Effects of the angiotensin receptor blocker azilsartan medoxomil versus olmesartan and valsartan on ambulatory and clinic blood pressure in patients with stages 1 and 2 hypertension

Azilsartan medoxomil is an angiotensin receptor blocker (ARB) being developed for hypertension treatment. To compare this ARB with others in the class, we studied the effects of 2 doses of azilsartan medoxomil, with valsartan 320 mg and olmesartan medoxomil (olmesartan) 40 mg, in a randomized, double-blind, placebo-controlled trial using ambulatory blood pressure (BP) monitoring and clinic BP measurements. The primary efficacy end point was the change from baseline in 24-hour mean systolic BP. Hierarchical analysis testing for superiority over placebo was followed by noninferiority analysis and then superiority testing of azilsartan medoxomil (80 mg and then 40 mg) versus the comparator ARBs. For 1291 randomized patients, mean age was 56 years, 54% were men, and baseline 24-hour mean systolic BP was 145 mm Hg. Azilsartan medoxomil at 80 mg had superior efficacy to both valsartan at 320 mg and olmesartan at 40 mg: placebo-adjusted 24-hour systolic BP was lowered (-14.3 mm Hg) more than 320 mg of valsartan (-10.0 mm Hg; P<0.001) and 40 mg of olmesartan (-11.7 mm Hg; P=0.009). Azilsartan medoxomil at 40 mg was noninferior to 40 mg of olmesartan (difference: -1.4 mm Hg [95% CI: -3.3 to 0.5]). For clinic systolic BP, both doses of azilsartan medoxomil were superior to the comparator ARBs. Safety and tolerability were similar among the placebo and 4 active treatments. These data demonstrate that azilsartan medoxomil at its maximal dose has superior efficacy to both olmesartan and valsartan at their maximal, approved doses without increasing adverse events. Azilsartan medoxomil could provide higher rates of hypertension control within the ARB class.     

Clinical effects of combined olmesartan medoxomil and amlodipine on clinic and ambulatory blood pressure in elderly patients with resistant hypertension

Elderly patients with resistant hypertension are at increased risk for cardiovascular events. Clinical trials suggest that resistant hypertension involves perhaps 10–15% of hypertension study participants. In this study, 157 resistant hypertension patients older than 60 years were randomized to 8 weeks double-blind treatment with placebo, AML 10 mg/day, OM 40 mg/day and AM × L (10 mg/day) + OM (40 mg/day). Research outcomes suggested that ALM + OM combination therapy had superior efficacy than ALM or OM monotherapies in terms of the clinic blood pressure and 24-h ambulatory blood pressure. In addition, more patients receiving combination therapy (62.5%) achieved BP goal than those treated with placebo (18.4%), AML (37.5) or OM (38.5%) monotherapies. The adverse events in both groups were comparable. Thus, the combination of AML + OM provides a safe and effective option for the treatment of resistant hypertension in challenging elderly patient populations.     

Clinical effects of combined olmesartan medoxomil and amlodipine on clinic and ambulatory blood pressure in elderly patients with resistant hypertension

Elderly patients with resistant hypertension are at increased risk for cardiovascular events. Clinical trials suggest that resistant hypertension involves perhaps 10–15% of hypertension study participants. In this study, 157 resistant hypertension patients older than 60 years were randomized to 8 weeks double-blind treatment with placebo, AML 10 mg/day, OM 40 mg/day and AM × L (10 mg/day) + OM (40 mg/day). Research outcomes suggested that ALM + OM combination therapy had superior efficacy than ALM or OM monotherapies in terms of the clinic blood pressure and 24-h ambulatory blood pressure. In addition, more patients receiving combination therapy (62.5%) achieved BP goal than those treated with placebo (18.4%), AML (37.5) or OM (38.5%) monotherapies. The adverse events in both groups were comparable. Thus, the combination of AML + OM provides a safe and effective option for the treatment of resistant hypertension in challenging elderly patient populations.     

