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

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

A comparison of the efficacy and safety of irbesartan/hydrochlorothiazide combination therapy with irbesartan monotherapy in the treatment of moderate or severe hypertension in diabetic and obese hypertensive patients: a post-hoc analysis review

Hypertension is difficult to treat in patients with type 2 diabetes mellitus (T2DM) or obesity. Combination therapies are often required to effectively lower blood pressure (BP) and attain BP goals. In this post-hoc analysis of 2 prospective, randomized, controlled studies in patients with uncontrolled or untreated moderate or severe hypertension, the efficacy and safety of treatment with irbesartan/hydrochlorothiazide (HCTZ) and irbesartan was assessed in 2 separate analyses: patients with diabetes (n=143) and by obesity status (n=1125). Patients received irbesartan/HCTZ (150 mg/12.5 mg titrated to 300 mg/25 mg) or irbesartan (150 mg titrated to 300 mg) for 7 (severe hypertension study) or 12 (moderate hypertension study) weeks. Efficacy comparisons between treatment groups were performed using Fisher's exact tests. After 7 to 8 weeks of treatment, systolic BP (SBP)/diastolic BP (DBP) decreased in patients with diabetes by 26.9/17.8 mm Hg and 21.8/15.8 mm Hg after irbesartan/HCTZ and irbesartan treatment, respectively (P [SBP]=0.09, P [DBP]=0.27). In obese patients (n=544), SBP/DBP decreased by 29.4/20.2 mm Hg and 20.1/15.9 mm Hg after irbesartan/HCTZ and irbesartan treatment, respectively (P<0.0001). More patients with T2DM reached the BP goal of <130/80 mm Hg at week 7 to 8 in the irbesartan/HCTZ group than in the irbesartan group (12% vs 5%), although not statistically significant (P=0.22). Significantly more obese patients reached their respective BP goals in the irbesartan/HCTZ group than in the irbesartan group (48% vs 23%; P<0.0001). Treatment-emergent adverse event rates were similar between treatment groups regardless of the presence of diabetes or body mass index (BMI) status. In patients with moderate or severe hypertension and with a BMI ≥ 30 kg/m(2), initial treatment with irbesartan/HCTZ combination therapy was more effective than irbesartan monotherapy.     

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

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

Comparison of a fixed-dose combination of 40 mg telmisartan plus 12.5 mg hydrochlorothiazide with 40 mg telmisartan in the control of mild to moderate hypertension

This study investigated whether a fixed-dose combination of 40 mg of the angiotensin II antagonist telmisartan plus 12.5 mg of the diuretic hydrochlorothiazide (HCTZ) was superior to 40 mg telmisartan in patients with mild to moderate hypertension who failed to respond adequately to 40 mg telmisartan monotherapy. One hundred forty-six patients were withdrawn before randomization. Nonresponders (n = 327) were double blind and randomized to 40 mg telmisartan + 12.5 mg HCTZ (n = 160) or 40 mg telmisartan (n = 167). After 8 weeks of treatment, 40 mg telmisartan + 12.5 mg HCTZ lowered diastolic blood pressure (DBP) by an additional 3.5 mm Hg (P <.01) and systolic blood pressure (SBP) by 7.4 mm Hg (P <.01) compared with 40 mg telmisartan. Most of the additional effect of the combination was seen after 4 weeks of treatment. At week 8, blood pressure was normalized (SBP <140 mm Hg and DBP <90 mm Hg) in 51.6% of patients on 40 mg telmisartan + 12.5 mg HCTZ compared with 23.5% on 40 mg telmisartan (P <.05). The combination of 40 mg telmisartan + 12.5 mg HCTZ normalized DBP in 64.8% of patients, whereas 40 mg telmisartan normalized DBP in 40.1% (P <.05). SBP decreased by > or =10 mm Hg from baseline in 63.5% of patients receiving the fixed-dose combination compared with 42.6% of those receiving 40 mg telmisartan (P <.05). Both treatments were well tolerated. Adverse events were predominantly mild, transient, and considered unrelated to therapy. These findings indicate that a fixed-dose combination of 40 mg telmisartan + 12.5 mg HCTZ is clinically and statistically superior to 40 mg telmisartan in patients with mild to moderate hypertension failing to respond to 40 mg telmisartan alone.     

Telmisartan plus hydrochlorothiazide versus telmisartan or hydrochlorothiazide monotherapy in patients with mild to moderate hypertension: a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial.

