The Effects of an Olmesartan Medoxomil–Based Treatment Algorithm on 24-Hour Blood Pressure Levels in Elderly Patients Aged 65 and Older

This study examined the effect of olmesartan medoxomil (OM) ± hydrochlorothiazide (HCTZ) on mean 24-hour ambulatory blood pressure, mean seated cuff (Se) blood pressure (BP), and SeBP goal achievement in elderly (65 years and older) patients with hypertension. After a 2- to 3-week placebo run-in period, patients received OM 20 mg, up-titrated to OM 40 mg, and then added HCTZ 12.5  mg to 25 mg in a stepwise manner at 3-week intervals if SeBP remained ≥120/70 mm Hg. The primary end point was change from baseline in mean 24-hour ambulatory systolic BP. At study end, mean 24-hour ambulatory BP had decreased by 25.7/12.3 mm Hg (n=150) and mean SeBP by 25.4/10.5 mm Hg (n=176; all P <.00001 vs baseline). Drug-related treatment-emergent adverse events, most commonly dizziness (3.4%), hypotension (2.2%), and headache (1.1%), were observed in 11.8% of patients. An OM-based treatment algorithm effectively lowers BP in an elderly patient population throughout the 24-hour dosing interval without compromising tolerability.     

Efficacy and Tolerability of Triple‐Combination Therapy With Olmesartan,Amlodipine, and Hydrochlorothiazide: A Subgroup Analysis of Patients Stratified by Hypertension Severity,Age, Sex,and Obesity

This prespecified subgroup analysis of a phase III study examined the effect of adding hydrochlorothiazide (HCTZ) to olmesartan (OLM)/amlodipine (AML) in patients with moderate to severe hypertension stratified by age, sex, body mass index, and hypertension severity. A total of 2690 patients, aged 18 years and older, with seated blood pressure (SeBP) ≥160/100 mm Hg received placebo or OLM/AML 20/5 mg, 40/5 mg, or 40/10 mg during a 2‐week, double‐blind, run‐in period, after which they were allocated to one of eight treatment groups with the same OLM/AML dose or with HCTZ 12.5 mg or 25 mg added for 8 weeks. By week 10, greater reductions in SeBP were observed in each OLM/AML/HCTZ group (P<.05, respectively) compared with the corresponding dual dose. Adding HCTZ increased blood pressure–lowering efficacy in all subgroups, with a higher proportion of blood pressure goal achievement vs dual therapy. OLM/AML/HCTZ reduced SeBP to a greater extent than OLM/AML in patients with moderate to severe hypertensive; this was unaffected by baseline hypertension severity, age, sex, and obesity.     

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.     

The antihypertensive efficacy of the combination of irbesartan and hydrochlorothiazide assessed by 24-hour ambulatory blood pressure monitoring. Irbesartan Multicenter Study Group

In a multicenter, double-blind, randomized trial, 178 patients with ambulatory diastolic blood pressure (BP) > or =85 mm Hg and seated diastolic BP (SeDBP) 95-110 mm Hg received either once-daily irbesartan 75 mg/hydrochlorothiazide (HCTZ) 12.5 mg, irbesartan 150 mg/HCTZ 12.5 mg, or placebo for 8 weeks to assess reductions in 24-hour ambulatory BP and office BP. Safety and tolerability of all treatment regimens were also evaluated. BP results and therapeutic response (trough SeDBP normalized to <90 mm Hg) were expressed as change from baseline to Week 8. Mean reductions in 24-hour ambulatory BP and office seated BP for irbesartan/HCTZ combinations were significantly greater compared with placebo (all, p<0.01). More patients were normalized with irbesartan/HCTZ (65%-69%) than placebo (24%, p<0.01). The frequency of adverse events was similar in all groups. Irbesartan/HCTZ given once-daily appears to be a well-tolerated, safe, and effective antihypertensive treatment.     

