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J Thireau, S Zalvidea, P Meschin, J-L Pasquie, F Aimond, S Richard
Angiotensin-converting enzyme inhibitors (ACE-I) improve clinical outcome in patients with myocardial infarction (MI) and chronic heart failure. We investigated potential anti-arrhythmic (AA) benefits in a mouse model of ischemic HF. We hypothesized that normalization of diastolic calcium (Ca(2+)) by ACE-I may prevent Ca(2+)-dependent reduction of inward rectifying K(+) current (IK1) and occurrence of arrhythmias after MI. Mice were randomly assigned to three groups: Sham, MI, and MI-D (6 weeks of treatment with ACE-I delapril started 24h after MI)...
2015: Current Molecular Medicine
Annalisa Zoppi, Amedeo Mugellini, Paola Preti, Andrea Rinaldi, Aldo Celentano, Emma Arezzi, Marco Alberici, Roberto Fogari
BACKGROUND: Failure to achieve good blood pressure (BP) control is probably the most important reason for high rates of morbidity and mortality in patients with hypertension. Combination therapy has been shown to increase the percentage of patients in whom BP control is achieved. One combination is a calcium channel blocker (CCB) and an angiotensin-converting enzyme inhibitor (ACE-I). OBJECTIVE: The aim of this study was to assess the effects of the fixed combination of the CCB manidipine and the ACE-I delapril in the treatment of hypertensive patients already given monotherapy with either component but with poor results (ie, insufficient BP control or adverse events [AEs])...
July 2003: Current Therapeutic Research, Clinical and Experimental
Giovanni Cremonesi, Luca Cavalieri, Stefano Bacchelli, Daniela Degli Esposti, Ivo Cikes, Jurij Dobovisek, Jan Zeman, Claudio Borghi, Ettore Ambrosioni
BACKGROUND: Several studies have shown that antihypertensive monotherapy is commonly insufficient to control blood pressure (BP) in hypertensive patients and that concomitant use of ≥2 drugs is necessary in ∼50% of these patients. The combination of an angiotensin-converting enzyme (ACE) inhibitor and a diuretic, delapril plus indapamide (D + I), has been shown to be effective and tolerable, with no interaction between the 2 components. Another widely used combination of ACE inhibitor and diuretic is lisinopril plus hydrochlorothiazide (L + H)...
May 2003: Current Therapeutic Research, Clinical and Experimental
Vítor Todeschini, Maximiliano da Silva Sangoi, Alianise da Silva Meira, Diogo Miron, Alini Dall Cortivo Lange, Nadia Maria Volpato
A stability-indicating micellar electrokinetic chromatography (MEKC) method was developed and validated for simultaneous analysis of delapril (DEL) and manidipine (MAN) using salicylic acid as an internal standard. The MEKC method was performed using a fused-silica capillary (effective length of 72 cm) with 50 mM of borate buffer and 5 mM of anionic surfactant sodium dodecylsulfate at pH 9.0 as the background electrolyte. The separation was achieved at 25 kV applied voltage and 35 degrees C. The injection was performed at 50 mbar for 5 s, with detection at 208 nm...
January 2014: Journal of AOAC International
Vítor Todeschini, Amanda Thomas Barden, Leticia Lenz Sfair, Maximiliano da Silva Sangoi, Nadia Maria Volpato
A first-order derivative spectrophotometric (1D-UV) method was developed and validated for simultaneous determination of delapril (DEL) and manidipine (MAN) in tablets. The 1D-UV spectra were obtained using change lambda = 4.0 nm and wavelength set at 228 nm for DEL and 246 nm for MAN. The method was validated in accordance with the ICH requirements, involving the specificity, linearity, precision, accuracy, robustness and limits of detection and quantitation. The method showed high specificity in the presence of two drugs and formulation excipients and was linear over the concentration range of 18-54 microg mL(-1) (r2 = 0...
