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1.
Kardiologiia ; 61(8): 14-22, 2021 Aug 31.
Artigo em Russo | MEDLINE | ID: mdl-34549689

RESUMO

Aim      To study the condition of coronary vasculature by data of coronarography (CG) in patients with chronic ischemic heart disease (IHD) and arterial hypertension (AH) associated with stage 2-4 chronic kidney disease (CKD) and to evaluate the effect of a 12-week complex treatment with perindopril or with a combination of perindopril/amlodipine on changes in vascular wall stiffness, endothelial function, and structure and function parameters in this patient category after coronary stenting.Material and methodsr This study included 87 patients with chronic IHD and AH associated with stage 2-3 CKD for whom CG was performed due to ineffectiveness of the antianginal therapy. The patients were divided into three subgroups: subgroup 1 included 28 patients who received a conservative treatment with perindopril 10 mg/day; subgroup 2 consisted of 25 patients who underwent coronary stenting and were prescribed perindopril; subgroup 3 consisted of 34 patients who underwent stenting and were prescribed the perindopril/amlodipine combination. The reference group included 47 patients with IHD and AH with preserved kidney function. Anatomic and functional parameters of the heart, arterial stiffness, pulse wave velocity, cardio-ankle vascular index, augmentation index, central aortic systolic and pulse pressure, endothelium-dependent vasodilation, plasma concentration of endothelin-1 (ET-1), and plasma concentration of nitric oxide metabolites were evaluated at baseline and after 12 weeks of treatment.Results In patients with IHD, AH, and stage 2-3 CKD, arterial stiffness was more pronounced than in patients with preserved kidney function. Concentrations of ET-1 were significantly higher and levels of nitric oxide were lower in CKD. Supplementing the complex therapy with perindopril resulted in a considerable hypotensive effect in all subgroups, improvement of the kidney function, and positive dynamics of arterial stiffness and endothelial function. Changes in these parameters were more pronounced in patients after coronary stenting than in patients receiving only a conservative treatment. The use of perindopril/amlodipine following stenting exerted the most significant angioprotective and cardioprotective effect.Conclusion      Patients with IHD and AH in combination with early CKD have pronounced impairment of the condition of arterial blood vessels and the heart. Addition of perindopril to the treatment not only exerted a hypotensive effect but also beneficially influenced mechanisms of progression of this combined pathology.


Assuntos
Doença das Coronárias , Hipertensão , Insuficiência Renal Crônica , Anlodipino/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Doença das Coronárias/tratamento farmacológico , Combinação de Medicamentos , Humanos , Hipertensão/tratamento farmacológico , Perindopril , Análise de Onda de Pulso , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico
2.
Kardiologiia ; 61(7): 68-78, 2021 Jul 31.
Artigo em Russo | MEDLINE | ID: mdl-34397344

RESUMO

Arterial hypertension (AH) is one of the most important risk factors for development of myocardial infarction, chronic heart failure, stroke, cognitive disorders and dementia, and chronic kidney disease. Currently, special attention is paid to increased blood pressure variability (BPV) as a new risk factor for development of cardiovascular and cerebrovascular complications. The available evidence-based body of clinical studies demonstrates the importance of reducing not only the blood pressure itself but also the increased BPV to provide significant improvement of the prognosis and limits the risk of complications. This notion has been validated in consensus documents on the management of patients with AH. Among antihypertensive drugs, the fixed-dose combination (FC) amlodipine/perindopril has demonstrated a unique capability for reducing all types of BPV (visit-to-visit, day-to-day, during 24 h). According to current clinical guidelines, this combination belongs to first-line FCs indicated for most patients with AH. A distinctive feature of the FC amlodipine/perindopril is numerous data from real-life clinical practice, which support both its high antihypertensive efficacy and the ability to decrease high BPV. Therefore, the FC amlodipine/perindopril can be recommended for a broad range of AH patients to achieve BP control and to improve the prognosis.


Assuntos
Insuficiência Cardíaca , Hipertensão , Infarto do Miocárdio , Anlodipino/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Combinação de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Hipertensão/tratamento farmacológico , Infarto do Miocárdio/tratamento farmacológico , Perindopril
3.
Vnitr Lek ; 67(2): 119-124, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34074111

RESUMO

Blockade of the renin angiotensin aldosterone system (RAAS) is currently considered to be the gold standard of antihypertensive therapy. ACE inhibitors and AT1-blockers are clinically the most relevant groups of RAAS blockers. Even though both drug groups block angiotensin II, ACE inhibitors typically reduce the degradation of bradykinin, which leads to the release of nitric oxide and prostaglandins with subsequent vasodilation. These differences in the mechanism of action can be of clinical relevance for hypertensive patients. Morbidity mortality studies of RAAS blockers have been reported in which ACE inhibitors, particularly perindopril, improved the overall survival in hypertensive patients. In the ONTARGET trial, a direct comparison of both drug groups yielded comparable results. Perindopril, which has been used in the clinical practice for more than 25 years, is a long-acting lipophilic angiotensin-converting enzyme inhibitor with a once-daily dosage schedule and a high affinity to tissue-converting enzyme. Its safety, efficacy, and very good tolerance have been shown in a number of studies. It is part of many fixed combinations which improve patient compliance and increase the effect of treatment of cardiovascular diseases.


