Mean Ambulatory Systolic Blood Pressure Research Articles

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

BackgroundFimasartan, a selective angiotensin II type 1 receptor blocker, was approved in Korea for the treatment of patients with mild to moderate hypertension. ObjectiveThe 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. MethodsA 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. ResultsNinety-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. ConclusionOnce-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.

Physician-pharmacist co-management and 24-hour blood pressure control.

The objectives of this study were to compare indices of 24-hour blood pressure (BP) following a physician-pharmacist collaborative intervention and to describe the associated changes in antihypertensive medications. This was a secondary analysis of a prospective, cluster-randomized clinical trial conducted in 6 family medicine clinics randomized to co-managed (n=3 clinics, 176 patients) or control (n=3 clinics, 198 patients) groups. Mean ambulatory systolic BP (SBP) was significantly lower in the co-managed vs the control group: daytime BP 122.8mm Hg vs 134.4mm Hg (P<.001); nighttime SBP 114.8mm Hg vs 123.7mm Hg (P<.001); and 24-hour SBP 120.4mm Hg vs 131.8mm Hg (P<.001), respectively. Significantly more drug changes were made in the co-managed than in the control group (2.7 vs 1.1 changes per patient, P<.001), and there was greater diuretic use in co-managed patients (79.6% vs 62.6%, P<.001). Ambulatory BPs were significantly lower for the patients who had a diuretic added during the first month compared with those who never had a diuretic added (P<.01). Physician-pharmacist co-management significantly improved ambulatory BP compared with the control group. Antihypertensive drug therapy was intensified much more for patients in the co-managed group.

Effect of dietary nitrate on blood pressure, endothelial function, and insulin sensitivity in type 2 diabetes

Diets rich in green, leafy vegetables have been shown to lower blood pressure (BP) and reduce the risk of cardiovascular disease. Green, leafy vegetables and beetroot are particularly rich in inorganic nitrate. Dietary nitrate supplementation, via sequential reduction to nitrite and NO, has previously been shown to lower BP and improve endothelial function in healthy humans. We sought to determine if supplementing dietary nitrate with beetroot juice, a rich source of nitrate, will lower BP and improve endothelial function and insulin sensitivity in individuals with type 2 diabetes (T2DM). Twenty-seven patients, age 67.2±4.9 years (18 male), were recruited for a double-blind, randomized, placebo-controlled crossover trial. Participants were randomized to begin, in either order, a 2-week period of supplementation with 250ml beetroot juice daily (active) or 250ml nitrate-depleted beetroot juice (placebo). At the conclusion of each intervention period 24-h ambulatory blood pressure monitoring, tests of macro- and microvascular endothelial function, and a hyperinsulinemic isoglycemic clamp were performed. After 2 weeks administration of beetroot juice mean ambulatory systolic BP was unchanged: 134.6±8.4mmHg versus 135.1±7.8mmHg (mean±SD), placebo vs active—mean difference of −0.5mmHg (placebo–active), p=0.737 (95% CI −3.9 to 2.8). There were no changes in macrovascular or microvascular endothelial function or insulin sensitivity. Supplementation of the diet with 7.5mmol of nitrate per day for 2 weeks caused an increase in plasma nitrite and nitrate concentration, but did not lower BP, improve endothelial function, or improve insulin sensitivity in individuals with T2DM.

Comparative Efficacy of Aliskiren/Valsartan vs Valsartan in Nocturnal Dipper and Nondipper Hypertensive Patients: A Pooled Analysis

This pooled analysis of ambulatory blood pressure (BP) monitoring data from two 8-week randomized controlled trials compared the antihypertensive efficacy and safety of combination aliskiren/valsartan vs valsartan alone in hypertensive patients (nocturnal dippers or nondippers). At study end, patients were taking aliskiren/valsartan 300/320 mg or valsartan 320 mg. In dippers (n=138) and nondippers (n=132), aliskiren/valsartan provided significantly (P<.05) greater reductions from baseline to week 8 than valsartan in 24-hour, daytime, and last-4-hour mean ambulatory systolic BP (maSBP). Treatment differences were more pronounced in nondippers. Nighttime maSBP reductions with aliskiren/valsartan were significantly greater vs valsartan in nondippers (-17.0 mm Hg vs -8.9 mm Hg; P<.05) but not dippers (-7.6 mm Hg vs -4.5 mm Hg; P=.16). In all time periods, combination therapy was generally associated with BP reductions that were greater in nondippers than dippers. Conversion from nondipper to dipper status was 32% vs 22% for aliskiren/valsartan vs valsartan (P=.48). Both treatments were similarly well tolerated. Although the addition of aliskiren to valsartan did not significantly alter dipper status, our data suggest an increased contribution of the renin-angiotensin-aldosterone system to the nondipper status of hypertensive patients.