2013: Acta Chimica Slovenica
José Ramón González-Juanatey, Alberto Cordero
Angiotensin-converting enzyme inhibitors (ACEIs) are the first-line therapy for the treatment of hypertension. However, not all ACEIs are equal. Delapril is a nonsulfhydryl ACEI with unique properties. Delapril has a high lipophilicity and weak bradykinin potentiating action. As a result, delapril has a more potent inhibition capacity of vascular wall angiotensin-converting enzyme activity and a lower incidence of cough than enalapril or captopril. With regard to efficacy, delapril has a long-lasting antihypertensive effect with a trough/peak ratio that is in the upper range of different ACEIs and a positively high smoothness index...
March 2013: Expert Review of Cardiovascular Therapy
A J García Ruiz, J A Divisón Garrote, N García-Agua Soler, F Morata García de la Puerta, A C Montesinos Gálvez, L Avila Lachica
OBJECTIVE: The aim of this study is to compare the efficiency of different fixed-dose combinations of renin-angiotensin-aldosterone system (RAAS) blockers and calcium channel blockers, to use it as a guide to assist the rational prescribing in antihypertensive therapy. METHODS: The efficacy of each drug was obtained from intervention studies randomized, double-blind, made with these combinations and a utility-cost modeling from the model proposed and used by NICE...
March 2013: Semergen
Maria Circelli, Gabriele Nicolini, Colin G Egan, Giovanni Cremonesi
The main objective of this meta-analysis was to compare the efficacy of the combination of delapril and indapamide (D+I) to different angiotensin-converting enzyme inhibitor (ACEi) plus hydrochlorothiazide (HCTZ) combinations for the treatment of mild-to-moderate hypertension. A secondary objective was to examine the safety of these two combinations. Studies comparing the efficacy of D+I to ACEi+HCTZ combinations in hypertensive patients and published on computerized databases (1974-2010) were considered. Endpoints included percentage of normalized patients, of responders, change in diastolic and systolic blood pressure (DBP/SBP) at different time-points, percentage of adverse events (AEs), and percentage of withdrawal...
2012: International Journal of General Medicine
Piero Ruggenenti, Esteban L Porrini, Flavio Gaspari, Nicola Motterlini, Antonio Cannata, Fabiola Carrara, Claudia Cella, Silvia Ferrari, Nadia Stucchi, Aneliya Parvanova, Ilian Iliev, Alessandro Roberto Dodesini, Roberto Trevisan, Antonio Bossi, Jelka Zaletel, Giuseppe Remuzzi
OBJECTIVE: To describe the prevalence and determinants of hyperfiltration (glomerular filtration rate [GFR] ≥120 mL/min/1.73 m(2)), GFR decline, and nephropathy onset or progression in type 2 diabetic patients with normo- or microalbuminuria. RESEARCH DESIGN AND METHODS: We longitudinally studied 600 hypertensive type 2 diabetic patients with albuminuria <200 μg/min and who were retrieved from two randomized trials testing the renal effect of trandolapril and delapril...
October 2012: Diabetes Care
S Zalvidea, L André, X Loyer, C Cassan, Y Sainte-Marie, J Thireau, I Sjaastad, C Heymes, J-L Pasquié, O Cazorla, F Aimond, S Richard
Prevention of adverse cardiac remodeling after myocardial infarction (MI) remains a therapeutic challenge. Angiotensin-converting enzyme inhibitors (ACE-I) are a well-established first-line treatment. ACE-I delay fibrosis, but little is known about their molecular effects on cardiomyocytes. We investigated the effects of the ACE-I delapril on cardiomyocytes in a mouse model of heart failure (HF) after MI. Mice were randomly assigned to three groups: Sham, MI, and MI-D (6 weeks of treatment with a non-hypotensive dose of delapril started 24h after MI)...
