RESUMO
BACKGROUND: The efficacy and safety of Qingda granule (QDG) in managing blood pressure (BP) among grade 1 hypertensive patients with low-moderate risk remain uncertain. METHODS: In the randomized, double-blind, double dummy, non-inferiority and multicenter trial, 552 patients with grade 1 hypertension at low-moderate risk were assigned at a ratio of 1:1 to receive either QDG or valsartan for 4 weeks, followed up by a subsequent 4 weeks. RESULTS: Post-treatment, clinic systolic/diastolic BPs (SBP/DBP) were reduced by a mean change of 9.18/4.04 mm Hg in the QDG group and 9.85/5.05 mm Hg in the valsartan group (SBP P = 0.47, DBP P = 0.16). Similarly, 24-hour, daytime and nighttime BPs were proportional in both groups (P > 0.05) after 4 weeks treatment. After discontinuing medications for 4 weeks, the mean reduction of clinic SBP/DBP were 0.29/0.57 mm Hg in the QDG group compared to -1.59/-0.48 mm Hg in the valsartan group (SBP P = 0.04, DBP P = 0.04). Simultaneously, the 24-hour SBP/DBP were reduced by 0.9/0.31 mm Hg in the QDG group and -1.66/-1.08 mm Hg in the valsartan group (SBP P = 0.006, DBP P = 0.02). And similar results were observed regarding the outcomes of daytime and nighttime BPs. There was no difference in occurrence of adverse events between two groups (P > 0.05). CONCLUSION: QDG proves to be efficacious for grade 1 hypertension at a low-to-medium risk, even after discontinuation of the medication for 4 weeks. These findings provide a promising option for managing grade 1 hypertension and suggest the potential for maintaining stable BP through intermittent administration of QDG. TRIAL REGISTRATION: ChiCTR2000033890.
Assuntos
Anti-Hipertensivos , Medicamentos de Ervas Chinesas , Hipertensão , Humanos , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea , China , Método Duplo-Cego , Tetrazóis/efeitos adversos , Valsartana/efeitos adversosRESUMO
Chronic kidney disease (CKD) is highly prevalent in patients with chronic heart failure (CHF) and increases the risk of overall and cardiovascular (CV) mortality. Despite evidence supporting the effectiveness of angiotensin-converting enzyme inhibitors (ACE-Is), angiotensin receptor blockers, and mineralocorticoid receptor antagonists in decreasing mortality in patients with CHF, CKD hampers the optimization of standard pharmacologic therapy for heart failure. Therefore, other treatment options are needed to optimize treatment outcomes in CHF patients with CKD. The first-in-class angiotensin receptor-neprilysin inhibitor, sacubitril/valsartan, has a complementary activity that counteracts the potential unwanted long-term effects of over-activation of the renin-angiotensin-aldosterone system. Sacubitril/valsartan reduced the risk of CV mortality compared to standard therapy with an ACE-I in patients with heart failure with reduced ejection fraction (HFrEF) in the PARADIGM-HF trial and has been shown to be safe and effective in a broad range of HFrEF patients. However, data on the efficacy and tolerability of sacubitril/valsartan in patients with more advanced CKD are limited. This review discusses the evidence for the role of sacubitril/valsartan in providing additional renal benefit in patients with HFrEF. Data from clinical trials and real-world experience in patients with HFrEF and advanced CKD support the benefits of dual angiotensin/neprilysin inhibition across the breadth of kidney disease stages, including patients with significant renal impairment that was not reported in the pivotal PARADIGM-HF trial, and suggests a central role for the cardiac benefits of sacubitril/valsartan in nephroprotection.
Assuntos
Insuficiência Cardíaca , Aminobutiratos , Compostos de Bifenilo , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Volume Sistólico , Tetrazóis/efeitos adversos , Valsartana/uso terapêuticoRESUMO
BACKGROUND: Malnutrition commonly occurs in patients with heart failure with reduced ejection fraction (HFrEF). Sacubitril/valsartan, which is an AT1 neprilysin inhibitor, has been shown to reduce mortality and hospitalization in patients with HFrEF. However, its effects on nutritional status remain unclear. METHODS: Sacubitril/valsartan was initiated in 164 symptomatic patients with HFrEF receiving an optimal medical treatment with angiotensin inhibition (mean age: 63â±â20 years; 120 males, 60% ischemic cause). The New York Heart Association (NYHA) functional class and nutritional statuses of the patients were evaluated at the switching to AT1 neprilysin inhibitor and at the 6th-month follow-up of the maximum sacubitril/valsartan dose using the geriatric nutritional risk index (GNRI), controlling nutritional status (CONUT) score, prognostic nutritional index (PNI), and prealbumin. RESULTS: After the sacubutril/valsartan treatment, a significant reduction in the number (%) of malnourished patients was observed according to CONUT (before 47% vs. after 7%, Pâ<â0.001), GNRI (before 39% vs. after 19%, Pâ<â0.001), PNI scores (before 36% vs. after 12%, Pâ=â0.002), and prealbumin (before 41% vs. after 12%, Pâ<â0.001). Also significant changes were observed at the baseline and follow-up in the mean scores of the three different nutritional indexes and prealbumin levels [CONUT: 2.68â±â2.5, 1.02â±â1.0 (Pâ<â0.001); GNRI: 97.1â±â9.7, 101.2â±â5.9 (Pâ<â0.001); PNI: 38.8â±â4.8, 41.6â±â3.7 (Pâ<â0.001); prealbumin: 14.6â±â6.9âmg/dl, 17.1â±â5.2âmg/dl (Pâ<â0.001)]. Overall, the patients exhibited a significant functional improvement following the initiation of sacubitril/valsartan: 23% of the patients improved by two NYHA classes, 48% improved by one NYHA class, and 39% remained stable. CONCLUSION: In patients with HFrEF, the switch from angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker therapy to sacubitril/valsartan resulted in a significant improvement in both nutritional and functional statuses.