Ambulatory blood pressure profile and left ventricular geometry in Nigerian hypertensives

Background:Left ventricular hypertrophy (LVH) is an independent cardiac risk factor in hypertensives and the structural classification of left ventricular (LV) geometry provides additional prognostic information. Ambulatory blood pressure (ABP) monitoring has been shown to be superior to office blood pressure (BP) in relation to hypertension LVH. We investigated ambulatory BP variables in relation to LV geometric patterns in Nigerian hypertensives.Materials and Methods:A total of 130 patients (males = 96, females = 34) with hypertension had their 24-hours ambulatory BP and trans-thoracic 2D/M- mode echocardiography. Data were analyzed with SPSS 13.0. P < 0.05 was considered statistically significant.Results:The mean age of the patients was 54.08±11.88 years. The prevalence rate of abnormal LV geometry was 48.4%. Mean ambulatory Systolic BP (day time, night time and 24-hour-average) was significantly higher in patients with LVH compared with those without LVH. Day-night systolic and diastolic BP decay (i.e. percentage nocturnal decline in BP) was also significantly lower in LVH group than in the group without LVH. Patients with eccentric LVH had abnormal day time mean ambulatory systolic BP, night time mean ambulatory systolic BP, elevated day time and night time systolic BP loads, as well as non-dipping diastolic BP pattern. Significant correlates of LV mass index in this study population were mean ambulatory systolic BP (day time: r = 0.355, P = 0.004; night time: r = 0.343, P = 0.005; 24- hour average: r = 0.358, P = 0.004) and day-night decay (systolic: r = -0.388, P = 0.007; diastolic: r = -0.290, P = 0.022) as well as 24-hour systolic BP variability.Conclusion:The presence of LVH in hypertension was associated with higher mean ambulatory systolic BP and lower percentage nocturnal decline in systolic and diastolic BP than its absence which appeared to be worse in patients with eccentric LV geometry when compared with other geometric patterns.

Comparison of the Novel Angiotensin II Receptor Blocker Azilsartan Medoxomil vs Valsartan by Ambulatory Blood Pressure Monitoring

Azilsartan medoxomil (AZL-M) is a unique angiotensin II receptor blocker (ARB) under development for the treatment of hypertension. To compare this ARB with another in the class, the authors studied the effects of AZL-M and valsartan (VAL) in 984 patients with primary hypertension in a randomized, double-blind, multicenter study using ambulatory and clinic blood pressure (BP) measurements. The primary end point was change from baseline in 24-hour mean ambulatory systolic BP following 24 weeks of treatment. Hierarchical analysis testing for noninferiority was followed by superiority testing of AZL-M (80 mg then 40 mg) vs VAL. The mean age of participants was 58 years, 52% were men, and 15% were black. Baseline 24-hour mean systolic BP was similar (approximately 145.6 mm Hg) in each group. AZL-M 40 mg and 80 mg lowered 24-hour mean systolic BP (-14.9 mm Hg and -15.3 mm Hg, respectively) more than VAL 320 mg (-11.3 mm Hg; P<.001 for 40-mg and 80-mg comparisons vs VAL). Clinic systolic BP reductions were consistent with the ambulatory results (-14.9 mm Hg for AZL-M 40 mg and -16.9 mm Hg for AZL-M 80 mg vs -11.6 mm Hg for VAL; P=.015 and P<.001, respectively). The reductions in 24-hour mean and clinic diastolic BPs were also greater with both doses of AZL-M than with VAL (P≤.001 for all comparisons). Small, reversible changes in serum creatinine occurred more often with AZL-M than with VAL; otherwise, safety and tolerability parameters were similar among the three groups. These data demonstrate that AZL-M across the effective dose range had superior efficacy to VAL at its maximal recommended dose without any meaningful increase in adverse events. These findings suggest that AZL-M could provide higher rates of hypertension control compared with other ARBs in the class.