BACKGROUND: Recent surveys reveal continuing deficiencies in the awareness, treatment, and control of hypertension. In many cases, failure to achieve blood pressure targets may be attributable to the use of antihypertensive monotherapy. OBJECTIVES: This study was undertaken to identify combinations of telmisartan, a new oral angiotensin II type 1-receptor antagonist, and hydrochlorothiazide (HCTZ) that might provide greater antihypertensive efficacy than monotherapy with either agent in the treatment of mild to moderate hypertension. It also examined the dose-response surface for the 2 drugs alone and in combination. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study that employed all cells of a 4 x 5 factorial design. After a 4-week, single-blind, placebo run-in period, men and women between 18 and 80 years of age with mild to moderate hypertension (defined as mean supine diastolic blood pressure [DBP] between 95 and 114 mm Hg during the last 2 weeks of the placebo run-in period and systolic blood pressure [SBP] between 114 and 200 mm Hg immediately before randomization) were eligible to enter the 8-week, double-blind, double-dummy treatment period. Study comparisons were between once-daily telmisartan monotherapy (20, 40, 80, or 160 mg), HCTZ monotherapy (6.25, 12.5, or 25 mg), 12 combinations of these telmisartan/HCTZ doses, and placebo. The focus was on 2 combinations: telmisartan 40 mg/HCTZ 12.5 mg and telmisartan 80 mg/HCTZ 12.5 mg. The primary efficacy variable was change in supine trough DBP from baseline to the last evaluable measurement during double-blind treatment. Plasma renin activity and safety parameters, including treatment-emergent adverse events, physical findings, electrocardiograms, and serum electrolyte levels (which are known to increase with HCTZ treatment), were also assessed. RESULTS: Of 1293 patients screened, 818 (63.3%) were enrolled at 47 centers. Of these 818, 749 (91.6%) completed the study. The intent-to-treat population (randomized with > or = 1 postrandomization blood pressure measurement) consisted of 807 patients (98.7%). Telmisartan 80 mg/HCTZ 12.5 mg significantly decreased mean supine trough SBP/DBP by 23.9/14.9 mm Hg, a benefit of 8.5/3.4 mm Hg compared with telmisartan 80 mg and of 17.0/7.6 mm Hg compared with HCTZ 12.5 mg (both comparisons, P < 0.01). Telmisartan 40 mg/HCTZ 12.5 mg significantly reduced mean supine SBP by 18.8 mm Hg, a benefit of 6.6 mm Hg compared with telmisartan 40 mg and 11.9 mm Hg compared with HCTZ 12.5 mg (both, P < 0.01). This same combination significantly reduced mean supine DBP by 12.6 mm Hg, a benefit of 5.3 mm Hg compared with HCTZ 12.5 mg (P < 0.01), but was not significantly different from telmisartan 40 mg. Telmisartan 80 mg/HCTZ 12.5 mg was significantly more effective than telmisartan 40 mg/HCTZ 12.5 mg in reducing mean supine DBP and SBP (both, P < 0.05). The response surface and responder analyses confirmed the additive antihypertensive efficacy of the combination of telmisartan and HCTZ. All regimens were well tolerated. CONCLUSIONS: Once-daily telmisartan 80 mg/HCTZ 12.5 mg was effective and well tolerated when used to reduce SBP and DBP in patients with mild to moderate hypertension. In addition to enhancing efficacy, this combination protected against potassium depletion, a common side effect of thiazide monotherapy.     

Antihypertensive efficacy and tolerability of two fixed-dose combinations of valsartan and hydrochlorothiazide compared with valsartan monotherapy in patients with stage 2 or 3 systolic hypertension: an 8-week, randomized, double-blind, parallel-group trial

BACKGROUND: Combination therapy with at least 2 antihypertensive agents is usually needed to achieve appropriate blood pressure (BP) control in patients with isolated or predominant systolic hypertension. A currently recommended combination is a diuretic added to an angiotensin-receptor blocker. OBJECTIVE: This was a study of the effects on sitting systolic BP (SBP)of 2 combinations of valsartan and hydrochlorothiazide (HCTZ) compared with valsartan monotherapy in patients with stage 2 or 3 systolic hypertension (SBP > or =160 mm Hg and < or =200 mm Hg) with or without other cardiovascular risk factors. METHODS: After a placebo run-in period, patients were randomized to receive double-blind treatment with either valsartan 80 mg OD(monotherapy group) or valsartan 160 mg OD (combination-therapy groups) for 4 weeks, followed by forced titration to valsartan 160 mg OD (V160), valsartan 160 mg plus HCTZ 12.5 mg OD (V160 +HCTZ12.5), or valsartan 160 mg plus HCTZ 25 mg OD (V160 +HCTZ25) for an additional 4 weeks. End points were the change in SBP between the groups receiving combination therapy and the monotherapy group, between-group changes in diastolic BP (DBP), responder rates (SBP <140 mm Hg or a reduction in SBP of > or =20 mm Hg), and tolerability. RESULTS: A total of 774 patients were randomized to treatment: 261 to V160, 258 to V160+HCTZ12.5, and 255 to V160 +HCTZ25. The intent-to-treat population consisted of 767 patients (411 men, 356 women; mean age, 60 years; mean weight, 84 kg; clinic mean [SD] baseline BP, 167.5 [8.1]/93.4 [9.1] mm Hg). All treatments produced significant reductions in SBP from baseline (mean [SD] reduction, 20.7 [15.7] mm Hg with V160, 27.9 [13.8] mm Hg with V160 +HCTZ12.5, and 28.3 [13.1] mm Hg with V160+HCTZ25; all, P < 0.05). DBP was reduced by 6.6 (8.9) mm Hg in the V160 group and by 10.2 (7.7) and 10.1 (7.8) mm Hg in the V160+HCTZ12.5 and V160 +HCTZ25 groups, respectively (all, P < 0.05). The additional reductions in BP with V160+HCTZ25 did not reach statistical significance compared with V160+HCTZ12.5. Responder rates were 56.9% in the V160 group, 74.4% in the V160+HCTZ12.5 group, and 75.0% in the V160 +HCTZ25 group P < 0.05, combination therapy vs monotherapy). Adverse events were reported by 27.5% of patients in the monotherapy group, compared with 28.6% and 34.0% in the groups that received V160+HCTZ12.5 and V160+HCTZ25, respectively; the differences were not significant between treatment groups. CONCLUSIONS: Monotherapy with V160 was effective in these patients with stage 2 or 3 systolic hypertension. Significant additional reductions in SBP and DBP and an increase in responder rates were achieved with the addition to V160 of HCTZ12.5 and HCTZ25, with no significant effect on tolerability.     