Assuntos
Aminobutiratos/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Desnutrição/tratamento farmacológico , Estado Nutricional/efeitos dos fármacos , Inibidores de Proteases/uso terapêutico , Volume Sistólico/efeitos dos fármacos , Tetrazóis/uso terapêutico , Função Ventricular Esquerda/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Aminobutiratos/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Compostos de Bifenilo , Combinação de Medicamentos , Substituição de Medicamentos , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Desnutrição/diagnóstico , Desnutrição/fisiopatologia , Pessoa de Meia-Idade , Neprilisina/antagonistas & inibidores , Avaliação Nutricional , Estudos Prospectivos , Inibidores de Proteases/efeitos adversos , Recuperação de Função Fisiológica , Tetrazóis/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , ValsartanaAssuntos
Aminobutiratos/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Ensaios Clínicos como Assunto , Suplementos Nutricionais , Aprovação de Drogas , Ácido Eicosapentaenoico/análogos & derivados , Insuficiência Cardíaca/tratamento farmacológico , Inibidores de Proteases/uso terapêutico , Projetos de Pesquisa , Tetrazóis/uso terapêutico , Aminobutiratos/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Compostos de Bifenilo , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Suplementos Nutricionais/efeitos adversos , Combinação de Medicamentos , Ácido Eicosapentaenoico/efeitos adversos , Ácido Eicosapentaenoico/uso terapêutico , Medicina Baseada em Evidências , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Neprilisina/antagonistas & inibidores , Inibidores de Proteases/efeitos adversos , Tetrazóis/efeitos adversos , Resultado do Tratamento , ValsartanaRESUMO
Aims: Anthracycline treatment may cause myocyte loss and expansion of the myocardial extracellular volume (ECV) fraction by oedema and fibrosis. We tested the hypotheses that adjuvant treatment for early breast cancer with the anthracycline epirubicin is dose dependently associated with increased ECV fraction and total ECV, as well as reduced total myocardial cellular volume, and that these changes could be prevented by concomitant angiotensin or beta-adrenergic blockade. Methods and results: PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy (PRADA) was a 2 × 2 factorial, placebo-controlled, double-blinded trial of candesartan and metoprolol. Sixty-nine women had valid ECV measurements. ECV fraction, total ECV, and total cellular volume were measured by cardiovascular magnetic resonance before and at the completion of anthracycline therapy. ECV fraction increased from 27.5 ± 2.7% to 28.6 ± 2.9% (P = 0.002). A cumulative doxorubicin equivalent dose of 268 mg/m2 was associated with greater increase in ECV fraction than doses <268 mg/m2 (mean change 3.4% [95% confidence interval (CI) 1.2, 5.5] vs. 0.7% [95% CI 0.0, 1.5], P = 0.006), as well as greater increase in total ECV (1.9 mL [95% CI 0.4, 3.5] vs. 0.1 mL [95% CI -0.6, 0.8], P = 0.04). In patients receiving candesartan, total cellular volume decreased (-3.5 mL [95% CI - 4.7, -2.2], P < 0.001) while in patients not receiving candesartan, it remained unchanged (P = 0.45; between group difference P = 0.003). Conclusions: Anthracycline therapy is associated with dose-dependent increase in ECV fraction and total ECV. Concomitant treatment with candesartan reduces left ventricular total cellular volume.