Increasing the doses of both diuretics and angiotensin receptor blockers is beneficial in subjects with uncontrolled systolic hypertension

Blood pressure (BP) control is frequently difficult to achieve in patients with predominantly elevated systolic BP. Consequently, these patients frequently require combination therapy including a thiazide diuretic such as hydrochlorothiazide (HCTZ) and an agent blocking the renin-angiotensin-aldosterone system. Current clinical practice usually limits the daily dose of HCTZ to 25 mg. This often leads to the necessity of using additional antihypertensive agents to control BP in a high proportion of patients. To compare the efficacy of two doses of losartan (LOS)⁄HCTZ combinations in patients with uncontrolled ambulatory systolic hypertension after six weeks of treatment with LOS 100 mg⁄HCTZ 25 mg (LOS100⁄HCTZ25). Following a two- to four-week washout period, subjects with a mean clinic sitting systolic BP of 160 mmHg or higher and a mean ambulatory daytime systolic BP (MDSBP) of 135 mmHg or higher on LOS100⁄HCTZ25 (n=105; 33 women and 72 men) were randomly assigned to receive LOS 150 mg⁄HCTZ 25 mg (group 1; n=53) or LOS 150 mg⁄HCTZ 37.5 mg (LOS150⁄HCTZ37.5, group 2; n=52). The primary end point was the difference in MDSBP reductions. At the end of the six-week treatment period, the respective additional decreases in MDSBP were 1.2 mmHg (P=0.335) on LOS 150 mg⁄HCTZ 25 mg and 5.6 mmHg (P<0.0001) on LOS150⁄HCTZ37.5 (difference of 4.4 mmHg; P=0.011). Daytime systolic ambulatory BP goal (lower than 130 mmHg) achievement tended to be higher (25% versus 17%; P=0.313) with LOS150⁄HCTZ37.5, while it was significantly higher (65% versus 43%; P=0.024) for mean daytime diastolic BP (lower than 80 mmHg). No deleterious metabolic changes were observed. In patients with uncontrolled systolic ambulatory hypertension receiving LOS100⁄HCTZ25, increasing both HCTZ and LOS dosages simultaneously to LOS150⁄HCTZ37.5 may be an effective strategy that does not affect metabolic parameters.

Effects of High- and Low-Sodium Diets on Ambulatory Blood Pressure in Patients With Hypertension Receiving Aliskiren

Dietary sodium reduction and, as necessary, pharmacologic treatment are recommended for hypertension management. This prospective, randomized, open-label, blinded-end point, multicenter, crossover study investigated the effect of dietary sodium intake on mean ambulatory systolic blood pressure (maSBP) in patients with hypertension receiving aliskiren 300 mg once daily. Following a 2- to 4-week washout period, patients were randomized to a high- (≥ 200 mmol/d) or low- (≤ 100 mmol/d) sodium diet and were started on aliskiren, 300 mg/d. After 4 weeks, patients were crossed over to the alternate diet for an additional 4 weeks. The primary efficacy variable was change in maSBP between diets. During treatment with aliskiren, maSBP was significantly lower with the low-sodium diet compared with the high-sodium diet (least squares mean difference, 9.4 mm Hg; 95% CI, 7.5-11.4; P < .0001). The percentage of patients achieving a maSBP response to aliskiren (<130 mm Hg or a ≥ 20-mm Hg reduction from baseline) was greater with the low- (76.5%) versus the high-sodium diet (42.6%; P < .0001). Overall, 40.9% patients had ≥ 1 adverse event and the rates were similar between groups. In this study, aliskiren was well tolerated and a low-sodium diet accentuated its antihypertensive effect.