Assuntos
Doenças Cardiovasculares , Hipertensão , Inibidores da Enzima Conversora de Angiotensina , Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , Humanos , Hipertensão/tratamento farmacológico , Perindopril , Sistema Renina-Angiotensina
4.
Adv Ther ; 38(6): 3299-3313, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33991323

RESUMO

INTRODUCTION: Combination antihypertensive therapy is required by most patients to achieve guideline-recommended blood pressure (BP) goals. This study assessed the effectiveness and tolerability of bisoprolol/perindopril (Bis/Per) single-pill combination (SPC) in Russian patients with hypertension and coronary artery disease (CAD) treated in routine clinical practice. METHODS: STYLE (NCT03730116) was an open-label, uncontrolled, prospective observational study conducted in patients who were already receiving Bis/Per SPC, switched to SPC from Bis or Per monotherapy, or switched from a free combination of Bis and Per. Primary endpoint criteria were assessed at 1 and 3 months and included change in mean office systolic/diastolic blood pressure (SBP/DBP), proportion achieving target BP (< 140/90 mmHg), and measures of antianginal effectiveness. RESULTS: The full analysis set comprised 1892 subjects. Mean age was 61.9 ± 8.8 years, 53.2% were women, and mean durations of hypertension and CAD were 12.5 ± 7.9 and 7.2 ± 6.4 years, respectively. Mean SBP/DBP decreased by 22.3/11.0 mmHg and 31.5/15.9 mmHg at 1 and 3 months, respectively (P < 0.0001 vs baseline). Target BP was achieved by 49.2% and 86.7% of patients at 1 and 3 months, respectively. Reductions in mean number of angina attacks and nitrate consumption and improvements in heart rate were statistically significant. Treatment was well tolerated. CONCLUSION: Treatment of patients with hypertension and CAD with Bis/Per SPC for 3 months was associated with significant decreases in SBP/DBP and a high proportion of patients achieving BP treatment goals. This was accompanied by an improvement in angina symptoms. Treatment was well tolerated in a broad patient population representative of those seen in everyday clinical practice.


Assuntos
Doença da Artéria Coronariana , Hipertensão , Idoso , Anti-Hipertensivos/uso terapêutico , Bisoprolol/uso terapêutico , Pressão Sanguínea , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/tratamento farmacológico , Combinação de Medicamentos , Feminino , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Perindopril , Federação Russa , Resultado do Tratamento
5.
Artigo em Inglês | MEDLINE | ID: mdl-33706186

RESUMO

Lots of studies showed the combination therapy of perindopril, indapamide and amlodipine could increase BP lowering efficacy and the benefits of high-risk patients. To evaluate potential pharmacokinetic interaction, a simultaneous UPLC-MS/MS quantification method of perindopril, perindoprilat and indapamide in human plasma was developed and validated. The plasma samples were prepared by solid phase extraction, and then separated on an X-terra MS C18 (2.1 mm × 150 mm, 3.5 µm) with isocratic elution. The ion transitions at m/z 369.165 â†’ 172.000 (perindopril), m/z 341.146 â†’ 170.112 (perindoprilat), m/z 366.010 â†’ 132.100 (indapamide), m/z 389.120 â†’ 206.200 (S10211-1, IS1) and m/z 394.080 â†’ 160.200 (S1641, IS2) were monitored under the positive ion mode of electrospray ionization with multiple reaction monitoring. This method exhibited great sensitivity, linearity, accuracy, and precision for the determination of perindopril, perindoprilat and indapamide over the range of 0.250-50.0 ng/mL. The average extraction recovery of perindopril, perindoprilat and indapamide samples at low, medium, and high concentration levels were between 85.9% and 93.6%, respectively. The stability of analytes over different storage and processing conditions in the whole study was also validated. The method is fast, accurate, sensitive and reproducible, which is suitable for the detection of the concentration of perindopril, perindoprilat and indapamide in human plasma.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Indapamida/sangue , Indóis/sangue , Perindopril/sangue , Espectrometria de Massas em Tandem/métodos , Estudos Cross-Over , Combinação de Medicamentos , Humanos , Indapamida/administração & dosagem , Indapamida/química , Indapamida/farmacocinética , Indóis/química , Indóis/farmacocinética , Modelos Lineares , Masculino , Perindopril/administração & dosagem , Perindopril/química , Perindopril/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Extração em Fase Sólida
6.
Adv Ther ; 38(4): 1776-1790, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33630277