Assuntos
Antraciclinas/efeitos adversos , Benzimidazóis/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética/métodos , Tetrazóis/efeitos adversos , Adulto , Idoso , Antraciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzimidazóis/uso terapêutico , Compostos de Bifenilo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Cardiotoxicidade/mortalidade , Cardiotoxicidade/fisiopatologia , Quimioterapia Adjuvante , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Relação Dose-Resposta a Droga , Método Duplo-Cego , Epirubicina/efeitos adversos , Epirubicina/uso terapêutico , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Hospitais Universitários , Humanos , Estimativa de Kaplan-Meier , Mastectomia/métodos , Pessoa de Meia-Idade , Noruega , Prognóstico , Estudos Prospectivos , Medição de Risco , Estatísticas não Paramétricas , Volume Sistólico/efeitos dos fármacos , Análise de Sobrevida , Tetrazóis/uso terapêuticoRESUMO
Heart failure is a disease with a high prevalence and incidence. New therapeutic approaches are needed to prevent the onset of heart failure and to reduce the high morbidity and mortality associated with this disease. An optimized therapy of arterial hypertension in patients with risk factors and the use of the SGLT2 inhibitor empagliflozin in type 2 diabetics are proven strategies to prevent heart failure. The therapeutic options in heart failure with preserved ejection fraction are still insufficient. In heart failure with reduced ejection fraction sacubitril/valsartan, the first approved angiotensin receptor-neprilysin inhibitor, is superior to an angiotensin converting enzyme (ACE) inhibitor. Whether digitalis affects the prognosis in heart failure remains unclear; however, serum concentration should be targeted at the lower therapeutic range. Iron supplementation in heart failure with reduced systolic function and iron deficiency improves symptoms and quality of life.
Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Aminobutiratos/efeitos adversos , Aminobutiratos/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Compostos de Bifenilo , Doença Crônica , Glicosídeos Digitálicos/efeitos adversos , Glicosídeos Digitálicos/uso terapêutico , Combinação de Medicamentos , Humanos , Neprilisina/efeitos adversos , Neprilisina/uso terapêutico , Tetrazóis/efeitos adversos , Tetrazóis/uso terapêutico , ValsartanaRESUMO
Fimasartan is the ninth, and most recent, angiotensin II receptor antagonist approved as an antihypertensive agent. Fimasartan, a pyrimidin-4(3H)-one derivative of losartan with the imidazole ring replaced, which enables higher potency and longer duration than losartan. Fecal elimination and biliary excretion are the predominant elimination pathways of fimasartan and the urinary excretion was found to be less than 3 % 24 h after administration. Fimasartan is primarily catabolized by cytochrome P450 isoform 3A and no significant drug interaction was observed when used in combination with hydrochlorothiazide, amlodipine, warfarin, or digoxin. Fimasartan at a dosage range of 60-120 mg once daily showed an antihypertensive effect over 24 h. In a large, population-based observational study, fimasartan showed an excellent safety profile. Anti-inflammatory and organ-protecting effects of fimasartan have been shown in various preclinical studies, including aortic balloon injury, myocardial infarct ischemia/reperfusion, doxorubicin cardiotoxicity, and ischemic stroke models.
Assuntos
Bloqueadores do Receptor Tipo 2 de Angiotensina II/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Hipertensão/tratamento farmacológico , Pirimidinas/uso terapêutico , Tetrazóis/uso terapêutico , Bloqueadores do Receptor Tipo 2 de Angiotensina II/administração & dosagem , Bloqueadores do Receptor Tipo 2 de Angiotensina II/efeitos adversos , Bloqueadores do Receptor Tipo 2 de Angiotensina II/farmacocinética , Animais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/farmacocinética , Compostos de Bifenilo/administração & dosagem , Compostos de Bifenilo/efeitos adversos , Compostos de Bifenilo/farmacocinética , Ensaios Clínicos como Assunto , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada , Humanos , Hipertensão/metabolismo , Estrutura Molecular , Estudos Observacionais como Assunto , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Pirimidinas/farmacocinética , Tetrazóis/administração & dosagem , Tetrazóis/efeitos adversos , Tetrazóis/farmacocinética , Resultado do TratamentoAssuntos
Anlodipino/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Cronofarmacoterapia , Hipertensão/tratamento farmacológico , Apneia Obstrutiva do Sono/tratamento farmacológico , Tetrazóis/administração & dosagem , Valina/análogos & derivados , Anlodipino/efeitos adversos , Estudos Cross-Over , Quimioterapia Combinada , Humanos , Tetrazóis/efeitos adversos , Valina/administração & dosagem , Valina/efeitos adversos , ValsartanaRESUMO
Prolonged treatment with the oxazolidinone linezolid is associated with myelosuppression, lactic acidosis, and neuropathies, toxicities likely caused by impairment of mitochondrial protein synthesis (MPS). To evaluate the potential of the novel oxazolidinone tedizolid to cause similar side effects, nonclinical and pharmacokinetic assessments were conducted. In isolated rat heart mitochondria, tedizolid inhibited MPS more potently than did linezolid (average [± standard error of the mean] 50% inhibitory concentration [IC50] for MPS of 0.31 ± 0.02 µM versus 6.4 ± 1.2 µM). However, a rigorous 9-month rat study comparing placebo and high-dose tedizolid (resulting in steady-state area under the plasma concentration-time curve values about 8-fold greater than those with the standard therapeutic dose in humans) showed no evidence of neuropathy. Additional studies explored why prolonged, high-dose tedizolid did not cause these mitochondriopathic side effects despite potent MPS inhibition by tedizolid. Murine macrophage (J774) cell fractionation studies found no evidence of a stable association of tedizolid with eukaryotic mitochondria. Monte Carlo simulations based on population pharmacokinetic models showed that over the course of a dosing interval using standard therapeutic doses, free plasma concentrations fell below the respective MPS IC50 in 84% of tedizolid-treated patients (for a median duration of 7.94 h) and 38% of linezolid-treated patients (for a median duration of 0 h). Therapeutic doses of tedizolid, but not linezolid, may therefore allow for mitochondrial recovery during antibacterial therapy. The overall results suggest that tedizolid has less potential to cause myelosuppression and neuropathy than that of linezolid during prolonged treatment courses. This, however, remains a hypothesis that must be confirmed in clinical studies.
