A comparison of the blood pressure changes of lumiracoxib with those of ibuprofen and naproxen

The 52-week Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) investigated the gastrointestinal and cardiovascular safety profile of lumiracoxib 400 mg once daily compared with 2 traditional nonsteroidal anti-inflammatory drugs (NSAIDs): ibuprofen 800 mg 3 times daily and naproxen 500 mg twice daily. Data from TARGET were analyzed to examine the effect of lumiracoxib compared with ibuprofen and naproxen on blood pressure (BP), incidence of de novo and aggravated hypertension, prespecified edema events, and congestive heart failure. Lumiracoxib resulted in smaller changes in BP as early as week 4. Least-squares mean change from baseline at week 4 for systolic BP was +0.57 mm Hg with lumiracoxib compared with +3.14 mm Hg with ibuprofen (P<.0001) and +0.43 with lumiracoxib compared with +1.80 mm Hg with naproxen (P<.0001). In conclusion, the use of lumiracoxib and traditional NSAIDs results in differing BP changes; these might be of clinical relevance.     

Comparison of telmisartan versus losartan: meta-analysis of titration-to-response studies

OBJECTIVES: To compare the ability of telmisartan and losartan to reduce mean diastolic blood pressure (DBP) during the last 6 h of the 24-h dosing interval in a prospectively planned meta-analysis of ambulatory blood pressure monitoring (ABPM) data from two independent studies. METHODS: Data were from two independent randomized, double-blind, double-dummy, titration-to-response studies conducted in patients with mild-to-moderate hypertension (seated cuff DBP 95-109 mmHg, 24-h mean ambulatory DBP >or=85 mmHg). After a 4-week placebo run-in period, patients received once-daily telmisartan 40 mg or losartan 50 mg, with up-titration after 4 weeks to telmisartan 80 mg or losartan 100 mg, respectively, if seated trough cuff DBP >or=90 mmHg. Blood pressures were recorded using ABPM immediately before randomization and after 8 weeks of active treatment. In addition, seated trough cuff blood pressures were measured at baseline and after 4 and 8 weeks of active treatment. RESULTS: Titration to the higher dose was required in 60.1% of telmisartan patients and 69.5% of losartan patients (P=0.01). Reductions from baseline in the last 6 h mean ambulatory DBP with telmisartan and losartan were 6.6+/-0.4 and 5.1+/-0.4 mmHg, respectively (P<0.01, adjusted for baseline and study); the effects were homogeneous across the two studies. During the last 6 h of the 24-h dosing interval, telmisartan produced greater reductions in each of the observed hourly mean ambulatory DBP values. Telmisartan-induced reductions were also greater for the majority of the observed hourly mean ambulatory DBP values over the entire 24-h dosing interval. Reductions from baseline in the last 6 h adjusted mean ambulatory systolic blood pressure (SBP) for telmisartan and losartan were 9.9+/-0.6 and 7.8+/-0.6 mmHg, respectively (P=0.01). The 24-h profiles of ambulatory SBP hourly mean reductions were similar to those for DBP. Both telmisartan and losartan were found to be safe and well tolerated. CONCLUSIONS: Telmisartan 40/80 mg is superior to losartan 50/100 mg in controlling DBP and SBP during the last 6 h of the 24-h dosing interval.     

Adding hydrochlorothiazide to olmesartan dose dependently improves 24-h blood pressure and response rates in mild-to-moderate hypertension