Efficacy and Safety of Long-Term Treatment With the Combination of Amlodipine Besylate and Olmesartan Medoxomil in Patients With Hypertension

The authors report on the 44-week open-label extension of the 8-week, double-blind Combination of Olmesartan Medoxomil and Amlodipine Besylate in Controlling High Blood Pressure (COACH) trial in 1684 patients. Initial therapy was amlodipine (AML) plus olmesartan medoxomil (OM) 5+40 mg/d, up-titrated to AML+OM 10+40 mg/d plus hydrochlorothiazide (HCTZ) 12.5 mg then 25 mg if patients did not achieve blood pressure (BP) goal (<140/90 mm Hg or <130/80 mm Hg in patients with diabetes). Baseline mean BP decreased from 164/102 mm Hg to 131/82 mm Hg at end of study, with an overall 66.7% of patients, including those with diabetes, achieving BP goal. The BP goal achievement was 80% for AML+OM 5+40 mg/d, 70.6% for AML+OM 10+40 mg/d, 66.6% for AML+OM+HCTZ 10+40+12.5 mg/d, and 46.3% for AML+OM+HCTZ 10+40+25 mg/d. Study medication was safe and well tolerated. Combination antihypertensive therapy with AML+OM±HTCZ, up-titrated as necessary, allowed a majority of patients to achieve BP goal.     

Evaluation of antihypertensive therapy with the combination of olmesartan medoxomil and hydrochlorothiazide

BACKGROUND: Most patients with hypertension require more than one agent to control blood pressure (BP). The purpose of this study was to assess the efficacy and safety of the angiotensin II receptor blocker olmesartan medoxomil in combination with hydrochlorothiazide (HCTZ). METHODS: This was a randomized, double-blind, factorial design study. After a placebo run-in period, eligible patients (n = 502) with a baseline mean seated diastolic blood pressure (SeDBP) of 100 to 115 mm Hg were randomized to one of 12 groups: placebo, olmesartan medoxomil monotherapy (10, 20, or 40 mg/day, HCTZ monotherapy (12.5 or 25 mg/day), or one of six groups of olmesartan medoxomil/HCTZ combination therapy. The primary endpoint was the change in mean trough SeDBP from baseline at week 8. Statistical analyses were conducted to determine whether at least one combination produced a larger reduction in SeDBP at week 8 than the individual corresponding component doses, but did not compare BP reductions with different combination doses. RESULTS: Olmesartan medoxomil plus HCTZ produced greater reductions in both SeDBP and seated systolic blood pressure (SeSBP) at week 8 than did monotherapy with either component. All olmesartan medoxomil/HCTZ combinations significantly reduced SeDBP and SeSBP compared with placebo in a dose-dependent manner. Reductions from baseline in mean trough SeSBP/SeDBP were 3.3/8.2 mm Hg, 20.1/16.4 mm Hg, and 26.8/21.9 mm Hg with placebo, olmesartan medoxomil/HCTZ 20/12.5 mg, and olmesartan medoxomil/HCTZ 40/25 mg, respectively. All treatments were well tolerated. CONCLUSIONS: Olmesartan medoxomil/HCTZ combination therapy produced BP reductions of up to 26.8/21.9 mm Hg and was well tolerated.     

The long-term antihypertensive activity and tolerability of irbesartan with hydrochlorothiazide.

The long-term safety, tolerability, and antihypertensive effects of irbesartan/hydrochlorothiazide (HCTZ) were assessed in hypertensive patients (seated diastolic blood pressure [SeDBP] 95-110 mm Hg). Patients (n = 1098) completing two randomised, double-blind trials of irbesartan alone, HCTZ alone, irbesartan/HCTZ combinations, or placebo, took 1 year of open-label therapy starting with irbesartan 75 mg/HCTZ 12.5 mg once daily. If target blood pressure (BP) (<140/<90 mm Hg) was not achieved, the dose was titrated sequentially at 2- to 4-week intervals to irbesartan 150 mg/HCTZ 12. 5 mg, then to irbesartan 300 mg/HCTZ 25 mg. If necessary, adjunctive therapies were added. Mean changes in trough seated systolic BP/SeDBP at months 2, 6, and 12 were -19.1/-14.2 mm Hg (n = 941), -20.7/ -15.7 mm Hg (n = 948), and -20.6/-15.6 mm Hg (n = 898), respectively. From months 2 to 12, normalisation rates (trough SeDBP <90 mm Hg) ranged from 75-85% and total responder rates (normalised or >/=10 mm Hg trough SeDBP reduction) ranged from 81-91%, while target BP was achieved in 65-75% of patients. At all time-points, most patients (>/=87%) were receiving irbesartan/HCTZ alone. Eighty-two patients (7.5%) discontinued the study due to adverse events, with half of these events considered unrelated to study medication. There were no reports of serious adverse events related to study medication. Long-term therapy with irbesartan/HCTZ is safe, well tolerated, and maintains normalised BP in >80% of patients.     