RESUMO

INTRODUCTION: To assess real-life effectiveness of a perindopril/indapamide (Per/Ind) single-pill combination (SPC) in patients with hypertension (HT) and type 2 diabetes mellitus (T2DM), obesity and/or metabolic syndrome (MetS). METHODS: This post hoc analysis pooled raw data from four large observational studies (FORTISSIMO, FORSAGE, ACES, PICASSO). Patients, most with uncontrolled blood pressure (BP) on previous treatments were switched to Per/Ind (10 mg/2.5 mg) SPC at study entry. Office systolic and diastolic blood pressures (SBP and DBP) were measured at baseline, 1 month and 3 months. RESULTS: In the overall pooled population (N = 16,763), mean age was 61 ± 12 years, HT duration 11 ± 8 years, and baseline SBP/DBP 162/94 mmHg. T2DM, obesity and MetS were present in 21%, 49% and 27% of patients, respectively. Subgroups had similar mean age and HT duration to the overall population; patients with T2DM were slightly older (64 ± 10 years) with a longer HT duration (13 ± 8 years). Mean BP was approximately 160/95 mmHg in each subgroup. At 1 month, mean SBP decreased by approximately 20 mmHg in the overall population, and by a further 10 mmHg at 3 months. Similar results were observed in the three subgroups, with mean changes from baseline at 3 months of - 28 ± 15/- 13 ± 10 in T2DM; - 30 ± 15/- 14 ± 10 in obesity; and - 31 ± 15/- 15 ± 9 mmHg in MetS. BP decreases were greatest in patients with grade II or grade III HT. BP control rates (< 140/90 mmHg or 140/85 mmHg for T2DM) at 3 months were 59% in T2DM, 67% in obese, and 66% in MetS. No specific safety concerns were raised, particularly concerning ionic (Na, K) or metabolic profiles. CONCLUSIONS: Switching to Per/Ind SPC led to rapid and effective BP decreases in patients with T2DM, obesity, or MetS. BP control was achieved in 6-7 out of 10 previously treated but uncontrolled patients. Treatment was well tolerated. The results confirm the beneficial effects of a Per/Ind SPC for difficult-to-control patient populations.


Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Indapamida , Síndrome Metabólica , Idoso , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Combinação de Medicamentos , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Indapamida/uso terapêutico , Síndrome Metabólica/complicações , Síndrome Metabólica/tratamento farmacológico , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/tratamento farmacológico , Perindopril/uso terapêutico , Resultado do Tratamento
7.
Rev Med Liege ; 76(2): 128-133, 2021 Feb.
Artigo em Francês | MEDLINE | ID: mdl-33543860

RESUMO

Fixed combination atorvastatin-perindopril (Lipercosyl®) for substitution treatment of cardiovascular risk management Lipercosyl® is a fixed combination of atorvastatin and perindopril, a cholesterol-lowering and an antihypertensive agent, which allows blood pressure and cholesterol levels to be controlled in hypertensive patients with dyslipidemia : atorvastatin, an inhibitor of HMG-CoA reductase, and perindopril, an angiotensin converting enzyme inhibitor. Six presentations with different dosages of each molecule are available so the treatment can be individualized. Specific precautions of use to each medication must obviously be observed. The use of such a combination helps to ensure a good level of cholesterol while controlling blood pressure.


Assuntos
Doenças Cardiovasculares , Hipertensão , Anlodipino , Anti-Hipertensivos/farmacologia , Atorvastatina , Pressão Sanguínea , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Combinação de Medicamentos , Fatores de Risco de Doenças Cardíacas , Humanos , Hipertensão/tratamento farmacológico , Perindopril/farmacologia , Fatores de Risco
8.
Biomed Pharmacother ; 135: 111221, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33433351

RESUMO

BACKGROUND: To evaluate the bioequivalence between test and reference formulations of perindopril tert-butylamine under fasting and fed conditions and to assess their pharmacokinetic (PK) and safety profiles. METHOD: A randomized, open-label, single-dose, crossover trial was conducted in healthy Chinese subjects. Test or reference perindopril tert-butylamine tablets (4 mg) were randomly given to subjects under fasting (2-period crossover, with an administration sequence of test tablet (T), reference tablet (R) or RT) and fed (4-period crossover, with an administration sequence of TRTR or RTRT) conditions, while each single administration was followed by a 14-day washout period. The plasma concentrations and corresponding non-compartmental PK parameters of perindopril and perindoprilat were determined. The two formulations were considered to be bioequivalent if the 90 % confidence intervals (CIs) of the geometric mean (GM) ratio (test/reference) for Cmax, AUC0-t, and AUC0-∞ (perindopril) was both within the range of 80-125 %. Safety assessments including vital signs, physical examination, laboratory examination, 12-lead ECG and reports of treatment emergent adverse events (TEAEs) were carefully documented. RESULTS: A total of 64 subjects (32 in each trial) were randomized and all completed the trials. Regardless of fasting or fed trials, the PK characteristics of perindopril and perindoprilat for the test formulation were similar to those of the reference formulation (all P > 0.05). The 90 % CIs of the geometric mean (GM) ratio for Cmax, AUC0-t, and AUC0-∞, respectively, were 92.86-106.81 %, 98.44-102.88 % and 98.48-103.02 % under the fasting condition and 90.64-110.04 %, 96.95-101.90 % and 96.83-101.78 % under the fed condition, which were both within the pre-specified range of 80-125 %. A total of 10 (31.3 %) fasted subjects and 11 (34.4 %) fed subjects experienced 11 and 24 TEAEs, respectively, all of which were within the severity of grade 1. The incidence of TEAEs and drug-related TEAEs were similar between test and reference formulations (all P > 0.05) and no serious TEAEs or deaths occurred during the trials. CONCLUSIONS: The test and reference formulations of perindopril tert-butylamine tablets (4 mg) were bioequivalent and well tolerated in healthy Chinese subjects under fasting and fed conditions.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacocinética , Anti-Hipertensivos/farmacocinética , Butilaminas/farmacocinética , Medicamentos Genéricos/farmacocinética , Perindopril/análogos & derivados , Perindopril/farmacocinética , Administração Oral , Adulto , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Butilaminas/administração & dosagem , Butilaminas/efeitos adversos , China , Estudos Cross-Over , Composição de Medicamentos , Medicamentos Genéricos/administração & dosagem , Medicamentos Genéricos/efeitos adversos , Jejum/sangue , Feminino , Humanos , Masculino , Perindopril/administração & dosagem , Perindopril/efeitos adversos , Período Pós-Prandial , Comprimidos , Equivalência Terapêutica , Adulto Jovem
9.
Adv Ther ; 38(1): 479-494, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33150570