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

Background

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

Objective

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

Methods

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

Results

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

Conclusion

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

Association between human atrial natriuretic peptide Val7Met polymorphism and baseline blood pressure, plasma trough irbesartan concentrations, and the antihypertensive efficacy of irbesartan in rural Chinese patients with essential hypertension

BACKGROUND: Individual variations in the pharmacokinetics and pharmacodynamics of antihypertensive drugs are influenced by genetic and environmental factors. The ANP gene, which encodes the precursor of atrial natriuretic peptide (ANP), is among the candidate genes for genetic susceptibility to hypertension. OBJECTIVE: This study examined the relationship between ANP Val7Met polymorphism (Single Nucleotide Polymorphism database ID: rs5063) and baseline blood pressure (BP), plasma trough irbesartan concentrations, and the antihypertensive efficacy of irbesartan in rural Chinese patients with essential hypertension. METHODS: Patients with essential hypertension who had taken no antihypertensive medications within 4 weeks of study initiation received oral irbesartan 150 mg/d for 4 weeks. Genotyping was performed for all patients. BP was measured before dosing on the 1st and 28th days of treatment. Plasma irbesartan concentrations were measured using high-performance liquid chromatography with fluorescent detection. Antihypertensive efficacy was defined as attainment of a diastolic BP (DBP) <90 mm Hg (DBP analysis), a systolic BP (SBP) <140 mm Hg (SBP analysis), and a DBP <90 mm Hg and SBP <140 mm Hg (DBP and SBP analysis). RESULTS: The study included 756 patients, 621 with the Val/Val genotype and 135 with the Val/Met+Met/Met genotypes. There were no significant differences in age, body mass index, sex, education level, occupation, alcohol consumption, or smoking status between the 2 groups. Patients with the Val/Met+Met/Met genotypes had a significantly lower mean baseline DBP compared with those with the Val/Val genotype (adjusted regression coefficient [SE]: -2.5 [1.0] mm Hg; P = 0.012) and significantly lower mean steady-state plasma trough irbesartan concentrations (adjusted regression coefficient: -12.6 [4.1]; P = 0.002). No significant association was found between antihypertensive efficacy and Val7Met polymorphism in the overall population, but in an analysis by baseline DBP status, patients with the Val/Met+Met/Met genotype a baseline DBP > or =100 mm Hg had significantly smaller reductions in DBP (adjusted regression coefficient: -5.7 [1.4] mm Hg; P < 0.001) and SBP compared with those with the Val/Val genotype and a baseline DBP > or =100 mm Hg (adjusted regression coefficient: -9.8 [2.9] mm Hg; P < 0.001). CONCLUSION: The findings of this study suggest that in these rural Chinese patients with essential hypertension, ANP Val7Met polymorphism may be a genetic marker for baseline DBP, plasma irbesartan concentrations, and the antihypertensive efficacy of short-term irbesartan therapy.     

Hydrochlorothiazide added to valsartan is more effective than when added to olmesartan in reducing blood pressure in moderately hypertensive patients inadequately controlled by monotherapy

