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1.
J Assoc Physicians India ; 67(9): 65-68, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31561692

RESUMO

Background: Current European hypertension guidelines recommend to initiate the treatment of patients with moderate to severe hypertension with a Single Pill Combination (SPC) containing two drugs, as SPC use leads to more effective and faster blood pressure control. The guidelines also recommend tighter blood pressure control in hypertensive patients with cardiovascular risk factors such as diabetes mellitus. Objective: To evaluate efficacy on blood pressure reduction and acceptability of the single pill combination of Perindopril/Indapamide in patients with moderate to severe hypertension. Methods: In this multicentre, prospective, observational study, patients with moderate to severe hypertension were prescribed Perindopril 4mg/ Indapamide 1.25 mg for 90 days. The primary outcomes were blood pressure decrease and achievement of BP control. Patients were up-titrated to Perindopril 8 mg/Indapamide 2.5 mg SPC, if target BP control (≤140/90 mm Hg) could not be achieved by day 30. Results: In this study, 173 hypertensive patients, with a mean age of 51 years were enrolled at 3 centres from different geographic areas within India. Mean SBP/DBP decreased significantly from baseline (155.70 (±10.39) / 95.72 (±6.99) mmHg) over 90 days (30.31 (±14.15) / 17.14 (±9.33) mmHg; p < 0.0000). Few side effects were reported during the 90-day period. Conclusion: : Perindopril/Indapamide given as a SPC was found to be an effective and well-tolerated antihypertensive combination resulting in rapid blood pressure control in patients with moderate to severe hypertension.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Indapamida/uso terapêutico , Perindopril/uso terapêutico , Pressão Sanguínea , Combinação de Medicamentos , Humanos , Índia , Pessoa de Meia-Idade , Estudos Prospectivos
2.
Molecules ; 24(9)2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31067700

RESUMO

A global approach that is based on a combination of mass spectrometry (MS) and nuclear magnetic resonance (NMR) data has been developed for a complete and rapid understanding of drug degradation mixtures. We proposed a workflow based on a sample preparation protocol that is compatible to MS and NMR, the selection of the most appropriate experiments for each technique, and the implementation of prediction software and multivariable analysis method for a better interpretation and correlation of MS and NMR spectra. We have demonstrated the efficient quantification of the remaining active pharmaceutical ingredient (API). The unambiguous characterization of degradation products (DPs) was reached while using the potential of ion mobility-mass spectrometry (IM-MS) for fragment ions filtering (HDMSE) and the implementation of two-dimensional (2D) NMR experiments with the non-uniform sampling (NUS) method. We have demonstrated the potential of quantitative NMR (qNMR) for the estimation of low level DPs. Finally, in order to simultaneously monitor multi-samples, the contribution of partial least squares (PLS) regression was evaluated. Our methodology was tested on three indapamide forced degradation conditions (acidic, basic, and oxidative) and it could be easily transposed in the drug development field to assist in the interpretation of complex mixtures (stability studies, impurities profiling, and biotransformation screening).


Assuntos
Desenvolvimento de Medicamentos , Estabilidade de Medicamentos , Indapamida/química , Cromatografia Líquida de Alta Pressão , Humanos , Indapamida/uso terapêutico , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Oxirredução/efeitos dos fármacos
3.
Kardiologiia ; 59(3): 18-26, 2019 Apr 12.
Artigo em Russo | MEDLINE | ID: mdl-30990137

RESUMO

OBJECTIVE: to investigate the impact of indapamide / perindopril single-pill combination (I / P SPC) on arterial stiffness parameters, blood pressure (BP) level and BP variability (BPV) in middle-aged patients with stage II grade 1-2 essential arterial hypertension (EAH). Materials and methods. We retrospectively formed a group of patients with stage II grade 1-2 EAH who had not previously received regular antihypertensive therapy (AHT) (n=52, mean age 52.9±6.0 years). All patients were treated with I / P SPC and all of them achieved target office BP level (less than 140 / 90 mm Hg). After 12 weeks of follow-up (from the time of reaching the target BP) assessment of AHT effectiveness (general clinical data, ambulatory blood pressure monitoring [ABPM], volume sphygmography, echocardiography), and vascular stiffness evaluation were performed. RESULTS: At the end of follow-up office systolic BP (SBP), diastolic BP (DBP), pulse BP, day-time, night-time and 24­hour SBP and DBP significantly (p<0.001 for all) decreased. According to the ABPM data day-time, nighttime, and 24­hour systolic BPV significantly decreased (p=0.029, p=0.006 and p<0.001, respectively); day-time and 24­hour diastolic BPV also significantly decreased (p=0.001 and p<0.001, respectively). Day-night standard deviation (SDdn) significantly decreased too (p=0.002 and p<0.001, respectively). Volumetric sphygmography showed significant decrease of right cardio-ankle vascular index (CAVI) (from 8.20±1.29 to 7.58±1.44, p=0.001) and of left CAVI (from 8.13±1.40 to 7.46±1.43, p<0.001), as well as reduction of the number o f patients with a right- and / or left-CAVI >9.0 (from 32.7 to 11.5 %, p=0.018). According to assessment of arterial stiffness using the Vasotens24 software package, the arterial stiffness index (ASI) significantly (p<0.001) decreased from 153.5±29.9 to 138.3±20.0 (by -9.2±13.1 %). Transthoracic echocardiography data demonstrated significant decrease (p<0.001) in effective arterial elastance (from 1.82±0.43 to 1.58±0.36 mm Hg; by -11.85±16.29 %) and significant (p<0.001) increase in the arterial compliance - from 1.27±0.34 to 1.54±0.38 mm Hg / ml (+26.95±38.06 %). CONCLUSION: In AHT naive patients 40-65 years old with stage II grade 1-2 EAH therapy with I / P SPC provided effective 24­hour BP control, reduced BPV and improved arterial stiffness parameters.


