Zofenopril plus hydrochlorothiazide fixed combination in the treatment of hypertension and associated clinical conditions.

Zofenopril, is a highly lipophilic ACE inhibitor, characterized by long-lasting tissue penetration and sustained cardiac ACE inhibition, indicated for the treatment of hypertension and myocardial infarction. Comparative studies with different antihypertensive drug classes have demonstrated the good efficacy and tolerability of this compound in the management of the patient with mild-moderate hypertension. Zofenopril may also be combined with hydrochlorothiazide, a combination which has proved to be effective and safe as compared with monotherapy with either agent in three studies, including more than 600 patients. In addition, recent post hoc analyses in high-risk patients, such as those with the metabolic syndrome, impaired fasting glucose or diabetes, atherogenic dyslipidemia, and impaired renal function, have confirmed the superiority of zofenopril 30 mg plus hydrochlorothiazide 12.5 mg once-daily combination as compared with zofenopril monotherapy also in these high-risk populations of patients with hypertension. These data suggest the usefulness of this fixed combination in the treatment of patients with hypertension requiring more prompt, intensive, and sustained blood pressure reduction, according to guidelines recommendation. © 2009 Blackwell Publishing Ltd

Clinical Study Blood Pressure Response to Zofenopril or Irbesartan Each Combined with Hydrochlorothiazide in High-Risk Hypertensives Uncontrolled by Monotherapy: A Randomized, Double-Blind, Controlled, Parallel Group, Noninferiority Trial

In this randomized, double-blind, controlled, parallel group study (ZENITH), 434 essential hypertensives with additional cardiovascular risk factors, uncontrolled by a previous monotherapy, were treated for 18 weeks with zofenopril 30 or 60 mg plus hydrochlorothiazide (HCTZ) 12.5 mg or irbesartan 150 or 300 mg plus HCTZ. Rate of office blood pressure (BP) response (zofenopril: 68% versus irbesartan: 70%; = 0.778) and 24-hour BP response (zofenopril: 85% versus irbesartan: 84%; = 0.781) was similar between the two treatment groups. Cardiac and renal damage was equally reduced by both treatments, whereas the rate of carotid plaque regression was significantly larger with zofenopril. In conclusion, uncontrolled monotherapy treated hypertensives effectively respond to a combination of zofenopril or irbesartan plus a thiazide diuretic, in terms of either BP response or target organ damage progression

P-181: Fixed-dose valsartan + hydrochlorothiazide combination therapy compared with amlodipine monotherapy in hypertensive patients with additional cardiovascular risk factors: The vast study

Objectives: To determine whether the combination of valsartan 160 mg and hydrochlorothiazide (HCTZ) 25 mg once-daily (od) is more effective than amlodipine 10 mg od in reducing systolic blood pressure (BP) in patients suffering from moderate hypertension combined with at least one other cardiovascular risk factor or concomitant condition. Further, to study the effects of treatment on vascular markers. Methods: A multicenter, randomized, double-blind, active-controlled, three-arm study over 24 weeks. After a two-week single-blind placebo run-in period, 1088 stage-II hypertensive patients with additional risk factors were randomized to three groups, two receiving valsartan 160 mg od and one group receiving amlodipine 5 mg od. At Week 4, HCTZ 12.5 mg and 25 mg respectively, were added to the valsartan groups and the amlodipine dose was force-titrated to 10 mg od. Patients were followed-up for a total of 24 weeks. Results: The combination of valsartan 160 mg+HCTZ 25 mg reduced systolic BP significantly (p<0.05) more than amlodipine monotherapy (least-squares mean changes from baseline 29.7±0.7 mmHg and 27.6± 0.7 mmHg, respectively). For diastolic BP the values were 11.1±0.4 mmHg and 10.8±0.4 mmHg, respectively (differences not significant). Levels of IL-6, t-PA antigen and hs-CRP were reduced with both combination therapies at week 12 (figure). Significantly more patients discontinued because of adverse events in the amlodipine group (18.2%) than in the combination-therapy groups (4.2% and 3.5%) over the 6 months treatment period. Conclusions: Valsartan 160 mg+HCTZ 25 mg is an effective and well-tolerated therapy in this patient population with possible beneficial effects on vascular marker