24‐Hour Ambulatory Blood Pressure Response to Combination Valsartan/Hydrochlorothiazide and Amlodipine/Hydrochlorothiazide in Stage 2 Hypertension by Ethnicity: The EVALUATE Study

Several studies reported racial/ethnic differences in blood pressure (BP) response to antihypertensive monotherapy. In a 10-week study of stage 2 hypertension, 320/25 mg valsartan/hydrochlorothiazide (HCTZ) reduced ambulatory BP (ABP) significantly more effectively than 10/25 mg amlodipine/HCTZ. Results (post hoc analysis) are described in Caucasians (n=256), African Americans (n=79), and Hispanics (n=86). Compared with clinic-measured BP (no significant treatment-group differences in ethnic subgroups), least-squares mean reductions from baseline to week 10 in mean ambulatory systolic BP (MASBP) and mean ambulatory diastolic BP (MADBP) favored valsartan/HCTZ over amlodipine/HCTZ in Caucasians (-21.9/-12.7 mm Hg vs -17.6/-9.5 mm Hg; P=.0004/P<.0001). No treatment-group differences in MASBP/MADBP were observed in African Americans (-17.3/-10.6 vs -17.9/-9.5; P=.76/P=.40) or Hispanics (-17.9/-9.7 vs -14.2/-7.2; P=.20/P=.17). Based on ABP monitoring, valsartan/HCTZ is more effective than amlodipine/HCTZ in lowering ABP in Caucasians. In African Americans and Hispanics, both regimens are similarly effective.

Effects of the renin inhibitor MK-8141 (ACT-077825) in patients with hypertension

The renin inhibitor MK-8141 (ACT-077825) demonstrates substantial immunoreactive active renin (ir-AR) increase (sevenfold) without a persistent plasma renin activity (PRA) decrease. The present study assessed the antihypertensive efficacy of MK-8141 in hypertensive patients. In this double-blind, placebo- and active comparator-controlled study, 195 patients with hypertension (trough sitting diastolic blood pressure ≥92 to <105 mm Hg, trough sitting systolic blood pressure <170 mm Hg, and 24-hour mean diastolic blood pressure [DBP] ≥80 mm Hg) were randomized to one of four treatments (stratified by race, black versus others): MK-8141 250 mg, MK-8141 500 mg, enalapril 20 mg, or placebo. Blood pressure was measured at trough and as 24-hour ambulatory blood pressure monitoring. The primary end point was change from baseline in 24-hour mean ambulatory DBP measured after 4 weeks. At week 4, the change from baseline in 24-hour mean (95% CI) ambulatory DBP compared with placebo was −1.6 mm Hg (−4.2, 1.1), −1.1 mm Hg (−3.9, 1.6), and −4.9 (−7.5, −2.2) for MK-8141 250 mg, MK-8141 500 mg, and enalapril 20 mg, respectively. Only mean ambulatory DBP-lowering with enalapril 20 mg was statistically significant. Enalapril, but not MK-8141, also significantly lowered 24-hour mean ambulatory systolic blood pressure (SBP) compared with placebo (−6.7 mm Hg [−10.5, −2.8]). Neither enalapril nor MK-8141 significantly lowered trough DBP and SBP compared with placebo. MK-8141 was generally well tolerated. In patients with hypertension, MK-8141 (ACT-077825) did not produce significant blood pressure–lowering efficacy despite a demonstrated effect of the drug on ir-AR, in the absence of durable PRA suppression.

Amlodipine and angiotensin-converting enzyme inhibitor combination versus amlodipine monotherapy in hypertension: a meta-analysis of randomized controlled trials

This study aimed to estimate the efficacy and tolerability of the combination of amlodipine and angiotensin-converting enzyme inhibitors as compared with amlodipine monotherapy in the treatment of hypertension. The Cochrane Central Register of Controlled Trials, PubMed, and Embase were searched for relevant articles. A random effect model of meta-analysis was used for the selected randomized controlled trials (RCTs). A total of 17 randomized controlled trials involving 3291 patients were identified using predefined criteria. The combination treatment of amlodipine and angiotensin-converting enzyme inhibitors resulted in a greater reduction of both systolic blood pressure (SBP) [weighted mean difference (WMD) 5.72, 95% CI: (confidence interval) 4.10-7.33] and diastolic blood pressure (DBP) (WMD 3.62, 95% CI: 4.85-2.39) than monotherapy. The combination treatment also generated significantly greater reductions for the mean ambulatory SBP and DBP during the full 24 hours (WMD: SBP 4.24, 95% CI: 6.82-1.67; DBP 2.23, 95% CI: 3.73-0.69), but not for the trough (WMD: SBP 4.52, 9.56 to -0.51; DBP 3.7, 7.65 to -0.25). The hypertension therapeutic control (SPB <140, DBP <90 mmHg) rate for the combination treatment is higher than that for monotherapy [relative risk (RR): 1.36, 95% CI: 1.07-1.73]. The combination treatment also resulted in a lower overall rate of adverse events (RR: 0.86, 95% CI: 0.75-0.99) and edema (RR: 0.40, 95% CI: 0.29-0.56), but a higher rate of cough (RR: 3.28, 95% CI: 2.03-5.29) as compared with monotherapy. This meta-analysis suggests that the combination treatment provides superior BP control, fewer adverse events, and better tolerability in hypertensive patients than monotherapy. Further research should explore the mechanism of the combination therapy and whether it is associated with the reduction of cardiovascular disease morbidity and mortality.