Assuntos
Hipertensão , Indapamida/uso terapêutico , Perindopril/uso terapêutico , Anti-Hipertensivos , Arginina , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Humanos , Hipertensão/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
4.
Kardiologiia ; 58(9): 21-30, 2018 09.
Artigo em Russo | MEDLINE | ID: mdl-30295196

RESUMO

AIM: to assess antihypertensive efficacy of the fixed-dose amlodipine/indapamide/perindopril arginine combination in hypertensive patients in real clinical setting. METHODS: We included in the 3­month clinical program 1 599 patients with arterial hypertension (AH) (38.8 % men, mean age 61.6±10 years). Primary outcomes were change of office and ambulatory (home blood pressure monitoring) systolic and diastolic blood pressure (SBP and DBP) from baseline to 3 months and rate of achievement of target BP.


Assuntos
Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Arginina/uso terapêutico , Hipertensão/tratamento farmacológico , Indapamida/uso terapêutico , Perindopril/uso terapêutico , Centros Médicos Acadêmicos , Idoso , Anlodipino/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Arginina/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Monitorização Ambulatorial da Pressão Arterial , Combinação de Medicamentos , Feminino , Humanos , Hipertensão/fisiopatologia , Indapamida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Perindopril/efeitos adversos , Federação Russa
5.
J Clin Hypertens (Greenwich) ; 20(10): 1507-1515, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30251403

RESUMO

Left ventricular hypertrophy develops in 36%-41% of hypertensive patients and independently predicts cardiovascular events and total mortality. Moreover, drug-induced reduction in left ventricular mass (LVM) correlates with improved prognosis. The optimal thiazide-type diuretic for reducing LVM is unknown. Evidence regarding potency, cardiovascular events, sodium, and potassium suggested the hypothesis that "CHIP" diuretics (CHlorthalidone, Indapamide, and Potassium-sparing diuretic/hydrochlorothiazide [PSD/HCTZ]) would reduce LVM more than HCTZ. Systematic searches of five databases were conducted. Among the 38 randomized trials, a 1% reduction in systolic blood pressure (SBP) predicted a 1% reduction in LVM, P = 0.00001. CHIP-HCTZ differences in reducing LVM differed across trials (ie, heterogeneity), making interpretation uncertain. However, among the 28 double-blind trials, heterogeneity was undetectable, and HCTZ reduced LVM (percent reduction [95% CI]) by -7.3 (-10.4, -4.2), P < 0.0001. CHIP diuretics surpassed HCTZ in reducing LVM: chlorthalidone -8.2 (-14.7, -1.6), P = 0.015; indapamide -7.5 (-12.7, -2.3), P = 0.005; and all CHIP diuretics combined -7.7 (-12.2, -3.1), P < 0.001. The comparison of PSD/HCTZ with HCTZ had low statistical power but favored PSD/HCTZ: -6.0 (-14.1, +2.1), P = 0.149. Thus, compared to HCTZ, CHIP diuretics had twice the effect on LVM. CHIP diuretics did not surpass HCTZ in reducing systolic or diastolic blood pressure: -0.3 (-5.0, +4.3) and -1.6 (-5.6, +2.4), respectively. The strength of evidence that CHIP diuretics surpass HCTZ for reducing LVM was high (GRADE criteria). In conclusion, these novel results have demonstrated that CHIP diuretics reduce LVM 2-fold more than HCTZ among hypertensive patients. Although generally related to LVM, blood pressure fails to explain the superiority of CHIP diuretics for reducing LVM.


