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

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

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

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

Comparative efficacy of perindopril and enalapril once daily using 24-hour ambulatory blood pressure monitoring

ACE inhibitors are important therapeutic agents in controlling hypertension, correcting some of its pathophysiological derangement and improving its prognosis. While there are many such agents, there may be some important differences between them. This placebo run-in, double blind, crossover study, using 24-hour ambulatory blood pressure monitoring, compares the efficacy of perindopril 4-8 mg and enalapril 10-20 mg as once daily antihypertensive agents on 32 patients. For diastolic blood pressure (DBP), perindopril had a placebo-corrected peak (P) reduction of blood pressure (BP) of -6.4 +/- 1.3 mmHg vs its placebo-corrected trough (T) of -5.2 +/- 1.7 mmHg. Enalapril had a reduction in DBP of -8.5 +/- 1.3 mmHg (P) and -5.7 +/- 1.7 mmHg (T). For systolic blood pressure (SBP), perindopril had a reduction of -7.5 +/- 1.6 mmHg (P) vs -7.3 +/- 2.2 mmHg (T) compared to enalapril with -10.8 +/- 1.6 mmHg (P) vs -8.3 +/- 2.3 mmHg (T). Placebo-corrected trough-to-peak ratio (SBP/DBP) for perindopril was 0.97/0.81 vs 0.77/0.67 for enalapril. There was no difference noted in 24-hour mean BP, area under the curve or post-dose casual BP measurements. Both perindopril and enalapril were well tolerated and the two treatment groups had similar safety profiles. Perindopril thus had a predictable and sustained blood pressure effect giving a 24-hour cover for the patient without excessive peak effect or poor trough effect.     

A double-blind ambulatory blood pressure monitoring study of the efficacy and tolerability of once-daily telmisartan 40 mg in comparison with losartan 50 mg in the treatment of mild-to-moderate hypertension in Taiwanese patients

Ambulatory blood pressure monitoring (ABPM) was used to compare the efficacy and tolerability of once-daily telmisartan 40 mg and once-daily losartan 50 mg in Taiwanese patients with mild-to-moderate essential hypertension in a randomised, double-blind, double-dummy, parallel-group study. The initial 2-week placebo run-in phase was followed by randomisation to treatment with telmisartan 40 mg (n = 31) or losartan 50 mg (n = 30) for 6 weeks. The reduction in 18- to 24-h mean (SE) ambulatory diastolic blood pressure (DBP) from baseline was significantly greater with telmisartan 40 mg (-12.1 +/- 1.6 mmHg, p = 0.036) than with losartan 50 mg (-7.0 +/- 1.8 mmHg). The reduction in 18- to 24-h mean (SE) ambulatory systolic blood pressure (SBP) from baseline was also greater with telmisartan 40 mg (-16.0 +/- 2.4 mmHg) than with losartan 50 mg (-11.8 +/- 2.7 mmHg), but did not achieve statistical significance. Telmisartan was well tolerated; no serious adverse events occurred.     

Antihypertensive effect of oral potassium aspartate supplementation in mild to moderate arterial hypertension.