Use of 24-h ambulatory blood pressure monitoring to assess blood pressure control: a comparison of olmesartan medoxomil and amlodipine besylate

OBJECTIVE: Olmesartan medoxomil is an angiotensin II receptor blocker with similar antihypertensive efficacy as the calcium channel blocker amlodipine besylate in patients with mild-to-moderate hypertension. In addition to a drug's ability to lower blood pressure, the effectiveness of the agent in enabling patients to achieve specific blood pressure targets is an important clinical consideration. This secondary analysis of a randomized, double-blind study compared the efficacy of olmesartan medoxomil with that of amlodipine besylate in achieving ambulatory blood pressure goals among patients with mild-to-moderate hypertension. METHODS: Following a 4-week placebo run-in, 440 study participants aged >or=18 years were randomized to olmesartan medoxomil (20 mg/day), amlodipine besylate (5 mg/day), or placebo for 8 weeks. The proportion of participants achieving specific systolic and diastolic ambulatory blood pressure goal levels was calculated by dividing the number of participants who had achieved a particular blood pressure goal by the total number of patients in the intent-to-treat population. RESULTS: After 8 weeks of treatment, a mean 24-h ambulatory blood pressure of <130/80 or <130/85 mmHg was achieved by significantly more participants in the olmesartan medoxomil group (18.1 and 30.4%, respectively) than in the amlodipine besylate (7.0 and 14.0%, respectively) or placebo (1.9% for both) groups. The target daytime ambulatory blood pressure of <135/85 mmHg was achieved by more participants in the olmesartan medoxomil group than in the amlodipine besylate group (15.8 vs. 5.8%, respectively; P<0.01). CONCLUSION: In a previous publication of the same study, we demonstrated that starting doses of olmesartan medoxomil and amlodipine besylate produced similar mean reductions in blood pressure. In this subanalysis of the blood pressure data from that primary publication, however, olmesartan medoxomil therapy was shown to result in a greater proportion of patients achieving specific ambulatory blood pressure goals than therapy with amlodipine besylate. As blood pressure goal attainment may be of more direct clinical relevance than numerical blood pressure lowering, the achievement of blood pressure goals should be a key efficacy parameter assessed in clinical trials of antihypertensive medications.     

Effects of olmesartan medoxomil on systolic blood pressure and pulse pressure in the management of hypertension

BACKGROUND: In this analysis, we evaluated the efficacy of the angiotensin II receptor blocker olmesartan medoxomil in reducing systolic blood pressure (SBP) and pulse pressure (PP) in hypertensive patients. METHODS: Data from seven randomized, double blind, placebo controlled, 6- to 12-week efficacy trials of olmesartan 20 mg and 40 mg/day were analyzed to determine changes in trough seated SBP and PP within three cohorts: 1) total cohort (n = 1777); 2) subjects with a wide PP: that is, those with a baseline PP >55 mm Hg (n = 917); and 3) a subpopulation of patients with a wide PP and age > or = 65 years (n = 296). Statistical comparisons used least squares mean values. RESULTS: In the total cohort, olmesartan 20 and 40 mg/day resulted in mean reductions in SBP of 15.1 and 17.6 mm Hg, respectively (P < .001 v placebo). In the wide PP cohort, olmesartan resulted in mean reductions in SBP of 17.7 and 22.0 mm Hg and mean reductions in PP of 7.4 Hg and 8.8 mm Hg for the groups receiving 20 and 40 mg/day, respectively (P < .001 v placebo). In the cohort with wide PP and age > or = 65 years, olmesartan 20 and 40 mg/day produced mean reductions in SBP of 21.8 and 22.5 mm Hg, and PP of 6.7 and 7.6 mm Hg, respectively (P < .05 v placebo). CONCLUSIONS: Olmesartan significantly reduces SBP and PP, and these reductions are more pronounced in patients with a wide baseline PP. In patients with a wide baseline PP and age > or = 65 years, the population at greatest risk for cardiovascular morbidity and mortality, olmesartan reduces PP to an extent similar to that in patients <65 years of age.     