Initial Combination Therapy With Irbesartan/Hydrochlorothiazide for Hypertension: An Analysis of the Relationship Between Baseline Blood Pressure and the Need for Combination Therapy

Hypertension treatment guidelines recommend initiating 2-drug therapy whenever blood pressure (BP) is ≥20 mm Hg systolic or ≥10 mm Hg diastolic above goal. This post hoc pooled analysis of 2 multicenter, randomized, double-blind, active-controlled forced-titration studies in 1235 patients with moderate and severe hypertension examined how baseline BP levels relate to the need for combination therapy by comparing the antihypertensive efficacy and tolerability of once-daily fixed-dose irbesartan/hydrochlorothiazide (HCTZ) 300/25 mg compared with irbesartan 300-mg or HCTZ 25-mg monotherapies. In study 1, patients with severe hypertension (seated diastolic BP [SeDBP] ≥110 mm Hg) were treated for 7 weeks with irbesartan or irbesartan/HCTZ combination therapy, with forced-titration after week 1. In study 2, patients with moderate hypertension (seated systolic BP [SeSBP] 160–180 mm Hg or SeDBP 100–110 mm Hg) were treated for 12 weeks with irbesartan/HCTZ, irbesartan monotherapy, or HCTZ monotherapy, with forced-titration after week 2. The relationship between baseline BP and the likelihood of achieving BP goals (SeSBP <140 mm Hg or SeDBP <90 mm Hg; SeSBP <130 mm Hg or SeDBP <80 mm Hg) as well as the antihypertensive response was evaluated at week 7/8. The need for combination therapy increased with increasing baseline BP and lower BP goals across the range of BP levels studied, with a comparable adverse effect profile to monotherapy. These results suggest that the likelihood of achieving an early BP goal for a given BP severity should be considered when choosing initial combination therapy vs monotherapy.     

A titrate-to-goal study of switching patients uncontrolled on antihypertensive monotherapy to fixed-dose combinations of amlodipine and olmesartan medoxomil ± hydrochlorothiazide

In the prospective, open-label, titrate-to-goal Blood Pressure Control in All Subgroups With Hypertension (BP-CRUSH) study, 999 patients with hypertension uncontrolled on monotherapy (mean age, 55.6 ± 11.4 years; baseline blood pressure [BP], 153.7 ± 9.2/91.9 ± 8.6 mm Hg) were switched to fixed-dose amlodipine/olmesartan medoxomil (AML/OM) 5/20 mg. Patients were uptitrated every 4 weeks to AML/OM 5/40 mg and 10/40 mg to achieve BP < 120/70 mm Hg. Patients were subsequently uptitrated every 4 weeks to AML/OM+hydrochlorothiazide (HCTZ) 10/40+12.5 mg and 10/40+25 mg to achieve BP <125/75 mm Hg. The primary end point, the cumulative percentage of patients achieving seated systolic BP < 140 mm Hg (< 130 mm Hg for patients with diabetes) by week 12, was 75.8%. The mean (± standard error) BP changes from baseline during the titration periods ranged from -14.2±0.4 mm Hg/-7.7 ± 0.3 mm Hg for AML/OM 5/20 mg to -25.1 ± 0.7 mm Hg/-13.7 ± 0.4 mm Hg for AML/OM+HCTZ 10/40+25 mg. By week 20, the cumulative BP threshold of <140/90 mm Hg was achieved by 90.3% of patients. An ambulatory BP monitoring substudy (n=243) showed that 24-hour efficacy was maintained. Treatment-emergent adverse events (TEAEs), mostly mild to moderate in severity, occurred in 529 patients (53.0%). Drug-related TEAEs occurred in 255 patients (25.5%). This well-tolerated, treat-to-goal algorithm enabled a large proportion of patients with uncontrolled hypertension on monotherapy to safely achieve BP control on single-pill AML/OM combination therapy or triple therapy with the addition of HCTZ. .     