Assuntos
Clortalidona/farmacologia , Diurético Poupador de Potássio/farmacologia , Hidroclorotiazida/farmacologia , Hipertensão/tratamento farmacológico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Indapamida/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Clortalidona/administração & dosagem , Clortalidona/uso terapêutico , Diurético Poupador de Potássio/administração & dosagem , Diurético Poupador de Potássio/uso terapêutico , Quimioterapia Combinada/métodos , Feminino , Humanos , Hidroclorotiazida/administração & dosagem , Hidroclorotiazida/uso terapêutico , Hipertensão/complicações , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/epidemiologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Hipertrofia Ventricular Esquerda/prevenção & controle , Indapamida/administração & dosagem , Indapamida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores de Simportadores de Cloreto de Sódio/farmacologia , Tiazidas/farmacologia , Tiazidas/uso terapêutico
6.
J Hypertens ; 36(6): 1247-1255, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29465713

RESUMO

BACKGROUND: Found in 36-41% of hypertension, elevated left ventricular mass (LVM) independently predicts cardiovascular events and total mortality. Conversely, drug-induced regression of LVM predicts improved outcomes. Previous studies have favored renin-angiotensin system inhibitors (RASIs) over other antihypertensives for reducing LVM but ignored differences among thiazide-type diuretics. From evidence regarding potency, cardiovascular events, and electrolytes, we hypothesized a priori that 'CHIP' diuretics [CHlorthalidone, Indapamide and Potassium-sparing Diuretic/hydrochlorothiazide (PSD/HCTZ)] would rival RASIs for reducing LVM. METHOD AND RESULTS: Systematic review yielded 12 relevant double-blind randomized trials. CHIPs were more closely associated with reduced LVM than HCTZ (P = 0.004), indicating that RASIs must be compared with each diuretic separately. Publication bias favoring RASIs was corrected by cumulative analysis. For reducing LVM, HCTZ tended to be less effective than RASIs. However, the following surpassed RASIs: chlorthalidone Hedge's G: -0.37 (95% CI -0.72 to -0.02), P = 0.036; indapamide -0.20 (-0.39 to -0.01), P = 0.035; all CHIPs combined (with 61% of patients in one trial) -0.25 (-0.41to -0.09), P = 0.002. Statistical significance (P < 0.05) did not depend on any one trial. CHIPs reduction in LVM was 37% greater than that from RASIs. CHIPs superiority tended to increase with trial duration, from a negligible effect at 0.5 year to a maximal effect at 0.9-1.0 years: -0.26 (-0.43 to -0.09), P = 0.003. Fifty-eight percent of patients had information on echocardiographic components of LVM: relative to RASIs, CHIPs significantly reduced end-diastolic LV internal dimension (EDLVID): -0.18 (-0.36 to -0.00), P = 0.046. Strength of evidence favoring CHIPs over RASIs was at least moderate. CONCLUSION: In these novel results in patients with hypertension, CHIPs surpassed RASIs for reducing LVM and EDLVID.


Assuntos
Diuréticos/uso terapêutico , Hidroclorotiazida/uso terapêutico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacos , Idoso , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Clortalidona/uso terapêutico , Diurético Poupador de Potássio/uso terapêutico , Método Duplo-Cego , Eletrólitos , Feminino , Humanos , Hipertensão/fisiopatologia , Indapamida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Regressão , Inibidores de Simportadores de Cloreto de Sódio/uso terapêutico , Resultado do Tratamento
7.
Nutr Diabetes ; 8(1): 7, 2018 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-29343817

RESUMO

BACKGROUND/OBJECTIVES: We aimed to evaluate the relationship between BMI and the risk of renal disease in patients with type 2 diabetes in the Action in Diabetes and Vascular Disease: PreterAx and DiamicroN Modified-Release Controlled Evaluation (ADVANCE) study. SUBJECTS/METHODS: Participants were divided into six baseline BMI categories: <18.5 (underweight, n = 58); ≥18.5 to <25 (normal, n = 2894); ≥25 to <30 (overweight, n = 4340); ≥30 to <35 (obesity grade 1, n = 2265); ≥35 to <40 (obesity grade 2, n = 744); and ≥40 kg/m2 (obesity grade 3, n = 294); those underweight were excluded. The composite outcome "major renal event" was defined as development of new macroalbuminuria, doubling of creatinine, end stage renal disease, or renal death. These outcomes and development of new microalbuminuria were considered individually as secondary endpoints. RESULTS: During 5-years of follow-up, major renal events occurred in 487 (4.6%) patients. The risk increased with higher BMI. Multivariable-adjusted HRs (95% CIs), compared to normal weight, were: 0.91 (0.72-1.15) for overweight; 1.03 (0.77-1.37) for obesity grade 1; 1.42 (0.98-2.07) for grade 2; and 2.16 (1.34-3.48) for grade 3 (p for trend = 0.006). These findings were similar across subgroups by randomised interventions (intensive versus standard glucose control and perindopril-indapamide versus placebo). Every additional unit of BMI over 25 kg/m2 increased the risk of major renal events by 4 (1-6)%. Comparable results were observed with the risk of secondary endpoints. CONCLUSIONS: Higher BMI is an independent predictor of major renal events in patients with type 2 diabetes. Our findings encourage weight loss to improve nephroprotection in these patients.