奥美沙坦酯与缬沙坦对原发性高血压患者血压晨峰的影响

目的比较奥美沙坦酯和缬沙坦治疗高血压患者血压晨峰的疗效。方法选择我院76例原发性高血压患者随机分为2组,分别接受奥美沙坦酯20-40mg／d或缬沙坦80-160mg／d治疗,共8周,观察服药前及服药后清晨血压变化。结果奥美沙坦酯组和缬沙坦组治疗后晨峰血压均有明显下降,与治疗前比较差异有统计学意义（P〈0．05）。奥美沙坦酯组和缬沙坦组晨峰血压下降的幅度分别为：／kSBP（10．22±0．35）mmHg、（5．63±0．21）mmHg;△DBP（7．71±0．29）mmHg、（3．55±0．14）mmHg,奥美沙坦酯组血压晨峰下降幅度高于缬沙坦组,差异有统计学意义（P〈0．05）。结论奥美沙坦酯和缬沙坦均可以有效地控制原发性高血压患者血压晨蜂现象,奥美沙坦酯优于缬沙坦。     

Antihypertensive efficacy of olmesartan medoxomil,a new angiotensin II receptor antagonist,as assessed by ambulatory blood pressure measurements

Olmesartan medoxomil is a new angiotensin II receptor blocker. In this randomized, double-blind, placebo-controlled study, the efficacy and safety of olmesartan medoxomil was assessed in 334 patients with moderate to severe essential hypertension. Patients were randomized to receive placebo; 5, 20, or 80 mg olmesartan medoxomil q.d.; or 2.5, 10, or 40 mg olmesartan medoxomil b.i.d. Ambulatory and cuff blood pressure were measured prior to and after 8 weeks of treatment. Treatment with olmesartan medoxomil resulted in a significant placebo-adjusted reduction of mean 24-hour ambulatory diastolic blood pressure of 9.6 mm Hg, 12.2 mm Hg, and 10.6 mm Hg in the 5-, 20-, and 80-mg q.d. groups, respectively. Corresponding reductions in mean ambulatory systolic blood pressure were 14.5 mm Hg, 16.5 mm Hg, and 15.4 mm Hg. Similar reductions of diastolic and systolic blood pressure were seen with b.i.d. dosing. The diastolic trough-to-peak ratios of the q.d. doses of olmesartan medoxomil ranged from 57%-70%, indicating 24-hour effectiveness. The safety profile of olmesartan medoxomil was similar to that of placebo. Olmesartan medoxomil appears to be a safe and effective once-a-day treatment for hypertension.     

Long‐term efficacy and tolerability of azilsartan medoxomil/chlorthalidone vs olmesartan medoxomil/hydrochlorothiazide in chronic kidney disease

An open‐label, long‐term study evaluated safety and tolerability of azilsartan medoxomil/chlorthalidone (AZL‐M/CLD) vs olmesartan/hydrochlorothiazide (OLM/HCTZ) in hypertensive participants with stage 3 chronic kidney disease. Initial therapy was AZL‐M/CLD 20/12.5 mg (n = 77) or OLM/HCTZ 20/12.5 mg (n = 76), but could be up‐titrated (AZL‐M/CLD to 40/25 mg; OLM/HCTZ to 40/25 mg [US] or 20/25 mg [Europe]) with other agents added during weeks 4‐52. Primary endpoint was proportion of participants with ≥ 1 adverse event (AE) through week 52. Baseline demographics were similar. AEs did not differ between groups (88.3%, AZL‐M/CLD vs 76.3%, OLM/HCTZ; P = .058). AZL‐M/CLD showed greater systolic BP reductions after initial dosing (P = .037) but not during long‐term follow‐up (P = .588). A greater proportion of participants up‐titrated to the highest dose with OLM/HCTZ (48.7%) vs AZL‐M/CLD (29.9%) (P = .021) and were taking additional antihypertensive medications (26.3% vs 16.9%). Both AZL‐M/CLD and OLM/HCTZ showed similar efficacy and tolerability.     