OBJECTIVE: To test whether adding hydrochlorothiazide (HCTZ) (12.5 or 25 mg) to olmesartan 20 mg improves 24-h blood pressure in patients whose conventional diastolic blood pressure is inadequately controlled by olmesartan monotherapy. PATIENTS: Male and female patients > or = 18 years with mean sitting diastolic blood pressure (DBP) of 100-115 mmHg, mean sitting systolic blood pressure (SBP) greater than 150 mmHg, mean 24-h DBP of at least 84 mmHg, and at least 30% of DBP daytime readings > 90 mmHg. INTERVENTIONS: Four weeks of single-blind treatment with olmesartan 20 mg once daily, followed in non-responders by 8 weeks of randomized double-blind treatment with placebo or HCTZ (12.5 or 25 mg) once-daily, added to olmesartan. RESULTS: HCTZ 25 mg added to olmesartan 20 mg decreased mean daytime DBP significantly more (P = 0.0012) than placebo added to olmesartan 20 mg. Compared to olmesartan monotherapy, mean 24-h DBP and SBP were significantly reduced by combination therapy with olmesartan/HCTZ 20/12.5 mg (-1.9 mmHg, P = 0.0167 and -3.9 mmHg, P = 0.0018, respectively) and 20/25 mg (-3.7 and -7.4 mmHg respectively, P < 0.0001 for both). Mean 24-h DBP and SBP and mean night-time SBP reductions were significantly greater for HCTZ 25 mg than for HCTZ 12.5 mg. Response rates (mean daytime DBP assessed by ambulatory blood pressure measurement < or = 85 mmHg) approximately doubled following the addition of HCTZ (12.5 mg = 57.6% and 25 mg = 69.5%). CONCLUSION: Combination of olmesartan 20 mg with HCTZ provides significantly better 24-h blood pressure reduction than olmesartan monotherapy in patients with mild-to-moderate hypertension. Moreover, increasing the dose of HCTZ from 12.5 to 25 mg is a reasonable step to reach better daytime and night-time blood pressure control.     

The effect duration of candesartan cilexetil once daily, in comparison with enalapril once daily, in patients with mild to moderate hypertension

OBJECTIVE: To determine the antihypertensive efficacy, effect duration and safety of the angiotensin II type 1 receptor blocker candesartan cilexetil and the angiotensin converting enzyme inhibitor enalapril once daily in patients with mild to moderate hypertension. METHODS: A multicenter, randomised, double-blind parallel group study was performed in Finland, France, the Netherlands, Spain and Sweden. Three-hundred-and-ninety-five men and women in the age range 20-80 years with primary hypertension were randomised to an 8-week double-blind treatment period with either candesartan cilexetil 8-16 mg or enalapril 10-20 mg once daily, with forced dose titration after 4 weeks. Non-invasive ambulatory blood pressure was measured for 36 h at baseline and after 8 weeks. The primary efficacy variable was the change in mean diastolic and systolic ambulatory blood pressure 22-24 h post-dose. RESULTS: There was a significant difference in the adjusted mean difference for the change from baseline to week 8 between candesartan cilexetil and enalapril 22-24 h post-dose by -3.5 mmHg (95% confidence interval, CI: -6.8 to -0.3 mmHg; p < 0.032) in ambulatory systolic blood pressure and -3.0 mmHg (95% CI: -5.1 to -0.8 mmHg; p < 0.008) in ambulatory diastolic blood pressure. There was a significant difference in adjusted mean daytime ambulatory blood pressure 24-36 h post-dose by -4.2 mmHg (95% CI: -6.8 to -1.6 mmHg; p < 0.002)/-3.5 mmHg (95% CI: -5.1 to -1.8 mmHg; p < 0.001). Both drugs were generally well tolerated. CONCLUSION: The results of the present study suggest that advantages may be attributed to the use of candesartan cilexetil, as compared to enalapril in the treatment of patients with essential hypertension. In comparison with enalapril 20 mg, candesartan cilexetil 16 mg more effectively lowered blood pressure at trough and in particular on the day following the day after the last dose.     