This study was undertaken to evaluate the effects on blood pressure of hydrochlorothiazide (HCTZ) 12.5 mg added to valsartan 160 mg or to olmesartan 20 mg in hypertensive patients. After a 2-wk placebo period, 130 patients, aged 35 to 75 y, with diastolic blood pressure (DBP) ≥99 and <110 mm Hg were randomly assigned to olmesartan 20 mg once daily or to valsartan 160 mg once daily according to a prospective, parallel-arm study design. After 4 wk of monotherapy, patients whose BP was not controlled (DBP ≥90 mm Hg) were given combination treatment with HCTZ 12.5 mg for an additional 4 wk. At the end of the placebo period and at the end of each treatment period, clinical and ambulatory BP measurements were recorded. At the end of the combination therapy period, venous blood samples were drawn 2, 4, and 24 h after drug intake for evaluation of HCTZ plasma concentrations. Both combinations induced a greater ambulatory BP reduction than monotherapy. However, mean reduction from baseline in the valsartan/HCTZ-treated patients (-21.5/-14.6 mm Hg for 24 h, -21.8/-14.9 mm Hg for daytime, and -20.4/-13.7 mm Hg for nighttime systolic blood pressure [SBP]/DBP) was greater than in the olmesartan/HCTZ-treated patients (-18.8/-12.3 mm Hg for 24 h, -19.3/-12.8 mm Hg for daytime, and -17.4/-10.6 mm Hg for nighttime SBP/DBP). The difference between the effects of the 2 treatments was significant (P<.01). In particular, compared with monotherapy, the add-on effect of HCTZ 12.5 mg was significantly greater in the valsartan group than in those treated with olmesartan; the difference was more evident for nighttime BP values. Plasma concentrations of HCTZ were significantly greater with valsartan than with olmesartan at each determination time (P<.05). These findings suggest that the addition of HCTZ 12.5 mg to valsartan 160 mg monotherapy produces a greater BP reduction than the addition of the same dose of HCTZ to olmesartan 20 mg monotherapy.     

Dose-related efficacy of irbesartan in patients, with mild-to-moderate essential hypertension

OBJECTIVE: A prospective open multicentre study was conducted in patients with mild-to-moderate hypertension to compare the efficacy on diastolic blood pressure (DBP) and tolerance of treatment with either irbesartan 150mg od (once daily) or irbesartan 300mg od in patients who were defined as non-normalised responders with irbesartan 150mg od. METHODS AND RESULTS: A total of 14 820 hypertensive patients were included in the study. After 6 weeks with irbesartan 150mg od, in terms of their response to treatment, 8861 (61.9%) were normalised (DBP <90mm Hg), 1963 (13.7%) non-normalised responders (DBP > or = 90mm Hg with a decrease in DBP > or = 10mm Hg) and 3154 (22%) non-normalised non-responders (DBP > or = 90mm Hg with a decrease in DBP <10mm Hg); 842 patients did not respect the protocol and could not be evaluated. The 1963 non-normalised responders were randomly assigned at week 6 to either irbesartan 150mg od (n = 963) or irbesartan 300mg od (n = 1000) for 5 weeks. A greater reduction in mean DBP was found in the group treated with irbesartan 300mg (p < 0.001). There were no significant differences in terms of number or severity of adverse events between the two groups of patients.     

Efficacy and safety of delapril plus manidipine compared with enalapril plus hydrochlorothiazide in mild to moderate essential hypertension: results of a randomized trial

BACKGROUND: The use of combination therapy is required to achieve blood pressure targets in 40% to 75% of patients with hypertension. There have been few studies comparing the efficacy and tolerability of the new fixed combination of the angiotensin-converting enzyme (ACE) inhibitor delapril 30 mg and the calcium channel antagonist manidipine 10 mg with those of a standard combination of another ACE inhibitor and a diuretic. OBJECTIVE: The aim of this study was to compare the antihypertensive efficacy and tolerability of delapril 30 mg given alone or with manidipine 10 mg with those of enalapril 20 mg given alone or with hydrochlorothiazide (HCTZ) 12.5 mg in patients with mild to moderate essential hypertension. METHODS: This was a multicenter, active-controlled, parallel-group trial. After an initial 2-week placebo run-in period, patients aged 18 to 75 years with diastolic blood pressure (DBP) > or =90 and < or =109 mm Hg were randomized in a 2:1 ratio to receive delapril or enalapril for 8 weeks. After the initial 8 weeks, nonresponders (DBP > or =85 mm Hg) received an additional 8 weeks of treatment with a fixed combination of delapril + manidipine or enalapril + HCTZ; patients whose DBP was normalized continued their initial monotherapy through the end of the study. The primary efficacy variable was the change in sitting DBP at the end of treatment. Secondary efficacy variables were the percentage of patients whose DBP was normalized (DBP Z:85 mm Hg) and the percentage of responders (> or =10-mm Hg reduction in DBP or DBP <85 mm Hg). RESULTS: One hundred sixty patients (84 men, 76 women) were randomized to receive delapril (n = 106) or enalapril (n = 54). After 16 weeks of treatment, the mean (SD) reduction in DBP was similar with the 2 treatments (delapril, -14 [8] mm Hg; enalapril, -15 [8] mm Hg). In the delapril and enalapril groups, DBP was normalized in a respective 55 (51.9%) and 29 (53.7%) patients, and 77 (72.6%) and 38 (70.4%) were responders; there was no significant difference between groups. Tolerability was also similar in both groups--10 (9.4%) patients in the delapril group and 5 (9.3%) in the enalapril group experienced adverse events that were judged related to treatment. CONCLUSIONS: The results of this study suggest that delapril alone or combined with manidipine is well tolerated and as effective as enalapril alone or combined with HCTZ in lowering blood pressure in patients with mild to moderate essential hypertension.     

