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1.
Medwave ; 23(11): e2753, 2023 Dec 07.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38061014

RESUMO

Introduction: Infantile hemangioma is the most frequent benign vascular tumor in childhood, with an incidence of 3 to 10%. When patients require treatment, oral propranolol, a non-selective lipophilic beta-blocker, is usually considered the therapy of choice. However, its use has been associated with several adverse events related to its ß-2 action and its ability to cross the blood-brain barrier. Because of this, oral atenolol, a hydrophilic ß-1 receptor-selective beta-blocker, may represent a valid treatment alternative. Nonetheless, there is still controversy regarding the efficacy and safety of atenolol when compared with propranolol as monotherapy for this condition. Methods: We searched Epistemonikos, the largest database of systematic reviews in health science, which is maintained by screening multiple sources of information, including MEDLINE/PubMed, EMBASE, and Cochrane, among others. Data were extracted from the identified reviews, data from the primary studies were analyzed, a meta-analysis was performed, and a summary table of the results was prepared using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. Results: Nine systematic reviews were identified, including 10 primary studies and three randomized trials. The three randomized trials were included in the analysis of this investigation. Conclusion: The use of oral atenolol compared with oral propranolol as monotherapies may result in little or no difference in terms of likelihood of complete remission, decrease in Hemangioma Activity Score, likelihood of post-treatment relapse, and risk of adverse events and severe adverse events, in infantile hemangioma (low certainty of evidence).


Introducción: El hemangioma infantil corresponde al tumor vascular benigno más frecuente de la infancia, con una incidencia de 3 a 10%. Entre los pacientes que requieren tratamiento el uso oral de propranolol, un betabloqueador no selectivo de tipo lipofílico, es usualmente considerado como la terapia de elección. Sin embargo, su uso se ha asociado a diversos efectos adversos, relacionados con su acción ß-2, y a su capacidad de cruzar la barrera hematoencefálica. Debido a esto, el uso oral de atenolol, un betabloqueador selectivo de receptores ß-1, de tipo hidrofílico, podría representar una alternativa válida de tratamiento. Sin embargo, aún existe controversia en relación con la eficacia y seguridad del tratamiento con atenolol como monoterapia, en comparación con el uso de propranolol como monoterapia para esta condición. Métodos: Se realizó una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el tamizaje de múltiples fuentes de información, incluyendo MEDLINE/PubMed, EMBASE, Cochrane, entre otras. Se extrajeron los datos desde las revisiones identificadas, se analizaron los datos de los estudios primarios, se realizó un metanálisis y se preparó una tabla de resumen de los resultados utilizando el método GRADE. Resultados: Se identificaron nueve revisiones sistemáticas, que en conjunto incluyeron 10 estudios primarios y tres ensayos aleatorizados. Se incluyeron los tres ensayos aleatorizados en el análisis del presente trabajo. Conclusiones: El uso de atenolol oral como monoterapia, comparado con el uso de propranolol oral como monoterapia, podría resultar en poca o nula diferencia en cuanto a la probabilidad de remisión completa, la disminución del , la probabilidad de recaída posterior al tratamiento y el riesgo de presentar efectos adversos y efectos adversos severos, en el hemangioma infantil (certeza de la evidencia baja).


Assuntos
Hemangioma Capilar , Hemangioma , Humanos , Propranolol/efeitos adversos , Atenolol/efeitos adversos , Resultado do Tratamento , Recidiva Local de Neoplasia/induzido quimicamente , Revisões Sistemáticas como Assunto , Antagonistas Adrenérgicos beta/efeitos adversos , Hemangioma Capilar/induzido quimicamente , Hemangioma/tratamento farmacológico , Hemangioma/induzido quimicamente
2.
Medwave ; 23(11): e2753, 31-12-2023. tab, ilus
Artigo em Inglês, Espanhol | LILACS | ID: biblio-1524728