Comparison of long‐term safety of fixed‐dose combinations azilsartan medoxomil/chlorthalidone vs olmesartan medoxomil/hydrochlorothiazide

This 52‐week, randomized, open‐label study evaluated long‐term safety/tolerability of fixed‐dose combination azilsartan medoxomil/chlorthalidone (AZL‐M/CLD) vs fixed‐dose combination olmesartan medoxomil/hydrochlorothiazide (OLM/HCTZ) in patients with essential hypertension (stage 2; clinic systolic blood pressure 160–190 mm Hg). Initial AZL‐M/CLD 40/12.5 mg/d (n=418) or OLM/HCTZ 20/12.5 mg/d (n=419) could be uptitrated during weeks 4 to 52 (AZL‐M/CLD to 80/25 mg; OLM/HCTZ to 40/25 mg [United States] or 20/25 mg [Europe]) to meet blood pressure targets. Treatment‐emergent adverse events/serious adverse events occurred in 78.5%/5.7% of patients taking AZL‐M/CLD vs 76.4%/6.2% taking OLM/HCTZ. The most frequent adverse events were dizziness (16.3% vs 12.6%), blood creatinine increase (21.5% vs 8.6%), headache (7.4% vs 11.0%), and nasopharyngitis (12.2% vs 11.5%). Hypokalemia was uncommon (1.0% vs 0.7%). Greater blood pressure reductions with AZL‐M/CLD by week 2 were maintained throughout the study, despite less uptitration (32.3% vs 48.9% with OLM/HCTZ). Fixed‐dose combination AZL‐M/CLD showed an encouraging benefit‐risk profile when used per standard clinical practice in a titrate‐to‐target strategy.     

Assessment of drug effects on blood pressure and pulse pressure using clinic,home and ambulatory measurements

This study investigated the differences in the effect of an angiotensin converting enzyme inhibitor (ACEI) compared with an angiotensin receptor blocker (ARB) on blood pressure (BP) and pulse pressure (PP) measured in the clinic (CBP and CPP, respectively), at home (HBP, HPP) and with ambulatory monitoring (ABP, APP). Twenty-seven hypertensive patients were randomised to receive lisinopril (20 mg) or losartan (50 mg) for 5 weeks, and were subsequently crossed-over to the alternative treatment for a second 5-week period. Measurements of CBP, 24-h ABP and 5-days HBP were performed before randomisation and at the end of each treatment period. All measurement methods showed that lisinopril was more effective than losartan in reducing BP. However, the difference between the two drugs was demonstrated with greater precision using HBP (P<0.001) than 24-h ABP (P<0.01), whereas the poorest precision for demonstrating this difference was provided by CBP (P<0.05). Lisinopril was also found more effective than losartan in reducing HPP (P=0.01) and 24-h APP (P=0.03) whereas no such a difference was detected using measurements of CPP. It was concluded that the antihypertensive drugs may differ in their effects not only on BP, but also on PP. HBP monitoring appears to be as reliable as 24-h ABP monitoring in detecting differences in the effect of drugs on both BP and PP. Clinic measurements seem to be the least reliable method, particularly in the detection of differences in PP.     

Multiple clinic and home blood pressure measurements versus ambulatory blood pressure monitoring.