Assuntos
Índice de Massa Corporal , Diabetes Mellitus Tipo 2/complicações , Nefropatias/etiologia , Rim/patologia , Obesidade/complicações , Idoso , Albuminúria/etiologia , Glicemia/metabolismo , Creatinina/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Combinação de Medicamentos , Feminino , Seguimentos , Humanos , Hipoglicemiantes , Indapamida/uso terapêutico , Nefropatias/sangue , Nefropatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Sobrepeso/complicações , Perindopril/uso terapêutico , Valores de Referência , Insuficiência Renal/sangue , Insuficiência Renal/epidemiologia , Insuficiência Renal/etiologia
8.
Kardiologiia ; 58(11): 63-71, 2018 Nov 24.
Artigo em Russo | MEDLINE | ID: mdl-30625078

RESUMO

Most patients with arterial hypertension (AH) for successful long-term blood pressure (BP) control require combination of antihypertensive drugs acting on various target organs. Accumulated experience shows that about 30 % of patients require combination therapy with 3 drugs from different pharmacological classes. Efficacy of BP control in real clinical practice with the use of various doses of perindopril, indapamide, and amlodipine as components of taken once-daily triple fixed combination was assessed in the 3-months prospective observational open-label PETRA study. In this study data of office BP measurements and 24-hour ambulatory BP monitoring (ABPM) were obtained from 11209 ambulatory patients (47.6 % women) with AH. Initial mean office BP (BPmoff) was 156.58±16.10 / 91.56±9.33 mm Hg, AH duration - 9.48±7.19 years. After switching to triple fixed dose combination of perindopril, indapamide, and amlodipine BPmoff decreased by 24.81±15.47 / 11.41±9.90 mm Hg (p<0.0001). Doses of perindopril, indapamide, and amlodipine in combination at the final visit were 5 / 1.25 / 5, 10 / 2.5 / 5, and 10 / 2.5 / 10 mg. 24-hour ambulatory BP monitoring (ABPM) was carried out in 76 patients. Mean 24-hour BP lowed from mean 155.51±17.43 / 85.28±11.48 down to 134.63±12.51 / 77.83±8.99 mm Hg (p<0.0001). Clinically relevant improvement of a number of parameters of metabolism occurred after 3 months of the study (in particular, lowering of levels of total and low-density lipoprotein cholesterol [-8.6 and - 11.4 %, respectively], triglycerides [-12,1 %], fasting blood glucose [-6.6 %]). Thus, results of the PETRA study confirmed 24-hour long antihypertensive efficacy of triple fixed dose combination of perindopril, indapamide, and amlodipine. This drug combination can present novel possibility in treatment of patients with AH who have not achieved target BP values on preceding dual combination therapy and fully corresponds with the single pill concept for formation of adherence to therapy.


Assuntos
Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Hipertensão , Indapamida/uso terapêutico , Perindopril/uso terapêutico , Pressão Sanguínea , Combinação de Medicamentos , Feminino , Humanos , Hipertensão/tratamento farmacológico , Masculino , Estudos Prospectivos , Resultado do Tratamento
9.
Ter Arkh ; 90(12): 28-33, 2018 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-30701830

RESUMO

AIM: To study the effectiveness of a fixed combination of perindopril and amlodipine, with the subsequent addition of indapamide-retard in male patients with arterial hypertension (AH), obesity and severe sleep apnea (OSAS). MATERIALS AND METHODS: The study included 43 male patients in whom antihypertensive therapy titration was performed to achieve target blood pressure values with a fixed combination of calcium antagonist amlodipine (10 mg) and an angiotensin-converting inhibitor perindopril (5-10 mg) and indapamide-retard. At baseline and after 4-6 weeks, the effectiveness of antihypertensive therapy was monitored according to clinical measurements and ambulatory blood pressure monitoring (ABPM). An assessment of the carotid-femoral pulse wave velocity (cfPWV), aortic PWV (aoPWV), and ankle-brachial PWV (abPWV) was performed. RESULTS: Target blood pressure values (according to clinical blood pressure, 24-hour blood pressure monitoring) during therapy with amlodipine 10 mg and perindopril 10 mg reached 65% of patients and another 30% reached target blood pressure when adding indapamide-retard 1.5 mg, that is - 95% of all patients included in the study. Upon reaching the target blood pressure values, a significant decrease in cfPWV, aoPWV and abPWV was observed. CONCLUSION: The fixed combination of perindopril arginine and amplodipine, with the addition of indapamide retard in male patients with hypertension 1st degree in the presence of obesity and severe OSAS allows to reach effective control of blood pressure and improve the elastic properties of large arteries, which can lead to a favorable organoprotective effect in this category of patients.


