Antihypertensive effect of valsartan 80 mg and hydrochlorothiazide 12.5 mg evaluated by ambulatory blood pressure monitoring

OBJECTIVE: The aim of the study was to evaluate by ambulatory blood pressure measurement (ABPM) the 24 hours antihypertensive efficacy of the fixed combination therapy, valsartan 80 mg + hydrochlorothiazide 12.5 mg (V + H), once daily, after 6 weeks of treatment, in patients with mild to moderate hypertension. STUDY DESIGN: It was a French, multicenter, double blind, randomized trial in parallel groups comparing V + H and placebo. After an initial two weeks placebo period, patients were assigned to receive either V + H or placebo for six weeks. Were eligible those with clinical arterial blood pressure, measured by sphygmomanometer, between 160/95 and 209/114 mmHg after monotherapy. A 26 hours ABPM, with Spacelabs 90,207, was done at J0 and J42 (one measurement every 15 minutes, in day time and at night). Responders were defined as a fall in day diastolic blood pressure > or = 5 mmHg and/or day diastolic blood pressure < 90 mmHg with ABPM. RESULTS: 123 of the 138 randomized patients had two interpretative measurements. Their average age was 59 + 10 years. 57% (78) of them were males and their average ABPM before treatment was 143 +/- 15/88 +/- 11 mmHg. With V + H, the reduction of the systolic and the diastolic blood pressure measured by ABPM, was significantly more important than with placebo (SBP: -15.4 +/- 10.9 mmHg versus -0.6 +/- 7.7 mmHg, p < 0.001; DBP: -9.1 +/- 7 mmHg versus -0.4 +/- 5.4 mmHg, p < 0.001). Pulse pressure (PP) was also significantly reduced with the combination therapy V + H, but it was not modified with placebo (-6.3 + 5.5 mmHg versus -0.2 + 4.1 mmHg, p < 0.001). ABPM responder rate was 73% with V + H versus 24% with placebo (p < 0.001). Trough/peak ratio was 80.3% for systolic blood pressure and 57.3% for diastolic blood pressure. The combination V + H was as well tolerated as placebo. CONCLUSION: The fixed combination V + H used for treatment of hypertension, after failure of monotherapy, is very effective in reducing pulse pressure, systolic and diastolic blood pressure, over 24 hours, homogeneously, and is as well tolerated as placebo.     

Morning versus evening administration of a calcium channel blocker in combination therapy for essential hypertension by ambulatory blood pressure monitoring analysis

Patients with moderate to severe hypertension may need more than two antihypertensive drugs in combination to achieve ideal blood pressure (BP) control. The purpose of this study was to compare the efficacy and safety of administering the antihypertensive agents either all together in the morning or separately with two agents in the morning and one calcium channel blocker (CCB) in the evening. Twenty-four-hour ambulatory BP monitoring (ABPM) was performed among 15 patients (mean, 59 years) with moderate to severe essential hypertension. All patients received at least 3 antihypertensive drugs for ideal BP control. Two treatment regimens were given to each patient: Regimen 1: All antihypertensive agents were given once a day in the morning; Regimen 2: All antihypertensive agents were given in the morning, except the CCB which was given at 4:00 pm. After receiving regimen 1 for 4 weeks, each patient underwent 24-hour ABPM to analyze the BP control. After the first ABPM, each patient was switched to regimen 2. After 4 weeks of treatment with regimen 2, each patient underwent the second ABPM measurement. The pretreatment mean systolic and diastolic BP were 179.6 +/- 21.7 and 107.4 +/- 19.9 mmHg, respectively. Between the two regimens, there was no significant difference in the mean 24-hour BP (126.1 +/- 5.8/73.3 +/- 3.8 versus 130.2 +/- 6.2/75.1 +/- 4.7 mmHg), daytime BP (128.2 +/- 6.5/75.3 +/- 3.8 versus 132.4 +/- 5.8/77.2 +/- 4.4 mmHg), nighttime BP (125.2 +/- 4.9/72.4 +/- 3.3 versus 130.9 +/- 6.2/73.8 +/- 4.1 mmHg), and 24-hour heart rate (65.1 +/- 3.8 versus 64.2 +/- 3.4 bpm). The circadian BP and heart rate profiles were almost identical between regimen 1 and regimen 2. We conclude that in patients with moderate to severe hypertension treated with at least 3 antihypertensive agents, administering a CCB simultaneously with other antihypertensive agents in the morning or separately in the evening did not affect the 24-hour BP control.     

