The efficacy and safety of low- and high-dose fixed combinations of irbesartan/hydrochlorothiazide in patients with uncontrolled systolic blood pressure on monotherapy: the INCLUSIVE trial

This multicenter, prospective, open-label, single-arm study determined the efficacy and safety of irbesartan/hydrochlorothiazide (HCTZ) fixed combinations in patients (n=1005), aged 18 years and older, with uncontrolled systolic blood pressure (SBP) of 140-159 mm Hg (130-159 mm Hg for type 2 diabetes mellitus) after at least 4 weeks of antihypertensive monotherapy. Treatment was sequential: placebo (4-5 weeks), HCTZ 12.5 mg (2 weeks), irbesartan/HCTZ 150/12.5 mg (8 weeks), and irbesartan/HCTZ 300/25 mg (8 weeks). Enrolled patients (n=844) were aged 57.3+/-11.2 years; 52% were women, 23% were African American, and 14% were Hispanic. Thirty percent had type 2 diabetes mellitus, 46% had metabolic syndrome, and baseline blood pressure was 154.0+/-10.3/91.3+/-8.8 mm Hg. The mean change in SBP from placebo end to the primary end point, Week 18 (intent-to-treat population, n=736) was -21.5+/-14.3 mm Hg (p<0.001). The mean change in diastolic blood pressure (DBP) was -10.4+/-8.7 mm Hg (p<0.001). The mean Week 18 SBP/DBP was 132.9+/-13.8/81.1+/-9.7 mm Hg. Overall, 77% (95% confidence interval, 74%-80%) of patients achieved SBP goal (<140 mm Hg; <130 mm Hg for type 2 diabetes mellitus); 83% (95% confidence interval, 80%-86%) achieved DBP goal (<90 mm Hg; <80 mm Hg for type 2 diabetes mellitus); and 69% (95% confidence interval, 66%-72%) achieved dual SBP/DBP goal. Treatments were well tolerated. This irbesartan/HCTZ treatment regimen achieved SBP goals in more than 75% of patients uncontrolled on monotherapy.     

Efficacy and safety of fixed combinations of irbesartan/hydrochlorothiazide in older vs younger patients with hypertension uncontrolled with monotherapy

Subgroup analysis of the Irbesartan/Hydrochlorothiazide Blood Pressure Reductions in Diverse Patient Populations (INCLUSIVE) trial evaluated the efficacy and safety of irbesartan/hydrochlorothiazide (HCTZ) fixed combinations in patients aged 65 years or older with uncontrolled systolic blood pressure (SBP) after >or= 4 weeks of antihypertensive monotherapy. The INCLUSIVE trial was a prospective, open-label, single-arm trial carried out in 119 sites. Of 844 patients completing placebo treatment, 212 were aged 65 years or older. Participants received treatment with placebo (4-5 weeks), HCTZ 12.5 mg (2 weeks), irbesartan/HCTZ 150/12.5 mg (8 weeks), and then irbesartan/HCTZ 300/25 mg (8 weeks). From baseline to week 18 (n=184, intent-to-treat population), mean change in SBP was -23.0+/-13.3 mm Hg (P<.001) and diastolic BP (DBP) was -10.9+/-7.7 mm Hg (P<.001). Mean SBP/DBP at study end was 134.0+/-14.7/75.1+/-8.4 mm Hg, and SBP, DBP, and SBP/DBP goal was achieved in 73%, 96%, and 72% of patients, respectively. Irbesartan/HCTZ combination therapy allowed SBP goal attainment in 73% of patients aged 65 years or older whose hypertension was previously uncontrolled with antihypertensive monotherapy.     

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.     