Assuntos
Anti-Hipertensivos , Hipertensão , Indapamida , Apneia Obstrutiva do Sono , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Combinação de Medicamentos , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Indapamida/uso terapêutico , Masculino , Obesidade/complicações , Perindopril/uso terapêutico , Análise de Onda de Pulso , Apneia Obstrutiva do Sono/complicações
10.
Kardiologiia ; 57(11): 76-83, 2017 Nov.
Artigo em Russo | MEDLINE | ID: mdl-29276921

RESUMO

Effective control of arterial pressure (AP) is achieved only in ⅓ of patients with arterial hypertension. It is especially difficult to achieve control of systolic (S) AP in elderly patients in whom SAP is the strongest prognostic factor of cardiovascular complications. Thiazide and thiazide-like diuretics and calcium antagonists are effective for lowering of elevated SAP and pulse (P) AP including aortic PAP elevation of which is associated with high stiffness of arterial wall and is typical for elderly people. Combination of a thiazide diuretic and a calcium antagonist has been recommended by modern guidelines on arterial hypertension (AH) management but until recently it has not found wide application because of absence of a fixed preparation. Evidence base of indapamide-retard and amlodipine use in AH, their profiles of efficacy and safety are such that their combination can become an alternative variant for treatment of patients with AH. Appearance of a fixed indapamide-retard/amlodipine combination opens new perspectives of effective therapy of AH with high SAP and PAP in elderly and other patients with high stiffness of arterial wall.


Assuntos
Anlodipino/uso terapêutico , Hipertensão , Indapamida/uso terapêutico , Anti-Hipertensivos , Pressão Arterial , Diuréticos , Combinação de Medicamentos , Humanos , Hipertensão/tratamento farmacológico , Resultado do Tratamento
11.
Kardiologiia ; 57(8): 60-70, 2017 08.
Artigo em Russo | MEDLINE | ID: mdl-29041894

RESUMO

The proportion of elderly in the population is growing. The two-thirds of those over the age of 65 has arterial hypertension (AH). There is a significant increase in the incidence of isolated systolic hypertension with age. The relationship between increased pulse pressure, arterial stiffness and aging processes has been repeatedly confirmed in population epidemiological studies. Some evidence has been found that the treatment of AH in the elderly is accompanied by a reduction in the risk of cardiovascular diseases. Target levels of blood pressure (BP) in elderly people with AH younger than 80 years, as well as over 80 years with a satisfactory physical and cognitive status with systolic BP ≥160 mm Hg is recommended to be reduce to 140-150 mm Hg. Low doses of thiazide diuretics and long-acting calcium channels blockers (mainly dihydropyridine) are attributed to first-line drugs in order to effectively reduce cardiovascular complications in the treatment of AH in the elderly. Their prescription as a fixed-dose combination appears to be an optimal solution when monotherapy is fails.


Assuntos
Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Indapamida/uso terapêutico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea/efeitos dos fármacos , Quimioterapia Combinada , Humanos , Inibidores de Simportadores de Cloreto de Sódio/uso terapêutico
12.
Kardiologiia ; 57(4): 33-37, 2017 04.
Artigo em Russo | MEDLINE | ID: mdl-28762903

RESUMO

AIM: to assess adherence of patients to antihypertensive therapy with fixed perindopril and indapamide combination (FPIC) as well as to elucidate causes of changes of therapy after 6 months. MATERIAL AND METHODS: In 6 months after termination of the FORSAGE observational program we interviewed over telephone 148 of 1299 patients who achieved target blood pressure (BP) values. RESULTS: Adherence to treatment was high - 67.5% of patients continued to take the drug. In 87.9% of patients BP was kept on target level (<140 and 90 mm Hg), in 12.1% BP was above this level. Most patients were satisfied by results of treatment. Infrequent hypertensive crises persisted in 6.1% of patients; 3% of patients sought emergency service. Among 48 patients who stopped taking FPIC 22 (45.8%) made this decision themselves, 11 - on physicians advice. Main causes of cancellation of treatment were high cost of the drug, its absence in the list of concessional mediciations, physicians statement "course treatment completed, condition improved". Among those who stopped treatment 10 patients could not report values of their BP; in 28 (58.3%) BP was at and in 10 (20.8%) above target level; crises were registered in 8.3% of patients, 4.2% of patients called ambulances, 1 patient suffered stroke. Of 48 patients who stopped treatment with FLIC 19 consented to self report assessment health status; 84% of reported scores were above 5, but no score was equal to 9 or 10.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Indapamida/uso terapêutico , Perindopril/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Monitorização Ambulatorial da Pressão Arterial , Combinação de Medicamentos , Quimioterapia Combinada , Humanos , Hipertensão/psicologia , Adesão à Medicação , Acidente Vascular Cerebral
13.
Kardiologiia ; 57(4): 79-88, 2017 04.
Artigo em Russo | MEDLINE | ID: mdl-28762910

RESUMO

High prevalence of arterial hypertension and low rate of blood pressure (BP) control in patients with arterial hypertension require more intensive approaches to antihypertensive therapy. Every patient with arterial hypertension is characterized by different predominant pathophysiologic mechanisms in different periods of his life. Because of impact on different pathophysiologic mechanisms combined antihypertensive therapy allows to achieve more pronounced BP reduction, decrease heterogeneity of response and alleviate side effects of each component. Use of fixed drug combinations improves adherence to treatment and thus its efficacy. Novel fixed-dose combination of amlodipine, indapamide and perindopril fully realizes principles underlying modern antihypertensive therapy. Antihypertensive effectiveness of components of this combination has been confirmed by the results of international trials.