Efficacy of manidipine/delapril versus losartan/hydrochlorothiazide fixed combinations in patients with hypertension and diabetes

BACKGROUND: Hypertension markedly increases the already high risk for cardiovascular complications in patients with diabetes mellitus. Less than one in eight patients with hypertension and type 2 diabetes have adequately controlled blood pressure. As a result, antihypertensive combinations are now widely used in management of hypertension associated with diabetes. METHODS: This double-blind study investigated efficacy of a new fixed dose combination of a calcium antagonist, manidipine 10 mg, and an angiotensin-converting enzyme inhibitor, delapril 30 mg, compared with a combination of an angiotensin receptor blocker, losartan 50 mg, and a diuretic, hydrochlorothiazide 12.5 mg. Patients with hypertension (blood pressure > or = 130/80 mmHg) with controlled type 2 diabetes (HbA1c < or = 7.5%) were randomized to manidipine/delapril (n = 153) or losartan/hydrochlorothiazide (n = 161), administered once daily for 12 weeks. Patients underwent ambulatory blood pressure monitor evaluation at baseline and end of treatment. RESULTS: Mean decreases in 24-h systolic blood pressure were seen with both manidipine/delapril (-9.3 mmHg) and losartan/hydrochlorothiazide (-10.7 mmHg) combinations. The mean (95% confidence interval) treatment difference was -1.4 (-4.5/1.8) mmHg, demonstrating noninferiority of the manidipine/delapril combination. Reduction in 24-h diastolic blood pressure (-4.6 versus -4.5 mmHg) and daytime (systolic blood pressure -10.5 versus -11.1 mmHg) and night-time (systolic blood pressure -7.1 versus -9.3 mmHg) blood pressure were also not significantly different between treatments. Compliance and adverse events were comparable for both groups. CONCLUSION: The study demonstrated that the combination of manidipine and delapril is as effective as losartan and hydrochlorothiazide in treatment of hypertension in type 2 diabetes.     

Eplerenone,a selective aldosterone blocker,in mild-to-moderate hypertension

BACKGROUND: Eplerenone, a selective aldosterone blocker (SAB) that is highly specific for the aldosterone receptor, has the potential to be efficacious in the treatment of hypertension. METHODS: This 8-week, multicenter, double-blind, placebo-controlled trial assessed the efficacy, safety, and tolerability of eplerenone in eligible patients randomized to eplerenone 50, 100, or 400 mg once daily; eplerenone 25, 50, or 200 mg twice daily; spironolactone 50 mg twice daily; or placebo. The primary efficacy variable was the adjusted mean change in baseline to final visit for seated diastolic blood pressure (DBP). RESULTS: Of 417 randomized patients, 409 were evaluated for efficacy. The adjusted mean change from baseline to final visit in seated and standing systolic blood pressure (SBP) and DBP was significantly greater (P < .05) in all eplerenone groups than in the placebo group. The adjusted mean change in 24-h ambulatory blood pressure monitoring (ABPM) measurements of SBP and DBP also documented a 24-h duration significantly greater (P < .05) than placebo in eplerenone-treated patients. For all measurements, the antihypertensive effect of eplerenone increased in a dose-response fashion. Eplerenone (100 mg) reduced BP by 75% compared with spironolactone (100 mg) and had an adverse events incidence rate similar to placebo. No antiandrogenic or progestational effects or clinically relevant safety issues were observed in eplerenone-treated patients. However, one spironolactone-treated patient reported menstrual irregularities. CONCLUSIONS: Eplerenone doses of 50 to 400 mg once daily are well tolerated and effective in reducing BP in patients with mild-to-moderate hypertension during a 24-h period.     

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.     

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.     