BACKGROUND: Previous studies showed that potassium chloride (48-120 mmol/day) supplementation reduced arterial blood pressure (BP) in hypertensive patients. OBJECTIVES: Our aim was to evaluate the effect of a lower dose of potassium aspartate salt on BP in individuals with essential arterial hypertension. METHODS: One hundred and four patients (65 males, age 53 +/- 12 years) with mild to moderate essential hypertension (systolic/diastolic BP 154.2/96.2 +/- 10.8/5.4 mmHg) were allocated in two comparable groups of 52 to receive or not 30 mmol/day per os of potassium aspartate supplementation for four weeks. Office and 24-h BP, as well as serum and urinary electrolytes, were measured at baseline and at the follow-up visit after four weeks. RESULTS: Office and 24-h BP did not change in the control group, while these values were significantly reduced in the potassium supplementation group. Changes in office (systolic BP: 154.4 +/- 8.2 vs. 142.2 +/- 7.6 mmHg; diastolic BP: 95.0 +/- 5.6 vs. 87.2 +/- 4.3 mmHg, P < 0.001 for both) and 24-h BP (systolic BP: 142.7 +/- 8.2 vs. 134.8 +/- 6.3 mmHg; diastolic BP: 90.8 +/- 4.4 vs. 84.6 +/- 3.8 mmHg, P < 0.001 for both) following potassium supplementation were highly significant. The changes in day time and night time BP were similar. The treated group showed significantly increased potassium serum level and 24-h urinary excretion of potassium (P < 0.01 in both cases) after four weeks, while the untreated group showed no significant changes of the same parameters. Urinary Na/K ratio decreased significantly with potassium supplementation (P < 0.001). In the treated group changes in office (r = 0.58, P < 0.001) and 24-h SBP (r = 0.51, P < 0.001), but not in DBP (r = 0.29 and r = 0.25, n.s.), correlated positively with the urinary Na/K ratio at baseline. CONCLUSIONS: A relatively low supplementation of 30 mmol/day of potassium as aspartate lowered office and 24-h ambulatory BP in subjects with mild to moderate essential hypertension. The antihypertensive effect was sustained throughout the day, and was greater in the patients with high basal urinary Na/K ratio.     

The efficacy and tolerability of barnidipine hydrochloride in Thai patients with hypertension

This open-label, blinded study was performed to evaluate the efficacy and tolerability of barnidipine at a titrated dose of 10-15 mg once daily for 8 weeks in the treatment of essential hypertension in 40 Thai patients. 'Office' blood pressure (BP) and 24-h ambulatory BP measurements were recorded. A systolic BP/diastolic BP (SBP/DBP) reduction of 18.0 +/- 13.6/9.1 +/- 6.6 mmHg was obtained. The full response rate among patients with systolic and diastolic hypertension was 63% using either SBP or DBP criteria, and 54% using both SBP and DBP criteria. One of the two patients with isolated systolic hypertension had a full response, and the BP in two of the three patients with isolated diastolic hypertension was normalized. The trough-to-peak ratio and smoothness index for SBP/DBP were acceptable (0.76 +/- 0.63/0.55 +/- 0.26 and 1.2 +/- 0.4/1.2 +/- 0.3, respectively). In conclusion, once-daily barnidipine monotherapy provides effective 24-h BP control and is generally well tolerated in ambulatory patients.     

ABPM comparison of the anti-hypertensive profiles of telmisartan and enalapril in patients with mild-to-moderate essential hypertension

In this multicentre, prospective, randomized, open-label, blinded-endpoint (PROBE) study, the efficacy of 12 weeks' treatment with once-daily telmisartan 40-80 mg and enalapril 10-20 mg was evaluated using ambulatory blood pressure monitoring (ABPM) in 522 patients with mild-to-moderate essential hypertension. Patients were titrated to the higher dose of study drug at week 6 if mean seated diastolic blood pressure (DBP) was > or = 90 mmHg. The primary endpoint was the change from baseline in ambulatory DBP in the last 6 h of the 24-h dosing interval after 12 weeks' treatment. Telmisartan and enalapril produced similar reductions from baseline in DBP and systolic blood pressure (SBP) over all ABPM periods evaluated (last 6 h, 24-h, daytime and night-time). Telmisartan produced a significantly greater reduction in mean seated trough DBP, measured unblinded with an automated ABPM device in the clinic, amounting to a difference of -2.02 mmHg (P < 0.01). A significantly greater proportion of patients achieved a seated diastolic response with telmisartan than enalapril (59% versus 50%; P < 0.05), also measured with the same ABPM device. Both treatments were well tolerated. Compared with telmisartan, enalapril was associated with a higher incidence of cough (8.9% versus 0.8%) and hypotension (3.9% versus 1.1%). Therefore, telmisartan may provide better long-term compliance and, consequently, better blood pressure control than enalapril.     