Safety and Tolerability of Fixed-Dose Irbesartan/Hydrochlorothiazide for Rapid Control of Severe Hypertension

This prospective, double-blind, multicenter trial compared the safety and tolerability of irbesartan/hydrochlorothiazide (HCTZ) fixed-dose combination therapy with irbesartan monotherapy in patients with severe hypertension (seated diastolic blood pressure (SeDBP) ≥110 mm Hg, mean BP 172/113 mm Hg at baseline). Patients were randomized 2:1 to 7 weeks' irbesartan/HCTZ 150/12.5 mg to 300/25 mg (n = 468) or irbesartan 150 mg to 300 mg (n = 227). The incidence of treatment-related adverse events (AEs) was similar with combination and monotherapy (11.3% and 10.1%), and most AEs were mild-to-moderate. The combined incidence of prespecified AEs was lower with irbesartan/HCTZ than with irbesartan (8.8% vs. 11.5%). There were no treatment-related serious AEs or deaths. At week 5, more patients achieved SeDBP < 90 mm Hg compared to irbesartan (47% vs. 33%; P = 0.0005). Despite more rapid and aggressive BP lowering, initial fixed-dose irbesartan/HCTZ demonstrated a comparable AE profile to irbesartan monotherapy in patients with severe hypertension.     

Matrix study of irbesartan with hydrochlorothiazide in mild-to-moderate hypertension

The purpose of this study was to assess the safety and antihypertensive dose-response effects of irbesartan and hydrochlorothiazide (HCTZ) in patients with mild-to-moderate hypertension. After a 4- to 5-week single-blind placebo lead-in period, 683 patients with seated diastolic blood pressure (SeDBP) between 95 and110 mm Hg were randomized to receive once-daily dosing with one of 16 different double-blind, fixed combinations of irbesartan (0, 37.5, 100, and 300 mg irbesartan) and HCTZ (0, 6.25, 12.5, and 25 mg HCTZ) for 8 weeks. The primary efficacy variable was the change from baseline in trough SeDBP after 8 weeks of therapy. Data were analyzed by response surface modeling. At Week 8, mean changes from baseline in trough SeDBP (mm Hg) ranged from −3.5 for placebo, −7.1 to −10.2 for the irbesartan monotherapy groups, −5.1 to −8.3 for the HCTZ monotherapy groups, and −8.1 to −15.0 for the combination groups. Irbesartan plus HCTZ produced additive reductions in both SeDBP and seated systolic BP, with at least one combination producing greater BP reduction than either drug alone (P < .001). All treatments were well tolerated; there were no treatment-related serious adverse events. Irbesartan tended to ameliorate the dose-related biochemical abnormalities associated with HCTZ alone. In conclusion, the combination of HCTZ in doses up to 25 mg with irbesartan, in doses up to 300 mg, is safe and produces dose-dependent reductions in BP.     

Long-term efficacy and safety of triple-combination therapy with olmesartan medoxomil and amlodipine besylate and hydrochlorothiazide for hypertension

J Clin Hypertens (Greenwich). 2012;14:149–157. ©2012 Wiley Periodicals, Inc. Most patients with hypertension require combination therapy in order to achieve blood pressure (BP) goals. This 40‐week open‐label extension of the 12‐week double‐blind Tri ple Therapy With Olmesartan Medoxomil, Amlodipine, and Hydrochlorothiazide in Hyperten si ve Patient s Study (TRINITY) evaluated the efficacy and safety of triple‐combination treatments with olmesartan medoxomil, amlodipine besylate, and hydrochlorothiazide (OM/AML/HCTZ) in 2112 participants with moderate to severe hypertension. Following 2 weeks of initial treatment with OM 40/AML 5/HCTZ 12.5 mg, participants not achieving BP goal were titrated to OM 40/AML 5/HCTZ 25 mg or OM 40/AML 10/HCTZ 12.5 mg on a randomized basis. At week 16, participants who did not achieve BP goal were further titrated to OM 40/AML 10/HCTZ 25 mg. At the end of the study, 44.5% to 79.8% of participants reached BP goal and the mean BP decreased from 168.6/100.7 mm Hg (baseline BP at randomization) to 125.0 to 136.8 mm Hg/77.8 to 82.5 mm Hg, depending on treatment. Long‐term treatment with OM/AML/HCTZ was well tolerated and effective with no new safety concerns.     