Twenty-four-hour ambulatory blood pressure monitoring in atrial fibrillation

BACKGROUND: Due to large beat-to-beat blood pressure variation the use of 24-h ambulatory blood pressure monitoring in patients with atrial fibrillation has been questioned. METHODS: Repeatability and variability of 24-h ambulatory blood pressure (Accutraccer II or Diasys Integra), and daily blood pressure variation was examined in 42 patients aged 51-81 (median 73.5) years admitted for elective electrocardioversion of atrial fibrillation. RESULTS: Before cardioversion 24-h ambulatory systolic blood pressure was slightly lower and nocturnal blood pressure reduction was larger in the group of patients who achieved sinus rhythm than in the group who maintained atrial fibrillation (11.5/10.5 versus 4.1/4.7 mmHg; P < 0.05). No statistically significant change was observed in ambulatory blood pressure after cardioversion in any of the two groups. Blood pressure variability (SD/mean) was 10-14% both in patients with and without conversion to sinus rhythm. Coefficient of repeatability (2 SD of difference) was 13.6 mmHg (16.6%) for diastolic blood pressure and 30.2 mmHg (24.7%) for systolic blood pressure in patients with normalized heart rhythm and 17.0 and 29.0 mmHg (21.5 and 22.4%) in patients with maintained atrial fibrillation, respectively. CONCLUSION: Ambulatory blood pressure monitoring provides data with similar variability and repeatability in patients with atrial fibrillation as in subjects with normal cardiac rhythm. Twenty-four-hour ambulatory blood pressure measurement is applicable in atrial fibrillation in the same way as during sinus rhythm.     

Lercanidipine vs lacidipine in isolated systolic hypertension

This randomised, double-blind, double-dummy, parallel group, multicentre study compared the efficacy and tolerability of lercanidipine with lacidipine. Elderly patients with isolated systolic hypertension (supine blood pressure >/=160/<95 mmHg) were enrolled and underwent a placebo run-in period of 14-27 days before random allocation to lercanidipine tablets 10 mg once daily (n=111) or lacidipine tablets 2 mg once daily (n=111) for the assessment period (112-160 days). Titration to lercanidipine 20 mg once daily (two 10 mg tablets) or lacidipine 4 mg once daily (two 2 mg tablets) was allowed after 8 weeks, if required. Both treatments decreased supine and standing systolic and diastolic blood pressure between the end of the run-in period and the end of the assessment period (P<0.0001). At the end of the assessment period, the estimated mean treatment difference (95% confidence intervals) in supine systolic blood pressure was -0.81 (-4.45, 2.84) mmHg. These confidence intervals were within the limits specified for equivalence, that is, (-5, 5) mmHg. Ambulatory blood pressure monitoring showed that the antihypertensive effects of both drugs lasted for the full 24-h dosing period and followed a circadian pattern. Both treatments were well tolerated with a low incidence of adverse drug reactions and a low withdrawal rate. Significantly fewer patients withdrew from treatment with lercanidipine (P=0.015). Neither treatment had any clinically significant effect on pulse rate or cardiac conduction. In conclusion, both treatments were equally effective in controlling supine systolic blood pressure in patients with isolated systolic hypertension.     

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.     

Safety and efficacy of the oral direct renin inhibitor aliskiren in elderly patients with hypertension

OBJECTIVES: To evaluate the efficacy, safety and tolerability of aliskiren in elderly patients (> or =65 years old) with essential hypertension. METHODS: In this double-blind, multicenter study, 355 elderly patients with hypertension [office mean sitting systolic blood pressure (msSBP) > or =145-<180 mmHg and mean 24-h ambulatory systolic BP (ASBP) > or =135 mmHg] were randomized to once-daily treatment for 8 weeks with aliskiren 75 mg (n = 91), 150 mg (n = 84), 300 mg (n = 94) or the comparator lisinopril 10 mg (n = 86). The primary efficacy variable was change in mean 24-h ASBP. RESULTS: At endpoint, aliskiren 75 mg, 150 mg, 300 mg and lisinopril 10 mg lowered mean 24-h ASBP (least-squares mean+/-SEM) by 8.4+/-0.8, 7.1+/-0.8, 8.7+/-0.8 and 10.2+/-0.9 mmHg, and mean 24-h ambulatory diastolic BP by 4.5+/-0.5, 3.6+/-0.5, 3.9+/-0.5 and 6.3+/-0.5 mmHg, respectively, with no significant difference between aliskiren doses. The trough-to-peak ratio for ASBP reduction with aliskiren 75 mg, 150 mg, 300 mg and lisinopril 10 mg was 0.77, 0.64, 0.79 and 0.87, respectively. All treatments lowered office msSBP and mean sitting diastolic BP (msDBP) compared with baseline. A significantly greater proportion of patients receiving aliskiren 300 mg achieved BP control (msSBP/msDBP <140/90 mmHg) compared with those receiving aliskiren 75 mg (36.2% vs 24.2%, p = 0.033). There was no evidence of dose-related increases in the rate of adverse events with aliskiren treatment. CONCLUSIONS: Aliskiren, a novel direct renin inhibitor, provides effective 24-h BP lowering with no evidence of dose-related increases in the incidence of adverse events in elderly patients with hypertension.     