RESUMO

INTRODUCTION: Our objective was to determine the effectiveness of a perindopril/indapamide (Per/Ind) single-pill combination (SPC) in a broad range of patient profiles, including subgroups with varying hypertension severity, age and cardiovascular risk profiles. METHODS: Patient data from four large prospective observational studies (FORTISSIMO, FORSAGE, PICASSO, ACES) were pooled. In each study, patients already treated for hypertension were switched to Per/Ind 10/2.5 mg SPC and systolic and diastolic blood pressure (SBP/DBP) measured at the 1-month (M1) and 3-month (M3) visits. Study endpoints included change in SBP and DBP from baseline to M1 and M3 and the percentage of patients achieving BP control (SBP/DBP < 140/90 mmHg for patients without diabetes or < 140/85 mmHg for patients with diabetes). RESULTS: A total of 16,763 patients were enrolled and received Per/Ind (94% received the full dose of 10/2.5). Mean patient age was 61.4 years (36% were ≥ 65 years old), 57% were women, and 16% had isolated systolic hypertension (ISH). Mean baseline office SBP/DBP was 162/94 mmHg, and mean duration of hypertension was 11 years. Cardiovascular risk factors and comorbid conditions were common in this population. Significant mean reductions in SBP (- 23 mmHg) and DBP (- 11 mmHg) were observed at M1 compared with baseline (P < 0.001), which were maintained at M3 (- 30 mmHg and - 14 mmHg, respectively). At M3, BP control was achieved by 70% of patients (78% for ISH). In patients with SBP ≥ 180 mmHg at baseline (grade III hypertension), the mean SBP/DBP decrease was - 51/- 20 mmHg and 53% achieved BP control. Per/Ind was well tolerated with an overall rate of adverse events of 1.3%, most frequently cough and dizziness at rates of 0.3% and 0.2%, respectively. CONCLUSION: In this hypertensive population including difficult-to-control patient subgroups, switching to Per/Ind 10/2.5 mg SPC led to rapid and important reductions in BP. BP control was achieved in 70% of patients overall in an everyday practice context.


Assuntos
Hipertensão , Indapamida , Idoso , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Combinação de Medicamentos , Feminino , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Indapamida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Perindopril/uso terapêutico , Taurina/análogos & derivados , Resultado do Tratamento
10.
Biomed Chromatogr ; 35(5): e5048, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33314205

RESUMO

A robust and rapid UPLC-MS/MS method has been developed, optimized and validated for determination of amlodipine (AML), indapamide (IND) and perindopril (PRN) in human plasma. A positive electrospray ionization mode was used in a Xevo TQD LC-MS/MS instrument. A single sample preparation step using extraction technique was applied to extract the three analytes from plasma samples. There was no need to extract indapamide from blood samples in a further step. Extraction of the three drugs and internal standards was done using a solvent mixture composed of methyl tertiary butyl ether, dichloromethane and ethyl acetate. The prepared samples were analyzed using an Acquity UPLC HSS C18 (100 × 2.1 mm, 1.7 µm) column. Ammonium acetate and methanol, pumped at a flow rate of 0.3 ml/min, were used as a mobile phase. Method validation was done as per the US Food and Drug Administration guidelines. Linearity was achieved in the range of 0.2-15 ng/ml for AML, 0.5-50 ng/ml for IND and 0.5-120 ng/ml for PRN. Accuracy and precision were estimated and found to be within the acceptable ranges. The rapid chromatography permits analysis of many samples per batch, making the method suitable for clinical and pharmacokinetic investigations. The developed and validated method was applied to estimate AML, IND, and PRN in a fasting bioequivalence study in healthy human volunteers.