A comparison of the efficacy and safety of irbesartan/HCTZ combination therapy with irbesartan and HCTZ monotherapy in the treatment of moderate hypertension

This prospective, double-blind, parallel-group study randomized patients with moderate hypertension (seated systolic blood pressure (SeSBP) 160-179 mm Hg when seated diastolic blood pressure (SeDBP) <110 mm Hg; or SeDBP 100-109 mm Hg when SeSBP <180 mm Hg) 3:1:1 to treatment with irbesartan 300 mg/hydrochlorothiazide (HCTZ) 25 mg combination therapy (n=328), irbesartan 300 mg monotherapy (n=106) or HCTZ monotherapy 25 mg (n=104). Treatment was initiated at half dose, with forced titration to full dose after two weeks followed by ten further weeks' treatment. The primary efficacy variable was the mean reduction in SeSBP from baseline to week 8. Baseline characteristics were similar between groups, with mean baseline blood pressure approximately 162/98 mm Hg; the mean age was 55 years. At week 8 there was a reduction in SeSBP of 27.1 mm Hg with irbesartan/HCTZ, compared with 22.1 mm Hg with irbesartan monotherapy (P=0.0016) and 15.7 mm Hg with HCTZ (P<0.0001). Both the rate of decline and the total degree of decline achieved were greatest with irbesartan/HCTZ and least with HCTZ. A significantly greater percentage of patients reached a treatment goal of SeSBP <140 mm Hg and SeDBP <90 mm Hg by week 8 with irbesartan/HCTZ (53.4%), compared with irbesartan (40.6%; P=0.0254) and HCTZ (20.2%; P<0.0001) alone. Treatment was well tolerated in all three-treatment groups with a slight increase in adverse events in the combination therapy group. In conclusion, irbesartan/HCTZ (300/25 mg) is well tolerated and achieves rapid and sustained reductions in both systolic blood pressure and diastolic blood pressure in patients with moderate hypertension.     

Peripheral and central blood pressure responses of combination aliskiren/hydrochlorothiazide and amlodipine monotherapy in African American patients with stage 2 hypertension: the ATLAAST trial

Efficacy of antihypertensive agents on central blood pressure (BP) in African Americans is not well studied. The authors report on an 8-week double-blind, randomized study of African American patients with stage 2 hypertension that compared brachial and central BP responses (substudy of 53 patients) to combination aliskiren/hydrochlorthiazide (HCTZ) and amlodipine monotherapy. Following a 1- to 4-week washout, initial therapy was aliskiren/HCTZ 150/12.5 mg (n=166) or amlodipine 5 mg (n=166) for 1 week, forced-titrated to aliskiren/HCTZ 300/25 mg or amlodipine 10 mg for 7 weeks. Mean seated systolic BP reductions from baseline was similar with both treatments (-28.6 mm Hg with aliskiren/HCTZ vs -28.2 mm Hg with amlodipine). In the substudy, significantly greater reductions in central systolic BP was observed with aliskiren/HCTZ vs amlodipine (-30.1 mm Hg vs -21.2; P=.031), although 24-hour mean ambulatory BP reductions between the two groups were similar. Central pressure is considered an important risk factor in African Americans, and these findings may suggest a new treatment option for these patients.     

Efficacy of amlodipine and olmesartan medoxomil in hypertensive patients with diabetes and obesity

A subgroup analysis of a prospective, open-label, single-arm titration study in patients with hypertension and type 2 diabetes or obesity is reported. The primary end point was the change from baseline in mean 24-hour ambulatory systolic blood pressure (BP) after 12 weeks. Patients received amlodipine 5 mg/d and were uptitrated (if seated [Se] BP was ≥ 120/80 mm Hg) at 3-week intervals to amlodipine/olmesartan medoxomil 5/20 mg/d, 5/40 mg/d, and 10/40 mg/d. In patients with diabetes and obesity, baseline 24-hour ambulatory BP (± standard deviation) was 145.6 ± 10.4/83.1 ± 9.0 mm Hg and 143.7 ± 9.8/84.9 ± 8.2 mm Hg, respectively, and baseline SeBP was 159.1 ± 11.3/90.3 ± 9.2 mm Hg and 158.2 ± 12.5/94.2 ± 8.5mm Hg, respectively. Changes from baseline in mean 24-hour ambulatory BP (± standard error of the mean) were -21.5 ± 1.8/-12.6 ± 1.1 mm Hg and 21.6 ± 1.1/13.4 ± 0.8 mm Hg in patients with diabetes and obesity, respectively. Prespecified 24-hour ambulatory BP targets of < 130/80 mm Hg, < 125/75 mm Hg, and < 120/80 mm Hg were achieved by 79.1%, 53.5%, and 39.5% of patients with diabetes and 75.3%, 58.4%, and 43.8% of obese patients, respectively. The SeBP goal of < 130/80 mm Hg was achieved by 26.1% of patients with diabetes and <140/90 mm Hg was achieved by 78.1% of obese patients.     