To compare multiple clinic and home blood pressure (BP) measurements and ambulatory BP monitoring in the clinical evaluation of hypertension, we studied 239 middle-aged pharmacologically untreated hypertensive men and women who were referred to the study from the primary healthcare provider. Ambulatory BP monitoring was successfully completed for 233 patients. Clinic BP was measured by a trained nurse with a mercury sphygmomanometer and averaged over 4 duplicate measures. Self-recorded home BP was measured with a semiautomatic oscillometric device twice every morning and twice every evening on 7 consecutive days. Ambulatory BP was recorded with an auscultatory device. Two-dimensionally controlled M-mode echocardiography was successfully performed on 232 patients. Twenty-four-hour urinary albumin was determined by nephelometry. Clinic BP was 144.5+/-12.6/94.5+/-7.4 mm Hg, home BP (the mean of 14 self-recorded measures) was 138.9+/-13.1/92.9+/-8.6 mm Hg, home morning BP (the mean of the first 4 duplicate morning measures) was 137.1+/-13.7/92.4+/-9.2 mm Hg, daytime ambulatory BP was 148.3+/-13. 9/91.9+/-7.8 mm Hg, nighttime ambulatory BP was 125.5+/-16.4/75. 6+/-8.9 mm Hg, and 24-hour ambulatory BP was 141.7+/-14.0/87.2+/-7.6 mm Hg. Pearson correlation coefficients of clinic, home, home morning, and daytime ambulatory BPs to albuminuria and to the characteristics of the left ventricle were nearly equal. In multivariate regression analyses, 36% (P<0.0001) of the cross-sectional variation in left ventricular mass index was attributed to gender and home morning systolic BP in models that originally included age, gender, and clinic, self-measured home morning, and ambulatory daytime, nighttime, and 24-hour systolic and diastolic BPs. We concluded that carefully controlled nonphysician-measured clinic and self-measured home BPs, when averaged over 4 duplicate measurements, are as reliable as ambulatory BP monitoring in the clinical evaluation of untreated hypertension.     

Systolic blood pressure reduction with olmesartan medoxomil versus nitrendipine in elderly patients with isolated systolic hypertension

OBJECTIVE: The prevalence of isolated systolic hypertension (ISH) is high in the elderly, and the objective of this study was to compare the antihypertensive efficacy of olmesartan medoxomil with that of nitrendipine in elderly (65-74 years) and very elderly (>/= 75 years) male and female patients with ISH. METHODS: Patients were randomized to 24 weeks of treatment with either olmesartan medoxomil 20 mg daily (n = 256) or nitrendipine 20 mg (n = 126) twice daily, with possible dose increase (to 40 mg daily) and addition of hydrochlorothiazide (HCTZ) 12.5 or 25 mg daily if required. RESULTS: On the primary endpoint [reduction in mean sitting systolic blood pressure (SBP) after 12 weeks of treatment], the two treatments were similar (olmesartan medoxomil, -30.0 mmHg; nitrendipine, -31.4 mmHg). No significant difference between the treatment groups was observed, and non-inferiority of olmesartan medoxomil to nitrendipine was demonstrated using an analysis of covariance (ANCOVA) model. Reductions in mean sitting and standing SBP and diastolic blood pressure (DBP) up to week 24 were also similar with both treatments. Blood pressure (BP) goal attainment rates (sitting SBP 相似文献   

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.     

Efficacy and safety of azilsartan medoxomil/chlortalidone fixed‐dose combination in hypertensive patients uncontrolled on azilsartan medoxomil alone: A randomized trial

Patients with grade 2‐3 essential hypertension and postplacebo mean clinic systolic blood pressure (SBP) 160‐190 mm Hg and 24‐hour SBP 140‐175 mm Hg by ambulatory blood pressure monitoring (ABPM) received 40 mg azilsartan medoxomil (AZL‐M) monotherapy for 4 weeks. “Nonresponders” were then randomized to 8 weeks of double‐blind treatment with AZL‐M 40 mg, AZL‐M/chlortalidone (CLD) 40/25, or AZL‐M/CLD 40/12.5 mg. After 8 weeks, mean clinic SBP change was −21.1 (±1.04) mm Hg for AZL‐M/CLD 40/25 mg, −15.8 (±1.08) mm Hg for AZL‐M/CLD 40/12.5 mg, and −6.4 (±1.05) mm Hg for AZL‐M 40 mg (P < 0.001 for both AZL‐M/CLD vs AZL‐M, ANCOVA). Drug discontinuation rates were 8.9% (AZL‐M/CLD 40/25 mg), 7.5% (AZL‐M 40 mg), and 3.9% (AZL‐M/CLD 40/12.5 mg). Creatinine increased in 8.1% (AZL‐M/CLD 40/25), 3.1% (AZL‐M/CLD 40/12.5 mg), and 3.0% (AZL‐M 40 mg) of patients. AZL‐M/CLD was effective and well tolerated in patients not achieving blood pressure targets with AZL‐M.     