Assuntos
Anlodipino , Anti-Hipertensivos , Cromatografia Líquida de Alta Pressão/métodos , Indapamida , Perindopril , Espectrometria de Massas em Tandem/métodos , Adulto , Anlodipino/sangue , Anlodipino/farmacocinética , Anti-Hipertensivos/sangue , Anti-Hipertensivos/farmacocinética , Humanos , Indapamida/sangue , Indapamida/farmacocinética , Limite de Detecção , Pessoa de Meia-Idade , Perindopril/sangue , Perindopril/farmacocinética , Manejo de Espécimes , Equivalência Terapêutica
11.
Kardiologiia ; 60(8): 65-70, 2020 Sep 17.
Artigo em Russo | MEDLINE | ID: mdl-33155960

RESUMO

Aim      To evaluate the effect of 12-month perindopril treatment on structure and function of microvasculature (MV) in patients with chronic heart failure with preserved (HFpEF) and intermediate (HFiEF) left ventricular ejection fraction.Material and methods  30 patients with HFpEF and HFiEF were evaluated. Perindopril at a maximum tolerated dose was administered to all patients for 12 months. Changes in MV structure and function were assessed with photoplethysmography and capillaroscopy prior to the treatment onset and at 12 months, i.e., after completion of the perindopril treatment.Results The 12-month perindopril treatment was associated with improvement of the endothelial function evident as increases in the occlusion index (OI) and the phase shift (PS). OI increased from 1.45 [1.3; 1.6] to 1.8 [1.6; 2.2] (p=0.00004). PS increased from 7.1 ms [4.8; 10.2] to 9.2 ms [6.7; 13.2] (p=0.0003). Stiffness of muscular large blood vessels was decreased. Arterial stiffness index (aSI) decreased from 8.8 [6.6; 11.0] to 7.45 [6.5; 9.4] m /s (р=0.01). The perindopril treatment was associated with increased density of the capillary network at rest (р=0.008) and in tests with venous occlusion (р=0.003) and reactive hyperemia (р=0.0003).Conclusion      The study showed an improvement of endothelial function associated with the 12-month perindopril therapy in patients with HFpEF and HFiEF.


Assuntos
Insuficiência Cardíaca , Rigidez Vascular , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Perindopril/farmacologia , Volume Sistólico , Função Ventricular Esquerda
12.
Kardiologiia ; 60(10): 132-140, 2020 Nov 12.
Artigo em Russo | MEDLINE | ID: mdl-33228516

RESUMO

Arterial hypertension (AH) and exertional headache (EHA) are comorbidities. The article presents a nonsystematic review focused on studying the AH+EHA phenotype. The authors addressed the history of studying the phenotype, several theories about its pathophysiological causes (psychosomatic, neuroanatomical, and baroreflector). The protective "hypertension-associated hypoalgesia" phenotype, a mechanism of its change in AH chronization, and difficulties of differential diagnosis are described. The AH+EHA phenotype requires further study since its incidence is quite high. This will allow developing an individualized approach in prevention and treatment of EHA attacks, decreasing the risk of life-threatening cardiovascular complications, and avoiding iatrogenic complications in patients with AH. The main way to prevent the development of AH+EHA phenotype is patient's compliance, which can be provided by using combination hypotensive drugs to reduce the number of pills and dosing. It is important to take into account possible adverse reactions of the nervous system (medication-overuse headache or EHA aggravation). Considering these conditions, the drug Triplixam can be used for prevention of complications in the AH+EHA phenotype. Triplixam is a fixed triple combination of amlodipine/indapamide/perindopril, and its individual components have low and medium risk for development of headache.


Assuntos
Hipertensão , Indapamida , Cefaleia do Tipo Tensional , Anlodipino/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Comorbidade , Combinação de Medicamentos , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Perindopril/farmacologia , Cefaleia do Tipo Tensional/tratamento farmacológico , Cefaleia do Tipo Tensional/epidemiologia
13.
Adv Ther ; 37(12): 4930-4943, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33026579

RESUMO

INTRODUCTION: The relationship between blood pressure (BP) and cerebral blood flow (CBF) is not fully understood. This study evaluated the impact of a perindopril arginine/indapamide (Pa/I) single-pill combination (SPC) on CBF in middle-aged patients. METHODS: A total of 22 treatment-naïve patients with essential hypertension and at least one hypertension-mediated organ damage and 41 healthy controls were enrolled. At baseline, all participants underwent brain magnetic resonance imaging (MRI); patients with hypertension underwent an additional MRI at end of follow-up. Arterial spin labeling (ASL) was used to calculate CBF in the frontal lobe cortical plate. Patients with hypertension received once-daily Pa/I 5 mg/1.25 mg SPC, which could be increased to Pa/I 10 mg/2.5 mg at 2 weeks if necessary. Patients with hypertension underwent 24-h ambulatory BP monitoring (ABPM) at baseline and end of follow-up. RESULTS: Mean baseline BP values were 146.2/93.1 and 119.1/76.1 mmHg in the hypertension and control groups, respectively. Patients with hypertension had significantly (p < 0.001) lower CBF in the cortical plate of both left (36.2 ± 8.3 vs. 45.3 ± 3.5 ml/100 g/min) and right (37.9 ± 7.9 vs. 45.8 ± 3.2 ml/100 g/min) frontal lobes compared to normotensive controls. At the end of follow-up, there was a statistically significant (p < 0.001) increase in CBF in the cortical plate of both left (from 36.2 ± 8.3 to 47.5 ± 9.8 ml/100 g/min) and right frontal lobes (from 37.9 ± 7.9 to 47.4 ± 10.1 ml/100 g/min) compared to baseline. No significant difference was found between end of follow-up CBF levels in frontal lobes of patients with hypertension and those of healthy controls at baseline. Office BP decreased by 24.2/15.5 mmHg and 24-h ABPM from 145.5/95.3 to 120.8/79.3 mmHg. CONCLUSION: In middle-aged, treatment-naïve patients with hypertension, Pa/I SPC was associated with increased CBF in the cortical plate of the frontal lobes, which achieved levels of normotensive controls. The increase in CBF had no clear association with observed BP changes. REGISTRATION NUMBER: ISRCTN67799751.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Indapamida/uso terapêutico , Perindopril/uso terapêutico , Adulto , Idoso , Pressão Sanguínea/efeitos dos fármacos , Monitorização Ambulatorial da Pressão Arterial , Circulação Cerebrovascular/efeitos dos fármacos , Combinação de Medicamentos , Hipertensão Essencial/tratamento farmacológico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
14.
J Assoc Physicians India ; 68(10): 39-43, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32978924