Is ambulatory blood pressure monitoring reliable in hypertensive patients with atrial fibrillation?]

Atrial fibrillation (AF) is commonly seen in patients (pts) with systemic hypertension. They are usually excluded from ambulatory blood pressure monitoring (ABPM) because its accuracy is unknown. The aim of our study was to determine if ABPM can be used to assess 24 hour BP in pts with AF. We included hypertensive pts with chronic (> 6 months) AF, controlled heart rate (60-100 c.p.m), under therapy and also hypertensive pts in sinus rhythm (control group--CG). They were submitted to 24 hour ABPM (Spacelabs 90207). Manual BP with a standard mercury sphygmomanometer was taken during 3 visits (office BP) and on the day of ambulatory monitoring. Simultaneous measurements with a T-Tube were also performed. Thirty pts with chronic AF (63% males), mean age 73 +/- 8 years (52-85) and 18 pts in sinus rhythm (CG) were studied. The age, gender, office BP, ambulatory BP and proportion of successful measurements was similar in the 2 groups. In CG systolic and diastolic office BP did not differ from day ambulatory BP (148 +/- 14/84 +/- 7 vs 138 +/- 18/76 +/- 11 mmHg) and the same was seen in pts in AF (table). In this group, only the systolic BP taken immediately before the ambulatory device was put on, was significantly different from day ambulatory BP (148 +/- 21 vs 137 +/- 19 mmHg, p = 0.04). The proportion of successful measurements in AF group was 94 +/- 8 (65-98) with 93% > 80%. In 64 simultaneous measurements the differences were 6 +/- 5 and 5 +/- 5 mmHg for systolic and diastolic BP. Casual and ambulatory heart rate was also similar in the two groups (76 +/- 7/76 +/- 12--AF group; 78 +/- 10/78 +/- 8--control group). In conclusion, this study demonstrates that ABPM can be used to assess BP in patients with atrial fibrillation. There was a high percentage of successful recordings (93%). As in patients in sinus rhythm, there was no significantly difference in mean office blood pressure and daytime ambulatory blood pressure.     

Study of the placebo effect in using the non-invasive ambulatory measurement of blood pressure

The aim of this study is to evaluate the antihypertensive effect of placebo assessed by 24 hr non invasive blood pressure monitoring. 20 patients (16 males, 4 females, 55 +/- 10 years old) with primary hypertension (WHO stage I or II) were included with a diastolic blood pressure greater than or equal to 100 mmHg (mean blood pressure from three clinical readings). Casual blood pressure and blood pressure monitoring (Spacelabs - 4 measurements per hour during a 24 hr period) were established before and at the end of the placebo run in period (one placebo tablet given once daily at 8 h-8 h 30 a.m. for 15 days). Overall sample data: There was no antihypertensive effect of the placebo with casual BP (167 +/- 16-109 +/- 6 mmHg before and 167 +/- 16-109 +/- 7 mmHg after placebo) and with 24 hr B.P. monitoring (142 +/- 14-96 +/- 8 mmHg before and 141 +/- 14-96 +/- 8 mmHg after placebo). The circadian curves were similar. Individual patient data: A clinical placebo effect (B.P. decrease of at least 10 mmHg) was found in 5 patients for the systolic B.P. and in 2 for diastolic B.P. A significant ambulatory placebo effect (p less than 0.05) was found in 5 patients for the 24 hr systolic B.P. and in 4 patients for the 24 hr diastolic B.P. However, patients with clinical placebo effect were not the same as those with ambulatory placebo effect. There was no correlation between the clinical and the ambulatory response to placebo treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative effects of angiotensin converting enzyme inhibitors and calcium inhibitors related to baseline ambulatory blood pressure. A French multicenter study]