February 2012: Current Molecular Medicine
Piero Ruggenenti, Giuseppe Lauria, Ilian Petrov Iliev, Anna Fassi, Aneliya Parvanova Ilieva, Stefano Rota, Carlos Chiurchiu, Drazenka Pongrac Barlovic, Angelo Sghirlanzoni, Raffaella Lombardi, Paola Penza, Guido Cavaletti, Maria Luisa Piatti, Barbara Frigeni, Marco Filipponi, Nadia Rubis, Greta Noris, Nicola Motterlini, Bogdan Ene-Iordache, Flavio Gaspari, Annalisa Perna, Jelka Zaletel, Antonio Bossi, Alessandro Roberto Dodesini, Roberto Trevisan, Giuseppe Remuzzi
To assess whether angiotensin-converting enzyme inhibitors and third-generation dihydropyridine calcium channel blockers ameliorate diabetic complications, we compared glomerular filtration rate (GFR; primary outcome), cardiovascular events, retinopathy, and neuropathy in 380 hypertensive type 2 diabetics with albuminuria <200 mg/min included in a multicenter, double-blind, placebo-controlled trial (DEMAND [Delapril and Manidipine for Nephroprotection in Diabetes]) and randomized to 3-year treatment with manidipine/delapril combination (10/30 mg/d; n=126), delapril (30 mg/d; n=127), or placebo (n=127)...
November 2011: Hypertension
Vítor Todeschini, Maximiliano da Silva Sangoi, Nadia Maria Volpato
A simple, specific, fast and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous analysis of delapril (DEL) and manidipine (MAN) from their combination formulation was developed and validated using fesoterodine as the internal standard (IS). The LC-MS/MS method was carried out on a Luna C8 column (50 × 3.0 mm i.d., 3 µm) with a mobile phase consisting of methanol and 10 mmol L(-1) ammonium acetate (90 : 0, v/v), run at a flow rate of 0.25 mL min(-1). The mass spectrometry method was performed employing positive electrospray ionization operating in multiple reaction monitoring mode, monitoring the transitions of m/z 453...
2011: European Journal of Mass Spectrometry
Roberto Fogari, Amedeo Mugellini, Maria Circelli, Giovanni Cremonesi
The majority of patients with hypertension, and in particular high-risk patients or those with diabetes mellitus or renal dysfunction, are likely to require combination therapy with at least two antihypertensive agents (from different classes) to achieve their blood pressure (BP) target. The delapril/manidipine fixed-dose combination consists of two antihypertensive agents with different, yet complementary, mechanisms of action. Delapril/manidipine has demonstrated short- and long-term antihypertensive efficacy in a number of clinical studies in patients with hypertension with an inadequate response to monotherapy...
2011: Clinical Drug Investigation
J Zaletel, D Pongrac Barlovic, J Prezelj
AIMS: Adiponectin and leptin are adipocytokines associated with insulin resistance. The objective of this study was to evaluate the performance of the adiponectin-leptin ratio as a measure of insulin resistance in comparison with other surrogate measures of insulin resistance based on fasting insulin and glucose levels [homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI), fasting glucose/insulin ratio] and with measures based on fasting insulin and triglyceride levels (McAuley index) in Caucasian patients with Type 2 diabetes (T2D)...
September 2010: Journal of Endocrinological Investigation
Osvaldo Kohlmann, Alejandro Roca-Cusachs, Stéphane Laurent, Roland E Schmieder, René R Wenzel, Roberto Fogari
INTRODUCTION: Patients with diabetes complicated by hypertension and microalbuminuria have elevated cardiovascular risk, and controlling blood pressure in these patients is an urgent clinical priority. The present study aimed to examine the effects of a fixed-dose combination of antihypertensives on blood pressure and microalbuminuria. METHODS: Patients with type 2 diabetes, mild-to-moderate hypertension (diastolic blood pressure 85-105 mmHg, systolic blood pressure <160 mmHg, and 24-hour mean systolic blood pressure >130 mmHg), and microalbuminuria were randomized to 1 year of doubleblind treatment with fixed-dose manidipine/delapril (n=54) or losartan/hydrochlorothiazide (HCTZ) (n=56)...