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

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

厄贝沙坦对老年高血压晨峰患者微量白蛋白尿的影响及降压疗效

目的 探讨厄贝沙坦对老年高血压晨峰患者尿微量白蛋白的影响及降压疗效.方法 选择经24 h动态血压监测血压未达标的老年高血压晨峰患者92例,观察睡前加用厄贝沙坦治疗后血压及血压晨峰的变化和对尿微量白蛋白的影响.结果 治疗前92例老年高血压患者24 h平均收缩压(140.1±12.7)mm Hg,晨峰收缩压(45.6±10.8)mm Hg,尿微量白蛋白[(58.6±3.7)mg/L]明显升高,与治疗前比较,睡前加服厄贝沙坦治疗后患者24 h平均收缩压[(129.5±11.8)mm Hg]下降(t=3.18,P＜0.05),晨峰收缩压[(14.2±4.1)mm Hg]下降(t=5.74,P＜0.01),尿微量白蛋白[(31.7±3.1)mg/L]显著降低(t=5.24,P＜0.01).结论 厄贝沙坦可以有效降低老年高血压患者的血压及血压晨峰,提高血压达标率,降低尿微量白蛋白.     

A multicenter, randomized, double-blind study of the antihypertensive efficacy and tolerability of irbesartan in patients aged > or = 65 years with mild to moderate hypertension

BACKGROUND: Blockade of the renin-angiotensin-aldosterone system (RAAS) is the preferred mechanism of action for controlling hypertension in select groups of patients, including those with diabetic nephropathy and heart failure. Currently, 2 classes of drugs work by blocking the RAAS, albeit by differing mechanisms: angiotensin-converting enzyme (ACE) inhibitors and angiotensin II angiotensin type 1 receptor blockers (ARBs). OBJECTIVE: The goal of this study was to assess the comparative efficacy and tolerability of the ARB irbesartan and the ACE inhibitor enalapril in patients > or = 65 years of age with mild to moderate hypertension (sitting diastolic blood pressure [DBP], 95 to 110 mm Hg). METHODS: Elderly (> or = 65 years of age) patients were recruited from 26 Canadian study centers for a randomized, double-blind, 8-week clinical trial. Exclusion criteria included sitting DBP >110 mm Hg or sitting systolic blood pressure (SBP) >200 mm Hg, angina pectoris, myocardial infarction, cardiac procedure, stroke, or transient ischemic attack within 6 months of randomization, as well as other preexisting or present severe medical or psychologic conditions. Patients were randomly assigned to receive a single daily dose of irbesartan 150 mg (n = 70) or enalapril 10 mg (n = 71) with treatment doses of study drugs doubled at week 4 for sitting DBP > or = 90 mm Hg. Reductions from baseline blood pressure measurements at trough (24 +/- 3 hours after the last dose of medication) were assessed for sitting DBP and sitting SBP. Comparative tolerability to study drugs was also assessed. RESULTS: The intent-to-treat analysis demonstrated similar reductions at week 8 in both DBP and SBP for both groups. For the primary efficacy analysis of sitting DBP, there was a mean reduction from baseline of 9.6 mm Hg and 9.8 mm Hg for the irbesartan and enalapril groups, respectively (P = 0.93). The mean reduction from baseline in sitting SBP was 10.1 mm Hg and 11.6 mm Hg for the irbesartan and enalapril groups, respectively (P = 0.54). Normalization rates (sitting DBP <90 mm Hg) at week 8 did not differ between groups (52.9% in the irbesartan group and 54.9% in the enalapril group; P = 0.81). No statistical difference existed between the 2 groups with respect to serious adverse events or discontinuations due to adverse events. Irbesartan was associated with a significantly lower incidence of cough than was enalapril (4.3% vs 15.5%, respectively; P = 0.046). CONCLUSIONS: Irbesartan is an effective and well-tolerated antihypertensive for elderly patients with mild to moderate hypertension. This study establishes that irbesartan has better tolerability than enalapril with respect to cough and suggests that irbesartan is as effective at lowering blood pressure but better tolerated than an ACE inhibitor in hypertensive patients > or = 65 years of age.     