RESUMO

Background: Hypertension is the biggest contributor to global burden of disease and mortality. Increasing compliance with antihypertensive treatment and achieving a wide BP control in the population represents a major challenge for clinical practice. The benefits of single pill combination versus free-equivalent combination has been demonstrated in several meta-analyses and is now strongly supported by the latest 2018 ESC/ESH guidelines. The RAAS blocker with CCB and thiazide like diuretic is proposed as the optimal combination in patients inadequately controlled by two drugs. Objective: To assess the blood pressure control rate, safety, tolerability and quality of life with triple-drug SPC in patients with grade II/ III hypertension. Methods: Hypertensive patients uncontrolled (BP ≥ 140/90 mmHg) on two-drug therapy were recruited in an open-label, phase III clinical trial conducted in outpatient setting in India with 6 months treatment period. No other antihypertensive medication except the study medication was received by the patients. Results: Out of 218 evaluable patients the observed average blood pressure reduction achieved from baseline to end of study at 6 months was Systolic Blood Pressure (SBP) 28.5 mm Hg / Diastolic Blood Pressure (DBP) 13.8 mm Hg. The quality of life (QoL) questionnaire demonstrated improvement in QoL for all patients. Conclusion: This study showed the clinical efficacy, safety and acceptability of the perindopril/indapamide/amlodipine SPC in patients with grade 2/3 hypertension inadequately controlled with two-drug therapy. The clinical effectiveness was observed in more than 96 % patients. The benefit of single-pill combination (SPC) therapy in hypertension control was reconfirmed in this study.


Assuntos
Hipertensão/tratamento farmacológico , Indapamida , Anlodipino/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Combinação de Medicamentos , Humanos , Índia , Perindopril/efeitos adversos , Qualidade de Vida , Resultado do Tratamento
15.
Vnitr Lek ; 66(3): 190-195, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32972174

RESUMO

Over the last 30 years, the number of cardiovascular causes of death has decreased, but Cardi-ovascular Disease has been the leading cause of mortality and morbidity in the Czech Republic. In spite of a clear decline, this still persisting primacy is due to the failure to achieve the target recommended values and the late initiation of pharmacotherapy. We know that lifetime LDL cholesterol exposure reduced by 1 mmol/l is associated with a 54% reduction in the incidence of coronary events. A lifetime lower systolic BP of 10 mmHg is associated with a 45% reduction in the incidence of coronary events. Lifetime exposure to a combination of LDL cholesterol lower by 1 mmol/l and systolic BP lower by 10 mm Hg was associated with a 78% reduction in the lifetime risk of coronary events and a 68% reduction in the lifetime risk of a cardiovascular death. The benefits of this intervention increase over time - long-term exposure to even a small difference in LDL cholesterol and systolic pressure can significantly reduce the lifetime risk of cardiovascular disease, if it persists over the time. In this respect, the recently presented new common ESC/ EAS recommendations from 2019, that is to focus treatment on dyslipidemia on a lifelong approach of reducing CV risk and therapeutic lifelong intervention with aim to achieve lower LDL cholesterol levels at all risk levels. Perindorpil antihypertezive and atorvasatin hypolipidemic drugs, ideally in a fixed combination, are able to reduce the patient's CV risk early. The ideal motivation for adherence of patients is the introduced concept of the vascular age, respectively the aging.