Ambulatory Blood Pressure Response to Once-Daily Fimasartan: An 8-Week,Multicenter, Randomized,Double-Blind,Active-Comparator,Parallel-Group Study in Korean Patients With Mild To Moderate Essential Hypertension

Background

Fimasartan, a selective angiotensin II type 1 receptor blocker, was approved in Korea for the treatment of patients with mild to moderate hypertension.

Objective

The aim of this study was to evaluate the 24-hour blood pressure (BP) profiles before and after 8-week treatment with fimasartan and to compare them with those of valsartan.

Methods

A multicenter, randomized, double-blind, active-controlled, parallel-group study was conducted using ambulatory BP monitoring (ABPM). Korean patients with mild to moderate essential hypertension were enrolled and randomly received once-daily oral fimasartan 60 or 120 mg or valsartan 80 mg for 8 weeks. ABPM was performed before and after 8-week treatment, and clinic BP was also measured. Based on ABPM data, trough-to-peak ratio and smoothness index were derived. Tolerability was monitored throughout the study.

Results

Ninety-two patients were enrolled (mean [SD] age, 54.1 [8.2] years; weight, 67.9 [10.2] kg). After 8 weeks, 24-hour, daytime, and nighttime mean ambulatory systolic and diastolic BPs (SBP and DBP, respectively) were significantly decreased in all 3 treatment groups (range: SBP, –9.2 to –15.6 mm Hg; DBP, –5.0 to –10.7 mm Hg; P <0.0001–<0.05). The global trough-to-peak ratios of ambulatory DBP in the fimasartan groups were 0.74 (60 mg/d) and 0.81 (120 mg/d)—45.1% and 58.8% higher, respectively, than the ratio of 0.51 in the valsartan group. Fimasartan 60 mg/d was associated with 53.5% (SBP) and 68.3% (DBP) greater smoothness index scores compared with those with valsartan 80 mg/d (SBP, 1.52 vs. 0.99; DBP, 1.38 vs. 0.82). The decrease in clinic-measured DBP was significantly greater in the fimasartan 60-mg/d group compared with that in the valsartan 80-mg/d group (–14.0 vs –8.7 mm Hg; P = 0.0380). Fimasartan was well tolerated; headache was the most common adverse event.

Conclusion

Once-daily fimasartan effectively maintained a BP-reduction profile over the full 24-hour dosing interval; this profile was comparable to or slightly better than that of once-daily valsartan. Fimasartan was well tolerated; headache was the most common adverse event. ClinicalTrials.gov identifier: NCT00922441.     

Randomized,comparative, double-blind study of amlodipine vs. nicardipine as a treatment of isolated systolic hypertension in the elderly

A 90-day, multicenter, randomized, double-blind, parallel-group study was conducted to compare the efficacy of amlodipine (once a day) with nicardipine (two to three times a day), in the treatment of isolated systolic hypertension (ISH) in the elderly. Patients (n = 133) aged > or = 60 years, with ISH were randomized to receive either amlodipine 5 mg/day, or nicardipine 60 mg/day (titrated if necessary to 10 mg/day and 100 mg/day, respectively) for 90 days. Efficacy was assessed by measuring office blood pressure (BP), and 24-h ambulatory blood pressure monitoring (ABPM). The two treatments substantially and comparably reduced office systolic blood pressure (SBP) and pulse pressure (PP), and also produced a slight decrease in diastolic blood pressure (DBP). Amlodipine reduced SBP, as assessed by ABPM, to a significantly greater extent than nicardipine. Both treatments were well-tolerated. The sustained effect of amlodipine, compared with nicardipine, was reflected in its significantly greater antihypertensive activity, particularly during the nocturnal period, as assessed by ABPM. The study demonstrates that once a day dose of amlodipine is an effective antihypertensive treatment for elderly ISH patients.     