Ambulatory 24-h blood pressure assessment of the felodipine-metoprolol combination versus amlodipine in mild to moderate hypertension. Lorraine General Physician Investigators Group.

OBJECTIVE: To measure the time effect profiles of a once daily administered combination tablet felodipine-metoprolol 5/50 mg (Logimax, Astra) and amlodipine 5 mg (Norvasc, Pfizer) on blood pressure and heart rate using 24-h ambulatory blood pressure monitoring. DESIGN: Randomized multicentre parallel-group study with a single-blind placebo run-in period of 4 weeks duration and a 6-week double-blind active treatment period. PATIENTS AND METHODS: Out of 245 randomized outpatients (90 men, 155 women) with uncomplicated mild-to-moderate primary hypertension and mean sitting diastolic blood pressure (DBP) 95-115 mmHg inclusive, 212 (102 on felodipine-metoprolol, 110 on amlodipine) were eligible for analysis. 24-h ambulatory blood pressure monitoring was performed at the end of the placebo run-in (baseline) and after 6 weeks active treatment (posttreatment). RESULTS: Both felodipine-metoprolol and amlodipine induced smooth and consistent reduction in DBP and systolic blood pressure throughout the 24-h period, hence not altering the diurnal rhythm. However, felodipine-metoprolol reduced all average blood pressures (24-h, day- and night-time) more than amlodipine (for 24-h average blood pressure 14.4/9.5 mmHg and 8.9/5.5 mmHg, respectively). Medians of individual diastolic trough-to-peak (T/P) ratios were similar for felodipine-metoprolol and amlodipine (54 and 50%, respectively), while for the systolic T/P ratios, the corresponding values were 74 and 35%, repectively; no significant difference between treatments was seen. As distinguished from amlodipine, both heart rate and rate pressure product were markedly decreased on felodipine-metoprolol throughout the 24-h period and even during the early morning hours. In general, both treatments were well tolerated. CONCLUSIONS: Both felodipine-metoprolol and amlodipine achieved optimal control of blood pressure during the inter-dosing interval in line with their pharmokinetic profiles. The vasodilatory adverse events were slightly more reported with felodipine-metoprolol combination, but due to more pronounced lowering of the average blood pressures and the potent additional effect on heart rate and rate pressure product, the efficacy/tolerability balance seems to be equal to or better than that obtained with monotherapy such as amlodipine.     

Evaluation of the 24-hour blood pressure effects of eprosartan in patients with systemic hypertension

BACKGROUND: Eprosartan is a new nonphenyl angiotensin II receptor blocker, which has been approved for the treatment of hypertension. Although the drug has a relatively short plasma half-life of 5 to 9 h, clinical studies have suggested that its antihypertensive effect persists for 24 h. METHODS: We assessed both the changes in 24-h and trough blood pressure (BP) (last 4 h of the ambulatory BP while the patient was awake) of eprosartan at doses of 600 and 1,200 mg once daily in a randomized, double-blind, placebo-controlled trial. Ambulatory BP was monitored at placebo baseline and after 8 weeks of double-blind therapy. RESULTS: Two hundred patients randomized in the study with 177 patients completing the trial. The 24-h change in BP from baseline was 0.2/0.1 +/- 1.4/1.0 mm Hg, -7.9/ -5.4 +/- 1.0 mm Hg (P < .0001), and -7.4/-5.0 +/- 0.9 mm Hg (P < .0001) in the placebo, 600-mg eprosartan, and 1,200-mg eprosartan groups, respectively. Changes in trough ambulatory BP showed significant reductions of -6.3/-4.1 +/- 1.6/1.1 mm Hg and -7.7/-5.5 +/- 1.5/1.0 mm Hg for 600 mg of eprosartan and 1,200 mg of eprosartan, respectively. CONCLUSIONS: These data demonstrate that eprosartan at doses of 600 or 1200 mg significantly reduced BP throughout an entire 24-h dosing period. There were no differences between the 600- and 1,200-mg dose; thus, 600 mg once daily should be the only dose used in the treatment of hypertension with eprosartan.     