The JNC 7 approach compared to conventional treatment in diabetic patients with hypertension: a double-blind trial of initial monotherapy vs. combination therapy

The JNC 7 states that persons with blood pressure (BP) more than 20/10 mm Hg above goal should be started on combination drug therapy. This criterion includes patients with BP >160/100 mm Hg and diabetics with hypertension. The goal BP for persons with diabetes mellitus is <130/80 mm Hg. A randomized, double-blind trial force titrated initial combination therapy utilizing an angiotensin receptor blocker (ARB) combination (losartan/hydrochlorothiazide [LOS/HCTZ]) compared with an angiotensin-converting enzyme (ACE) inhibitor (ramipril), for 8 weeks, and tested the hypothesis that combination therapy is more likely to achieve goal BP vs. monotherapy. At 4 weeks, 30.5% of LOS/HCTZ and 14.4% of ramipril recipients achieved goal diastolic BP (p<0.001). More participants achieved goal systolic BP in the ARB/HCTZ group at 4 weeks (29.8% vs. 14.4%; p<0.001). At 4 weeks, mean diastolic BP had decreased 10.2+/-7.4 mm Hg in the LOS/HCTZ group compared with 6.4+/-6.8 mm Hg in the ramipril group (p<0.001), and systolic BP had fallen 15.4+/-13.1 mm Hg in the ARB/HCTZ compared with 9.2+/-10.2 mm Hg in the ACE-inhibitor group (p<0.001). Significant differences favoring the combination were also noted at 8 weeks. Drug-related adverse experiences were 10.3% for the combination compared with 12.7% for the monotherapy group. Initial combination therapy with an ARB/HCTZ was more effective than ACE-inhibitor monotherapy in achieving BP goals in participants with diabetes with no significant differences in the incidence of adverse experiences. These observations confirm other studies of combination therapies, such as b blocker/diuretic, ACE inhibitor/diuretic, or ACE inhibitor/calcium channel blocker. The use of two medications will achieve goal BP in more patients than monotherapy. This observation is important in treatment of high-risk patients with diabetes.     

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.     

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.     

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.     

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.     

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.     

Comparison of the antihypertensive efficacy of irbesartan/HCTZ and valsartan/HCTZ combination therapy: impact of age and gender

This analysis aimed to explore whether low-dose irbesartan/hydrochlorothiazide (HCTZ) has superior blood pressure (BP)-lowering efficacy over low-dose valsartan/HCTZ in the elderly and across both genders. This is a post-hoc analysis of data from a multicenter, parallel group, open-label, blinded-endpoint study in patients with hypertension uncontrolled with HCTZ monotherapy. The reduction in systolic BP (SBP)/diastolic BP (DBP) and rate of BP control achieved following 8 weeks of treatment with irbesartan/HCTZ 150/12.5 mg or valsartan/HCTZ 80/12.5 mg were analyzed for older (≥65 years) vs. younger (<65 years) patients and for men vs. women. Blood pressure measurements were by home BP monitoring (HBPM). In the age and gender subgroups, both treatments significantly decreased home SBP and DBP (p < 0.0001). The reduction in home SBP and DBP was numerically greater with irbesartan/HCTZ compared to valsartan/HCTZ for all subgroups: the difference in DBP was significant for all except the elderly (p < 0.05), and the difference in SBP was significant in the elderly and in men (p < 0.03). In all subgroups, more patients achieved BP control (HBPM ≤135/85 mmHg) in the irbesartan/HCTZ arm (range 45%-58%) than in the valsartan/HCTZ arm (range, 23%-39%; p < 0.02). Both combination therapies were well tolerated and safety parameters were similar in both age and gender subgroups. More patients with mild or moderate hypertension, uncontrolled in HCTZ monotherapy alone, had their BP controlled with irbesartan/HCTZ 150/12.5 mg than with valsartan/HCTZ 80/12.5 mg, irrespective of age or gender.     

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.     

Efficacy and tolerability of a fixed-dose combination of telmisartan plus hydrochlorothiazide in patients uncontrolled with telmisartan monotherapy.