Assuntos
Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Indapamida/uso terapêutico , Perindopril/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Combinação de Medicamentos , Quimioterapia Combinada , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Humanos
14.
J Hum Hypertens ; 31(12): 848-854, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28703124

RESUMO

The aim of the study is to compare the effects of hydrochlorothiazide and indapamide on the kidney in patients with hypertension inadequately controlled with losartan. A total of 140 patients who met the criteria and inadequately controlled with losartan 50 mg per day for 2 weeks were randomized in two groups and administered either hydrochlorothiazide 12.5 mg per day (n=70) or indapamide (sustained release) 1.5 mg per day (n=70) in combination with losartan 50 mg per day. Office blood pressure (BP) were collected at baseline and upon each follow-up visit. Creatinine, urine albumin-creatinine ratio (ACR), urine neutrophil gelatinase-associated lipocalin (NGAL) and renal resistive index (RRI) were also collected at baseline and at the 24-week follow-up. None of the baseline characteristics was statistically significantly different between the two groups. After excluding those patients with office BP uncontrolled, 46 patients in the hydrochlorothiazide group (45.7% males, 58.8±10.8 years) and 44 patients in the indapamide group (38.4% males, 61.5±10.9 years) were analysed. There were insignificant changes in creatinine and significant decreases in ACR, NGAL and RRI compared to baseline levels in the two groups. The decrease in ACR (3.8 (0, 28.7) vs 4.2 (0.4, 64.8) mg g-1, P=0.485) was not significantly different between the two groups, while the decrease in NGAL (16.07±7.07 vs 28.77±7.64 ng ml-1, P<0.001) and RRI (0.04±0.02 vs 0.07±0.04, P<0.001) was more significant in the indapamide group than in the hydrochlorothiazide group. In conclusion, indapamide is superior to hydrochlorothiazide to improve renal tubular injury and renal haemodynamics in combination with losartan in hypertensive patients with controlled BP.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Indapamida/uso terapêutico , Rim/efeitos dos fármacos , Idoso , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Creatinina/urina , Feminino , Humanos , Hidroclorotiazida/farmacologia , Hipertensão/urina , Indapamida/farmacologia , Lipocalina-2/urina , Losartan/farmacologia , Losartan/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Falha de Tratamento
15.
J Clin Hypertens (Greenwich) ; 19(10): 965-972, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28721700

RESUMO

To examine the antihypertensive efficacy and safety of indapamide sustained-release (SR)/amlodipine compared with enalapril/amlodipine in patients 65 years and older with uncontrolled blood pressure (BP) on monotherapy, a post hoc analysis of the NESTOR trial (Natrilix SR vs Enalapril in Hypertensive Type 2 Diabetics With Microalbuminuria) was conducted. NESTOR randomized 570 patients (n=197, aged ≥65 years) with hypertension (systolic BP 140-180/diastolic BP <110 mm Hg) to indapamide SR 1.5 mg or enalapril 10 mg. If target BP (<140/85 mm Hg) was not achieved at 6 weeks, amlodipine 5 mg was added with uptitration to 10 mg if required. A total of 107 patients aged 65 years and older received dual therapy (53 indapamide SR/amlodipine and 54 enalapril/amlodipine). Amlodipine uptitration occurred in 22 and 24 patients, respectively. At 52 weeks, mean systolic BP (±SE) reduction was significantly greater with indapamide SR/amlodipine vs enalapril/amlodipine 6.2±2.7 mm Hg (P=.02). Indapamide SR/amlodipine was also associated with a greater BP response rate (88% vs 75%, respectively). Both regimens were well tolerated. Indapamide SR/amlodipine may be more effective than enalapril/amlodipine for lowering systolic BP in patients with hypertension aged 65 years and older.


Assuntos
Albuminúria/etiologia , Anlodipino/farmacologia , Diabetes Mellitus Tipo 2/complicações , Indapamida/farmacologia , Idoso , Idoso de 80 Anos ou mais , Albuminúria/tratamento farmacológico , Anlodipino/administração & dosagem , Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Quimioterapia Combinada , Enalapril/administração & dosagem , Enalapril/farmacologia , Enalapril/uso terapêutico , Feminino , Humanos , Hipertensão/tratamento farmacológico , Indapamida/administração & dosagem , Indapamida/uso terapêutico , Masculino , Resultado do Tratamento , Rigidez Vascular/fisiologia
16.
Cardiovasc Diabetol ; 16(1): 95, 2017 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-28750645