Effects of weight loss on clinic and ambulatory blood pressure in normotensive men

Obesity and physical inactivity are associated with both elevated cardiovascular risk and blood pressure (BP), but the interrelation of exercise, weight loss and BP is poorly understood. This study examines the independent effects of exercise and weight loss on both standard clinic and automated, ambulatory BP in 115 overweight, sedentary, normotensive men (aged 30 to 59 years) who were randomly assigned to control status or to lose weight over 1 year by moderate caloric restriction (dieting) or by increased caloric expenditure (exercise). Median daytime and evening BP were determined from measurements made every 20 minutes while the subjects were awake. After 1 year, the control group gained (mean +/- standard deviation) 0.5 +/- 3.8 kg while the diet group lost 6.9 +/- 4.4 kg and the exercise group lost 4.6 +/- 3.5 kg. Clinic BP decreased similarly in all 3 groups, but daytime and evening ambulatory BP decreased in both intervention groups and increased in the control group. Relative to the 1-year change in control subjects, net change in daytime ambulatory BP averaged -2 to -3 mm Hg in both dieters and exercisers, while net change in evening ambulatory BP averaged -3 to -4 mm Hg. These changes were all statistically significant (p less than 0.05) when compared with control subjects except for daytime systolic BP in both intervention groups and evening diastolic BP in dieters. Weight loss achieved through caloric restriction or expenditure may cause important decreases in BP in normotensive men; exercise appears to confer no unique benefit. If confirmed, these results have important public health implications for the prevention of cardiovascular disease.     

Side effects of ambulatory blood pressure monitoring

OBJECTIVE: To study the experiences and complaints of patients who underwent 24 h blood pressure monitoring. METHODS: Two groups of hypertensive patients of a tertiary outpatient clinic were asked to fill in a nine-item questionnaire about the side effects of ambulatory blood pressure monitoring (ABPM). The first group (n=75) used the auscultatory Oxford Medilog device (OM) and the second group (n=110) the oscillometric Spacelabs 90207 (SL). RESULTS: The OM showed significantly less error readings (OM versus SL, 9 versus 19%; P=0.005) but was also less tolerated by the subjects. Sleep disturbance was noted in 53% of the OM patients group in comparison with 18% in the SL group (P<0.0001). Adjustment of daily activities occurred more often in the OM group (OM versus SL, 37 versus 19%; P=0.013) as did complaints of pain in the cuffed arm (OM versus SL, 31 versus 11 %; P=0.007). There was no difference in the proportion of patients that refused a second ABPM (OM versus SL, 11 versus 10%). Linear regression analyses showed that differences in side effects between the two devices were not due to differences in blood pressure, heart rate, age or sex. CONCLUSIONS: This study demonstrates that side effects of ABPM are not negligible and that there are differences between devices.     

Azilsartan medoxomil plus chlorthalidone reduces blood pressure more effectively than olmesartan plus hydrochlorothiazide in stage 2 systolic hypertension