Assuntos
Antibacterianos/farmacocinética , Linezolida/farmacocinética , Mitocôndrias/efeitos dos fármacos , Oxazolidinonas/farmacocinética , Tetrazóis/farmacocinética , Animais , Antibacterianos/efeitos adversos , Antibacterianos/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Humanos , Técnicas In Vitro , Linezolida/efeitos adversos , Linezolida/farmacologia , Masculino , Camundongos , Mitocôndrias/metabolismo , Proteínas Mitocondriais/biossíntese , Método de Monte Carlo , Síndromes Neurotóxicas/etiologia , Oxazolidinonas/efeitos adversos , Oxazolidinonas/farmacologia , Ratos Endogâmicos LEC , Tetrazóis/efeitos adversos , Tetrazóis/farmacologia , Testes de Toxicidade Crônica/métodosRESUMO
AIMS: The primary objective of this study was to evaluate the effects of Ginkgo biloba extracts (GBE) on the pharmacokinetics of cilostazol and its metabolites. The secondary objective was to assess the effect of GBE on the pharmacodynamics of cilostazol. METHODS: A randomized, double-blind, two-way crossover study was conducted with 34 healthy Korean subjects. All subjects were given an oral dose of cilostazol (100 mg) plus GBE (80 mg) or cilostazol (100 mg) plus placebo twice daily for 7 days. Plasma concentrations of cilostazol and its active metabolites (3,4-dehydrocilostazol and 4'-trans-hydroxycilostazol) were measured using liquid chromatography-tandem mass spectroscopy on day 7 for pharmacokinetic assessment. The adenosine diphosphate-induced platelet aggregation and bleeding time were measured at baseline and on day 7 for pharmacodynamic assessment. RESULTS: The geometric mean ratios of area under the concentration-time curve for dosing interval for cilostazol plus GBEâ vs. cilostazol plus placebo were 0.96 (90% confidence interval, 0.89-1.03; P = 0.20) for cilostazol, 0.96 (90% confidence interval, 0.90-1.02; P = 0.30) for 3,4-dehydrocilostazol and 0.98 (90% confidence interval, 0.93-1.03; P = 0.47) for 4'-trans-hydroxycilostazol. The change of aggregation after administration of cilostazol plus GBE seemed to be 1.31 times higher compared with cilostazol plus placebo, without statistical significance (P = 0.20). There were no significant changes in bleeding times and adverse drug reactions between the treatments. CONCLUSIONS: Co-administration of GBE showed no statistically significant effects on the pharmacokinetics of cilostazol in healthy subjects. A large cohort study with long-term follow-up may be needed to evaluate the possible pharmacodynamic interaction between cilostazol and GBE, given that there was a remarkable, but not statistically significant, increase in inhibition of platelet aggregation.
Assuntos
Ginkgo biloba , Interações Ervas-Drogas , Extratos Vegetais/farmacologia , Tetrazóis/farmacocinética , Adulto , Área Sob a Curva , Cilostazol , Estudos Cross-Over , Método Duplo-Cego , Humanos , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária/efeitos dos fármacos , Tetrazóis/efeitos adversos , Tetrazóis/metabolismo , Tetrazóis/farmacologiaRESUMO
The prevalence of hypertension is high in patients with diabetes mellitus (DM), chronic kidney disease (CKD) and chronic cardiovascular disease (CVD), as well as in black and elderly subjects. In addition, these subjects have the lowest control of blood pressure (BP) among the hypertensive population, and also the risk of having a morbid or fatal cardiovascular event >20% in 10 years. For these reasons, aggressive control of BP to <130/80 mm Hg for these subjects is strongly recommended by National and International guidelines. To accomplish this goal, combination therapy with two or more antihypertensive drugs with a complementary mechanism of action is necessary. Drugs that block the renin-angiotensin system (RAS) in combination with a calcium channel blocker (CCB) and a diuretic have been shown to be the most effective combinations to accomplish this goal. However, this will require the administration of multiple drugs given separately, which will decrease the patient compliance and adherence to treatment. Poor patient compliance and adherence to treatment is a major factor for poor BP control. Several studies have shown that patient compliance is inversely related to the number of drugs being administered. To overcome this problem, several dual and triple-drug, fixed-dose combinations with a RAS blocker, a CCB and a diuretic have been developed and marketed, which are easier to administer, and have been shown to increase patient compliance and adherence to treatment. In this concise review, the effectiveness and safety of the fixed-dose, triple-combination of the RAS blocker olmesartan medoxomil, the CCB amlodipine besylate and the diuretic hydrochlorothiazide, as well as other similar combinations for the treatment of hypertension, will be discussed. These drug combinations have been shown to be effective, safe and well tolerated by most patients.