Comparison of the effects on 24-h ambulatory blood pressure of valsartan and amlodipine, alone or in combination with a low-dose diuretic, in elderly patients with isolated systolic hypertension (Val-syst Study)

OBJECTIVE: The aim of this study was to compare the time-effect profiles of a once-daily administration of valsartan and amlodipine, each given alone or in combination with hydrochlorothiazide, in terms of ambulatory blood pressure (BP) and heart rate in elderly patients with isolated systolic hypertension. METHODS: One hundred and sixty-four elderly outpatients with systolic hypertension received valsartan 80 mg (n=79) or amlodipine 5 mg (n=85) once daily for eight weeks, after which the patients with poorly controlled office BP were up-titrated to valsartan 160 mg or amlodipine 10 mg once daily. If their office systolic BP was still >140 mmHg after eight weeks at these doses, 12.5 mg hydrochlorothiazide was added for a further eight weeks. The hourly BP decreases in all of the patients were calculated on the basis of 24-h ambulatory recordings made after the placebo period and at the end of active treatment. The trough/peak ratio and smoothness index were calculated in the responders. RESULTS: Both the valsartan- and amlodipine-based treatments effectively lowered mean 24-h, daytime and night-time systolic ambulatory BP (all p<0.001) without any significant differences between the two regimens. Ambulatory heart rate decreased in the subjects on valsartan and slightly increased in those on amlodipine (the differences in 24-h and daytime heart rate were significant (p=0.008 and 0.002 respectively). Among the 138 responders, the valsartan-based treatment had a greater anti-hypertensive effect during the daytime hours (p=0.02), a difference that was also significant for average 24-h BP (p=0.02). The mean systolic BP trough/peak ratio was 0.56 in the patients on valsartan, and 0.77 in those on amlodipine (NS). The smoothness index was respectively 1.70 and 1.58 (NS). CONCLUSIONS: The present results show that both the valsartan- and amlodipine-based treatments lead to a similar long-term reduction in 24-h systolic BP. However, in treatment responders, valsartan has a greater anti-hypertensive effect during the daytime.     

Persistence of the antihypertensive effect of low-dose combination therapy in mild hypertension

The persistence of the antihypertensive effect of perindopril 2 mg + indapamide 0.625 mg once daily for up to 72 h was evaluated using the "missed-dose" technique. After 4 weeks on perindopril 2 mg+indapamide 0.625 mg, 79 of 216 hypertensive patients at goal (diastolic blood pressure < 85 mmHg) continued on perindopril 2 mg+indapamide 0.625 mg for a further 8 weeks. During either week 9 or 11, placebo was substituted for perindopril 2 mg+indapamide 0.625 mg on either 1 day or on 2 consecutive days. Twenty-four-hour ambulatory blood pressure was recorded at baseline, after 9 or 11 weeks of perindopril 2 mg+indapamide 0.625 mg and during the simulated missed doses, 24-48 and 48-72 h after perindopril 2 mg+indapamide 0.625 mg. Significant (p < 0.001) reductions in mean (+/- SD) 24-h blood pressure (mmHg) during the first 24 h after perindopril 2 mg+indapamide 0.625 mg vs baseline were noted for the two sub-groups subsequently allocated to one missed dose (-13.5 +/- 10.4/-8.0 +/- 6.6) or two missed doses (-12.2 +/- 7.4/-6.9 +/- 4.2). The antihypertensive effect persisted (p < 0.001 to p < 0.05 vs baseline) on the days when placebo was substituted for perindopril 2 mg+indapamide 0.625 mg with reductions in mean 24-h blood pressure from 24-48 h and 48-72 h after dosing being -11.6 +/- 9.6/-6.3 +/- 6.4 and -6.4 +/- 6.0/-3.9 +/- 4.2, respectively. Use of the "missed-dose" technique demonstrated persistence of an antihypertensive effect for perindopril 2 mg + indapamide 0.625 mg for up to 72 h after dosing.     