24-hour efficacy and safety of Triple-Combination Therapy With Olmesartan, Amlodipine, and Hydrochlorothiazide: the TRINITY ambulatory blood pressure substudy

This 12-week, multicenter, randomized, double-blinded, 4-arm study in 440 patients with moderate to severe hypertension compared ambulatory blood pressure (ABP) responses with a triple-combination regimen (olmesartan medoxomil [OM] 40 mg, amlodipine besylate [AML] 10 mg, and hydrochlorothiazide [HCTZ] 25 mg) and its component dual-combination regimens at similar doses. At week 12, the triple combination resulted in a greater reduction in mean 24-hour systolic and diastolic blood pressure (-30.3/-18.0 mm Hg) compared with the 3 dual-combination regimens (OM 40 mg/AML 10 mg: -23.5/-13.9, OM 40 mg/HCTZ 25 mg: -23.9/-14.5, and AML 10 mg/HCTZ 25 mg: -18.5 mm Hg/-10.7 mm Hg; P<.0001 each). Greater efficacy was also found during daytime and nighttime hours and during the last 6, 4, or 2 hours of the dosing interval. The authors conclude that the triple combination of OM 40 mg/AML 10 mg/HCTZ 25 mg demonstrated superior efficacy and sustained reductions in ABP compared with its dual-combination components.     

Efficacy and safety of irbesartan/HCTZ combination therapy as initial treatment for rapid control of severe hypertension

Severe hypertension is difficult to control. This prospective, randomized, double-blind, active-controlled, multicenter trial compared efficacy and safety of once-daily irbesartan/hydrochlorothiazide (HCTZ) combination therapy with irbesartan monotherapy in severe hypertension. Patients who were untreated or uncontrolled on monotherapy (seated diastolic blood pressure [BP] ≥110 mm Hg) received fixed-dose irbesartan 150 mg/HCTZ 12.5 mg combination therapy for 7 weeks, force-titrated to irbesartan 300 mg/HCTZ 25 mg at week 1 (n=468); or irbesartan 150 mg monotherapy, force-titrated to 300 mg at week 1 (n=269). Significantly more patients on combination therapy achieved seated diastolic BP <90 mm Hg at week 5 (primary end point) compared with monotherapy recipients (47.2% vs 33.2%; P= .0005). Likewise, significantly more patients attained goals per the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) (<140/90 mm Hg) at week 5 (34.6% vs 19.2%, respectively; P< .0001), while the mean difference between combination and monotherapy in seated diastolic BP and seated systolic BP was 4.7 mm Hg and 9.7 mm Hg ( P< .0001). Greater and more rapid BP reduction with irbesartan/HCTZ was achieved without additional side effects.     

A home blood pressure monitoring study comparing the antihypertensive efficacy of two angiotensin II receptor antagonist fixed combinations

BACKGROUND: The objective of this prospective, randomized, open-label, blinded-endpoint study was to compare the antihypertensive efficacy of valsartan 80 mg v irbesartan 150 mg when combined with hydrochlorothiazide (HCTZ) 12.5 mg. METHODS: Untreated or uncontrolled hypertensive adults (n = 800) were enrolled by primary care physicians. After a 5-week open-label lead-in phase in which all patients received 12.5 mg HCTZ once daily, subjects whose blood pressure (BP) remained uncontrolled were randomized (n = 464) to valsartan/HCTZ (80/12.5 mg) or irbesartan/HCTZ (150/12.5 mg) for 8 weeks. Home BP monitoring (HBPM) was performed in the morning and in the evening for 5 days, at baseline, and after 8 weeks. Office BP measurements were obtained at baseline and after 8 weeks. RESULTS: Irbesartan/HCTZ produced greater reductions in average systolic BP (SBP) and diastolic BP (DBP) measured by HBPM than valsartan/HCTZ (SBP: -13.0 v -10.6 mm Hg, P = .0094; DBP: -9.5 v -7.4 mm Hg, P = .0007). These differences were more pronounced in the morning (trough) than in the evening. Office BP measurements also showed greater reductions in trough seated SBP and DBP with irbesartan/HCTZ compared with valsartan/HCTZ. Normalization rates observed with HBPM (SBP <135 mm Hg and DBP <85 mm Hg) were significantly greater with irbesartan/HCTZ than with valsartan/HCTZ (50.2 v 33.2%; P = .0003). The overall safety was similar in the two groups. CONCLUSIONS: The superior BP-lowering potency of the fixed combination irbesartan/HCTZ (150/12.5 mg) over valsartan/HCTZ (80/12.5 mg), evidenced independently from the investigators by HBPM, supports the use of this technique in trials with prospective, randomized, open-label, blinded-endpoint designs.     