COMBINATION THERAPY WITH ALISKIREN+HYDROCHLOROTHIAZIDE REDUCES 24-HOUR AMBULATORY BLOOD PRESSURE MORE EFFECTIVELY THAN RAMIPRIL IN OBESE PATIENTS WITH STAGE 2 HYPERTENSION: PP.5.191

Objective: Ambulatory blood pressure monitoring (ABPM) is a better predictor of cardiovascular events than clinic blood pressure (BP). Analysis of ABPM in a subset of patients in clinical trials is important to confirm observed changes in clinic BP. We previously showed in an 8-week, prospective, multicenter, randomized, double-blind study (N=380) that a single-pill combination of aliskiren (A) with hydrochlorothiazide (HCTZ) provided greater clinic BP reductions than ramipril (R) in obese patients (average body mass index = 35.3 ± 4.4 kg/m2) with hypertension (mean sitting systolic BP [SBP] >=160 mmHg and <200 mmHg). Here we present the efficacy and safety of A+HCTZ vs R on BP control in a subset of patients who underwent ABPM (n=89). Design and Methods: After a 1–4 week washout period, eligible patients received A+HCTZ 150/12.5 mg (n=45) or R 5 mg (n=44) for 1 week; force-titrated to A+HCTZ 300/25 mg or R 10 mg for 7 weeks. Results: Significantly greater reductions in both clinic BP and 24-hour ambulatory blood pressure (ABP) were observed at week 8 with A+HCTZ vs R (P < 0.05). Reductions in the hourly daytime (6AM-10PM) mean ambulatory systolic BP (maSBP), mean ambulatory diastolic BP (maDBP), and hourly nighttime (10PM-6AM) maDBP were also significantly greater for A+HCTZ vs R (Table). In the overall study, adverse event rates were similar in both groups (35.8%, A+HCTZ vs 37.3%, R), the most common being headache, nasopharyngitis, dizziness, and fatigue. Conclusion: The ABPM results suggest that A+HCTZ provides more effective and consistent 24-hour BP reductions than R in obese patients with stage 2 hypertension.

The effects of lumiracoxib 100 mg once daily vs. ibuprofen 600 mg three times daily on the blood pressure profiles of hypertensive osteoarthritis patients taking different classes of antihypertensive agents

Aims:To examine whether the blood pressure (BP) profiles of lumiracoxib and high-dose ibuprofen differed in patients treated with different classes of antihypertensive medications.Methods:A 4-week, multicentre, randomised, double-blind study has compared the effects of lumiracoxib 100 mg once daily (od) (n = 394) and ibuprofen 600 mg three times daily (tid) (n = 393) on ambulatory BP in osteoarthritis (OA) patients with controlled hypertension. Here, we present subgroup analyses for patients receiving different antihypertensive classes. The primary outcome was a comparison of the change in 24-h mean systolic ambulatory BP (MSABP) from baseline to week 4. Patients receiving angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEIs) represented the largest subgroups receiving antihypertensive monotherapy.Results:For patients receiving an ARB monotherapy, the least squares mean (LSM) 24-h MSABP at week 4 fell with lumiracoxib 100 mg od and increased with ibuprofen 600 mg tid, creating an estimated treatment difference of 8.1 mmHg in favour of lumiracoxib (p < 0.001). For patients receiving an ACEI and a beta-blocker monotherapy, the estimated treatment difference was 8.2 mmHg (p < 0.001) and 5.8 mmHg (p = 0.002) in favour of lumiracoxib respectively. These treatment differences were greater than observed in the overall population (5.0 mmHg in favour of lumiracoxib). In patients receiving diuretics or calcium channel blockers, treatment differences in MSABP were smaller and not statistically significant, although they remained in favour of lumiracoxib.Conclusion:Lumiracoxib 100 mg od resulted in less destabilisation of BP than high-dose ibuprofen 600 mg tid, and this effect was the greatest in subgroups treated with drugs blocking the renin-angiotensin system.