Assuntos
Anlodipino/uso terapêutico , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Imidazóis/uso terapêutico , Tetrazóis/uso terapêutico , Fatores Etários , Anlodipino/administração & dosagem , Anlodipino/efeitos adversos , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/tratamento farmacológico , Complicações do Diabetes/tratamento farmacológico , Quimioterapia Combinada/métodos , Humanos , Hidroclorotiazida/administração & dosagem , Hidroclorotiazida/efeitos adversos , Hipertensão/complicações , Imidazóis/administração & dosagem , Imidazóis/efeitos adversos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Tetrazóis/administração & dosagem , Tetrazóis/efeitos adversosRESUMO
BACKGROUND: Hypertension represents a major health problem, affecting more than one billion adults worldwide. Irbesartan, an angiotensin II receptor blocker, is considered to be a highly effective treatment in the management of hypertension. The purpose of this review is to evaluate the efficacy, safety and tolerability profile, and cost-effectiveness of treatment with irbesartan in hypertension. METHODS: A review of the literature was conducted using the electronic PubMed and Cochrane Library databases and the Health Economic Evaluations Database of search terms relating to irbesartan efficacy, tolerability, and cost-effectiveness, and the results were utilized. RESULTS: Findings from the present analysis show that irbesartan either as monotherapy or in combination with other antihypertensive agents can achieve significant reductions in blood pressure, both systolic and diastolic, compared with alternative treatment options. Irbesartan was also found to have a renoprotective effect independent of its blood pressure-lowering in patients with type 2 diabetes and nephropathy. Furthermore, irbesartan demonstrated an excellent safety and tolerability profile, with either lower or equal adverse events compared with placebo and other alternative treatments. In terms of economic analyses, compared with other antihypertensive therapy alternatives, irbesartan was found to be a preferred option, that is less costly and more effective. CONCLUSION: The evidence indicates that treating patients with hypertension alone or with type 2 diabetes and nephropathy using irbesartan can control hypertension, prolong life, and reduce costs in relation to existing alternatives.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/economia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Anti-Hipertensivos/economia , Anti-Hipertensivos/uso terapêutico , Compostos de Bifenilo/economia , Compostos de Bifenilo/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Custos de Medicamentos , Hipertensão/tratamento farmacológico , Hipertensão/economia , Tetrazóis/economia , Tetrazóis/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Compostos de Bifenilo/efeitos adversos , Análise Custo-Benefício , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/fisiopatologia , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Irbesartana , Modelos Econômicos , Anos de Vida Ajustados por Qualidade de Vida , Tetrazóis/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
A case of autoimmune liver hepatitis is reported: the onset was triggered by consumption of green tea infusion in a patient taking oral contraceptives and irbesartan. We hypothesize that our patient, carrying genetic variant of hepatic metabolism making her particularly susceptible to oxidative stress, developed an abnormal response to a mild toxic insult, afforded by a combination of agents (oral contraceptives+irbesartan+green tea) that normally would not be able to cause damage. Her particular hepatic metabolism further increased the drugs' concentration, favoring the haptenization of liver proteins, eventually leading to the development of an autoimmune hepatitis.
Assuntos
Compostos de Bifenilo/efeitos adversos , Anticoncepcionais Orais/efeitos adversos , Hepatite Autoimune/genética , Polimorfismo de Nucleotídeo Único/genética , Chá/efeitos adversos , Tetrazóis/efeitos adversos , Adulto , Feminino , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/tratamento farmacológico , Humanos , Irbesartana , Fígado/efeitos dos fármacos , Estresse OxidativoRESUMO
This article discusses racial/ethnic disparities in hypertension, with particular focus on non-white populations including blacks, Hispanics/Latinos, and Asians. Hypertension and its related morbidity and mortality affect a disproportionate number of black patients compared with white patients. Blacks, Hispanics/Latinos, and Asians have poor rates of hypertension awareness, treatment, and control. Given the high prevalence of comorbidities (e.g., obesity, diabetes, and metabolic syndrome) in these populations, renin-angiotensin-aldosterone system blockers are a good choice for foundation therapy. This review also discusses the importance of adherence and persistence with antihypertensive medication, which remain suboptimal in these non-white populations. Evidence suggests improvement with the use of single-pill combination therapy. Lastly, clinical trial data on the antihypertensive efficacy and safety of the combination of a dihydropyridine calcium channel blocker and an angiotensin receptor blocker, a widely utilized combination, in non-white populations are presented. PubMed was searched using the title/abstract key words (amlodipine AND valsartan AND [hypertension OR hypertensive] AND [black(s) OR African American(s) OR Hispanic(s) OR Latino(s) OR Mexican(s) OR Asian(s)]). In total, eight studies in patients with stage 1 or 2 hypertension were identified (n = 1,111 black, n = 389 Hispanic/Latino, and n = 3,094 Asian). Results showed that treatment with the combination of amlodipine plus valsartan is a reasonable choice for initial therapy or in patients who fail to respond to monotherapy. These drug classes have complementary mechanisms of action and, when used concomitantly, the magnitude of blood pressure lowering in these non-white populations is generally comparable with that seen in non-Hispanic white patients.