RESUMO

BACKGROUND: Microvascular disease is associated with a high risk of macrovascular events in patients with type 2 diabetes, but the impact of macrovascular disease on the risk of microvascular events remains unknown. We sought to evaluate the respective effects of prior microvascular and macrovascular disease on the risk of major outcomes, including microvascular events, in these patients. METHODS: Participants in the Action in Diabetes and Vascular Disease: PreterAx and DiamicroN Modified-Release Controlled Evaluation (ADVANCE) trial (n = 11,140) and the ADVANCE-ON post-trial study (n = 8494) were categorized into 4 groups at baseline: dual absence of microvascular or macrovascular disease (n = 6789), presence of microvascular disease alone (n = 761), macrovascular disease alone (n = 3196), and both (n = 394). Outcomes were all-cause mortality, major macrovascular events (MACE), and major clinical microvascular events. RESULTS: All-cause mortality, MACE, and major clinical microvascular events occurred in 2265 (20%), 2166 (19%), and 807 (7%) participants respectively, during a median follow-up of 9.9 (inter-quartile interval 5.6-10.9) years. The adjusted hazard ratios [95% CI] of death, MACE, and major clinical microvascular events were each greater in patients with baseline microvascular disease (1.43 [1.20-1.71], 1.64 [1.37-1.97], and 4.74 [3.86-5.82], respectively), macrovascular disease (1.43 [1.30-1.57], 2.04 [1.86-2.25], and 1.26 [1.06-1.51]) or both (2.01 [1.65-2.45], 2.92 [2.40-3.55], and 6.30 [4.93-8.06]) compared with those without these conditions. No interaction was observed between baseline microvascular and macrovascular disease for these events. The addition of microvascular disease (change in c-statistic [95% CI] 0.005 [0.002-0.008], p = 0.02) or macrovascular disease (0.005 [0.002-0.007], p < 0.0001) considered separately or together (0.011 [0.007-0.014], p < 0.0001) improved the discrimination and the classification (integrated discrimination improvement (IDI): 0.013 [0.010-0.016], p < 0.001; net reclassification improvement (NRI): 0.021 [0.011-0.032], p < 0.001) of the risk of all-cause mortality. Microvascular disease improved discrimination (0.009 [0.003-0.014]) and classification (IDI: 0.008 [0.006-0.010]; NRI: 0.011 [0.001-0.020]) of MACE. Baseline macrovascular disease modestly enhanced IDI (0.002 [0.001-0.002]) and NRI (0.041 [0.002-0.087]), but not discrimination, of major clinical microvascular events. CONCLUSIONS: Microvascular and macrovascular disease are independently associated with the 10-year risk of death, MACE, and major clinical microvascular events in patients with type 2 diabetes. The coexistence of these conditions was associated with the highest risks.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Gliclazida/uso terapêutico , Hipoglicemiantes/uso terapêutico , Indapamida/uso terapêutico , Perindopril/uso terapêutico , Adulto , Idoso , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/mortalidade , Angiopatias Diabéticas/etiologia , Combinação de Medicamentos , Feminino , Humanos , Masculino , Microvasos , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento
17.
Adv Ther ; 34(7): 1753-1763, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28646394

RESUMO

INTRODUCTION: The etiology of essential hypertension is multifactorial. Therefore, treatment with combinations of antihypertensive agents acting on multiple targets is necessary for successful therapy in the majority of patients. According to the experience and clinical data accumulated so far, combination therapy with three agents from different pharmacological classes is required in approx. 30% of patients in order to achieve long-term blood pressure control. The primary objective of the PETRA study was to evaluate the efficacy of blood pressure (BP) control with once daily administration of the different dosage strengths of the once-daily, triple fixed combination of perindopril, indapamide, and amlodipine. The evaluation was based on office BP readings and ambulatory blood pressure monitoring (ABPM) data gathered in routine clinical practice. METHODS: Data from 11,209 hypertensive patients (the proportion of female subjects was 47.6%) were processed and interpreted in a 3-month-long prospective, observational, non-interventional, open-label study conducted in 997 centers in Hungary. RESULTS: Mean baseline office BP was 156.58 ± 16.10/91.56 ± 9.33 mmHg (mean ± SD), whereas the mean duration of hypertension was 9.48 ± 7.19 years. Mean office BP decreased by 24.81 ± 15.47/11.41 ± 9.90 mmHg after switching to the triple fixed combination of perindopril, indapamide, and amlodipine (p < 0.0001). At the final visit 45.1% of patients took the 5/1.25/5 mg, 33.5% of them 10/2.5/5 mg, and 21.4% of them 10/2.5/10 mg strength of the perindopril/indapamide/amlodipine triple fixed combination. The 24-h blood pressure was obtained in 76 subjects. The mean 24-h BP decreased from 155.51 ± 17.43/85.28 ± 11.48 to 134.63 ± 12.51/77.83 ± 8.99 mmHg (p < 0.0001). Statistically significant (p < 0.0001) and clinically relevant improvement of a number of metabolic parameters-including total cholesterol (-8.6%), LDL-cholesterol (-11.4%), triglyceride (-12.1%), and fasting blood glucose (-6.6%) levels-was observed over the 3-month study period. CONCLUSIONS: During the 3 months of the PETRA study, the outstanding 24-h antihypertensive efficacy of the triple fixed combination of perindopril, indapamide, and amlodipine was confirmed both by office BP readings and by ABPM recordings. This combination may offer a new therapeutic option for hypertensive patients who have failed to achieve the desired BP target on their previous dual combination therapy. FUNDING: EGIS Pharmaceuticals PLC.