March 2009: Advances in Therapy
Roberto Fogari, Giuseppe Derosa, Annalisa Zoppi, Andrea Rinaldi, Paola Preti, Pierangelo Lazzari, Amedeo Mugellini
The purpose of this study was to compare the combination treatments of manidipine/delapril and olmesartan/hydrochlorothiazide (HCTZ) in elderly diabetic hypertensives. After a 4-week placebo period, 158 hypertensive patients with type 2 diabetes (age range: 66 to 74 years) were randomized to receive combination treatment of 10 mg manidipine plus 30 mg delapril or 20 mg olmesartan plus 12.5 mg HCTZ for 48 weeks in a prospective, parallel arm trial. After 12 weeks, manidipine or HCTZ was doubled in nonresponders (systolic blood pressure [SBP] > or =130 mmHg and/or diastolic blood pressure [DBP] > or =80 mmHg)...
January 2008: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Alejandro Roca-Cusachs, Roland E Schmieder, Filippos Triposkiadis, René R Wenzel, Stéphane Laurent, Osvaldo Kohlmann, Roberto Fogari et al.
BACKGROUND: Hypertension markedly increases the already high risk for cardiovascular complications in patients with diabetes mellitus. Less than one in eight patients with hypertension and type 2 diabetes have adequately controlled blood pressure. As a result, antihypertensive combinations are now widely used in management of hypertension associated with diabetes. METHODS: This double-blind study investigated efficacy of a new fixed dose combination of a calcium antagonist, manidipine 10 mg, and an angiotensin-converting enzyme inhibitor, delapril 30 mg, compared with a combination of an angiotensin receptor blocker, losartan 50 mg, and a diuretic, hydrochlorothiazide 12...
April 2008: Journal of Hypertension
Roberto Fogari, Giuseppe Derosa, Annalisa Zoppi, Pierangelo Lazzari, Luca Corradi, Paola Preti, Amedeo Mugellini
OBJECTIVE: To compare the effect of delapril/manidipine vs olmesartan/hydrochlorothiazide (HCTZ) combination on insulin sensitivity and plasma fibrinogen in obese hypertensive patients. PATIENTS AND METHODS: After a 4-week placebo period, 88 obese, hypertensive (DBP >95 and <110 mmHg) outpatients were randomized to delapril 30 mg/manidipine 10 mg combination or to olmesartan 20 mg/HCTZ 12.5 mg combination for 24 weeks according to a prospective, randomized, open-label, blinded endpoint, parallel group design...
2008: Internal Medicine
Manuel Luque Otero
High blood pressure (BP) is the major cardiovascular risk factor and the main cause of death around the world. Control of blood pressure reduces the high mortality associated with hypertension and the most recent guidelines recommend reducing arterial BP values below 140/90 mmHg for all hypertensive patients (130/80 in diabetics) as a necessary step to reduce global cardiovascular risk, which is the fundamental objective of the treatment. To achieve these target BP goals frequently requires combination therapy with two or more antihypertensive agents...
2007: Vascular Health and Risk Management
Roberto Fogari, GianDomenico Malamani, Annalisa Zoppi, Amedeo Mugellini, Andrea Rinaldi, Elena Fogari, Tiziano Perrone
BACKGROUND: Use of the combination of an angiotensin-converting enzyme inhibitor (ACEI) and a calcium channel blocker (CCB) is considered a rational approach in patients whose hypertension is not controlled by monotherapy, providing better blood pressure (BP) control than the individual components with a lower incidence of adverse effects. In particular, such combinations have been found to reduce the incidence of ankle edema, the most common adverse effect of dihydropyridine annhypertensives...
March 2007: Clinical Therapeutics
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