Assuntos
Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Tetrazóis/uso terapêutico , Negro ou Afro-Americano , Anlodipino/administração & dosagem , Anlodipino/efeitos adversos , Combinação Anlodipino e Valsartana , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Povo Asiático , Combinação de Medicamentos , Disparidades nos Níveis de Saúde , Hispânico ou Latino , Humanos , Hipertensão/etnologia , Adesão à Medicação , Tetrazóis/administração & dosagem , Tetrazóis/efeitos adversos , Resultado do TratamentoRESUMO
AIMS: ADVISE was a 12-week, multicenter, randomized, prospective, open-label, parallel-group study comparing combination therapy of nifedipine GITS 30 mg plus valsartan 80 mg (N + V) with high-dose valsartan (160 mg) monotherapy (V160) in Asian patients with hypertension. METHODS: Patients with hypertension inadequately controlled with valsartan 80 mg for at least 4 weeks were randomized. The coprimary endpoints were the mean changes in clinic systolic and diastolic blood pressures (SBP and DBP, respectively) at Week 12. Other endpoints included blood pressure (BP) control rate, response rate, and adverse events. RESULTS: The full analysis set (FAS) comprised 359 patients. Least squares (LS) mean changes in SBP were -18.3 mmHg (N + V; n = 177) and -16.5 mmHg (V160; n = 182) (difference: -1.9 mmHg; P = 0.0998). DBP LS mean changes were -9.8 mmHg (N + V) and -7.4 mmHg (V160) (difference: -2.4 mmHg; P = 0.0011). BP control rates were significantly higher in the N + V group (Week 4: 51.2% vs. 38.4%, P = 0.0138; Week 8: 68.3% vs. 50.3%, P = 0.0004; and Week 12: 71.2% vs. 55.5%, P = 0.0024). Similar findings were observed when patients were stratified according to smoking status, SBP baseline quartiles, and ESC/ESH guideline-defined added-risk category. The BP response rate was also higher in the N + V group compared with the V160 group. Rates of adverse drug reactions (all mild-to-moderate) were similar: 4.5% (N + V) and 4.4% (V160). CONCLUSIONS: Although one of the coprimary endpoints did not reach statistical significance, combination treatment with N + V provided a greater early and more consistent BP-lowering effect than monotherapy with V160, including superior reduction in DBP and BP control rates.
Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Nifedipino/uso terapêutico , Tetrazóis/uso terapêutico , Valina/análogos & derivados , Adolescente , Adulto , Idoso , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Povo Asiático , Comorbidade , Combinação de Medicamentos , Feminino , Humanos , Hipertensão/etnologia , Masculino , Pessoa de Meia-Idade , Nifedipino/administração & dosagem , Nifedipino/efeitos adversos , Estudos Prospectivos , Tetrazóis/administração & dosagem , Tetrazóis/efeitos adversos , Valina/administração & dosagem , Valina/efeitos adversos , Valina/uso terapêutico , Valsartana , Adulto JovemRESUMO
OBJECTIVE: To investigate the effects and safety of Western medicine combined with Chinese medicine (CM) based on syndrome differentiation in the treatment of elderly polarized hypertension (PHPT), or isolated systolic hypertension with low diastolic blood pressure (DBP). METHODS: A total of 125 elderly patients with PHPT were randomly assigned to two groups: 59 in the control group treated by Western medicine and 66 in the intervention group treated by Western medicine combined with CM treatment. Based on syndrome differentiation, the patients in the intervention group were further divided into subgroups of yang-qi deficiency and yin-qi deficiency. All subjects were treated with Western medicine of Amlodipine Besylate Tablets and Irbesartan Tablets (or Irbesartan and Hydrochlorothiazide Tablets), to decrease their systolic blood pressure (SBP) slowly to 125-135 mm Hg in 2-6 weeks. In the intervention group, Shiyiwei Shenqi Capsule was given additionally to the subgroup of yang-qi deficiency at the dosage of 3-5 capsules, thrice a day, while Dengzhan Shengmai Capsule was given additionally to the subgroup of yin-qi deficiency at the dosage of 2 capsules, 2-3 times per day. For all subjects, SBP, pulse pressure (PP), and DBP were measured before treatment and at the terminal of a 6-week treatment. For subjects in the intervention group, left ventricular ejection fraction (LVEF) was also recorded. RESULTS: After a 6-week treatment, the SBP in the two groups and the PP in the intervention group decreased significantly compared to those before treatment (P<0.05), while the PP in the control group showed no significant difference between prior and post-treatment (P>0.05). After treatment, the DBP in the control group decreased (P>0.05), while the DBP and LVEF in the intervention group showed an increase tendency although it had no statistical significance (P>0.05). When subjects in the intervention group were classified further by the course of disease, the DBP and LVEF of subjects whose course of disease were less than 2 years, increased significantly after treatment (P<0.05). CONCLUSION: Western medicine combined with CM treatment based on syndrome differentiation was safer and more effective than Western medicine alone in the treatment of elderly PHPT, because it not only reduced SBP but also improved DBP, which might lower the incidence of the cardiovascular and cerebrovascular events.