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

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

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

BACKGROUND: Several studies have found that measurement of blood pressure (BP) in the clinical setting may lead to overestimation of hypertension and may yield inaccurate assessments of the efficacy of antihypertensive treatment. OBJECTIVE: The aim of this study was to determine whether the use of clinic BP in the Valsartan and Amlodipine for the Treatment of Isolated Systolic Hypertension in the Elderly (Val-Syst) study accurately identified those elderly outpatients with systolic hypertension who had true 24-hour elevations in BP, as well as those who required dose increases in antihypertensive therapy during follow-up. METHODS: In Val-Syst, patients aged between 60 and 80 years with a clinic sitting systolic BP (SBP) of 160 to 220 mm Hg and a diastolic BP <90 mm Hg after a 2-week placebo washout period were randomized to receive valsartan 80 mg or amlodipine 5 mg once daily (level 1). In those with a trough SBP > or =140 mm Hg after 8 weeks of double-blind treatment, doses were titrated upward to valsartan 160 mg or amlodipine 10 mg once daily (level 2). If clinic SBP was > or =140 mm Hg after a further 8 weeks, hydrochlorothiazide 12.5 mg was added for an additional 8 weeks (level 3). Clinical decisions during the active-treatment period were based on clinic BP measurements. Thirteen of the 35 participating centers assessed ambulatory BP as well as clinic BP at baseline and the end of the treatment, making it possible to compare the results of the 2 modes of measurement. The Student test was used to compare drug-induced changes in clinic and ambulatory BP in individual patients. Differences between the decreases in clinic and ambulatory BP at the 3 treatment levels were tested using repeated-measures analysis of covariance (ANCOVA), with baseline as the covariate. RESULTS: One hundred sixty-four elderly patients (age range, 60-80 years; 85 men, 79 women) were included in the study (79 valsartan, 85 amlodipine), and valsartan and amlodipine were reported to have comparable effects on the level and rhythm of 24-hour BP In the present study, 22 of 164 patients had white-coat hypertension at baseline (clinic SBP > or =160 mm Hg and mean 24-hour SBP <130 mm Hg). For both treatments combined, the mean (SD) decreases in clinic SBP were inversely proportional to the treatment level (level 1 = -33.2 (7.9) mm Hg; level 2 = -31.6 (11.8) mm Hg; level 3 = -29.3 (11.6) mm Hg; P = 0.001, overall ANCOVA). In contrast, after adjusting for baseline values, the decreases in mean 24-hour SBP did not differ between treatment levels (level 1 = -10.8 [10.4] mm Hg; level 2 = -13.0 [11.2] mm Hg; level 3 = -16.4 [13.8] mm Hg). The decrease in clinic BP during therapy was similar in patients with white-coat hypertension and sustained hypertension (clinic SBP > or 160 mm Hg and mean 24-hour SBP > or =130 mm Hg), whereas 24-hour and 8- to 9-am SBP decreased significantly only in patients with sustained hypertension (P < 0.001). At the end of the study, mean 24-hour SBP continued to be uncontrolled (> or =130 mm Hg) in 16 of 53 patients (30.2%) at treatment level 1, 27 of 62 (43.5%) at level 2, and 19 of 49 (38.8%) at level 3 (P = NS). CONCLUSION: Based on the findings in this population of elderly patients with systolic hypertension, the management of hypertension may vary depending on whether decisions concerning the selection of patients for clinical trials and treatment adjustments during follow-up are made using clinic or ambulatory BP measurement.     