A comparison of the efficacy and duration of action of telmisartan, amlodipine and ramipril in patients with confirmed ambulatory hypertension

OBJECTIVES: The aim of the study was to compare the antihypertensive effects and the duration of action of telmisartan, amlodipine and ramipril in patients with mild-to-moderate hypertension using ambulatory blood pressure (ABP) monitoring. METHODS: After a 2-4-week single-blind, placebo run-in period, qualifying patients were randomized to receive telmisartan 80 mg (n=18); amlodipine 5 mg (n=22); titrated to 10 mg after 4 weeks; or ramipril 2.5 mg (n=17); titrated to 5 mg and 10 mg after 1 and 3 weeks, respectively, administered once daily in the morning (0700 h). Ambulatory blood pressure monitoring was performed at baseline and at the end of the 8-week treatment period. Plasma renin activity was measured over 24 h at the same time points. RESULTS: Telmisartan and amlodipine provided significant reductions from baseline (P<0.0001) and not statistically different reductions between treatments in ABP during daytime (9.3/6.0 and 14.7/9.4 mmHg, respectively) and night-time (12.4/7.7 and 13.3/8.6 mmHg, respectively) at the end of 8 weeks' treatment. In contrast, although ramipril provided significant reductions in ambulatory systolic and diastolic BP from 2-6 h post dose (peak effect), it failed to induce significant reductions in mean daytime (4.5/1.6 mmHg) and night-time (1.8/0.1 mmHg) ambulatory BP. In addition, the greater reductions in ABP with telmisartan and amlodipine were associated with a significant rise in plasma renin activity whereas ramipril only increased renin during the first 4 h of the administration interval. CONCLUSION: The results of the present study confirm the efficacy of both telmisartan and amlodipine in reducing ABP during each period of the 24-h interval. Because ABP reduction with ramipril was restricted to its peak effect, the present data do not support the use of this agent when administered once daily in the morning.     

White-coat effect in normotension and hypertension

OBJECTIVES: The difference between clinic and daytime ambulatory blood pressure is referred to as the white-coat effect. In this study, we investigated (i) the magnitude of the white-coat effect in subjects with different daytime ambulatory blood pressure levels, and (ii) the association of the white-coat effect with left ventricular mass. METHODS: A total of 1581 subjects underwent clinic blood pressure readings, 24-h ambulatory blood pressure monitoring and left ventricular echocardiographic assessment. Their mean daytime systolic blood pressure varied from 88.0 to 208.9 mmHg and their mean daytime diastolic blood pressure from 40.3 to 133.0 mmHg. RESULTS: A negative correlation was found between the systolic or diastolic white-coat effect and the systolic or diastolic daytime ambulatory blood pressure (r = -0.22, P < 0.000 and r = -0.50, P < 0.000, respectively). Left ventricular mass significantly correlated with ambulatory blood pressure (P < 0.001), but there was no association between left ventricular mass and clinic blood pressure or white-coat effect. Furthermore, the white-coat effect was reversed at the highest level of systolic or diastolic daytime ambulatory blood pressure (systolic over 170 mmHg or diastolic over 100 mmHg) when systolic or diastolic daytime ambulatory blood pressure was higher than systolic or diastolic clinic blood pressure (ambulatory blood pressure hypertension). CONCLUSIONS: The white-coat effect shows an inverse association with daytime ambulatory blood pressure level (systolic or diastolic), being significantly more prominent for levels below 140/80 mmHg for systolic/diastolic daytime ambulatory blood pressure and reversed with daytime ambulatory blood pressure levels above 170/100 mmHg.     