Maintenance of blood-pressure-lowering effect following a missed dose of aliskiren, irbesartan or ramipril: results of a randomized, double-blind study

Most patients inadvertently miss an occasional dose of antihypertensive therapy, and hence drugs that provide sustained blood-pressure (BP) reduction beyond the 24-h dosing interval are desirable. The primary objective of this study was to compare the 24-h mean ambulatory BP reductions from baseline after a simulated missed dose of the direct renin inhibitor aliskiren, irbesartan or ramipril. In this double-blind study, 654 hypertensive patients (24-h mean ambulatory diastolic BP (MADBP) >or=85 mm Hg) were randomized 1:1:1 to once-daily aliskiren 150 mg, irbesartan 150 mg or ramipril 5 mg. Doses were doubled after 2 weeks. At day 42, patients were again randomized equally within each group to receive 1 day of placebo ('missed dose') on either day 42 or day 49. Patients with a successful 24-h ambulatory BP measurement at baseline and on day 42/49 were included in the analyses. The 24-h mean ambulatory systolic BP (MASBP)/MADBP reductions from baseline after a missed dose of aliskiren 300 mg (9.3/7.0 mm Hg) were similar to irbesartan 300 mg (9.5/7.3 mm Hg) and significantly larger than ramipril 10 mg (7.1/5.0 mm Hg, P<or=0.008). Loss of BP-lowering effect with aliskiren in the 24 h after a missed dose (1.0/0.7 mm Hg for 24-48-h vs 0-24-h MASBP/MADBP) was significantly lower than with irbesartan (3.6/2.2 mm Hg, P<0.01) or ramipril (4.0/2.6, P<0.0001). This equates to maintenance of 91/91% of the MASBP/MADBP-lowering effect with aliskiren, greater than irbesartan (73/77%) or ramipril (64/65%). The incidence of adverse events was similar across treatments (32.9-36.0%), although ramipril treatment was associated with an increased incidence of cough (ramipril, 6.1%; aliskiren, 0.5%; irbesartan, 1.8%). Aliskiren 300 mg provided a sustained BP-lowering effect beyond the 24-h dosing interval, with a significantly smaller loss of BP-lowering effect in the 24-48 h period after dose than irbesartan 300 mg or ramipril 10 mg.

Antihypertensive efficacy of telmisartan vs ramipril over the 24-h dosing period, including the critical early morning hours: a pooled analysis of the PRISMA I and II randomized trials

Cardiovascular risk is subject to circadian variation, with peak morning incidence of myocardial infarction and stroke correlating with the early morning blood pressure (BP) surge (EMBPS). Ideally, antihypertensive therapy should maintain control of BP throughout the 24-h dosing cycle. In two sister studies, Prospective, Randomized Investigation of the Safety and efficacy of Micardis vs Ramipril Using ABPM (ambulatory BP monitoring) (PRISMA) I and II, BP control was compared in patients with essential hypertension (24-h mean baseline ambulatory BP approximately 148/93 mm Hg) randomized to the angiotensin receptor blocker, telmisartan (80 mg; n=802), or the angiotensin-converting enzyme inhibitor, ramipril (5 or 10 mg; n=811), both dosed in the morning. The primary end point was the change from baseline in mean ambulatory systolic BP (SBP) and diastolic BP (DBP) during the final 6 h of the 24-h dosing cycle. The adjusted mean treatment differences in the last 6-h mean ambulatory SBP/DBP were -5.8/-4.2 mm Hg after 8 weeks and -4.1/-3.0 mm Hg after 14 weeks, in favour of telmisartan (P<0.0001 for all four comparisons). Secondary end point results, including the mean 24-h ambulatory BP monitoring, day- and night-time BP and 24-h BP load, also significantly favoured telmisartan (P<0.0001). Both treatments were well tolerated; adverse events, including cough, were less common with telmisartan. These findings suggest that telmisartan is more effective than ramipril throughout the 24-h period and during the EMBPS; this may be attributable to telmisartan's long duration of effect, which is sustained throughout the 24-h dosing period.