RESUMO

INTRODUCCIÓN: El hemangioma infantil corresponde al tumor vascular benigno más frecuente de la infancia, con una incidencia de 3 a 10%. Entre los pacientes que requieren tratamiento el uso oral de propranolol, un betabloqueador no selectivo de tipo lipofílico, es usualmente considerado como la terapia de elección. Sin embargo, su uso se ha asociado a diversos efectos adversos, relacionados con su acción ß-2, y a su capacidad de cruzar la barrera hematoencefálica. Debido a esto, el uso oral de atenolol, un betabloqueador selectivo de receptores ß-1, de tipo hidrofílico, podría representar una alternativa válida de tratamiento. Sin embargo, aún existe controversia en relación con la eficacia y seguridad del tratamiento con atenolol como monoterapia, en comparación con el uso de propranolol como monoterapia para esta condición. MÉTODOS: Se realizó una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el tamizaje de múltiples fuentes de información, incluyendo MEDLINE/PubMed, EMBASE, Cochrane, entre otras. Se extrajeron los datos desde las revisiones identificadas, se analizaron los datos de los estudios primarios, se realizó un metanálisis y se preparó una tabla de resumen de los resultados utilizando el método , GRADE. RESULTADOS: Se identificaron nueve revisiones sistemáticas, que en conjunto incluyeron 10 estudios primarios y tres ensayos aleatorizados. Se incluyeron los tres ensayos aleatorizados en el análisis del presente trabajo. CONCLUSIONES: El uso de atenolol oral como monoterapia, comparado con el uso de propranolol oral como monoterapia, podría resultar en poca o nula diferencia en cuanto a la probabilidad de remisión completa, la disminución del , la probabilidad de recaída posterior al tratamiento y el riesgo de presentar efectos adversos y efectos adversos severos, en el hemangioma infantil (certeza de la evidencia baja).


INTRODUCTION: Infantile hemangioma is the most frequent benign vascular tumor in childhood, with an incidence of 3 to 10%. When patients require treatment, oral propranolol, a non-selective lipophilic beta-blocker, is usually considered the therapy of choice. However, its use has been associated with several adverse events related to its ß-2 action and its ability to cross the blood-brain barrier. Because of this, oral atenolol, a hydrophilic ß-1 receptor-selective beta-blocker, may represent a valid treatment alternative. Nonetheless, there is still controversy regarding the efficacy and safety of atenolol when compared with propranolol as monotherapy for this condition. METHODS: We searched Epistemonikos, the largest database of systematic reviews in health science, which is maintained by screening multiple sources of information, including MEDLINE/PubMed, EMBASE, and Cochrane, among others. Data were extracted from the identified reviews, data from the primary studies were analyzed, a meta-analysis was performed, and a summary table of the results was prepared using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. RESULTS: Nine systematic reviews were identified, including 10 primary studies and three randomized trials. The three randomized trials were included in the analysis of this investigation. CONCLUSION: The use of oral atenolol compared with oral propranolol as monotherapies may result in little or no difference in terms of likelihood of complete remission, decrease in Hemangioma Activity Score, likelihood of post-treatment relapse, and risk of adverse events and severe adverse events, in infantile hemangioma (low certainty of evidence).


Assuntos
Humanos , Hemangioma Capilar/induzido quimicamente , Hemangioma/induzido quimicamente , Hemangioma/tratamento farmacológico , Propranolol/efeitos adversos , Atenolol/efeitos adversos , Resultado do Tratamento , Antagonistas Adrenérgicos beta/efeitos adversos , Revisões Sistemáticas como Assunto , Recidiva Local de Neoplasia/induzido quimicamente
3.
Eur J Pediatr ; 182(2): 757-767, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36478294