Blood Pressure Response to Zofenopril or Irbesartan Each Combined with Hydrochlorothiazide in High-Risk Hypertensives Uncontrolled by Monotherapy: A Randomized, Double-Blind, Controlled, Parallel Group, Noninferiority Trial

In this randomized, double-blind, controlled, parallel group study (ZENITH), 434 essential hypertensives with additional cardiovascular risk factors, uncontrolled by a previous monotherapy, were treated for 18 weeks with zofenopril 30 or 60 mg plus hydrochlorothiazide (HCTZ) 12.5 mg or irbesartan 150 or 300 mg plus HCTZ. Rate of office blood pressure (BP) response (zofenopril: 68% versus irbesartan: 70%; p=0.778) and 24-hour BP response (zofenopril: 85% versus irbesartan: 84%; p=0.781) was similar between the two treatment groups. Cardiac and renal damage was equally reduced by both treatments, whereas the rate of carotid plaque regression was significantly larger with zofenopril. In conclusion, uncontrolled monotherapy treated hypertensives effectively respond to a combination of zofenopril or irbesartan plus a thiazide diuretic, in terms of either BP response or target organ damage progression

Olmesartan vs ramipril in the treatment of hypertension and associated clinical conditions in the elderly: A reanalysis of two large double-blind, randomized studies at the light of the most recent blood pressure targets recommended by guidelines

In this paper, we present the results of a reanalysis of the data of two large randomized, double-blind, parallel group studies with a similar design, comparing the efficacy of an angiotensin-receptor blocker (olmesartan medoxomil) with that of an angiotensin-converting enzyme inhibitor (ramipril), by applying two different blood pressure targets recently recommended by hypertension guidelines for all patients, irrespective of the presence of diabetes (<140/90 mmHg), and for elderly hypertensive patients (<150/90 mmHg). The efficacy of olmesartan was not negatively affected by age, sex, hypertension type, diabetes status or other concomitant clinical conditions, or cardiovascular risk factors. In most cases, olmesartan provided better blood pressure control than ramipril. Olmesartan was significantly more effective than ramipril in male patients, in younger patients (aged 65-69 years), in those with metabolic syndrome, obesity, dyslipidemia, preserved renal function, diastolic ± systolic hypertension, and, in general, in patients with a high or very high cardiovascular risk. Interestingly, patients previously untreated or treated with two or more antihypertensive drugs showed a significantly larger response with olmesartan than with ramipril. Thus, our results confirm the good efficacy of olmesartan in elderly hypertensives even when new blood pressure targets for antihypertensive treatment are considered. Such results may be relevant for the clinical practice, providing some hint on the possible different response of elderly hypertensive patients to two different drugs acting on the renin-angiotensin system, when patients are targeted according to the blood pressure levels recommended by recent hypertension guidelines

Antihypertensive Efficacy and Safety of Olmesartan Medoxomil and Ramipril in Elderly Mild to Moderate Essential Hypertensive Patients With or Without Metabolic Syndrome A Pooled Post Hoc Analysis of Two Comparative Trials