Serum Uric Acid and Ambulatory Blood Pressure in Children With Primary Hypertension

Hyperuricemia is associated with primary hypertension (HTN) in adults and children. Furthermore, uric acid levels during childhood are associated with blood pressure (BP) levels in adulthood. We measured 24-h ambulatory BP and serum uric acid (SUA) in 104 children referred for possible hypertension. Mean age was 13.7 +/- 2.6 y (range, 7-18 y) with 67 males and 37 females; 74 were African-American, 29 Caucasian and one Asian. SUA was associated with age (r = 0.38, p = 0.0001) and BMI Z-score (r = 0.23, p = 0.021). SUA was significantly associated with mean ambulatory systolic (S) and diastolic (D) BP. Mean ambulatory BP was normalized to gender- and height-specific reference standards using BP index. SUA was significantly associated with 24-h DBP index and nocturnal DBP index after adjusting for age, gender, race, BMI Z-score and urinary sodium excretion. SUA was also significantly associated with 24-h DBP load and nocturnal DBP load. Uric acid was significantly associated with increased likelihood for diastolic HTN (OR = 2.1, CI = 1.2, 3.7; p = 0.0063) after adjusting for other co-variables. Among children at risk for HTN, the likelihood for diastolic HTN (as defined by ambulatory blood pressure monitoring) increases significantly as SUA increases. SUA may be associated with increased severity of HTN during youth.

Effect on blood pressure of lumiracoxib versus ibuprofen in patients with osteoarthritis and controlled hypertension: a randomized trial

Nonsteroidal anti-inflammatory drugs vary in their impact on blood pressure and the effect of lumiracoxib 100 mg once daily has not been studied previously. To examine whether lumiracoxib 100 mg once daily would result in lower 24-h mean systolic ambulatory blood pressure than ibuprofen 600 mg three times daily in osteoarthritis patients with controlled hypertension, a 4-week, randomized, double-blind, parallel-group study was conducted in 79 centres in nine countries. Hypertensive osteoarthritis patients of 50 years at least whose office blood pressure was less than 140/90 mmHg on stable antihypertensive treatment were randomized to lumiracoxib (n = 394) 100 mg once daily or ibuprofen 600 mg three times daily (n = 393) and 24-h ambulatory blood pressure monitoring was performed at baseline and end of study. The primary outcome measure was a comparison of the change in 24-h mean systolic ambulatory blood pressure from baseline to week 4. Secondary analyses included other blood pressure-related endpoints and efficacy (pain) measurements. Compared with baseline, the 24-h mean systolic ambulatory blood pressure (least square mean) decreased in lumiracoxib-treated patients (-2.7 mmHg) and increased in ibuprofen-treated patients (+2.2 mmHg) at 4 weeks, estimated difference -5.0 mmHg (95% confidence interval -6.1 to -3.8) in favour of lumiracoxib. The 24-h mean diastolic ambulatory blood pressure changes were -1.5 mmHg (lumiracoxib), +0.5 mmHg (ibuprofen), difference -2.0 mmHg (95% confidence interval -2.7 to -1.3). Efficacy results were comparable. Treatment with lumiracoxib 100 mg once daily resulted in clinically significant lower blood pressure compared with ibuprofen 600 mg three times daily in osteoarthritis patients with well controlled hypertension.

Reduction of Proteinuria During Intensified Antihypertensive Therapy in Children After Renal Transplantation

Background Proteinuria together with hypertension are known risk factors for poor allograft as well as patient survivals after renal transplantation. In adults, proteinuria can be reduced by lowering blood pressure and by using angiotensin-converting enzyme inhibitors. In children, no study has investigated the antiproteinuric effects of antihypertensive therapy. Herein we investigated changes in proteinuria among a subgroup of children with proteinuria ≥200 mg/m 2d in an interventional study primary aimed to improve the efficacy of antihypertensive therapy. Patients and Methods Twelve children with proteinuria ≥200 mg/m 2d were included in the study. Proteinuria was investigated at baseline and at 1 year after changes in antihypertensive therapy. Blood pressure (BP) was measured using ambulatory BP monitoring. Results The median protein excretion of 226 mg/m 2/d (range, 41–1478 mg/m 2/d) at 1 year before the study did not change significantly at study baseline (278 mg/m 2/d; range, 205–1264 mg/m 2/d), but decreased significantly to 199 mg/m 2/d (range, 65–749 mg/m 2/d) after 1 year ( P < .05 vs baseline). The number of antihypertensive drugs was increased from 1.6 ± 1.0 to 2.2 ± 0.9 drugs/patient after 1 year ( P < .05). The use of different classes of antihypertensive drugs did not change significantly. Mean ambulatory systolic and diastolic BP at daytime and diastolic BP at nighttime did not change significantly after 1 year; mean ambulatory systolic BP at night decreased from 1.60 ± 1.54 to 1.04 ± 0.97 standard deviation score ( P < .05). Graft function did not change significantly. Conclusion We demonstrated that proteinuria among children after renal transplantation was reduced by intensified antihypertensive therapy using all classes of antihypertensive drugs.