Assuntos
Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Hipertensão/tratamento farmacológico , Tetrazóis/uso terapêutico , Idoso , Anlodipino/efeitos adversos , Anlodipino/farmacologia , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/farmacologia , Compostos de Bifenilo/efeitos adversos , Compostos de Bifenilo/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Diástole/efeitos dos fármacos , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Humanos , Hipertensão/fisiopatologia , Irbesartana , Masculino , Volume Sistólico/efeitos dos fármacos , Síndrome , Tetrazóis/efeitos adversos , Tetrazóis/farmacologiaRESUMO
BACKGROUND: The regular dose of an angiotensin II type-1 receptor blocker (ARB) in renal transplant patients for hypertension is shown to be safe and effective; however, information on the appropriate dosing of ARBs in renal transplant patients is limited. We evaluate the efficacy and safety of the maximal dose of candesartan administered to renal transplant patients. METHODS: Sixty-nine recipients were enrolled in this study. Patients were divided into three groups based on the basal dose of candesartan: patients not taking candesartan (Group A); patients taking a low to medium dose of candesartan (2-4 mg/day; Group B); and patients taking a high dose of candesartan (8 mg/day; Group C). During the course of the study, the dose of candesartan was gradually increased to a final dose of 12 mg/day. Physiological and biochemical parameters were measured before and after the 12-month study period. RESULTS: Ninety-one percent of patients succeeded in continuing their administration of candesartan for 1 year and 75% tolerated the administration of the maximal dose of candesartan. Significant differences in proteinuria, albuminuria, serum creatinine, and estimated glomerular filtration rate (eGFR) level among the groups were detected. In Group A, candesartan reduced systolic blood pressure, decreased the levels of proteinuria, albuminuria, eGFR, and hemoglobin and increased plasma potassium, creatinine level, and plasma renin activity. CONCLUSION: The gradual increase of an ARB to its maximal dose in renal transplant patients is safe when carefully monitored. We were able to demonstrate the impact of maximal renin-angiotensin system (RAS) blockade on both proteinuria and albuminuria, which indicates the need for future, long-term randomized prospective trials to further establish the impact of maximal RAS blockade on renal and cardiovascular protection in transplant patients.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Benzimidazóis/administração & dosagem , Hipertensão/tratamento farmacológico , Transplante de Rim , Tetrazóis/administração & dosagem , Adulto , Idoso , Albuminúria/tratamento farmacológico , Albuminúria/etiologia , Análise de Variância , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Benzimidazóis/efeitos adversos , Compostos de Bifenilo , Pressão Sanguínea/efeitos dos fármacos , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Japão , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Proteinúria/tratamento farmacológico , Proteinúria/etiologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Tetrazóis/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: This study compared the effects of morning and evening dosing of amlodipine/valsartan combination on 24-h blood pressure (BP) in patients uncontrolled by amlodipine (5 mg). METHODS: This was a multicenter study that used a prospective, randomized, open-label, blinded endpoint design. Patients with essential hypertension, who's ambulatory BP was uncontrolled after 4 weeks on amlodipine (5 mg) were randomized to receive amlodipine/valsartan (5/160 mg) for 8 weeks in the morning or evening (n=231, 232, respectively), with optional uptitration up to 10/160 mg after 4 weeks if the office BP was uncontrolled. A 30-h ambulatory BP measurement was taken at randomization and at the end of the study. RESULTS: Morning and evening dosing with amlodipine/valsartan had equivalent effects on systolic BP (mean 24 h, daytime, night-time, and 24-30 h) and diastolic BP (mean 24 h, daytime, night-time, and 24-30 h). There was a small difference in the night-time diastolic BP (-4.92 vs.-6.20 mmHg; P=0.02) and a slight but nonsignificant trend for higher BP reduction during daytime for morning intake and during night-time for evening intake. BP control rates based on 24-h ambulatory BP measurement values (<120/80 mmHg) were similar between morning and evening dosing (47 vs. 45%). CONCLUSION: These results indicate that, in patients with BP uncontrolled by amlodipine (5 mg), morning and evening treatment with amlodipine/valsartan combination have similar effects on circadian BP, especially when 24-h mean values are considered.