Population study of ambulatory blood pressure in a rural community in northern Japan

A cross sectional survey was performed on ambulatory blood pressure (ABP) in a rural community in northern Japan. ABP was measured in 468 participants (148 men and 320 women, or 27.3% of the less than or equal to 20 year-old population in the study region) with a Colin ABPM 630, an ABP monitoring system. ABP was determined every 30 min for 24 hr. All-day average of 24 hr ambulatory systolic, (SBP) and diastolic BP (DBP) in these subjects were 121.5 +/- 11.8 and 71.7 +/- 8.0 mmHg (mean +/- S.D.), respectively. Ambulatory SBP and DBP levels increased gradually with an increase in age in both sexes. The age dependent increase in SBP was, however, extremely small in men compared with that in the casual SBP of the ordinary Japanese reported. The minimal age-dependent increase in ambulatory SBP in men reflects a high ambulatory SBP in those below 50 years-old as well as a minimal increase in ambulatory SBP in those over 50. Ambulatory SBPs in women were lower than those in men until they reach the age of 50 years. Ambulatory SBP levels in men and women were similar after their 60's. Ambulatory DBP tended to fall or remain at the same level after 60 years-old. Thus, a greater pulse pressure was observed in elderly subjects. Casual SBP and DBP in the ordinary Japanese were significantly higher than the daytime average ambulatory SBP and DBP in all age groups of both sexes in the population except those in their 20's. The results suggests that ABP has different clinical characteristics and may have a different clinical significance from casual BP.     

Angiotensin II receptor blocker telmisartan: effect on blood pressure profile and left ventricular hypertrophy in patients with arterial hypertension

In this open-label, non-comparative study, the anti-hypertensive efficacy and effect on left ventricular hypertrophy (LVH) of 24 weeks' treatment with once-daily telmisartan 40-80 mg was evaluated in 24 patients with mild-to-moderate hypertension and LVH. Patients were titrated to the higher dose of study drug at week 4 if they did not achieve blood pressure normalization (i.e. systolic blood pressure [SBP]/diastolic blood pressure [DBP] remained > or = 140/90 mmHg). The anti-hypertensive action of telmisartan was assessed using clinic cuff measurements and 24-h ambulatory blood pressure monitoring, and left ventricular mass index (LVMI) was determined by two-dimensional echocardiography at baseline and after 24 weeks of therapy. Telmisartan significantly reduced mean 24-h, daytime and night-time SBP and DBP compared with baseline after 12 and 24 weeks of therapy. Target blood pressure levels, defined as SBP/DBP < 140/90 mm Hg, were achieved in 16 (69.6%) patients at the end of the treatment period. After 24 weeks of telmisartan treatment, LVMI decreased from 151.6 +/- 5.4 to 135.1 +/- 5.9 g/m2. In conclusion, anti-hypertensive treatment with telmisartan for 24 weeks produced significant reductions in blood pressure and regression of LVH, as assessed by LVMI, in patients with hypertension and LVH.     

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

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

A pilot study of continuous ambulatory monitoring of blood pressure in repeated preoperative autologous blood donation

BACKGROUND: The aim of this study was to investigate the occurrence of hypotension in the 24-hour period after preoperative autologous blood donation (PABD) in patients with and without hypertension. STUDY DESIGN AND METHODS: In 20 patients, 24-hour ambulatory blood pressure monitoring (ABPM) was performed before PABD was started and on every donation day in two repeated phlebotomies. RESULTS: Seven patients had no hypertension and 11 patients had hypertension. In 2 additional patients, hypertension was diagnosed during the study. Overall, the mean systolic BP (SBP) decreased from 131+/-15 mmHg before donation to 128+/-13 and 127+/-10 mmHg after Donations 1 and 2; the corresponding values for the diastolic BP (DBP) were 77+/-9, 75+/-9, and 73+/-7 mmHg, both without significant differences between the groups with and without hypertension. In single patients, substantial decreases of BP occurred, especially during the night. Two patients with and 2 without hypertension showed a nightly decrease in SBP and DBP of more than 10 percent (in 1 of these patients, more than 20%). Concerning diurnal BP variability, 1 patient with and 1 without hypertension, the latter showing a nightly decrease of SBP and DBP of more than 10 percent, also changed to the pattern of a nightly "extreme dipper" after PABD. CONCLUSION: In 25 percent of the patients, changes of BP were observed during the 24-hour period after PABD, especially during the night, which are known to be associated with an increased risk of cerebral or myocardial ischemia. Whether those changes of BP lead to major morbidity or mortality requires further investigation.     