OBJECTIVE: This multicenter study was aimed at determining whether the baseline ambulatory blood pressure (BP) level does influence the efficacy of angiotensin-converting enzyme inhibitors (CEI) and that of calcium antagonists (CA) to the same degree. METHODS: The BP recordings of 236 patients with mild to moderate hypertension were reviewed: these subjects previously entered clinical trials comprising a mean 2-week placebo period and a mean 6-week active treatment phase (CEI = 115, CA = 121). The 24-hour baseline ambulatory BP was considered as high when greater than 139/87 mmHg, according to Staessen's meta-analysis. RESULTS: In the patients with an high baseline ambulatory BP, CEI and CA have had roughly a similar effect (reduction in systolic = 9.5 +/- 7.8% vs 7.7 +/- 6.3%, NS; reduction in diastolic = 9.8 +/- 8.6% vs 8.3 +/- 5.8%, NS). Conversely, the patients with a baseline ambulatory BP level lower than or equal to 139/87 mmHg experienced a greater reduction in ambulatory BP with CEI than with CA (systolic = 7.9 +/- 7.0% vs 0.6 +/- 6.7%, p = 0.0001; diastolic: 5.0 +/- 7.4% vs 1.9 +/- 7.6%, p = 0.040). Finally, further analysis found the threshold of drug efficacy to be 120/80 and 135/85 mmHg in CEI and CA patients respectively. CONCLUSIONS: 1) CEI are more effective than CA in patients with a low ambulatory BP only. 2) The risk of a visceral hypoperfusion seems however to be limited, since CEI do not reduce diastolic ambulatory BP further, when its baseline level is lower than 80 mmHg.     

Lisinopril for the treatment of hypertension within the first 24 hours of acute ischemic stroke and follow-up

BACKGROUND: Hypertension immediately after acute ischemic stroke is associated with impaired morbidity and mortality, although there are few data on antihypertensive use immediately after ictus. This randomized, double-blinded, placebo-controlled, parallel-group study explored the hemodynamic effect and safety of oral lisinopril initiated within 24 h after an ictus. METHODS: Forty hypertensive (systolic blood pressure [BP] >/=140 or diastolic BP >/=90 mm Hg) acute ischemic stroke patients (14 lacunar, 13 partial anterior, 7 total anterior, 6 posterior circulation infarct) were randomized to 5 mg of oral lisinopril (n = 18) or matching placebo (n = 22). Dose was increased to 10 mg (or 2 x placebo) on day 7 if casual systolic BP was >/=140 mm Hg and continued to day 14. After the initial dose, automated BP levels were monitored for 16 h. The BP levels and stroke outcome measures were assessed at day 14, and all patients were followed to day 90. RESULTS: At h 4 after the first dose, systolic/diastolic BP change was -20 +/- 21/-6 +/- 10 mm Hg (mean +/- SE) in the lisinopril group and 1 +/- 11/0 +/- 8 mmHg in the placebo group (group differences: systolic BP, P < .05; diastolic BP, P = .07). With a daily dosing regime, systolic BP, mean arterial pressure (MAP), diastolic BP, and pulse pressure (PP) were significantly lower in the lisinopril group compared to the placebo group at day 14 (P < .01). Neurologic and functional measures were similar between groups at follow-up. CONCLUSIONS: Lisinopril, even at small dosages, is well tolerated and an effective hypotensive agent after acute ischemic stroke, gradually reducing BP by 4 h after oral first-dose administration. Oral lisinopril is now being studied in a larger outcome-based trial in acute hypertensive stroke patients.     

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.     

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.     

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.     

Antihypertensive effect of diltiazem in a slow-release formulation for mild to moderate essential hypertension

The antihypertensive efficacy and frequency of adverse reactions following administration of diltiazem in a new slow-release formulation were compared with placebo in 34 patients with mild to moderate essential hypertension in a randomized, double-blind, crossover study. After 6 weeks of treatment with diltiazem (240 or 360 mg/day), average supine blood pressure (BP) decreased from 165 +/- 21/101 +/- 5 mm Hg at baseline to 152 +/- 16/93 +/- 4 mm Hg compared with 160 +/- 19/100 +/- 7 mm Hg with placebo (p less than 0.01/p less than 0.001). Standing BP decreased from 162 +/- 20/107 +/- 6 mm Hg at baseline to 150 +/- 14/101 +/- 5 mm Hg compared to 159 +/- 18/107 +/- 8 mm Hg with placebo (p less than 0.01/p less than 0.001). The supine heart rate after diltiazem was 65 +/- 7 beats/min and after placebo 69 +/- 9 beats/min (p less than 0.01). There were no hematologic side effects. Only minor differences between diltiazem and placebo were observed in some of the biochemical laboratory values. Four patients were withdrawn due to side effects during treatment with diltiazem and 2 with placebo. Diltiazem in a slow-release formulation given twice a day lowered blood pressure significantly as monotherapy in patients with mild to moderate hypertension and was well tolerated.     