Telmisartan/hydrochlorothiazide versus valsartan/hydrochlorothiazide in obese hypertensive patients with type 2 diabetes: the SMOOTH study

BackgroundThe Study of Micardis (telmisartan) in Overweight/Obese patients with Type 2 diabetes and Hypertension (SMOOTH) compared hydrochlorothiazide (HCTZ) plus telmisartan or valsartan fixed-dose combination therapies on early morning blood pressure (BP), using ambulatory BP monitoring (ABPM).MethodsSMOOTH was a prospective, randomized, open-label, blinded-endpoint, multicentre trial. After a 2- to 4-week, single-blind, placebo run-in period, patients received once-daily telmisartan 80 mg or valsartan 160 mg for 4 weeks, with add-on HCTZ 12.5 mg for 6 weeks (T/HCTZ or V/HCTZ, respectively). At baseline and week 10, ambulatory blood pressure (ABP) was measured every 20 min and hourly means were calculated. The primary endpoint was change from baseline in mean ambulatory systolic and diastolic blood pressure (SBP; DBP) during the last 6 hours of the 24-hour dosing interval.ResultsIn total, 840 patients were randomized. At week 10, T/HCTZ provided significantly greater reductions versus V/HCTZ in the last 6 hours mean ABP (differences in favour of T/HCTZ: SBP 3.9 mm Hg, p < 0.0001; DBP 2.0 mm Hg, p = 0.0007). T/HCTZ also produced significantly greater reductions than V/HCTZ in 24-hour mean ABP (differences in favour of T/HCTZ: SBP 3.0 mm Hg, p = 0.0002; DBP 1.6 mm Hg, p = 0.0006) and during the morning, daytime and night-time periods (p < 0.003). Both treatments were well tolerated.ConclusionIn high-risk, overweight/obese patients with hypertension and type 2 diabetes, T/HCTZ provides significantly greater BP lowering versus V/HCTZ throughout the 24-hour dosing interval, particularly during the hazardous early morning hours.

Influence of a single dose of 20 mg tadalafil, a phosphodiesterase 5 inhibitor, on ambulatory blood pressure in subjects with hypertension

To test the non-inferiority of a single dose of tadalafil 20 mg compared with placebo with respect to 26-h mean ambulatory systolic and diastolic blood pressure in treated and untreated hypertensive subjects. A multicentre, randomized, double-blind, placebo-controlled crossover study in 114 subjects with hypertension (36 subjects on no therapy with daytime mean ambulatory blood pressure >/= 140/85 mmHg; 38 subjects on two to four classes of antihypertensive agents with daytime mean ambulatory blood pressure >/=140/85 mmHg and 40 subjects on two to four classes of antihypertensive agents with ambulatory blood pressure < 140/85 mmHg). Overall tadalafil reduced mean ambulatory blood pressure monitor systolic and diastolic blood pressure by 4.8 mmHg [95% confidence interval (Cl) 3.7, 5.9; P < 0.01] and 2.9 mmHg (95% CI 1.9, 3.6; P < 0.01), respectively, compared with placebo. In hypertensive subjects with uncontrolled blood pressure on two to four classes of antihypertensive agents (n = 36) tadalafil reduced mean ABPM systolic and diastolic blood pressure by 7.5 mmHg (95% CI 5.4, 9.6; P < 0.01) and 4.3 mmHg (95% CI 6.1, 8.9; P < 0.01) compared with placebo. In patients with uncontrolled hypertension on multiple agents the addition of tadalafil 20 mg lowered mean 26-h blood pressure.