The antihypertensive effects of a telmisartan 80 mg/hydrochlorothiazide (HCTZ) 12.5 mg fixed-dose combination and telmisartan 80 mg monotherapy were compared in patients with a history of mild-to-moderate essential hypertension and inadequate BP control (DBP > or = 90 mm Hg) following 8 weeks of telmisartan monotherapy. At the end of this period, 491 patients (62.9% men; mean age 55.3 years) whose DBP was > or = 90 mm Hg were double-blind randomised to once-daily telmisartan 80 mg/HCTZ 12.5 mg (n = 246) or telmisartan 80 mg (n = 245). Trough (24 h post-dose) clinic BP was measured after 4 and 8 weeks of double-blind therapy. At the end of double-blind treatment, patients receiving telmisartan 80 mg/HCTZ 12.5 mg had significant additional decrements in clinic SBP/DBP over telmisartan 80 mg of -5.7/-3.1 mm Hg (P < 0.01). Most of the additional effect occurred during the first 4 weeks of treatment. The proportion of patients with normalised BP (SBP < 140 mm Hg and DBP < 90 mm Hg) was significantly greater in the telmisartan 80 mg/HCTZ 12.5 mg group than the telmisartan 80 mg group (41.5%vs 26.1%;P < 0.05). Both treatments were well tolerated. The incidence of adverse events was similar except for diarrhoea, which occurred more frequently in the telmisartan 80 mg/HCTZ 12.5 mg group, and oedema, which occurred more frequently in the telmisartan group. Our results indicate that a telmisartan 80 mg/HCTZ 12.5 mg fixed-dose combination confers significant additional BP reductions compared with continuation of telmisartan monotherapy in non-responders.     

厄贝沙坦/氢氯噻嗪复方片剂治疗中国高血压病患者的达标率分析

目的分析高血压患者接受厄贝沙坦／氢氯噻嗪复方制剂（商品名：安博诺）治疗的达标率。方法本研究为多中心、开放、单一治疗组的研究。共入选968例轻、中度高血压病患者,均采用安博诺治疗8周。经药物清洗1～2周后,给予初始剂量安博诺1片／d治疗,治疗2周末,如未达标（目标血压：舒张压〈85mm Hg,1mm Hg = 0．133 kPa）则增加厄贝沙坦150mg继续服用2周;在第4周末仍未达标则再增加氢氯噻嗪12．5mg（即安博诺2片／d）直至8周试验结束。结果对入选的968例轻、中度高血压病患者进行意向治疗人群分析,完成8周随访的920例患者进行符合方案人群分析。（1）治疗1周时,收缩压／舒张压与治疗前比较,分别降低11．8／8．56mm Hg,P 〈 0．01;治疗8周时,收缩压／舒张压分别降低21．97／16．08mm Hg,P 〈 0．01。（2）治疗2周血压达标的患者526例,占57．17％;4周时血压达标患者703例,占76．41％;8周时达标患者769例,占83．59％。（3）在治疗的8周中服用安博诺1片／d为637例,占总病例数的69．24％;服用安博诺1片＋厄贝沙坦150mg／d为211例,占总病例数的22．93％;安博诺2片／d为72例,占总病例数的7．82％。（4）入组的968例高血压病患者进行意向治疗人群分析,其中有903例患者没有任何不良反应,占总研究病例数的93．29％。结论安博诺治疗中国轻、中度高血压病达标率高,不良反应较少。     

Comparison of the Antihypertensive Efficacy of Irbesartan//HCTZ and Valsartan//HCTZ Combination Therapy: Impact of Age and Gender