Effects of amlodipine and fosinopril on heart rate variability and left ventricular mass in mild-to-moderate essential hypertension

The differences between long-acting dihydropyridines and angiotensin-converting enzyme inhibitors with regard to their long-term effects on 24-h heart rate variability (HRV) and left ventricular (LV) mass are less clear in mild-to-moderate essential hypertension. We studied the long-term effects of amlodipine and fosinopril on 24-h HRV and LV mass in mild-to-moderate essential hypertension. In this study, 27 patients with never treated mild-to-moderate essential hypertension were randomised to receive either amlodipine or fosinopril once daily as monotherapy. At baseline and at the end of the third and sixth months, each of the patients underwent 24-h HRV and ambulatory systolic (SBP) and diastolic (DBP) blood pressure analysis. LV mass index was calculated from echocardiographic examination at baseline and at the end of the sixth month. In amlodipine group (n = 14), 24-h SBP/DBP (mmHg) decreased from 144 +/- 8/94 +/- 4 to 128 +/- 6/83 +/- 3 at the end of the third month and to 125 +/- 5/81 +/- 2 at the end of the sixth month (p < 0.0001). In fosinopril group (n = 13), the respective changes were 143 +/- 9/97 +/- 7, 132 +/- 6/87 +/- 5 and 127 +/- 6/82 +/- 3 (p < 0.0001). At the end of the sixth month, LV mass index (g/m(2)) decreased from 122 +/- 26 to 105 +/- 21 in amlodipine group (p < 0.0001) and from 118 +/- 23 to 101 +/- 14 in fosinopril group (p < 0.0001). There were no significant changes in HRV parameters in both the groups. It was concluded that both drugs caused significant decrease in SBP and DBP, and LV mass in patients with mild-to-moderate essential hypertension did not have significant long-term effects of either amlodipine or fosinopril on 24-h HRV parameters reflecting sympathetic or parasympathetic activity in these patients.     

Comparison of fixed-dose combinations of telmisartan/hydrochlorothiazide 40/12.5 mg and 80/12.5 mg and a fixed-dose combination of losartan/hydrochlorothiazide 50/12.5 mg in mild to moderate essential hypertension: pooled analysis of two multicenter, prospective, randomized, open-label, blinded-end point (PROBE) trials