Manidipine versus enalapril monotherapy in patients with hypertension and type 2 diabetes mellitus: a multicenter, randomized, double-blind, 24-week study

BACKGROUND: Blood pressure reduction is associated with a reduced risk for cardiovascular events and death, particularly in patients with both hypertension and type 2 diabetes mellitus. OBJECTIVE: The aim of this study was to compare the antihypertensive efficacy, tolerability, and effect on metabolic risk factors of manidipine, a new dihydropyridine calcium channel antagonist, and enalapril, a widely used angiotensin-converting enzyme inhibitor, in patients with mild to moderate essential hypertension and type 2 diabetes. METHODS: This multicenter, double-blind trial compared manidipine and enalapril in patients with type 2 diabetes and hypertension (diastolic blood pressure [DBP] 90-104 mm Hg, systolic blood pressure [SBP] < or =190 mm Hg). Following a 3-week, single-blind placebo run-in period, eligible patients were randomized to receive either manidipine 10 mg or enalapril 10 mg once daily for 24 weeks. The dose was doubled after 3 weeks in patients who had not responded to treatment (DBP > or =90 mm Hg). The primary efficacy end point was change in DBP from baseline to the end of the study. Secondary outcomes were the responder rate (DBP <90 mm Hg and/or a DBP reduction of > or =10 mm Hg) at the end of the study. Other secondary measures were changes from baseline to the end of the study in heart rate and in the following measures obtained by ambulatory blood pressure monitoring (ABPM): 24-hour, daytime, and nighttime mean DBP and SBP, and the trough:peak ratio. Blood glucose, glycosylated hemoglobin (HbA1c), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, uric acid, and creatinine were measured at the end of the placebo run-in period and the end of treatment. The study had 80% power to detect a between-treatment difference in mean sitting DBP of >3 mm Hg. RESULTS: One hundred twenty-four patients were enrolled in the study. After the placebo run-in period, 13 patients were excluded from the study: 4 for DBP values outside the specified limits, 7 at their request, and 2 for adverse events. Thus, 111 patients met the eligibility criteria and were randomized to treatment (53 manidipine, 58 enalapril). The population consisted of 61 men and 50 women with a mean (SD) age of 62 (11) years and a body mass index of 28.2 (2.4) kg/m2. Among patients who completed the study, drug doses were doubled in 67.6% (25/37) of patients in the manidipine group and 60.0% (24/40) of patients in the enalapril group (P = NS). Similar reductions in blood pressure were observed in both groups, from a mean (SD) of 164 (12)/97.5 (5) mm Hg at baseline to 141 (12)/84.5 (6) mm Hg at the end of the study in the manidipine group (P < 0.01), and from 159 (12)/98 (4) mm Hg to 139 (12)/86 (8) mm Hg in the enalapril group (P < 0.01). The proportion of responders was 66.7% (32/48) in the manidipine group and 60.0% (30/50) in the enalapril group; the difference between groups was not significant. Twenty-four-hour ABPM revealed significant (P < 0.01) and similar reductions in blood pressure in both groups, with a trough:peak ratio of approximately -50%. Neither drug affected heart rate. Among the statistically significant changes in metabolic parameters, significant reductions in HbA(1c) (from 6.7% [1.4%] to 6.2% [1.1%]) and blood glucose concentrations (from 152 [44] to 143 [44] mg/dL) were observed only in the manidipine group (P < 0.05). The incidence of adverse events was similar between groups. CONCLUSIONS: In the present study, manidipine was as metabolically neutral and as effective as enalapril in reducing blood pressure in hypertensive patients with type 2 diabetes, providing a sustained 24-hour antihypertensive effect.     

Effectiveness of hydrochlorothiazide in combination with telmisartan and olmesartan in adults with moderate hypertension not controlled with monotherapy: a prospective, randomized, open-label, blinded end point (PROBE), parallel-arm study

Background:The potential combinations of antihypertensive agents are many, and making rational choices depends on the characteristics of each drug and on their complementary mechanisms of action.Objective: The aim of this study was to evaluate the effectiveness of adding hydrochlorothiazide (HCTZ) 12.5 mg to olmesartan 20 mg or telmisartan 80 mg on blood pressure (BP) in patients with moderate hypertension.Methods: Consecutive outpatients at the Centro per l'Ipertensione e la Fisiopatologia Cardiovascolare, University of Pavia, Pavia, Italy, of both sexes aged 39 to 75 years were considered eligible for enrollment if they had a sitting diastolic BP (DBP) ->99 mm Hg and <110 mm Hg at the end of an initial 2-week washout period. Patients were random- ized to olmesartan 20 mg QD or telmisartan 80 mg QD according to a prospective, open-label, blinded end point, parallel-arm design. After 8 weeks of monotherapy, patients whose BP was not controlled (DBP ->90 mm Hg) received HCTZ 12.5 mg QD for 8 additional weeks. Clinical and ambulatory BPs were measured at the end of the washout period and at the end of both treatment periods. Adverse events (AEs) were recorded from spontaneous reports and direct inquiry from investigators.Results: One hundred forty-five patients, all of whom were white, were recruited for the study. After the initial washout period, 13 patients did not meet the inclusion criteria and 6 refused to continue. A total of 126 white patients (69 men, 57 women; mean [SD] age, 60.2 [11.6] years) were randomized to receive monotherapy. Of these, 35 patients (56%) in the olmesartan group and 33 (52%) in the telmisartan group had previously received antihypertensive therapy. At the end of monotherapy, the 52 patients in the olmesartan group and the 49 patients in the telmisartan treatment group who were still in the study and had their BP inadequately controlled by treatment had HCTZ 12.5 mg QD added to their treatment regimen. Both combinations induced a greater ambulatory mean (SD) systolic BP (SBP) and DBP reduction than monothera- py (SBP: 145.3 [6.1] in the olmesartan group and 140.1 [6.4] in the telmisartan group, P < 0.05; DBP: 88.1 [5.1] in the olmesartan group and 84.9 [4.9] in the telmisartan group, P < 0.05). The mean (SD) reduction from baseline in the telmisartan/HCTZ-treated patients (21.5 [10.1]/14.6 [5.2] mm Hg for 24 hours, 21.8 [10.2]/14.9 [5.2] mm Hg for daytime, and 20.4 [10.3]/13.7 [5.9] mm Hg for nighttime; all, P < 0.001 vs baseline) was significantly greater than that observed in the olmesartan/HCTZ-treated patients (18.8 [9.8]/12.3 [4.9] mm Hg for 24 hours, 19.3 [9.8]/12.8 [4.9] mm Hg for daytime, and 17.4 [10.2]/10.6 [5.5] mm Hg for nighttime; all, P < 0.001 vs baseline), with a significant difference between the 2 treatment groups (P < 0.01). Compared with mono- therapy, the add-on effect of HCTZ 12.5 mg QD administration was significantly greater in the telmisartan group than in the olmesartan group (P < 0.05); the differ- ence being more evident for nighttime BP values (SBP, P 0.031; DBP, P 0.025). Reported AEs were similar in the olmesartan/HCTZ and the telmisartan/HCTZ groups (4 patients [7%] vs 3 patients [6%]).Conclusion: The addition of HCTZ 12.5 mg to telmisartan 80 mg monothera- py was associated with greater BP reduction than the addition of the same dose of HCTZ to olmesartan 20 nag monotherapy in these patients previously uncontrolled on monotherapy.     

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

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

Zofenopril Plus Hydrochlorothiazide and Irbesartan Plus Hydrochlorothiazide in Previously Treated and Uncontrolled Diabetic and Non-diabetic Essential Hypertensive Patients

Introduction

In most treated patients with hypertension, a two or more drug combination is required to achieve adequate blood pressure (BP) control. In our study we assessed whether the combination of zofenopril + hydrochlorothiazide (HCTZ) was at least as effective as irbesartan + HCTZ in essential hypertensives with at least one additional cardiovascular risk factor, uncontrolled by a previous monotherapy.

Methods

After a 2-week placebo washout, 361 treated hypertensive patients [office sitting diastolic BP (DBP), ≥90 mmHg], aged 18–75 years, were randomized double blind to 18-week treatment with zofenopril 30 mg plus HCTZ 12.5 mg or irbesartan 150 mg plus HCTZ 12.5 mg once daily, in an international, multicenter study. After the first 6 and 12 weeks, zofenopril and irbesartan doses could be doubled in non-normalized subjects. The primary study end point was the office sitting DBP reduction after 18 weeks of treatment. Secondary end points included office systolic BP (SBP), ambulatory BP and high sensitivity C-reactive protein (hs-CRP).

Results

The between-treatment difference for office DBP averaged to +1.0 (95% CI ?0.4, +0.8) mmHg (P = 0.150), the upper limit of the 95% confidence interval being inferior to the protocol-defined non-inferiority limit (3 mmHg). In the subset of patients with valid ambulatory BP, no difference in 24-h average DBP [n = 181; 6.7 (8.7, 4.6) zofenopril + HCTZ vs. 6.3 (8.8, 3.7) mmHg irbesartan + HCTZ, P = 0.810] and SBP reductions [11.7 (15.4, 8.0) vs. 12.6 (17.2, 8.0) mmHg, P = 0.758] were observed between the two treatment groups. hs-CRP was reduced by zofenopril + HCTZ [?0.52 (?1.05, 0.01) mg/L], while it was increased by irbesartan plus HCTZ [0.97 (0.29, 1.65) mg/L, P = 0.001 between treatments].

Conclusion

In previously monotherapy-treated, uncontrolled patients with hypertension, zofenopril 30–60 mg + HCTZ 12.5 mg is as effective as irbesartan 150–300 mg plus HCTZ 12.5 mg, with the added value of a potential protective effect against vascular inflammation.     

Comparative Efficacy of Irbesartan/ Hydrochlorothiazide and Valsartan/Hydrochlorothiazide Combination in Lowering Blood Pressure: A Retrospective Observational Study in Oman

Objective

To compare blood pressure (BP) control in patients receiving irbesartan/hydrochlorothiazide (HCTZ) and valsartan/HCTZ at a tertiary care university hospital in Oman.

Subjects and Methods

This was a retrospective observational study, where 232 patients'' medical records were reviewed during a 3-month period, July to September 2010, at Sultan Qaboos University Hospital in Oman. BP readings of the previous 6 months were also retrieved from the electronic medical records. Analyses were conducted using univariate statistical techniques.

Results

The mean age of the cohort was 58 ± 11 years (range: 21–88). Sixty-nine (30%) patients were on the irbesartan/HCTZ combination (150/12.5 mg) and 163 (70%) were on the valsartan/HCTZ combination. The patients on the valsartan/HCTZ combination were divided into two subgroups: 117 (72%) received 160/12.5 mg and 46 (28%) 80/12.5 mg. Diabetic patients (43/69, 62%, vs. 61/163, 37%, p < 0.001) and those with diabetic nephropathy (8/69, 12%, vs. 7/163, 4%, p = 0.039) were prescribed more often irbesartan/HCTZ than valsartan/HCTZ. In comparison to the valsartan/HCTZ cohort, the irbesartan/HCTZ group was associated with significant reductions in both systolic BP (SBP; −9 vs. −2 mm Hg; p = 0.021) and diastolic BP (DBP; −5 vs. 0 mm Hg; p = 0.022). BP reductions were noted more in diabetics than nondiabetics with the irbesartan/HCTZ patients associated with significant reductions in both SBP (−12 vs. 5.1 mm Hg; p < 0.001) and DBP (−6.4 vs. 1.9 mm Hg; p = 0.001).

Conclusions

The irbesartan/HCTZ combination was associated with significant reductions in both SBP and DBP when compared with the valsartan/HCTZ combination. Specifically, the reductions were noted more in diabetics than nondiabetics.Key Words: Irbesartan, Valsartan, Hypertension, Diabetes mellitus, Nephropathy     

Blood pressure control in patients with mild to moderate essential hypertension switched from nifedipine gastrointestinal therapeutic system (GITS) 30 mg to nifedipine GITS 20 mg

BACKGROUND: Nifedipine gastrointestinal therapeutic system (GITS) is a once-daily formulation of nifedipine that provides sustained plasma nifedipine concentrations throughout the 24-hour dosing interval. OBJECTIVE: This study was undertaken to determine if adult patients with mild to moderate essential hypertension whose blood pressure had been controlled for > or = 3 months with nifedipine GITS 30 mg could be successfully switched to a 20-mg daily dose with continued antihypertensive efficacy. METHODS: This was a randomized, double-blind, parallel-group study. Patients entered a 1-week run-in period during which they continued to receive their usual antihypertensive medication, including nifedipine GITS 30 mg. After baseline assessment, patients entered a 6-week treatment period during which they were randomly assigned to receive nifedipine GITS 30 or 20 mg. Men and women were eligible to participate if they were > or = 55 years of age, had received a diagnosis of mild to moderate essential hypertension (sitting diastolic blood pressure [DBP] 95-114 mm Hg), and had exhibited good blood pressure control (sitting DBP < or = 90 mm Hg) while taking nifedipine GITS 30 mg once daily for > or = 3 months. Systolic blood pressure (SBP), DBP, and heart rate were recorded at baseline and after 1, 3, and 6 weeks of treatment. Adverse events were reported by patients. The responder rate was defined as the percentage of patients whose sitting DBP was < 95 mm Hg at the final study assessment. Results were based on the intent-to-treat analyses, which included data for all patients who received > or = 1 dose and had 1 postbaseline blood pressure assessment. Statistical significance was set at P < 0.05. RESULTS: Seventy-five patients entered the 1-week run-in period; 71 patients (94.7%) were randomized to treatment. Twenty-four patients received nifedipine GITS 30 mg for 43.0 +/- 3.3 days, and 47 patients received nifedipine GITS 20 mg for 42.5 +/- 6.7 days. Both groups exhibited a sustained decrease in blood pressure throughout the study; minor variations were not statistically significant. End-point SBP and DBP for the 30- and 20-mg groups were 135.5 +/- 9.8/81.7 +/- 5.4 mm Hg and 138.6 +/- 11.8/82.9 +/- 7.6 mm Hg, respectively. Changes from baseline in end-point SBP and DBP did not differ significantly between groups. At the end of treatment, goal DBP (< 95 mm Hg) was achieved by 24 of 24 patients (100%) receiving the 30-mg dose and 45 of 47 patients (95.7%) receiving the 20-mg dose. Blood pressure control (sitting DBP < 90 mm Hg) was achieved by 21 of 24 (87.5%) patients in the 30-mg group and 35 of 47 (74.5%) patients in the 20-mg group. The most commonly reported adverse event was headache; 2 patients discontinued the study because of adverse events. Overall, 9 of 24 patients (37.5%) in the 30-mg group and 14 of 47 patients (29.8%) in the 20-mg group experienced > or = 1 treatment-related adverse event. CONCLUSIONS: Patients whose mild to moderate essential hypertension is controlled with nifedipine GITS 30 mg once daily may be able to switch to 20 mg once daily with continued antihypertensive efficacy. In addition to safety and economic advantages, such a switch may be a reasonable alternative in patients with lower body weight or as an adjunct to existing antihypertensive therapy.