Relation between exercise-induced hypertension and sustained hypertension in adult patients after successful repair of aortic coarctation

OBJECTIVES: To investigate whether exercise-induced hypertension in successfully repaired adult post-coarctectomy patients is associated with hypertension on 24-h blood pressure measurement and increased left ventricular mass. METHODS: One hundred and forty-four consecutive post-coarctectomy patients (mean age 31.5 years, range 17-74 years; mean age at repair 7.9 years, range 0-45 years) from three tertiary referral centres were studied using ambulatory blood pressure monitoring, treadmill exercise testing and echocardiography. RESULTS: Of the 144 patients, 27 (19%) were known to have sustained hypertension, based on their history, and all were on antihypertensive medication. However, 32 (27%) of the remaining 117 patients showed elevated mean daytime systolic blood pressure readings at 24-h ambulatory blood pressure monitoring (systolic blood pressure > or = 140 mmHg). Of the remaining 85 patients with normal mean daytime systolic blood pressure, 18 patients (21%) had exercise-induced hypertension (maximal exercise systolic blood pressure > 200 mmHg). Mean daytime systolic blood pressure was higher in the exercise-induced hypertensive patients compared to the normotensive patients with normal exercise blood pressure (134 +/- 5 versus 129 +/- 7 mmHg, P = 0.008). By multivariate analysis, both maximal exercise systolic blood pressure (P = 0.007) and resting systolic blood pressure (P < 0.0001) were independently associated with mean daytime systolic blood pressure. Maximal exercise systolic blood pressure had no independent predictive value for left ventricular mass (P = 0.132). CONCLUSIONS: In adult post-coarctectomy patients, maximal exercise systolic blood pressure is independently associated with mean daytime systolic blood pressure at ambulatory blood pressure monitoring. In this study no independent predictive value of maximal exercise systolic blood pressure for left ventricular mass could be demonstrated.     

Potassium supplementation reduces clinic and ambulatory blood pressure in elderly hypertensive patients.

OBJECTIVES: To determine the effects of potassium chloride 60 mmol/day supplementation on clinic and 24-h ambulatory blood pressure values in elderly untreated hypertensive patients. DESIGN: A double-blind randomized placebo-controlled crossover study lasting 8 weeks, following a 4-week run-in period. SETTING: Outpatient clinic in a district general hospital. PATIENTS: Eighteen untreated elderly hypertensive patients (mean age 75 years, range 66-79) with a systolic blood pressure of > or = 160 mmHg and/or a diastolic blood pressure of > or = 95 mmHg were recruited from the clinics of local general practitioners and from the current hospital outpatient department. Patients had not received any antihypertensive medication for at least 4 weeks before entry into the study. INTERVENTIONS: Before entry into the study, the daily dietary electrolyte intake of each individual was established and this was maintained during the run-in and intervention periods. Following a 4-week run-in period patients received potassium supplements or matching placebo, each for 4 weeks. MAIN OUTCOME MEASURES: The within-patient changes in clinic and 24-h ambulatory blood pressures at the end of each intervention period. RESULTS: After 4 weeks potassium supplementation compared with placebo there was a significant fall in supine clinic blood pressure, standing and 24-h ambulatory systolic blood pressure. There was no significant change in clinic standing diastolic blood pressure, 24-h ambulatory diastolic blood pressure or pulse rate. Plasma renin activity increased and body weight fell after potassium supplementation. Twenty-four-hour urinary potassium rose significantly, whereas urinary sodium excretion was unchanged. CONCLUSIONS: A 60-mmol daily supplement of potassium chloride reduces clinic and 24-h ambulatory blood pressure in elderly hypertensive patients.