Background Two recent identically designed trials (one Italian and one European multinational) have compared the head-to-head efficacy and safety of the angiotensin II receptor blocker olmesartan medoxomil and the angiotensin converting enzyme inhibitor ramipril, in elderly patients with essential hypertension. Objective The aim of the present study was to assess the antihypertensive efficacy of olmesartan and ramipril in elderly patients with hypertension, with or without metabolic syndrome, by performing a pooled analysis of data from the two head-to-head trials. Methods After a 2-week, placebo wash-out, 1,453 treated or untreated elderly hypertensive patients aged 65-89 years [with sitting office diastolic blood pressure (DBP) 90-109 mmHg and/or sitting office systolic BP (SBP) 140-179 mmHg] were randomized to 12-weeks of double-blind treatment with olmesartan 10 mg or ramipril 2.5 mg once daily. Treatment could be up-titrated to 20 and 40 mg for olmesartan, and 5 and 10 mg for ramipril, after the first 2 and 6 weeks, respectively, in patients with inadequately controlled BP (BP >= 140/90 mmHg for non-diabetics and >= 130/80 mmHg for diabetics). Office BP was measured at randomization and after 2, 6 and 12 weeks of treatment. 24-h ambulatory BP recordings were obtained at randomization and after 12 weeks. Results Of the 1,426 patients in the intent-to-treat analysis, 735 (51.5 %) had metabolic syndrome (olmesartan, n = 372; ramipril, n = 363). After 12 weeks of treatment, baseline-adjusted office BP reductions were greater (p < 0.05) with olmesartan (SBP 17.0 mmHg; 95 To CI 18.4, 15.6; DBP 9.6 mmHg; 95 % CI 10.4, 8.8) than with ramipril (SBP 14.7 mmHg; 95 % CI 16.1, 13.2; DBP 8.4 mmHg; 95 % CI 9.2, 7.6) in patients with metabolic syndrome. In these patients, BP normalization rates were also greater with olmesartan than with ramipril (46.0 vs. 35.8 %, p < 0.01). Similarly, in patients without metabolic syndrome, the antihypertensive efficacy of olmesartan was also significantly (p < 0.05) better than that of ramipril. In the subgroup of patients with valid ambulatory BP (ABP) recordings and metabolic syndrome (olmesartan, n = 182; ramipril, n = 170), the reduction in mean 24-h ABP was greater with olmesartan (SBP 10.2 mmHg; 95 % CI 11.8, 8.6; DBP 6.6 mmHg; 95 % CI 7.5, 5.6) than with ramipril (SBP 8.5 mmHg; 95 % CI 10.2, 6.9; DBP 4.7 mmHg; 95 % CI 5.7, 3.7), with a statistically significant (p < 0.01) difference for the DBP comparison. The proportion of patients experiencing drug-related adverse events was comparable in patients with (olmesartan 2.4 % vs. ramipril 2.8 To) and without (3.5 vs. 3.7 %) metabolic syndrome. Conclusions Olmesartan provides more effective BP control than ramipril in elderly hypertensive patients with and without metabolic syndrome

Antihypertensive efficacy and safety of olmesartan medoxomil and ramipril in elderly patients with mild to moderate essential hypertension: the ESPORT study.

Objective: To compare the efficacy and safety of the angiotensin II antagonist olmesartan medoxomil (O) and the ACE inhibitor ramipril (R) in elderly patients with essential arterial hypertension. Methods: After a 2-week placebo wash-out 1102 treated or untreated elderly hypertensive patients aged 65-89 years (office sitting diastolic blood pressure, DBP, 90-109 mmHg and/or office sitting systolic blood pressure, SBP, 140-179 mmHg) were randomized double-blind to 12-week treatment with O 10 mg or R 2.5 mg once-daily. After the first 2 and 6 weeks doses could be doubled in non-normalized [blood pressure (BP) < 140/90 mmHg for nondiabetic and < 130/80 mmHg for diabetic) individuals, up to 40 mg for O and 10 mg for R. Office BPs were assessed at randomization, after 2, 6 and 12 weeks of treatment, whereas 24-h ambulatory BP was recorded at randomization and after 12 weeks. Results: In the intention-to-treat population (542 patients O and 539 R) after 12 weeks of treatment baseline-adjusted office SBP and DBP reductions were greater (P < 0.01) with O [17.8 (95% confidence interval: 16.8/18.9) and 9.2 (8.6/9.8) mmHg] than with R [15.7 (14.7/16.8) and 7.7 (7.1/8.3) mmHg]. BP normalization rate was also greater under O (52.6 vs. 46.0% R, P < 0.05). In the subgroup of patients with valid ambulatory BP recording (318 O and 312 R) the reduction in 24-h average BP was larger (P < 0.05) with O [SBP: 11.0 (12.2/9.9) and DBP: 6.5 (7.2/5.8) mmHg] than with R [9.0 (10.2/7.9) and 5.4 (6.1/4.7) mmHg]. The larger blood pressure reduction obtained with O was particularly evident in the last 6 h from the dosing interval; a better homogeneity of the 24-h BP control with O was confirmed by higher smoothness indices. The proportion of patients with drug-related adverse events was comparable in the two groups (3.6 O vs. 3.6% R), as well as the number of patients discontinuing study drug because of a side effect (14 O vs. 19 R). Conclusion: In elderly patients with essential arterial hypertension O provides an effective, prolonged and well tolerated BP control, representing a useful option among first-line drug treatments of hypertension in this age group. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins