ACE Inhibitor Zofenopril Research Articles

Gender differences efficiency of various dosage regimes of antihypertensive agents by patients with arterial hypertension and coronary heart disease

Aim - to assess the effect of different dosing regimens for combined antihypertensive therapy with the use of ACE inhibitor zofenopril or angiotensin II receptor blocker valsartan on the blood pressure (BP) profile in men and women with arterial hypertension (AH) and stable coronary heart disease (CHD). Materials and methods. 198 patients (98 men and 100 women) with AH and stable CHD (stable angina of II functional class) were examined. In men and women, the effectiveness of 3 variants of antihypertensive therapy was evaluated: a combination of metoprolol succinate/hydrochlorothiazide + zofenopril or valsartan 160 mg once or valsartan 80 mg 2 times/day. Initially and 24 weeks later, 24-hour BP monitoring was performed. Results. Among men, BP

Cardioprotective role of zofenopril in hypertensive patients with acute myocardial infarction: a pooled individual data analysis of the SMILE studies

Purpose: The four SMILE studies demonstrated that early administration of zofenopril following acute myocardial infarction is prognostically beneficial compared to placebo or other angiotensin-converting enzyme (ACE) inhibitors. In the present retrospective pooled analysis of individual SMILE studies, we evaluated the efficacy of zofenopril on cardiovascular (CV) outcomes in 1880 hypertensive and 1662 normotensive patients.Materials and methods: Four hundred and forty-nine hypertensives and 486 normotensives were treated with placebo, 980 and 786 with zofenopril 30–60 mg daily, 252 and 259 with lisinopril 5–10 mg daily, 199 and 131 with ramipril 10 mg daily, for 6 to 48 weeks.Results: The 1-year risk of death or hospitalization for CV causes was significantly reduced with zofenopril and lisinopril vs. placebo in both hypertensive (HR: 0.65; 95%CI: 0.48–0.86; p = .003 and .60, .36–.99; p = .049, respectively) and normotensive patients (0.56, 0.42–0.75; p = .0001 and .51, .28–.90; p = .020), whereas this was not the case for ramipril (hypertensives: 1.02, 0.69–1.52; p = .918; normotensives: 0.91, 0.59–1.41; p = .670). Zofenopril significantly reduced the risk of CV outcomes vs. the other two ACE-inhibitors pooled together in hypertensive (0.76; 0.58–0.99; p = .045), but not in normotensive patients (0.77; 0.55–1.10; p = .150).Conclusions: In cardiac patients of the SMILE studies with arterial hypertension treatment with the ACE-inhibitor zofenopril was beneficial in reducing the 1-year risk of CV events as compared to placebo and ramipril. An efficacy similar to that of zofenopril was observed with lisinopril.

Гендерные особенности эффективности комбинированной антигипертензивной терапии у пациентов с артериальной гипертонией и ишемической болезнью сердца

Aim. To evaluate gender specifics of the efficacy of combination antihypertensive therapy by zofenopril and valsartan by QD or BID schedule in patients with arterial (AH) and stable coronary heart disease (CHD). Material and methods. Totally 98 men and 100 women were included with AH and CHD, who were randomized into 6 groups according to their gender differences and type of the therapy taken: I and IV groups (women and men) – zofenopril 30 mg/day in the morning, II and V groups (women and men) – valsartan 160 mg in the morning, III and VI groups (men and women) – valsartan 80 BID. All patients took β-adrenoblocker metoprolol succinate and diuretic hydrochlorothiazide. Follow-up period was 24 weeks. At the baseline and in 24 weeks, also ambulatory blood pressure monitoring performed (ABPM). Results. In men zofenopril intake and valsartan BID led to the achievement of target blood pressure values in most of the patients, as significant increase of the main ABPM parameters and profile normalization in 70% and 66,7% patients, resp. In women there were more patients with target BP, more significant positive changes in ABPM with “dipper” profile in 78,8% cases in the group of BID valsartan. Conclusion. In AH and stable CHD maximum antihypertensive efficacy in men was shown with ACE inhibitor zofenopril and ARA valsartan BID, in women – in valsartan, especially two times per day.

Modern opportunities for optimising the treatment of patients with coronary heart disease and arterial hypertension: role of zofenopril

The wide prevalence (82%) of coronary heart disease (CHD) in combination with arterial hypertension (AH), as well as its initiating role in the development of fatal complications, such as myocardial infarction (MI) or heart failure, emphasise the need for the choice of optimal ACE inhibitors with organ-protective characteristics. This paper presents a literature review on the effectiveness of a SH-containing ACE inhibitor zofenopril in patients with CHD and AH, in terms of its anti-anginal and antihypertensive activity. The authors summarise the results of the international SMILE studies which included patients after acute MI. It was demonstrated that zofenopril therapy is associated with reduced combined incidence of cardiovascular death or cardiovascular hospitalisation, and is also safe in the acute post-MI period. In patients with preserved left ventricular function, zofenopril reduced the incidence of angina attacks and arrhythmias of coronary genesis, as well as improved exercise capacity. A clinical case of zofenopril therapy, as a part of a complex treatment regimen, is also presented.

Safety and efficacy of the sulfydryl ACE-inhibitor zofenopril in the management of cardiovascular disease

In the 1970s, pharmacological therapy interrupting the renin-angiotensin system was considered beneficial for patients with high-renin hypertension. Angiotensin-converting enzyme (ACE) inhibitors proved to be effective not only in patients with high renin and elevated blood pressure, but also in many hypertensive patients with normal levels of plasma renin activity. ACE inhibitors are used in a wide range of chronic illnesses such as atherosclerosis, hypertension, myocardial infarction, heart failure, diabetic complications, and stroke. To date, more than ninety controlled clinical trials evaluating the beneficial effects of 14 different ACE inhibitors were conducted. Moreover, data from experimental studies showed that ACE inhibitors can attenuate the development of atherosclerosis, oxidative stress, and vascular inflammation in a wide range of species indicating that ACE inhibition also favourably affects the vasculature. More than fifteen years ago, the bi-sulfydryl ACE-inhibitor zofenopril has shown an excellent clinical safety and efficacy in patients with hypertension and in those with myocardial infarction. More recently, this compound exhibited a potent antioxidant and antiatherosclerotic effect indicating a clinical useful vasoprotective action.

Whether all ACE inhibitors enzyme are identical? Focus on zofenopril.

The results of randomized clinical trials were analyzed. The therapy with an ACE inhibitor zofenopril in patients with cardiovascular disease resulted to reduction of cardiovascular complications and mortality risk. Zofenopril was safe and well-tolerated patients. Ongoing zofenopril trials are also reviewed.

Safety and Efficacy of the bi-Sulfydryl ACE-Inhibitor Zofenopril in the Management of Cardiovascular Disease

In the 1970s, pharmacological therapy interrupting the renin-angiotensin system was considered beneficial for patients with high-renin hypertension. Angiotensin-converting enzyme (ACE) inhibitors proved to be effective not only in patients with high renin and elevated blood pressure, but also in many hypertensive patients with normal levels of plasma renin activity. ACE inhibitors are used in a wide range of chronic illnesses such as atherosclerosis, hypertension, myocardial infarction, heart failure, diabetic complications, and stroke. To date, more than ninety controlled clinical trials evaluating the beneficial effects of 14 different ACE inhibitors were conducted. Moreover, data from experimental studies showed that ACE inhibitors can attenuate the development of atherosclerosis, oxidative stress, and vascular inflammation in a wide range of species indicating that ACE inhibition also favourably affects the vasculature. More than fifteen years ago, the bi-sulfydryl ACE-inhibitor zofenopril has shown an excellent clinical safety and efficacy in patients with hypertension and in those with myocardial infarction. More recently, this compound exhibited a potent antioxidant and antiatherosclerotic effect indicating a clinical useful vasoprotective action.

Mitochondrial ATP-sensitive potassium channels and mitochondrial protein kinase C: sometimes it's good to have a close neighbor

the fine study by Jiang et al. ([8][1]) in this issue of the American Journal of Physiology Heart and Circulatory Physiology is an important milestone in the ongoing studies on the role of the mitochondrial ATP-sensitive K+ (mitoKATP) channels in myocardial ischemia. It is not particularly

11C-Radiosynthesis and preliminary human evaluation of the disposition of the ACE inhibitor [ 11C]zofenoprilat

(4 S)-1-[( S)-3-Mercapto-2-methylpropanoyl]-4-phenylthio- l-proline (Zofenoprilat, 2), the active metabolite of the potent ACE inhibitor Zofenopril Calcium ( 1), was labelled with carbon-11 ( t 1/2=20.4 min) to evaluate its pharmacokinetics behaviour in human body using Positron Emission Tomography (PET). [ 11C]2 labelling procedures were based on the use of immobilized Grignard reagent and the acylation of ( S)-4-phenylthio- l-proline methyl ester ( 5) with 11C-labelled methacryloyl chloride, followed by a Michael addition with thiobenzoic acid. The radiochemical yield was 5–10% (EOB, decay corrected) and specific radioactivity ranged from 0.5 to 1.5 Ci/μmol (18.5–55.5 GBq/μmol). Preliminary in vivo human evaluation of [ 11C] 2 showed that the drug accumulates in organs which express high levels of ACE, like lungs and kidneys, and in organs involved in drug metabolism such as the liver and gall bladder. Results of the distribution of [ 11C] 2 showed a measurable concentration of the drug in the target tissues such as the kidney and to a minor extent, the heart, where it can afford organ protection.

Assignment of absolute configuration of chiral carboxylic acids via exciton-coupled CD treatment: 4-phenylthioproline as a case study.

The 4-hydroxybenzoate chromophore was used as an exciton reporter group for the assignment of the absolute configuration of a chiral carboxylic acid of pharmaceutical interest, (-)-(2S,4S)-4-phenylthioproline, precursor of the ACE-inhibitor zofenopril. The nondegenerate coupling with the preexisting phenylthio chromophore was observed. A detailed conformational analysis, accomplished by means of (1)H-NMR NOESY and semiempirical PM3 computational methods, and quantitative CD calculations were necessary to substantiate the assignment based on a weak experimental couplet.

Chronic treatment with sulfhydryl angiotensin-converting enzyme inhibitors reduce susceptibility of plasma LDL to in vitro oxidation, formation of oxidation-specific epitopes in the arterial wall, and atherogenesis in apolipoprotein E knockout mice

The effects of chronic treatment with the new sulfhydryl angiotensin-converting enzyme (ACE)-inhibitor, zofenopril, in comparison with the classical sulfhydryl ACE-inhibitor captopril or enalapril or placebo on the development of atherosclerosis were determined in apolipoprotein-E knockout (apoE −/−) mice. Groups of 2-month-old male mice received either placebo ( N=10), 0.05 mg/kg/day of zofenopril ( N=10), 1 mg/kg/day of zofenopril ( N=10), 5 mg/kg/day of captopril ( N=10) or 0.5 mg/kg/day of enalapril ( N=8). After 29 weeks of treatment, computer-assisted imaging analysis revealed that zofenopril reduced the aortic cumulative lesion area by 78% at 0.05 mg/kg/day and by 89% at 1 mg/ml/day of zofenopril compared to that of the placebo ( P<0.0001). Captopril reduced by 52% aortic lesions compared to placebo ( P<0.01 vs. placebo; P<0.05 vs. zofenopril at both doses). Enalapril did not reduce aortic lesions. Furthermore, 0.05 mg/kg/day of zofenopril reduced susceptibility of plasma LDL to in vitro oxidation compared to captopril, enalapril or placebo, as shown by significant reduction of malondialdehyde content ( P<0.001 vs. placebo or enalapril; P<0.05 vs. captopril), as well as by the prolongation of lag-time ( P<0.01 vs. placebo or enalapril P<0.05 vs. captopril). More importantly, mice treated with 1 mg/ml/day of zofenopril had a significant decrease in the intimal immunohistochemical presence of oxidation-specific epitopes on oxLDL (NA59 monoclonal antibody, P<0.01), macrophages derived foam cells (F4/80 monoclonal antibody, P<0.05) and native LDL (NP monoclonal antibody, P<0.01) compared to placebo, captopril or enalapril. Thus, chronic treatment with the new sulfhydryl ACE-inhibitor zofenopril has antiatherosclerotic and antioxidant effects in the arterial wall of hypercholesterolemic apoE −/− mice. This protection was significantly higher than that reached with captopril and at lower doses of the drug. Treatment with 0.5 mg/kg/day of enalapril did not provide any protective effect.