Clinical trial of arotinolol in the treatment of hypertension: dippers vs. non-dippers.

To compare the effects of an alpha, beta blocker, arotinolol, in the treatment of essential hypertension between patients with a dipper and those with a non-dipper profile by means of 24-h ambulatory blood pressure monitoring (ABPM), a multicenter single blind parallel trial was carried out in five clinical centers. After a one-week single blind placebo run-in period, the patients underwent ABPM if their clinic diastolic blood pressure (DBP) ranged from 90-109 mmHg and their clinic systolic blood pressure (SBP) was <180 mmHg. They were divided into two groups according to the absence (non-dipper group, 24 cases) or presence (dipper group, 23 cases) of nocturnal BP reduction > or =10% of daytime BP. ABPM was measured again at the end of the active treatment phase. All patients were given Arotinolol 10-20 mg twice daily for 4 weeks. Twenty four-hour systolic and diastolic average BPs (MSBP, MDBP), 24-h systolic and diastolic blood pressure load (LS BP, LDBP), daytime systolic and diastolic average BPs (dMSBP, dMDBP), daytime systolic and diastolic blood pressure load (dLSBP, dLDBP), nighttime systolic and diastolic average BPs (nMSBP, nMDBP) and nighttime systolic and diastolic blood pressure load (nLSBP, nLDBP) were calculated. Arotinolol was effective in 78.2% of dippers and 54.2% of non-dippers, but the difference in effectiveness between these groups was not statistically significant. After treatment, SBP and DBP-including 24-h, daytime and nighttime systolic and diastolic BPs- were significantly reduced in both groups. During the daytime period, the systolic and diastolic blood pressures were significantly reduced in both dippers and non-dippers, while nighttime systolic and diastolic blood pressures were significantly reduced only in the non-dipper group. No significant changes were found in the dipper group over this period. In conclusion, Arotinolol, which can be dosed twice daily, is an effective antihypertensive agent which effectively lowers blood pressure during the day while reducing nighttime blood pressure more in non-dippers than in dippers, without excessive lowering blood pressure in the latter.     

24 hour blood pressure control with once-daily versus twice-daily formulations of diltiazem

Summary The antihypertensive effects of once-daily diltiazem CD over a 24 hour period were compared with twice-daily diltiazem SR in 95 patients with mild to moderate hypertension using ambulatory blood pressure monitoring. This trial was designed as a multicenter, double-blind, parallel-group study. Following a 2 to 4 week placebo run-in period, diltiazem was administered as once-daily CD or twice-daily SR, starting with 180 mg daily and increasing to a maximum of 360 mg daily, to achieve a seated diastolic blood pressure goal of 90 mmHg as measured by cuff between 08:00 and 10:00 in the morning. Following drug titration, patients received a maintenance dose of diltiazem for an additional 6 week follow-up phase. Twenty-four hour ambulatory blood pressure monitoring recordings were obtained at the end of the placebo, titration, and maintenance phases. Both diltiazem CD and diltiazem SR significantly reduced both systolic and diastolic blood pressure over the 24 hour day and maintained a normal circadian pattern. As well, treatment with once-a-day diltiazem CD significantly decreased the slope of the early morning rise of diastolic and mean blood pressure. Thus, diltiazem CD is as effective as diltiazem SR in lowering diastolic blood pressure over a 24 hour period and has the advantage of a once-daily formulation.See appendix for list of participants.     