Assuntos
Doenças Cardiovasculares , Dislipidemias , Hipertensão , Atorvastatina , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , República Tcheca , Dislipidemias/tratamento farmacológico , Humanos , Hipertensão/tratamento farmacológico , Perindopril/uso terapêutico
16.
J Chromatogr Sci ; 58(8): 747-758, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32705119

RESUMO

Two fast, accurate and selective stability-indicating methods were developed and validated for the simultaneous determination of bisoprolol, perindopril and three of their possible degradation products. The first proposed method was a gradient reversed phase-high-performance liquid chromatography (HPLC) method, whereas the second was a capillary electrophoresis method. The structures of the obtained degradation products were elucidated using infrared and mass spectrometry. They were also confirmed to be either a drug impurity in the British Pharmacopoeia or a precursor to such impurity. The linearity for bisoprolol and perindopril was achieved in the range of 1-20 µg mL-1 and 5-30 µg mL-1 for HPLC and capillary electrophoresis methods, respectively. The proposed methods were validated according to the International Conference on Harmonisation guidelines. The HPLC method proved to be more sensitive and succeeded in the quantitative determination of the obtained degradation products. Also, it was able to quantify perindopril impurity up to three times lower than the desired limit set by the British Pharmacopoeia. They were successfully employed in the determination of bisoprolol and perindopril in their combined pharmaceutical formulation.


Assuntos
Bisoprolol , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia de Fase Reversa/métodos , Eletroforese Capilar/métodos , Perindopril , Bisoprolol/análise , Bisoprolol/química , Contaminação de Medicamentos , Estabilidade de Medicamentos , Limite de Detecção , Modelos Lineares , Perindopril/análise , Perindopril/química , Reprodutibilidade dos Testes , Comprimidos
17.
Kardiologiia ; 60(5): 1149, 2020 Jun 03.
Artigo em Russo | MEDLINE | ID: mdl-32515706

RESUMO

Aim To study tactics of outpatient physicians in choosing the treatment when the previous double antihypertensive therapy (AHT) fails and to analyze the effectivity of an amlodipine/indapamide/perindopril arginine triple combination (TC).Material and methods The program included 1252 patients with arterial hypertension (AH); the TC group consisted of 992 (79.23 %) patients (38.3 % males; age, 61.6 [55.0; 67.9]); the control group included 260 (20.77 %) patients (37.7 % males; age, 60.6 [53.3; 67.4]). The main inclusion criteria were essential AH, age 18-79 years, insufficient response to previous AHT (clinical systolic blood pressure (SBP) >140-179 mm Hg). The study duration was three months. The following parameters were evaluated: dynamics of clinical and ambulatory BP (BP self-monitoring (BPSM); frequency of achieving the first goal of <140 / 90 mm Hg and the goal of <130 / 80 mm Hg); and changes in glomerular filtration rate (GFR) and quality of life (QoL). Responses to TC were analyzed in groups with different ranges of increased baseline SBP in patients with AH and diabetes mellitus (DM)/impaired glucose tolerance (IGT), overweight or obesity, and chronic kidney disease (CKD, reduced estimated GFR (eGFR <60 ml/min/1.73 m2). Safety was evaluated based on records of adverse events (AEs).Results The TC group had a more severe condition at baseline by clinical parameters and history and had higher baseline BP, which made difficult the intergroup comparison. Nevertheless at three months, the decrease in clinical SBP was more pronounced in the TC group (from 162.1  to 126.8 mm Hg, Δ=35.7  mm Hg) than in the control group (from 157.8 to 128.4  mm Hg, Δ=29.4  mm Hg). 87.8% of patients in the TC group and 81.9 % (р=0.012) in the control group achieved the first BP goal of <140 / 90 mm Hg; 34.3% and 28.2% of patients, respectively, achieved the BP goal of <130 / 80 mm Hg (р=0.055). The more effective SBP control in the TC group was associated with a pronounced BP decrease with higher BP values at baseline, which was also confirmed by an analysis in subgroups with SBP 140-160, 160-180, and >180 mm Hg. The TC treatment was associated with a pronounced antihypertensive effect with respect of BPSM values, improved QoL, and renal function. Significant decreases in BP and achievement of BP goals by a vast majority of patients receiving TC were also observed in subgroups with DM or IGT, overweight and/or obesity, and CKD. AEs were observed during the treatment only in 8 patients (0.64 %), which confirmed good tolerability and high safety of the therapy.Conclusion The study results demonstrated a therapeutic effect of the amlodipine/indapamide/perindopril arginine fixed-dose combination (Triplixam®). This effect was evident as control of clinical BP with any baseline BP level, including different ranges of increased SBP, in AH combined with DM, IGT, obesity, and CKD, which offers advantages over a subjective choice of AHT. TC improved BPSM values, QoL indexes, provided nephroprotection, and was well tolerated.


Assuntos
Hipertensão , Idoso , Anlodipino , Anti-Hipertensivos , Arginina , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Combinação de Medicamentos , Feminino , Humanos , Indapamida , Masculino , Pessoa de Meia-Idade , Perindopril , Qualidade de Vida , Resultado do Tratamento
18.
Acta Pharm ; 70(4): 515-525, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32412432