BACKGROUND: High incidences of cardiovascular events coincide with a surge in blood pressure (BP) that occurs in the early morning hours at the time of arousal. Thus, control of BP at this time of day, using oral fixed-dose combinations (FDCs) as required, is important in reducing cardiovascular risk in hypertensive patients. OBJECTIVE: The aim of this analysis was to compare the antihypertensive efficacy in the early morning hours and tolerability of oral FDCs of telmisartan/hydrochlorothiazide (HCTZ) (40/12.5 mg [T40/H12.5] and 80/12.5 mg [T80/H12.5]) versus a low-dose FDC of losartan 50 mg/HCTZ 12.5 mg (L50/H12.5). METHODS: Data from 2 similarly designed prospective, randomized, open-label, blinded-end point (PROBE) studies were pooled and analyzed. The studies were conducted at 72 centers across the United States, and 70 centers in Canada, Europe (9 countries), and the Philippines. Adult male and female patients with mild to moderate essential hypertension (24-hour mean ambulatory diastolic BP [DBP], > or =85 mm Hg; seated cuff DBP, 90-109 mm Hg) were enrolled. Patients were randomly assigned to receive T40/H12.5, L50/H12.5, or T80/H12.5, QD (morning) for 6 weeks. Antihypertensive efficacy was assessed using 24-hour ambulatory BP monitoring (ABPM) and cuff sphygmomanometry at trough, performed at baseline and on completion of active treatment. The primary end point was the reduction from baseline in mean ambulatory DBP over the last 6 hours of the dosing interval. Secondary end points included other ABPM- and clinic-derived changes in DBP and systolic BP (SBP), and control and response rates (SBP response defined as 24-hour mean SBP <130 mm Hg and/or reduction from baseline > or =10 mm Hg; DBP response defined as 24-hour mean DBP <85 mm Hg or reduction from baseline > or =10 mm Hg; DBP control defined as 24-hour mean DBP <85 mm Hg). Tolerability was assessed using patient interview, spontaneous reporting, and clinical evaluation. RESULTS: A total of 1402 patients were enrolled(876 men, 525 women; mean [SD] age, 53.1 [9.9] years) (T40/H12.5, n = 517; L50/H12.5, n = 518; and T80/H12.5, n = 367). With T40/H12.5, the mean reduction in last-6-hour mean ambulatory DBP was 1.8 mm Hg greater compared with that achieved with L50/H12.5 (-11.3 [0.4] vs -9.4 [0.4] mm Hg; P < 0.001), and with T80/H12.5, the mean reduction was 2.6 mm Hg greater compared with that achieved with L50/H12.5 (-12.0 [0.4] vs -9.4 [0.4] mm Hg; P < 0.001). Analysis of secondary end points found that greater BP reduction occurred with T40/H12.5 and T80/H12.5 compared with L50/H12.5. ABPM SBP control and response rates were similar between the 3 groups, but the ABPM DBP control and response rates were significantly higher with T80/H12.5 compared with L50/H12.5 (46.6% vs 34.0% [P < 0.002] and 69.4% vs 55.0% [P < 0.001], respectively). Clinic SBP and DBP control and response rates were higher with T40/H12.5 and T80/H12.5 compared with L50/H12.5 (SBP response, 80.4% and 80.8% vs 68.5% [both, P < 0.001]; DBP response, 66.1% and 67.4% vs 54.4% [both, P < 0.001]; DBP control, 56.5% and 56.4% vs 44.1% [both, P < 0.001] ). The 2 most commonly recorded adverse events (AEs) were headache (T40/H12.5, 2.9%; L50/H12.5, 3.3%; and T80/H12.5, 3.0%) and dizziness (1.2%, 2.1%, and 3.0%, respectively). Most AEs were mild to moderate. CONCLUSIONS: The results of this pooled analysis of2 PROBE studies in adult patients with mild to moderate essential hypertension suggest that T40/H12.5 and T80/H12.5 conferred greater DBP and SBP control compared with low-dose L50/H12.5, including during the last 6 hours of the dosing interval. All 3 treatments were well tolerated.     

Blood pressure behaviour in chronic daily headache

The objective was to examine the association between high blood pressure (BP) and chronic daily headache using 24-h ambulatory blood pressure monitorization (24-h ABPM). This was a cross sectional study in an out-patient clinic. Women were selected among patients referred for first evaluation, 62 with chronic daily headache and 57 without chronic daily headache. The main outcome measures were mean office systolic and diastolic blood pressure (BP), mean systolic and diastolic daytime and night-time BP and BP load, and mean systolic and diastolic nocturnal fall. Office systolic BP was 138.2 mmHg for women with chronic daily headache and 141.7 mmHg for women without headache (P = 0.36). Office diastolic BP was 88.9 mmHg for women with headache and 92.7 mmHg for women without headache (P = 0.17). Mean daytime and mean night-time systolic BP was, respectively, 122.2 mmHg and 108.8 mmHg for women with headache and 122.9 mmHg and 109.5 for women without headache (P = 0.82 and P = 0.80, respectively). Mean daytime and mean night-time diastolic BP was, respectively, 78.6 mmHg and 65.4 mmHg for women with headache and 79.9 mmHg and 67.1 mmHg for the women without headache (P = 0.80 and P = 0.45, respectively). There was no difference between the two groups regarding systolic and diastolic BP load and nocturnal systolic and diastolic fall. No significant difference in BP values was observed in women with chronic daily headache compared with women without headache using 24-h ABPM.