Treatment of arterial hypertension in the aged with a calcium antagonist: nicardipine

The purpose of this study was to test in double-blind trial the tolerance and antihypertensive effect of nicardipine versus placebo in 32 elderly patients (mean age: 84 years). Nicardipine was given three times a day (mean dose: 69.4 mg per day). After four weeks, nicardipine lowered blood pressure (BP) from 186 +/- 4 mmHg/99.5 +/- 3 mmHg to 150 +/- 6/84 +/- 3 mmHg (p less than 0.001). 10 out of 16 patients were normalized (BP less than 160-95 mmHg). The placebo group remained hypertensive: 181 +/- 7/96 +/- 4 mmHg versus 183 +/- 4/101 +/- 3 mmHg (NS). 3 placebo treated patients were nevertheless normalized. The changes in systolic BP and diastolic BP were significantly greater in the Nicardipine group: respectively -36 +/- 4 versus -2 +/- 6 mmHg (p less than 0.001), -16 +/- 3 versus -5 +/- 4 mmHg (p less than 0.05). Treatment was very well tolerated. Orthostatic hypotension, change in heart rate, variation in biological parameters were never observed. These data agree with Buhler's statement suggesting that calcium channel inhibitors can represent an interesting alternative to diuretics as first line monotherapy in the treatment of hypertension in the elderly.     

Antihypertensive effect of diltiazem administered once and twice daily

This study was undertaken to compare the antihypertensive effect of diltiazem administered once or twice daily. After a two week wash-out period, eight hypertensive patients were treated for two consecutive four week phases with 180 mg once daily or 90 mg twice daily of a sustained-release formulation of diltiazem. The sequence of the treatments was randomised and the trial carried out in a double-blind fashion. Ambulatory daytime BP profiles were obtained using a portable BP recorder (Remler M2000). The average of all BP readings taken during the monitoring period was 159/104 +/- 21/10 mgHg (mean +/- SD) at the end of the wash-out period and 145/90 +/- 20/12 and 148/95 +/- 21/11 mmHg under treatment with diltiazem 180 mg once daily and 90 mg twice daily, respectively. These data indicate that 180 mg of a slow-release formulation of diltiazem are as effective in lowering the BP of hypertensive patients when administered daily in a single dose as when divided into two doses.     

Effects of the oral testosterone undecanoate Kyzatrex™ on ambulatory blood pressure in hypogonadal men

Testosterone replacement therapies have been shown to increase blood pressure (BP) in hypogonadal men. We studied the effects of a new formulation of testosterone undecanoate (Kyzatrex™) on ambulatory blood pressure (ABP) and heart rate, in 155 men with hypogonadism (mean age, 50.5 years, 76.8% white, 36.1% on antihypertensive therapy). The ABP, heart rate and clinical assessments were obtained at baseline and following 120 and 180 days of therapy. Mean changes from baseline in 24‐h ambulatory systolic BP of 1.7 mmHg (95% CI, 0.3, 3.1) at day 120 and 1.8 mmHg (95% CI, 0.3, 3.2) at day 180 were observed post‐treatment. For those men on antihypertensive drug therapy, increases in mean 24‐h systolic BP were greater than those not taking antihypertensive drugs (3.4 vs 0.7 mmHg at day 120 and 3.1 vs 1.0 mmHg at day 180, respectively). Changes from baseline in 24‐h diastolic BP and heart rate at day 120 were smaller (<1 mmHg and <1 beat/min, respectively). There were no relationships observed between testosterone concentration or hemoglobin levels with ABP. Multivariable analyses showed that baseline ambulatory BP and antihypertensive therapy were significantly correlated with BP changes. These data demonstrate small increases in ambulatory BP following 120 days on this oral testosterone undecanoate with no further changes at 180 days. Changes in ambulatory BP were minimal in patients not taking antihypertensive therapy.     

Using different methods to evaluate the efficacy of olmesartan medoxomil in Chinese patients with mild to moderate essential hypertension according to ambulatory blood pressure monitoring

OBJECTIVE: To evaluate the efficacy of olmesartan medoxomil in Chinese patients with mild to moderate essential hypertension using different methods according to ambulatory blood pressure monitoring. METHODS: Chinese patients 18-75 years of age with clinic diastolic blood pressure (BP) 90-109 mmHg and systolic BP less than 180 mmHg were treated with olmesartan medoxomil 20-40 mg once daily for 24 weeks to reach the goal BP (<140/90 and <130/80 mmHg in diabetes) in a multicenter study. The trough-to-peak ratio (T/P ratio) and the smoothness index (SI) for systolic/diastolic BP were calculated using different methods according to ambulatory blood pressure monitoring. RESULT: Olmesartan medoxomil 20-40 mg once daily reduced the systolic/diastolic ambulatory BP for 24-h, daytime, and night-time by 13.3±16.3/7.6±9.5, 13.9±17.4/8.0±10.4, and 12.3±18.1/6.8±10.2 mmHg in all eligible patients at week 24 from baseline (n=87, P<0.0001). The global and individual T/P ratios were 0.64/0.62 and 0.32/0.30 (n=87) for systolic/diastolic BP, whereas these were 0.71/0.70 and 0.31/0.39 in fair responders (n=71). Global and individual SI were 6.81/5.37 and 0.92/0.67 (n=87) for systolic/diastolic BP, whereas these were 7.04/5.44 and 1.03/1.03 in fair responders (n=71). Global and individual T/P ratios for systolic/diastolic BP were 0.75/0.82 and 0.45/0.46 in the 20 mg subgroup (n=41), whereas these were 0.44/0.59 and 0.30/0.29 in the 40 mg subgroup (n=30). Global and individual SI were 5.70/5.32 and 1.03/0.87 for systolic/diastolic BP in the 20 mg subgroup (n=41), but these were 3.64/2.46 and1.01/0.60 in the 40 mg subgroup (n=30). CONCLUSION: The duration of the antihypertensive action of olmesartan medoxomil with 20-40 mg once daily can be assessed by the global T/P ratio and SI rather than the individual values, even in different populations and dosages.     

Effects of atenolol and diltiazem-SR on exercise and pressure load in hypertensive patients

The effects of monotherapy with atenolol or diltiazem-SR on blood pressure, 24-h blood pressure (BP) load, and exercise capacity were tested in patients with mild to moderate (stages I and II) essential hypertension. After 3-week single blind placebo therapy, patients with sitting diastolic blood pressure (SDBP) of 94-114 mmHg were randomized to atenolol 50 mg/day (62 patients) or diltiazem-SR 90 mg b.i.d. (60 patients) in a double-blind parallel study. Depending on SDBP response, the dose was increased to 100 mg/day for atenolol and 180 mg b.i.d. for diltiazem-SR. Twenty-four-hour ambulatory blood pressure measurements and exercise tolerance lest by the Bruce protocol were done at the end of placebo and active treatment. Compared with placebo, both atenolol and diltiazem-SR significantly decreased heart rate (HR), sitting systolic blood pressure (SSBP), SDBP, ambulatory BP, BP load for waking and sleeping hours, area under the BP curve, rate-pressure product (p < 0.001), and exercise time (NS). Atenolol exerted a greater effect on ambulatory BP, HR, rate-pressure product, waking diastolic BP load, and area under the 24-h BP curve. The drugs were well tolerated and caused no serious side effects necessitating discontinuation of treatment. These findings indicate that (1) monotherapy for hypertension with atenolol or diltiazem SR is effective and well tolerated, (2) it decreases the 24-h BP load, (3) it does not interfere with exercise capacity.     

Persistence of the antihypertensive efficacy of amlodipine and nifedipine GITS after two 'missed doses': a randomised,double-blind comparative trial in Asian patients

Suboptimal management of hypertension is often a result of poor patient compliance in the form of missed doses of their antihypertensive medication. This multicentre, randomised, double-blind, parallel-group trial was designed to compare the persistence of the antihypertensive efficacy of the amlodipine and nifedipine gastrointestinal therapeutic system (GITS) after two 'missed doses', and also to compare the drugs' overall efficacy and safety in Asian patients with mild-to-moderate essential hypertension. Following a 2-week placebo run-in period, 222 patients were randomised to receive either amlodipine (5 mg daily, increased after 6 weeks if necessary to 10 mg daily, n=109) or nifedipine GITS (30 mg daily, increased after 6 weeks if necessary to 60 mg daily; n=113) for 12 weeks. A placebo was then substituted for further 2 days with continuous ambulatory blood pressure (BP) monitoring. The increases in the last 9 h of mean ambulatory BP on day 2 after treatment withdrawal were significantly less with amlodipine than with nifedipine GITS: 4.4+/-7.0 vs 11.2+/-11.3 mmHg for systolic BP (P相似文献   

ST-segment depression in hypertensive patients is linked to elevations in blood pressure,pulse pressure and double product by 24-h Cardiotens monitoring