Azilsartan medoxomil, an effective, long-acting angiotensin II receptor blocker, is a new treatment for hypertension that is also being developed in fixed-dose combinations with chlorthalidone, a potent, long-acting thiazide-like diuretic. We compared once-daily fixed-dose combinations of azilsartan medoxomil/chlorthalidone force titrated to a high dose of either 40/25 mg or 80/25 mg with a fixed-dose combination of the angiotensin II receptor blocker olmesartan medoxomil plus the thiazide diuretic hydrochlorothiazide force titrated to 40/25 mg. The design was a randomized, 3-arm, double-blind, 12-week study of 1071 participants with baseline clinic systolic blood pressure 160 to 190 mm Hg and diastolic blood pressure ≤119 mm Hg. Patients had a mean age of 57 years; 59% were men, 73% were white, and 22% were black. At baseline, mean clinic blood pressure was 165/96 mm Hg and 24-hour mean blood pressure was 150/88 mm Hg. Changes in clinic (primary end point) and ambulatory systolic blood pressures at week 12 were significantly greater in both azilsartan medoxomil/chlorthalidone arms than in the olmesartan/hydrochlorothiazide arm (P<0.001). Changes in clinic systolic blood pressure (mean±SE) were -42.5±0.8, -44.0±0.8, and -37.1±0.8 mm Hg, respectively. Changes in 24-hour ambulatory systolic blood pressure were -33.9±0.8, -36.3±0.8, and -27.5±0.8 mm Hg, respectively. Adverse events leading to permanent drug discontinuation occurred in 7.9%, 14.5%, and 7.1% of the groups given azilsartan medoxomil/chlorthalidone 40/25 mg, azilsartan medoxomil/chlorthalidone 80/25 mg, and olmesartan/hydrochlorothiazide 40/25 mg, respectively. This large, forced-titration study has demonstrated superior antihypertensive efficacy of azilsartan medoxomil/chlorthalidone fixed-dose combinations compared with the maximum approved dose of olmesartan/hydrochlorothiazide.     

The clinical utility of ambulatory blood pressure monitoring in a multispecialty clinic setting

Since 1988, ambulatory blood pressure monitoring (ABPM) as an outpatient assessment of patients with high blood pressure has been offered through the Department of Hypertension and Nephrology at the Marshfield Clinic. This article summarizes that experience from a review of 318 patients who have undergone 24 h ABPM. The purpose of the review was to assess the reasons for ordering the ABPM, the use of those results, and the apparent value to the ordering clinician in the light of established guidelines and information in the literature on clinical use. The justification for at least 90% of requests for ABPM specified reasons that may be regarded as accepted indications for the procedure. In some 49% of cases one or more changes in patient management were recommended on the basis of ABPM results. These results indicate that ABPM can be of practical value in the management of hypertension. Furthermore, this study suggests that clinicians use this tool quite appropriately.     

Effects of high dose olmesartan medoxomil plus hydrochlorothiazide on blood pressure control in patients with grade 2 and grade 3 hypertension

High dose (40 mg) olmesartan medoxomil (OM) blocks the angiotensin II receptor, significantly reducing blood pressure (BP). Adding hydrochlorothiazide (HCTZ) to OM increases efficacy, but has not been evaluated in patients inadequately controlled by OM 40 mg. Patients with grade 2 and grade 3 hypertension with inadequately controlled BP (seated diastolic blood pressure [SeDBP] 90-115 mm Hg and seated systolic blood pressure [SeSBP] 140-180 mm Hg, plus ambulatory BP criteria) after 8 weeks of OM 40 mg open-label treatment were randomized to 8 weeks of double-blind treatment with OM/HCTZ 40/25 (n=140), 40/12.5 (n=278), 20/12.5 mg (n=280) or OM 40 mg (n=274). Treatment with OM/HCTZ 40/25 mg and 40/12.5 mg significantly reduced SeDBP (-5.3 and -3.4 mm Hg, respectively), and SeSBP (-7.4 and -5.2 mm Hg, respectively), vs OM 40 mg monotherapy (P<0.0001 for each) in patients inadequately controlled on OM 40 mg alone. OM/HCTZ 40/12.5 mg reduced SeSBP significantly more than OM/HCTZ 20/12.5 mg (-2.6 mm Hg, P=0.0255), and also produced a further reduction in SeDBP vs the lower dose. All treatments were well tolerated, with similar low proportions of patients reporting treatment-emergent adverse events in all treatment groups. In conclusion, adding HCTZ to OM 40 mg significantly improves BP reductions and target BP rates in harder-to-treat patients and a clear dose-response was observed for efficacy.