This analysis aimed to explore whether low-dose irbesartan//hydrochlorothiazide (HCTZ) has superior blood pressure (BP)-lowering efficacy over low-dose valsartan//HCTZ in the elderly and across both genders. This is a post-hoc analysis of data from a multicenter, parallel group, open-label, blinded-endpoint study in patients with hypertension uncontrolled with HCTZ monotherapy. The reduction in systolic BP (SBP)//diastolic BP (DBP) and rate of BP control achieved following 8 weeks of treatment with irbesartan//HCTZ 150//12.5 mg or valsartan//HCTZ 80//12.5 mg were analyzed for older (≥65 years) vs. younger (<65 years) patients and for men vs. women. Blood pressure measurements were by home BP monitoring (HBPM). In the age and gender subgroups, both treatments significantly decreased home SBP and DBP (p < 0.0001). The reduction in home SBP and DBP was numerically greater with irbesartan//HCTZ compared to valsartan//HCTZ for all subgroups: the difference in DBP was significant for all except the elderly (p < 0.05), and the difference in SBP was significant in the elderly and in men (p < 0.03). In all subgroups, more patients achieved BP control (HBPM ≤135//85 mmHg) in the irbesartan//HCTZ arm (range 45%%–58%%) than in the valsartan//HCTZ arm (range, 23%%–39%%; p < 0.02). Both combination therapies were well tolerated and safety parameters were similar in both age and gender subgroups. More patients with mild or moderate hypertension, uncontrolled in HCTZ monotherapy alone, had their BP controlled with irbesartan//HCTZ 150//12.5 mg than with valsartan//HCTZ 80//12.5 mg, irrespective of age or gender.     

Efficacy and Safety of Irbesartan/HCTZ in Severe Hypertension According to Cardiometabolic Factors

J Clin Hypertens (Greenwich).2010;12:487–494. © 2010 Wiley Periodicals, Inc. This post hoc analysis of a 7-week, randomized, double-blind trial evaluated the efficacy and safety of initial irbesartan/hydrochlorothiazide treatment in 468 patients with severe, uncontrolled, hypertension (diastolic blood pressure [DBP] ≥100 mm Hg) at high cardiovascular risk. Systolic blood pressure (SBP)/DBP reductions ranged from 28.0 to 42.9/22.9 to 27.2 mm Hg in patients with obesity, diabetes, baseline SBP ≥180 mm Hg, and in the elderly. Blood pressure control to <140/90 mm Hg in the age and obesity subgroups ranged from 32.1% to 39.2% while control to <130/80 mm Hg in patients with diabetes was 11.5%. After 1 week of therapy, 72.5% of patients no longer had SBP ≥180 mm Hg; by 7 weeks, 51.3% had SBP 140 to 159 mm Hg and 26.5% had SBP <140 mm Hg. Treatment was well tolerated regardless of the subgroup. No excess of prespecified events was noted. Thus, initial treatment with irbesartan/hydrochlorothiazide was rapidly effective in high-risk, difficult-to-treat, severely hypertensive patients.     

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.     

Direct Renin inhibition with aliskiren in obese patients with arterial hypertension

Current guidelines from the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure recommend first-line treatment with a thiazide diuretic but do not provide specific guidance for obese patients. The renin system is activated in obesity-associated arterial hypertension. Therefore, we tested the hypothesis that the oral direct renin inhibitor aliskiren could provide additive blood pressure lowering in obese patients with hypertension (body mass index >or=30 kg/m(2); mean sitting diastolic blood pressure: 95 to 109 mm Hg) who had not responded to 4 weeks of treatment with hydrochlorothiazide (HCTZ) 25 mg. After a 2- to 4-week washout, 560 patients received single-blind HCTZ (25 mg) for 4 weeks; 489 nonresponders were randomly assigned to double-blind aliskiren (150 mg), irbesartan (150 mg), amlodipine (5 mg), or placebo for 4 weeks added to HCTZ (25 mg), followed by 8 weeks on double the initial doses of aliskiren, irbesartan, or amlodipine. After 8 weeks of double-blind treatment (4 weeks on the higher dose), aliskiren/HCTZ lowered blood pressure by 15.8/11.9 mm Hg, significantly more (P<0.0001) than placebo/HCTZ (8.6/7.9 mm Hg). Aliskiren/HCTZ provided blood pressure reductions similar to those with irbesartan/HCTZ and amlodipine/HCTZ (15.4/11.3 and 13.6/10.3 mm Hg, respectively), with similar tolerability to placebo/HCTZ. Adverse event rates were highest with amlodipine/HCTZ because of a higher incidence of peripheral edema (11.1% versus 0.8% to 1.6% in other groups). In conclusion, combination treatment with aliskiren is a highly effective and well-tolerated therapeutic option for obese patients with hypertension who fail to achieve blood pressure control with first-line thiazide diuretic treatment.     