BACKGROUND: Various statements are made concerning peaks of heart rate (HR), blood pressure (BP) and double product (product of HR and systolic BP) as triggers for ST-segment depression. The aim of the present study was to identify determinants of ST-segment depression with a new ambulatory device for simultaneous 24-h electrocardiogram (ECG) and BP monitoring. METHODS: A total of 63 treated patients (63 +/- 9 years, 33 women and 30 men) with arterial hypertension and ischemic heart disease were studied with a new ambulatory 24-h BP measurement (ABPM) device evaluated according to the BHS protocol (Cardiotens, Meditech, Hungary). This device allows simultaneous ST-segment analysis with extra BP recordings triggered by episodes of ST-segment depression. RESULTS: ST-segment (Holter ECG) depression (> 1 mm and > 60 s) was demonstrated in 26 patients with a mean duration of 4.95 +/- 2.6 min and a peak in the early morning hours. All ST-segment depressions were silent and occurred during a significant increase of BP (15 +/- 11 mmHg systolic and 10 +/- 5 mmHg diastolic, compared with the mean ABPM values) and a significant increase of the double product from 10 921 +/- 2 395 (24-h mean) to 14 515 +/- 2329 (during ST-depression). The recorded systolic and diastolic BP (SBP, DBP) values from the pre ST-event were significant higher compared with 24-h values (153 +/- 19 versus 145 +/- 22 mmHg systolic, 83 +/- 12 versus 78 +/- 14 diastolic). The mean pulse pressure (PP) value in the group with ST-depression was significantly higher than in the group without ST changes (69 +/- 16 versus 58 +/- 10 mmHg; P < 0.005). A total of 73% of patients with ST-events compared with 35% without ST-events showed a PP >or= 60 mmHg (P = 0.025). CONCLUSION: Simultaneous ABPM and ST-segment analysis identifies episodes of silent myocardial ischemia during increases of BP and HR. Hypertensive patients with ischemic heart disease and ST events show higher mean pulse pressure values than are observed in patients without events. A PP of >or= 60 mmHg is linked to an increased risk of silent myocardial ischemias.     

Comparative effects of amlodipine and nifedipine GITS during treatment and after missing two doses

OBJECTIVE: To compare the antihypertensive efficacy of amlodipine and nifedipine gastrointestinal therapeutic system (GITS) measured by office and ambulatory blood pressure monitoring (ABPM) during treatment and, after patients have missed two doses. METHOD: After a single blind run-in 4-week placebo period, 58 patients were randomly allocated to amlodipine (5mg/daily, n=30) or nifedipine GITS (30mg/daily; n=28) in a double-blind, double dummy fashion. Patients received active medication for 4 weeks. Then, to simulate failure of compliance, patients received two single blinded doses of placebo. Ambulatory blood pressure monitoring was carried out at the end of run-in placebo phase, the first day, the last day of active treatment and up to 72h after the last active dose. RESULTS: Diastolic blood pressure was controlled in 61.9% patients on amlodipine and 52.9% on nifedipine GITS. Reductions in blood pressure were similar in both groups. ABPM showed significant reduction in blood pressure from the first day in the nifedipine GITS group, while amlodipine group had marginal effect. Peak reduction in systolic/diastolic blood pressure was 26/15mmHg at 5-6h after ingestion of amlodipine tablets. The trough reduction was 22/13mmHg; with a trough-to-peak ratio of 84.61% for systolic and 86.67% for diastolic blood pressure. Peak reduction in systolic/diastolic blood pressure with nifedipine GITS was 19/15mmHg and the trough reduction was 21/17mmHg, giving a trough-to-peak ratio of 100% for both systolic and diastolic blood pressure. When patients received placebo after 4 weeks of active treatment, simulating a compliance failure, amlodipine maintained reduction in systolic and diastolic blood pressure for at least up to 72h after the last active dose, maintaining 57.71% of the effect for systolic blood pressure and 60.00% for diastolic blood pressure. In contrast, nifedipine GITS effect was rapidly lost during this study phase, with a reduction in systolic and diastolic blood pressure of only 14-16%, 72h after the last active dose. CONCLUSION: This study showed that amlodipine and nifedipine GITS reduce blood pressure to about the same extent during chronic treatment. In the case of compliance failure, such as missing one or two doses, amlodipine maintained significant and important antihypertensive effect with the trough-to-peak ratio still over 50% 72h after the last active dose. On the other hand, the coverage of nifedipine GITS was limited to about 36h after the last active dose.