RESUMO

The purpose of this study was to compare long-term neurocognitive functioning (working memory, processing speed, and attention) between children who had been treated with either propranolol or atenolol for infantile hemangioma during infancy. All eligible children (n = 158) aged 6 years or older and treated with propranolol or atenolol as infants were invited to participate in this two-center cross-sectional study. The primary outcome was the Wechsler Intelligence Scale for Children-V Cognitive Proficiency Index (CPI), a measure of working memory, processing speed, and attention. Secondary outcomes were general intelligence, auditory, visuospatial, and narrative memory, as well as executive functioning and sleep. A total of 105 children, of whom 36 had been treated with propranolol (age 6.0-11.8 years, follow-up time 1.6-9.7 years, 19% male) and 69 had been treated with atenolol (age 6.9-9.7 years, follow-up time 4.5-8.4 years, 19% male), were analyzed. The CPI and other neurocognitive outcomes did not differ between the propranolol and atenolol groups and were in line with general population test norms. Post hoc analyses revealed lower CPI scores for males, both compared to participating females (10.3 IQ points, medium effect size) and compared to matched test norms (12.4 IQ points, medium effect size). CONCLUSIONS:  Long-term neurocognitive functioning did not differ between children treated with propranolol and those treated with atenolol for IH. Overall, propranolol and atenolol appear to be safe treatments for IH regarding long-term neurocognitive functioning. The substantially lower CPI scores in males warrant further investigation. TRIAL REGISTRATION:  Netherlands Trial Register, NL7703 https://www.trialregister.nl/trial/7703 What is Known: • Infants with infantile hemangioma are effectively treated with propranolol or atenolol. • Parents and professionals are concerned about long-term neurocognitive effects. WHAT IS NEW: • No long-term (≥ 6 years) differences in neurocognitive functioning were found between children treated with propranolol or atenolol. • Males treated with beta-blockers had substantially lower IQ scores than treated females and males from the general population, which is a matter of concern and should be considered when evaluating the risk/benefit ratio in less severe forms of infantile hemangioma.


Assuntos
Hemangioma Capilar , Hemangioma , Lactente , Feminino , Humanos , Masculino , Criança , Propranolol/efeitos adversos , Atenolol/efeitos adversos , Estudos Transversais , Antagonistas Adrenérgicos beta/efeitos adversos , Resultado do Tratamento
4.
Acta Derm Venereol ; 102: adv00788, 2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-35506358

RESUMO

Infantile haemangiomas are common benign tumours of infancy, which can be treated effectively with beta-blockers such as propranolol and atenolol. Different types of beta-blockers may result in different long-term aesthetic outcomes. This study evaluated the difference in long-term aesthetic outcomes between infantile haemangiomas treated with either propranolol or atenolol, including the perspective of physicians, parents, and children. Children, aged ≥6 years, treated with propranolol or atenolol for infantile haemangioma during infancy, participated in this 2-centre cross-sectional study. The primary endpoint was change in appearance of the infantile haemangioma from pre-treatment to follow-up, using a physician-rated visual analogue scale (VAS). Secondary outcomes were the Patient Observer Scar Assessment Scale (physician- and parent-rated) and a VAS (child-rated), assessing the residual lesion. In total, 103 children (35 treated with propranolol, 68 with atenolol) were analysed. No differences were found between children treated with propranolol and children treated with atenolol on physician-rated VAS (p = 0.10) or any secondary outcomes. Physicians indicated a large aesthetic improve-ment from pre- treatment to follow-up. Physicians, parents and children were positive about the current state of the residual lesion. Minor sequelae were common (86%). These results, in combination with the favourable safety profile of atenolol, should be considered when choosing beta-blocker treatment for infantile haemangioma.


Assuntos
Hemangioma Capilar , Hemangioma , Antagonistas Adrenérgicos beta/efeitos adversos , Atenolol/efeitos adversos , Estudos Transversais , Estética , Hemangioma/tratamento farmacológico , Hemangioma/patologia , Humanos , Lactente , Propranolol/efeitos adversos , Resultado do Tratamento
5.
Ther Adv Cardiovasc Dis ; 14: 1753944720912071, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32186246