Assuntos
Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Combinação de Medicamentos , Hipertensão/tratamento farmacológico , Indapamida/uso terapêutico , Perindopril/uso terapêutico , Adulto , Monitorização Ambulatorial da Pressão Arterial , Feminino , Humanos , Hungria , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
19.
Clin Exp Hypertens ; 39(3): 290-294, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28448180

RESUMO

The effect of renal denervation on the efficacy of antihypertensive drugs has not yet been elucidated. Twenty-week-old spontaneously hypertensive rats were treated with metoprolol, losartan, indapamide, or saline (controls) and assigned to renal denervation or a sham procedure. Acute hemodynamic measurements were performed ten days later. Series showing a significant interaction between renal denervation and the drugs were repeated with chronic telemetry measurements. In the saline series, denervated rats showed a significantly lower mean arterial blood pressure (blood pressure) than the sham-operated rats. In contrast, in the metoprolol series denervated rats showed a significantly higher blood pressure than sham rats. There were no differences in blood pressure between denervated and sham rats in the losartan and indapamide series. In chronic studies, a 4-week treatment with metoprolol caused a decrease in blood pressure. Renal denervation and sham denervation performed 10 days after the onset of metoprolol treatment did not affect blood pressure. Denervated rats showed markedly reduced renal nerve tyrosine hydroxylase levels. In conclusion, renal denervation decreases blood pressure in hypertensive rats. The hypotensive action of metoprolol, indapamide, and losartan is not augmented by renal denervation, suggesting the absence of synergy between renal denervation and the drugs investigated in this study.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Arterial , Hipertensão/terapia , Simpatectomia , Animais , Anti-Hipertensivos/farmacologia , Pressão Arterial/efeitos dos fármacos , Indapamida/uso terapêutico , Losartan/uso terapêutico , Masculino , Metoprolol/uso terapêutico , Ratos , Ratos Endogâmicos SHR , Artéria Renal/inervação , Sistema Nervoso Simpático/enzimologia , Sistema Nervoso Simpático/cirurgia , Tirosina 3-Mono-Oxigenase/metabolismo
20.
Adv Ther ; 34(4): 975-985, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28299716

RESUMO

INTRODUCTION: Blood pressure (BP) control is the main clinical goal in the management of hypertensive patients; however, BP in most of these patients remains uncontrolled, despite the widespread availability of antihypertensive drugs as free-combination therapy. This study compared the efficacy of a fixed-dose triple combination (FDTC) of antihypertensive drugs with that of a free combination of three antihypertensives in patients with uncontrolled hypertension. METHODS: Ninety-two patients (mean age 60.8 ± 12.1, 58.0% male) with uncontrolled essential hypertension (office systolic BP ≥ 140 or diastolic BP ≥ 90 mmHg) previously treated with a renin-angiotensin-aldosterone system (RAAS) inhibitor plus hydrochlorothiazide were switched to once-daily FDTC therapy with perindopril/indapamide/amlodipine (5-10/1.25-2.5/5-10 mg). Patients were age- and sex-matched with a control group of hypertensive patients receiving free-combination therapy with three drugs including a RAAS inhibitor, a diuretic, and a calcium channel blocker. Office BP and 24-h ambulatory BP monitoring (ABPM) were evaluated at baseline and after 1 and 4 months. RESULTS: Significant reductions in ambulatory 24-h, daytime, and nighttime systolic BP, and pulse pressure (PP) were found in the FDTC group relative to reductions seen with free-combination therapy, after the first month only of follow-up. Target BP values (mean 24-h ambulatory systolic/diastolic BP < 130/80 mmHg) were reached by more recipients of FDTC than free-combination therapy (64.8% vs. 46.9%, p < 0.05) at month 4 of follow-up, despite reductions in 24-h ABPM values from baseline being similar in both groups at this time point. CONCLUSION: FDTC of perindopril/indapamide/amlodipine was effective at reducing SBP and PP in previously treated patients with uncontrolled hypertension, and well tolerated, providing support for clinicians in choosing a fixed-dose triple combination over the free-combination of a RAAS inhibitor, a diuretic, and a calcium antagonist.


Assuntos
Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Indapamida/uso terapêutico , Perindopril/uso terapêutico , Idoso , Anlodipino/administração & dosagem , Anlodipino/efeitos adversos , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Monitorização Ambulatorial da Pressão Arterial , Bloqueadores dos Canais de Cálcio/uso terapêutico , Diuréticos/uso terapêutico , Combinação de Medicamentos , Feminino , Humanos , Indapamida/administração & dosagem , Indapamida/efeitos adversos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Perindopril/administração & dosagem , Perindopril/efeitos adversos
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