Management of hypertension in patients with diabetes using an amlodipine-, olmesartan medoxomil-, and hydrochlorothiazide-based titration regimen

The safety and efficacy of an amlodipine/olmesartan medoxomil (OM)-based titration regimen was assessed in patients with type 2 diabetes mellitus and hypertension. After a 2- to 3-week placebo run-in period, 207 patients received amlodipine 5 mg and were uptitrated to amlodipine/OM 5/20, 5/40, and 10/40 mg and then amlodipine/OM 10/40 mg plus hydrochlorothiazide 12.5 and 25 mg in a step-wise manner at 3-week intervals if the seated blood pressure (BP) remained ≥120/70 mm Hg. The primary end point was the change from baseline in the mean 24-hour ambulatory systolic BP after 12 weeks of treatment. The baseline mean ± SD seated cuff systolic/diastolic BP was 158.8 ± 13.1/89.1 ± 10.1 mm Hg and the mean ± SD 24-hour ambulatory systolic/diastolic BP was 144.4 ± 11.7/81.6 ± 9.8 mm Hg. At week 12, the change from baseline in the mean ± SEM 24-hour ambulatory systolic/diastolic BP was -19.9 ± 0.8/-11.2 ± 0.5 mm Hg (p<0.0001 vs baseline), and 70% of patients had achieved a 24-hour ambulatory BP target of <130/80 mm Hg. At the end of 18 weeks of active treatment in patients uptitrated to amlodipine/OM 10/40 mg plus hydrochlorothiazide 25 mg, the change from baseline in the mean ± SEM seated BP was -28.0 ± 1.5/-13.7 ± 1.0 mm Hg (p<0.0001 vs baseline), with 62% of patients reaching the guideline-recommended seated BP goal of <130/80 mm Hg. Drug-related treatment-emergent adverse events occurred in 19.3% of patients. The most frequent events were peripheral edema (6%), dizziness (3%), and hypotension (2%). In conclusion, this amlodipine/OM-based titration regimen was well tolerated and effectively lowered BP throughout the 24-hour dosing interval in patients with hypertension and type 2 diabetes.     

Improving Blood Pressure Control: Increase the Dose of Diuretic or Switch to a Fixed‐Dose Angiotensin Receptor Blocker/Diuretic? The Valsartan Hydrochlorothiazide Diuretic for Initial Control and Titration to Achieve Optimal Therapeutic Effect (Val‐DICTATE) Trial

To assess the strategy of increasing the dose of a diuretic compared with using an angiotensin receptor blocker in combination with a diuretic, the authors performed a multicenter, randomized, parallel group trial in hypertensive patients (baseline blood pressure [BP], 153/97 mm Hg) whose BP remained uncontrolled on initial low-dose diuretic monotherapy (hydrochlorothiazide [HCTZ] 12.5 mg Hg). Patients with stage 1 and 2 hypertension were randomized to treatment with valsartan/HCTZ (160/12.5 mg) or to doubling of the HCTZ dose (25 mg). The primary end point was the percentage of patients whose clinic BP values were <140/90 mm Hg following 4 weeks of double-blind therapy. A significantly higher proportion (P<.001) of hypertensive patients met BP control levels in the valsartan/HCTZ (160/12.5 mg) group compared with the HCTZ 25 mg group (37% vs 16%). Changes from baseline in BP were significantly greater (P<.001) for both systolic BP and diastolic BP in the combination therapy arm compared with the diuretic monotherapy arm (-12. 4/-7.5 mm Hg in valsartan/HCTZ 160/12.5 mg group vs -5.6/-2.1 mm Hg in HCTZ 25 mg group). Tolerability and adverse events were similar in the 2 treatment groups. This study suggests that in the management of hypertension, utilizing an angiotensin receptor blocker/diuretic combination was more effective in lowering BP and achieving BP goals when compared with increasing the dose of the diuretic.