RESUMO

BACKGROUND: Adherence to treatment after a myocardial infarction (MI) is poor, even in the early postinfarction period. Combining evidence-based drugs into a multicap could improve adherence in this population. No previous randomized trial assessing fixed-dose combination therapy has included patients early after a MI. We aimed to assess if a multicap containing four secondary prevention drugs increases adherence to treatment at 6 months after MI hospitalization. The study was designed as a randomized, parallel, open-label, controlled trial. METHODS: Patients were randomized within 7 days of a MI to either multicap or control group. The multicap group received a capsule containing aspirin, atenolol, ramipril, and simvastatin. The control group received each drug in separate pills. The primary outcome was adherence at 6 months. We also measured blood pressure, heart rate, serum cholesterol levels, C-reactive protein, and platelet aggregation. RESULTS: The study was stopped prematurely when 100 patients were included for futility. At 6 months, 92 (95.8%) patients were adherent to medical treatment: 98.0% in the multicap group and 93.5% in the control group [relative risk (RR) 1.05; 95% confidence interval (CI) 0.96-1.14; p = 0.347]. There were no differences between groups in systolic blood pressure (p = 0.662), diastolic blood pressure (p = 0.784), heart rate (p = 0.533), total cholesterol (p = 0.760), LDL-c (p = 0.979), C-reactive protein (p = 0.399), or in the proportion of patients with adequate platelet aggregation inhibition (p = 0.600). CONCLUSIONS: The study did not find any improvement in the adherence at 6 months after a MI with a multicap-based strategy (Multicap for Increase Adherence After Acute Myocardial Infarction; [ ClinicalTrials.gov identifier: NCT02271178]).


Assuntos
Síndrome Coronariana Aguda/terapia , Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Aspirina/administração & dosagem , Atenolol/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Adesão à Medicação , Infarto do Miocárdio/tratamento farmacológico , Inibidores da Agregação Plaquetária/administração & dosagem , Ramipril/administração & dosagem , Sinvastatina/administração & dosagem , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/fisiopatologia , Administração Oral , Antagonistas de Receptores Adrenérgicos beta 1/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Argentina , Aspirina/efeitos adversos , Atenolol/efeitos adversos , Combinação de Medicamentos , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/fisiopatologia , Inibidores da Agregação Plaquetária/efeitos adversos , Ramipril/efeitos adversos , Prevenção Secundária , Sinvastatina/efeitos adversos , Comprimidos , Fatores de Tempo , Resultado do Tratamento
6.
J Hypertens ; 38(3): 536-545, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32028517

RESUMO

BACKGROUND: ß-blockers are no longer considered as first-line antihypertensive drugs due to their lower cardioprotection. METHOD: Considering the differences in the pharmacological properties of ß-blockers, the present work compared the effects of third-generation ß-blockers - carvedilol and nebivolol - with a first-line agent - amlodipine - on hemodynamic parameters, including short-term blood pressure variability (BPV), and their ability to prevent target organ damage in spontaneously hypertensive rats (SHR). SHR rats were orally treated with carvedilol, nebivolol, atenolol, amlodipine or vehicle for 8 weeks. Wistar Kyoto rats treated with vehicle were used as normotensive group. Echocardiographic evaluation, BP, and short-term BPV measurements were performed. Left ventricle and thoracic aorta were removed for histological evaluations and to assess the expression of transforming growth factor ß (TGF-ß), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). RESULTS: Carvedilol, nebivolol or amlodipine induced a greater reduction of carotid BP, short-term BPV and echocardiography parameters than atenolol in SHR rats. Carvedilol, nebivolol and amlodipine were more effective than atenolol in the prevention of cardiac hypertrophy, and cardiac and aortic collagen deposit. Carvedilol and nebivolol, but not atenolol, reduced the expressions of fibrotic and inflammatory biomarkers - TGF-ß, TNF-α and IL-6 - in SHR rats to a similar extent to that of amlodipine. CONCLUSION: Chronic treatment with carvedilol or nebivolol attenuates carotid BP and short-term BPV, and reduces target organ damage in SHR to a greater extent than atenolol. Our findings suggest that the lower cardiovascular protection of nonvasodilating ß-blockers, as atenolol, in hypertension must not be translated to third-generation ß-blockers.


