3 mmHg in PROBE trials, a rounded difference of 0.2 mmHg [95% confidence interval (CI): -1.8, 2.1]. The change from baseline in mean 24-h ambulatory DBP was -7.7 mmHg in DBPC trials versus -7.9 mmHg in PROBE trials, a difference of 0.2 mmHg (95% CI: -1.1, 1.5). Ambulatory pulse pressure results were identical. CONCLUSIONS: Thus, changes in mean 24-h ambulatory blood pressure from the DBPC and PROBE trials in this meta-analysis are statistically equivalent in terms of ruling out a difference of >or= 3 mmHg in SBP and >or= 2 mmHg in DBP. This supports the validity of the PROBE design in assessing antihypertensive efficacy based on blinded ABPM measurements.     

Meta-analysis of randomized controlled trials comparing telmisartan with losartan in the treatment of patients with hypertension

BACKGROUND: Hypertension is a major risk factor for cardiovascular disease, and data regarding the efficacy and tolerability of telmisartan compared with losartan on blood pressure (BP) control in patients with hypertension. METHODS: Pertinent studies were selected through extensive searches of PubMed (1966 to 29 December 2007), Embase (1980 to 29 December 2007), and the Cochrane library (29 December 2007). Randomized clinical trials comparing telmisartan with losartan in patients with hypertension were selected using predefined criteria. The main efficacy measures were reduction in diastolic and systolic BP (DBP and SBP), and therapeutic response of DBP and SBP. The pooled estimates were carried out using RevMan version 4.2 software. RESULTS: Eleven studies involving 1,832 patients were included in the analysis. Ten trials with 1,792 patients reported reduction in clinic BP; six trials with 1,163 patients reported ambulatory BP reduction; seven trials with 1,675 patients reported therapeutic response of BP. Funnel plots indicated that one trial had true heterogeneity. Use of telmisartan resulted in a significant reduction in clinic DBP (weighted mean difference 1.52, 95% confidence interval (CI) 0.85-2.19) and SBP (2.77, 1.90-3.63) when compared with losartan. There was also a significant reduction in 24-h mean ambulatory DBP (2.49, 0.56-4.42) and SBP (2.47, 0.40-4.55) with telmisartan as compared to losartan. There was also a significant increase in therapeutic response of DBP (relative risk (RR) 1.14, 1.04-1.23) and SBP response (1.10, 1.01-1.20) with telmisartan as compared to losartan. Both telmisartan and losartan were well tolerated. CONCLUSIONS: In comparison with losartan, telmisartan provides superior control of BP and has no association with increased risk of adverse events.     

Effect of Low-Dose Manidipine on Ambulatory Blood Pressure in Very Elderly Hypertensives

Summary. To evaluate the effect of manidipine 10 mg on 24-hour ambulatory blood pressure (BP) and heart rate (HR) in very elderly hypertensive patients, 54 patients aged 76–89 years (mean age 81.8 years) with systolic blood pressure (SBP) >160 mmHg and diastolic blood pressure (DBP) >90 mmHg were studied. After a 4-week placebo washout period, patients were randomized to receive manidipine 10 mg or placebo, both administered once daily for 8 weeks. Patients were checked after the initial run-in placebo phase and every 4 weeks thereafter. At each visit casual BP and HR were measured. At the end of the placebo period and after 8 weeks of active treatment, noninvasive 24-hour ambulate blood pressure measurement ABPM was performed. Manidipine significantly lowered casual sitting and standing SBP (P <0.001) and DBP (P <0.001) at the trough level. ABPM showed a significant decrease in 24-hour SBP and DBP values (P < 0,001), daytime SBP and DBP (P <0.001), and night-time SBP (P <0.001) and DBP (P <0.005). In addition, ABPM confirmed a consistent antihypertensive activity throughout the 24-hour dosing interval, without effect on the circadian BP profile. The trough/peak ratio was 0.67 for SBP and 0.59 DBP. No statistically significant change in HR was observed. The treatment was well tolerated, and there were no serious side effects. In conclusion, in very elderly hypertensive patients, once-daily administration of manidipine 10 mg was well tolerated and effective in reducing casual as well ambulatory BP.     

24-hour efficacy of once-daily diltiazem in essential hypertension.

The safety and effectiveness of a once daily formulation of diltiazem hydrochloride (diltiazem CD) in the treatment of essential hypertension was assessed in a total of 127 patients with supine diastolic blood pressures (DBP) of 95 to 110 mmHg randomized to diltiazem CD (n = 61) or placebo (n = 66). Patients were titrated to doses of 120, 240, or 360 mg to achieve DBP reduction to less than 90 mmHg. At end study diltiazem CD changed trough supine SBP and DBP by -8.4 +/- 1.7 (p = 0.0009) and -8.6 +/- 1.1 mmHg (p = 0.0075), respectively. Heart rate was not significantly changed (-1.3 +/- 1.1 beats/min, p = 0.4362). The average dose of diltiazem CD was 268 mg with 69% achieving a clinical response. A subset of 47 patients underwent ambulatory blood pressure monitoring to assess the consistency of the effect over the full 24-h dosing interval. Diltiazem CD lowered DBP and SBP throughout the dosing interval. The overall side effect profile was similar to placebo. This study provides evidence of 24-h efficacy of this new, once daily formulation of diltiazem.     

24-Hour ambulatory blood pressure control with triple-therapy amlodipine, valsartan and hydrochlorothiazide in patients with moderate to severe hypertension

To determine the effectiveness and safety of once-daily combination therapy with amlodipine, valsartan and hydrochlorothiazide for reducing ambulatory blood pressure (ABP) in patients with moderate to severe hypertension, a multicenter, double-blind study was performed (N=2271) that included ABP monitoring in a 283-patient subset. After a single-blind, placebo run-in period, patients were randomized to receive amlodipine/valsartan/hydrochlorothiazide (10/320/25?mg), valsartan/hydrochlorothiazide (320/25?mg), amlodipine/valsartan (10/320?mg) or amlodipine/hydrochlorothiazide (10/25?mg) each morning for 8 weeks. Efficacy assessments included change from baseline in 24-h, daytime and night time mean ambulatory systolic BP (SBP) and diastolic BP (DBP). Statistically significant and clinically relevant reductions from baseline in all these parameters occurred in all treatment groups (P<0.0001, all comparisons versus baseline). At week 8, least squares mean reductions from baseline in 24-h, daytime and night time mean ambulatory SBP/DBP were 30.3/19.7, 31.2/20.5 and 28.0/17.8?mm?Hg, respectively, with amlodipine/valsartan/hydrochlorothiazide; corresponding reductions with dual therapies ranged from 18.8-24.1/11.7-15.5, 19.0-25.1/12.0-16.0 and 18.3-22.6/11.1-14.3?mm?Hg (P≤0.01, all comparisons of triple versus dual therapy). Treatment with amlodipine/valsartan/hydrochlorothiazide maintained full 24-h effectiveness, including during the morning hours; all hourly mean ambulatory SBP and mean ambulatory DBP measurements were ≤130/85?mm?Hg at end point. Amlodipine/valsartan/hydrochlorothiazide combination therapy was well tolerated. Once-daily treatment with amlodipine/valsartan/hydrochlorothiazide (10/320/25?mg) reduces ABP to a significantly greater extent than component-based dual therapy and maintains its effectiveness over the entire 24-h dosing period.