Long-Term Safety and Antihypertensive Efficacy of Irbesartan: Pooled Results of Five Open-Label Studies

An analysis of 5 multicenter, open-label studies was conducted to evaluate the long-term safety and efficacy of irbesartan in 1,006 patients with seated diastolic blood pressure (SeDBP) 95–110 mm Hg. Irbesartan monotherapy was started at 75 mg and titrated to 300 mg at 2- to 4-week intervals to achieve normalized blood pressure (SeDBP < 90 mm Hg). If normalized BP was not attained with irbesartan 300 mg alone, adjunctiye medications could be added. At 12 months of therapy, the mean reduction in seated systolic blood pressure/SeDBP was 21.0/15.8 mm Hg, and 83% (684/821) of patients were normalized. Of those normalized, 64% were receiving irbesartan monotherapy and 86% were receiving irbesartan or irbesartan/hydrochlorothiazide only. No evidence of tachyphylaxis to the antihypertensive effect of irbesartan was noted. Thus, long-term irbesartan therapy, with or without other antihypertensives, achieved and maintained normalized BP in the majority of patients and was well tolerated.     

Long-term safety and antihypertensive efficacy of irbesartan: pooled results of five open-label studies

An analysis of 5 multicenter, open-label studies was conducted to evaluate the long-term safety and efficacy of irbesartan in 1,006 patients with seated diastolic blood pressure (SeDBP) 95-110 mm Hg. Irbesartan monotherapy was started at 75 mg and titrated to 300 mg at 2- to 4-week intervals to achieve normalized blood pressure (SeDBP <90 mm Hg). If normalized BP was not attained with irbesartan 300 mg alone, adjunctive medications could be added. At 12 months of therapy, the mean reduction in seated systolic blood pressure/SeDBP was 21.0/15.8 mm Hg, and 83% (684/821) of patients were normalized. Of those normalized, 64% were receiving irbesartan monotherapy and 86% were receiving irbesartan or irbesartan/hydrochlorothiazide only. No evidence of tachyphylaxis to the antihypertensive effect of irbesartan was noted. Thus, long-term irbesartan therapy, with or without other antihypertensives, achieved and maintained normalized BP in the majority of patients and was well tolerated.     

Combination Therapy With Various Combinations of Aliskiren, Valsartan, and Hydrochlorothiazide in Hypertensive Patients Not Adequately Responsive to Hydrochlorothiazide Alone

This study investigated the efficacy and safety of several different multi-drug regimens including aliskiren, valsartan, and hydrochlorothiazide (HCTZ) in patients not adequately responsive to HCTZ as monotherapy. After 4 weeks of HCTZ treatment, patients (N=641) whose diastolic blood pressure (DBP) was ≥95 mm Hg were treated for 8 weeks with either aliskiren/valsartan/HCTZ, aliskiren/HCTZ, valsartan/HCTZ, or HCTZ alone. The primary efficacy variable was change in DBP from baseline to week 8 end point. The aliskiren/valsartan/HCTZ combination produced statistically significant additional reductions in systolic blood pressure (SBP)/DBP when compared with other groups. At week 8 end point, reductions in SBP/DBP in the respective treatment groups were 22/16, 15/11, 18/14, or 6/6 mm Hg. Aliskiren/valsartan/HCTZ produced significantly better blood pressure control (SBP/DBP <140/90 mm Hg; 66.7%) compared with other treatment groups (20.5%–48.7%). The safety profile of aliskiren/valsartan/HCTZ was similar to the 2-drug combinations, with a greater blood pressure–lowering effect in patients who had not responded to HCTZ monotherapy.