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Anlodipino/farmacologia , Anti-Hipertensivos/farmacologia , Atenolol/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Antagonistas Adrenérgicos beta/efeitos adversos , Anlodipino/efeitos adversos , Animais , Aorta/efeitos dos fármacos , Atenolol/efeitos adversos , Citocinas/metabolismo , Ventrículos do Coração/efeitos dos fármacos , Ratos , Ratos Endogâmicos SHR
8.
Environ Toxicol Pharmacol ; 63: 1-5, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30107356

RESUMO

Hypertension, a chronic non-transmissible multifactorial condition, it is highly frequent in Brazil, affecting about 32.5% of the population over 25 years of age. It is characterized by the sustained increase in systolic and diastolic blood pressure levels above 140 mmHg and 90 mmHg, respectively. It is the major aggravating factor in cardiovascular complications and the appearance of other comorbidities. Aiming to promote greater adherence to treatment and improve the population's access to basic medicament, in 2004 the Federal Government created the Programa Farmácia Popular do Brasil (PFPB); partnership with private institutions that provides the population with medicament to control hypertension, free of charge or subsidized at up to 90% of the value. The PFPB distributes the anti-hypertensives atenolol, captopril, enalapril, hydrochlorothiazide, losartan and propranolol. In this way, this work aims to evaluate the genotoxic potential of antihypertensives in human lymphocytes and macrophages, since they are widely used drugs and with few studies about their genotoxicological safety. The tests were developed from cell cultures treated with five different antihypertensive concentrations, all based on plasma peaks, evaluating cell viability, DNA damage index and DNA double strand breakdown. The results show that, as the concentration of captopril and enalapril maleate increased, cell viability decreased. In addition, a DNA damage was observed with the use Captopril and Enalapril in the higher concentrations. Hydrochlorothiazide also caused DNA damage in the five doses tested. Regarding the breaking of double strands of DNA, all the compounds showed increased ruptures. This decrease in dsDNA is dose dependent for all compounds tested. The set of results shows that the use although frequent still requires care and greater knowledge. In general, the antihypertensive drugs that proved to be safer in relation to the genetic damage tested were Losartan and Propranolol.


Assuntos
Anti-Hipertensivos/efeitos adversos , Hipertensão/tratamento farmacológico , Linfócitos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Anti-Hipertensivos/farmacologia , Atenolol/efeitos adversos , Atenolol/farmacologia , Brasil , Captopril/efeitos adversos , Captopril/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Dano ao DNA , Relação Dose-Resposta a Droga , Enalapril/efeitos adversos , Enalapril/farmacologia , Programas Governamentais , Humanos , Hidroclorotiazida/efeitos adversos , Hidroclorotiazida/farmacologia , Losartan/efeitos adversos , Losartan/farmacologia , Linfócitos/citologia , Macrófagos/citologia , Masculino , Testes de Mutagenicidade , Avaliação de Programas e Projetos de Saúde , Propranolol/efeitos adversos , Propranolol/farmacologia
11.
Pediatr Dermatol ; 34(4): 413-421, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28556385

RESUMO

BACKGROUND/OBJECTIVES: The nonselective beta-blocker propranolol is the current criterion standard for treatment of infantile hemangiomas (IHs) and the first therapy that the U.S. Food and Drug Administration has approved for the condition, but concern about adverse effects, such as bronchospasm, hypoglycemia, and sleep disturbances, has sparked interest in the use of alternative agents such as the selective ß1 antagonist atenolol. Our aim was to compare the efficacy and adverse effect profiles of atenolol with those of propranolol in the treatment of IHs in a retrospective noninferiority trial. METHODS: Twenty-seven children with IHs treated with atenolol according to the Cleveland Clinic foundation's standardized clinical assessment and management plan (SCAMP) met inclusion criteria and were compared with a matched group of 53 children with IHs treated with propranolol. Three reviewers assessed response to therapy using a modified version of the previously validated Hemangioma Activity Score (HAS). RESULTS: The mean change in HAS was -2.94 ± 1.20 for patients treated with atenolol and -2.96 ± 1.42 for those treated with propranolol. There was no statistically significant difference in pre- and posttreatment modified HAS scores between the two groups (p = 0.60). There was no significant difference in the overall rate of adverse effects (p = 0.10), although 11% of patients treated with propranolol experienced reactive airway symptoms, whereas this was not seen in any of the patients treated with atenolol. CONCLUSION: Our study supports previous findings that atenolol is at least as effective as propranolol for treatment of IHs and poses less risk of bronchospasm. Our SCAMP proposes guidelines for dosing and monitoring parameters.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Atenolol/uso terapêutico , Hemangioma/tratamento farmacológico , Propranolol/uso terapêutico , Antagonistas Adrenérgicos beta/efeitos adversos , Atenolol/efeitos adversos , Estudos de Casos e Controles , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Propranolol/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
12.
Eur J Prev Cardiol ; 24(9): 951-961, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28436727