RESUMO

Cisplatin-induced nephrotoxicity limits its anticancer effectiveness, thus this study's aim was to assess the potential modulatory effect of perindopril on cisplatin-induced nephrotoxicity and to elucidate the possible underlying mechanisms. Renal dysfunction was induced in mice by a single injection of cisplatin (10 mg kg-1, i.p.) and perindopril was administered orally (2 mg kg-1, once daily) for 5 days. Perindopril remarkably ameliorated cisplatin-induced perturbations in renal histology, renal levels of tumor necrosis factor-alpha, interleukin-6 and interleukin-10, apoptosis-regulating protein expressions (Bax and Bcl2), and partially normalized Bax to Bcl2 ratio and active caspase 3 protein expression. Conversely, perindopril had no significant effect on cisplatin-induced elevations in serum creatinine and urea, microalbuminuria, kidney to body weight ratio, lipid peroxidation marker, superoxide dismutase and catalase activities and reduced glutathione content. In conclusion, perindopril may be safely used with cisplatin in mice since it ameliorated cisplatin-induced histopathological changes, inflammation and apoptosis without affecting renal biomarkers or oxidative stress.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Antineoplásicos/toxicidade , Caspase 3/fisiologia , Cisplatino/antagonistas & inibidores , Cisplatino/toxicidade , Citocinas/fisiologia , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Perindopril/farmacologia , Albuminúria/induzido quimicamente , Albuminúria/prevenção & controle , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/biossíntese , Inflamação/patologia , Testes de Função Renal , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos
19.
Kardiologiia ; 60(4): 10-17, 2020 Apr 13.
Artigo em Russo | MEDLINE | ID: mdl-32394851

RESUMO

Aim To evaluate effects of different types of combination drug therapy on indexes of 24-h blood pressure monitoring (24-h BPM), arterial stiffness, and central aortic pressure (CAP) in patients with arterial hypertension (AH) and prediabetes.Materials and methods The study included 120 patients with AH and prediabetes. After randomization using envelopes, three treatment groups were formed: group 1, patients receiving perindopril, indapamide SR, and metformin (n=40); group 2, patients receiving perindopril, moxonidin, and metformin (n=40); and group 3, patients receiving perindopril, indapamide SR, and amlodipine (n=40). 24-h BPM, determination of arterial stiffness, and measurement of CAP were performed for all patients.Results After 24 weeks of treatment, patients of all groups showed statistically significant improvements of most indexes of 24-h BPM, arterial stiffness, and CAP. In groups 2 and 3, the treatment was associated with significantly more pronounced beneficial changes in 24-BPM, arterial stiffness, and CAP compared to group 1. Antihypertensive and vasoprotective effects of the perindopril+moxonidin+metformin and perindopril+indopamide SR+amlodipine combinations were comparable.Conclusion The observed statistically significant antihypertensive and vasoprotective effects of the perindopril+moxonidin+metformin combination along with its known positive metabolic effect allow recommendation of this combination therapy to patients with AH and prediabetes as an effective strategy for BP control.


Assuntos
Hipertensão , Estado Pré-Diabético , Anlodipino , Anti-Hipertensivos , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Combinação de Medicamentos , Humanos , Indapamida , Perindopril
20.
Cell Mol Biol (Noisy-le-grand) ; 66(2): 198-203, 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32415948

RESUMO

This experiment aimed to study the effect of trimetazidine combined with perindopril on NT-proBNP levels in rats with dilated cardiomyopathy (DCM). 40 SD rats were selected and 10 rats were randomly selected to continue to be fed as the blank group. The other 30 rats were injected with adriamycin to establish the DCM rat model. Then they were divided into 3 groups, namely control group (without any drug intervention), trimetazidine group (with trimetazidine single-agent intervention) and combination drug group (with trimetazidine combined with perindopril intervention), with 10 DCM rats in each group. After 4 weeks of intervention, left ventricular ejection fraction (LVEF), left ventricular end-diastolic dimension (LVEDD) and left ventricular end-systolic diameter (LVESD) of rats were measured by echocardiography. The changes of plasma brain natriuretic peptide (BNP) level and n-terminal pro-brain natriuretic peptide (NT-proBNP) were detected by ELISA. RT-PCR was used to detect the regulation of angiotensin II type 1 receptor (AT1Rs) and lamin A mRNA expression in rat myocardium. After the intervention, the LVEF%, LVEDD and LVESD measured values of the rats in the combination drug group were significantly better than those in the trimetazidine group and the control group (P< 0.05). The BNP, NT-proBNP and AT1Rs levels of the rats in the combination drug group were significantly lower than those in the trimetazidine group and the control group. The difference was statistically significant (p< 0.05). The lamin A expression of the rats in the combination drug group was significantly higher than that in the trimetazidine group and the control group. The difference was statistically significant (P< 0.05). Compared with trimetazidine single-agent, trimetazidine combined with perindopril can significantly improve the cardiac function of rats with dilated cardiomyopathy, reduce the serum NT-proBNP level and improve the expression of AT1Rs and lamin A in rats.


Assuntos
Cardiomiopatia Dilatada/sangue , Cardiomiopatia Dilatada/tratamento farmacológico , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Perindopril/uso terapêutico , Trimetazidina/uso terapêutico , Animais , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/fisiopatologia , Diástole/efeitos dos fármacos , Lamina Tipo A/metabolismo , Masculino , Perindopril/farmacologia , Ratos Sprague-Dawley , Receptor Tipo 1 de Angiotensina/metabolismo , Volume Sistólico/efeitos dos fármacos , Análise de Sobrevida , Sístole/efeitos dos fármacos , Trimetazidina/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos
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