Assuntos
Anlodipino/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Hipertensão/tratamento farmacológico , Tetrazóis/administração & dosagem , Idoso , Anlodipino/efeitos adversos , Anlodipino/uso terapêutico , Combinação Anlodipino e Valsartana , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Monitorização Ambulatorial da Pressão Arterial , Cronofarmacoterapia , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tetrazóis/efeitos adversos , Tetrazóis/uso terapêuticoRESUMO
OBJECTIVE: To evaluate the comparative efficacy and safety of once-daily olmesartan medoxomil (OM) and losartan potassium (LOS) in patients with hypertension. METHODS: This was a multicenter, prospective, randomized, double-blind, active-comparator, forced-titration study. After a 3-week placebo run-in, 941 patients were randomized in an 8:1:9 ratio to once-daily treatment with OM (20 mg for 4 weeks, then OM 40 mg for 4 weeks [n = 420]), placebo plus OM (placebo for 2 weeks, then OM 20 mg for 2 weeks and OM 40 mg for 4 weeks [n = 52]), or LOS (50 mg for 4 weeks, then LOS 100 mg for 4 weeks [n = 469]). A subset of 246 patients underwent ambulatory blood pressure (BP) monitoring. The primary endpoint was mean change from baseline in trough seated cuff diastolic BP (SeDBP) at week 8. Secondary endpoints were mean changes from baseline in trough SeDBP at week 4 and seated systolic BP (SeSBP) at weeks 4 and 8. Tertiary endpoints included change from baseline in mean 24-hour ambulatory BP at weeks 4 and 8 and percentage of patients achieving seated cuff BP (SeBP) goal of < 140/90 mm Hg and mean 24-hour ambulatory BP target of < 130/80 mm Hg at weeks 4 and 8. RESULTS: At week 8, least-squares (LS) mean (± standard error) SeDBP reductions from baseline were 9.7 ± 0.5 and 7.1 ± 0.5 mm Hg (treatment difference: -2.5 ± 0.6 mm Hg; P < 0.0001) and LS mean SeSBP reductions were 13.6 ± 0.7 and 9.7 ± 0.7 mm Hg (treatment difference: -3.9 ± 1.0 mm Hg; P = 0.0001) for OM versus LOS, respectively. A significantly greater proportion of patients receiving OM reached SeBP goal of < 140/90 mm Hg at week 8. There was a similar incidence of adverse events with OM and LOS. CONCLUSION: Treatment with low- and high-dose OM achieved superior SeBP reductions compared with low- and high-dose LOS, resulting in significantly more patients achieving SeBP goal, with similar tolerability.
Assuntos
Hipertensão/tratamento farmacológico , Imidazóis/uso terapêutico , Losartan/uso terapêutico , Tetrazóis/uso terapêutico , Adulto , Idoso , Pressão Sanguínea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Imidazóis/administração & dosagem , Imidazóis/efeitos adversos , Losartan/administração & dosagem , Losartan/efeitos adversos , Masculino , Pessoa de Meia-Idade , Olmesartana Medoxomila , Estudos Prospectivos , Tetrazóis/administração & dosagem , Tetrazóis/efeitos adversosRESUMO
OBJECTIVE: To evaluate the efficacy and safety of high-dose irbesartan in the treatment of mild and moderate proteinuria in patients with chronic kidney disease (CKD). METHODS: A single center, prospective, observational study was performed. A total of 96 subjects were given irbesartan 150 mg/d for 4 weeks. Twenty-six were divided into single-dose (150 mg/d) irbesartan group when their clinical efficacy were eligible for improvement criteria and 70 were divided into high-dose (300 - 600 mg/d) irbesartan group when there were no effect for single-dose treatment. Both groups received treatment for 48 weeks. Then 24-hour quantitative urine protein, systolic pressure, diastolic pressure, TC, LDL-C, plasma albumin, serum creatinine, blood urea nitrogen, blood uric acid, serum potassium and ALT were determined. RESULTS: The proteinuria level after treatment in the single-dose irbesartan group was decreased by 68.3% with a statistically significant difference (P < 0.001). In the high-dose group, the dose of irbesartan was increased based on the ineffectiveness when treating with single-dose, and the proteinuria was decreased by 63.4% (P < 0.001). Total effective rate in treating proteinuria in high-dose group was 72.9% (51/70). Among the blood pressure sub-groups, the effective rates for the normal blood pressure group and hypertension group in treating proteinuria were 68.2% and 76.9% respectively (P > 0.05). However, in the normal blood pressure group and hypertension group, the proteinuria was decreased by 61.9% and 67.5% respectively after treatment (P < 0.001, P < 0.01), while without difference between the two groups (P > 0.05). The effective rates of high doses of 300, 450 and 600 mg/d of irbesartan in treating proteinuria were 70.8%, 63.6% and 66.7%, respectively. The difference in effective rates of treating proteinuria among different doses had no statistical significance (P > 0.05). No obvious increase of SCr value before and after treatment in high-dose group (P = 0.583). The increasing level of serum potassium in high-dose group after treatment was higher than that in the single-dose group (P < 0.05), but the highest concentration (4.8 mmol/L) was still within the normal range. The blood pressure of 3 cases who quit observation because of low blood pressure in high-dose group returned to normal after drug withdrawal. CONCLUSION: High-dose irbesartan can effectively lower the mild and moderate proteinuria in CKD patients with a good safety and tolerance and the efficacy is independent of lowering blood pressure.