RESUMO

Aims Cardiovascular fixed-dose combination pills, or polypills, may help address the widespread lack of access and adherence to proven medicines. Initiation of polypill-based care typically entails switching from current separately taken medications. Given the heterogeneity in usual care, there is interest in the impact of polypill treatment across different patterns of prior medication regimen. Methods A total of 2004 participants with established cardiovascular disease or estimated 5-year cardiovascular risk of over 15% were randomised to polypill-based treatment (aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg and either atenolol 50 mg or hydrochlorothiazide 12.5 mg) or usual care. Baseline medications were classified by potency relative to polypill components. Estimated cardiovascular risk reduction was calculated by combining risk factor changes with results seen in meta-analyses of previous randomised trials. Results For cholesterol reduction conferred by polypills, there was a dose response across baseline statin groups, with mean low-density lipoprotein (LDL)-cholesterol differences of 0.37, 0.22, 0.14 and 0.07 mmol/L among patients taking no statin, less potent, equipotent and more potent statin at baseline, respectively. Similarly there were differences in mean systolic BP of 5.4, 6.2, 3.3 and 1.8 mmHg among patients taking 0, 1, 2 or 3 BP-lowering agents. Among patients taking more potent statins at baseline, there was no significant difference in LDL-cholesterol but there were benefits for BP and aspirin adherence. Similar results were seen among patients taking 3 BP-lowering agents at baseline. Switching to a polypill-based strategy resulted in estimated cardiovascular relative risk reductions across a wide range of usual care patterns of antiplatelet, statin and BP-lowering therapy prescribing. Conclusion Adherence benefits from switching to a polypill resulted in risk factor changes that were at least as good as usual care across a wide variety of treatment patterns, including equally potent or more potent regimens. The benefits of switching to polypill-based care were greatest among those stepped up from partial treatment or less potent treatment.


Assuntos
Anti-Hipertensivos/administração & dosagem , Aspirina/administração & dosagem , Atenolol/administração & dosagem , Doenças Cardiovasculares/tratamento farmacológico , Substituição de Medicamentos , Hidroclorotiazida/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Lisinopril/administração & dosagem , Inibidores da Agregação Plaquetária/administração & dosagem , Polimedicação , Sinvastatina/administração & dosagem , Administração Oral , Idoso , Anti-Hipertensivos/efeitos adversos , Aspirina/efeitos adversos , Atenolol/efeitos adversos , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , LDL-Colesterol/sangue , Combinação de Medicamentos , Europa (Continente) , Feminino , Humanos , Hidroclorotiazida/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Índia , Lisinopril/efeitos adversos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/efeitos adversos , Medição de Risco , Fatores de Risco , Sinvastatina/efeitos adversos , Comprimidos , Fatores de Tempo , Resultado do Tratamento
13.
Ned Tijdschr Geneeskd ; 159: A9798, 2015.
Artigo em Holandês | MEDLINE | ID: mdl-26732221

RESUMO

Guidelines on perioperative cardiovascular evaluation and management of patients undergoing non-cardiac surgery recommend initiation of beta-blocker therapy in at-risk patients who are undergoing intermediate- to high-risk surgery. Continuation of therapy in patients already receiving beta-blockers is also recommended. Recent literature, however, reported an increased risk of perioperative cardiovascular mortality among patients who continued with existing beta-blockade; most patients in this study were using metoprolol. There are important pharmacodynamic and pharmacokinetic differences between various beta-blockers, and these differences may explain the differences in clinical effects. Metoprolol has less beta1 receptor affinity compared with atenolol and bisoprolol, and beta1 receptor polymorphisms affect the clinical effects of metoprolol. Furthermore, metoprolol is dependent on activity of the CYP2D6 liver enzyme, which results in clinically important differences in plasma concentration. It is, therefore, wise to follow the European guidelines and to initiate beta-blocker therapy in the perioperative period with either atenolol or bisoprolol.


Assuntos
Antagonistas Adrenérgicos beta/efeitos adversos , Antagonistas Adrenérgicos beta/uso terapêutico , Assistência Perioperatória , Procedimentos Cirúrgicos Operatórios/mortalidade , Atenolol/efeitos adversos , Atenolol/uso terapêutico , Bisoprolol/efeitos adversos , Bisoprolol/uso terapêutico , Humanos , Metoprolol/efeitos adversos , Metoprolol/uso terapêutico , Guias de Prática Clínica como Assunto , Medição de Risco , Fatores de Risco
14.
N Engl J Med ; 371(22): 2061-71, 2014 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-25405392

RESUMO

BACKGROUND: Aortic-root dissection is the leading cause of death in Marfan's syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, the current standard therapy in most centers. METHODS: We conducted a randomized trial comparing losartan with atenolol in children and young adults with Marfan's syndrome. The primary outcome was the rate of aortic-root enlargement, expressed as the change in the maximum aortic-root-diameter z score indexed to body-surface area (hereafter, aortic-root z score) over a 3-year period. Secondary outcomes included the rate of change in the absolute diameter of the aortic root; the rate of change in aortic regurgitation; the time to aortic dissection, aortic-root surgery, or death; somatic growth; and the incidence of adverse events. RESULTS: From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants, 6 months to 25 years of age (mean [±SD] age, 11.5±6.5 years in the atenolol group and 11.0±6.2 years in the losartan group), who had an aortic-root z score greater than 3.0. The baseline-adjusted rate of change in the mean (±SE) aortic-root z score did not differ significantly between the atenolol group and the losartan group (-0.139±0.013 and -0.107±0.013 standard-deviation units per year, respectively; P=0.08). Both slopes were significantly less than zero, indicating a decrease in the aortic-root diameter relative to body-surface area with either treatment. The 3-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups. CONCLUSIONS: Among children and young adults with Marfan's syndrome who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aortic-root dilatation between the two treatment groups over a 3-year period. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00429364.).


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Aorta/efeitos dos fármacos , Aneurisma Aórtico/prevenção & controle , Atenolol/uso terapêutico , Losartan/uso terapêutico , Síndrome de Marfan/tratamento farmacológico , Antagonistas Adrenérgicos beta/efeitos adversos , Adulto , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Aorta/crescimento & desenvolvimento , Aorta/cirurgia , Insuficiência da Valva Aórtica , Atenolol/efeitos adversos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Modelos Lineares , Losartan/efeitos adversos , Masculino , Síndrome de Marfan/mortalidade , Síndrome de Marfan/fisiopatologia , Resultado do Tratamento , Adulto Jovem
15.
Pharmacotherapy ; 34(2): 123-30, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24122840

RESUMO

STUDY OBJECTIVE: To assess the relationship of the 33 single nucleotide polymorphisms (SNPs) previously associated with fasting glucose in Caucasians in genome-wide association studies (GWAS) with glucose response to antihypertensive drugs shown to increase risk for hyperglycemia and diabetes. DESIGN: Randomized, multicenter clinical trial. PATIENTS: A total of 456 Caucasian men and women with uncomplicated hypertension. MEASUREMENTS AND MAIN RESULTS: The Pharmacogenomic Evaluation of Antihypertensives Responses study evaluated blood pressure and glucose response in uncomplicated hypertensive patients randomized to either atenolol or hydrochlorothiazide (HCTZ) monotherapy, followed by combination therapy with both agents. Association of these SNPs with atenolol- or HCTZ-induced glucose response was evaluated in 456 Caucasian patients using linear regression adjusting for age, sex, body mass index, baseline glucose, baseline insulin, and principal component for ancestry. The SNP rs340874 in the 5' region of PROX1 gene was significantly associated with atenolol-induced glucose change (p=0.0013). Participants harboring the C allele of this SNP had greater glucose elevation after approximately 9 weeks of atenolol monotherapy (ß = +2.39 mg/dl per C allele), consistent with the direction of effect in fasting glucose GWAS, that showed the C allele is associated with higher fasting glucose. CONCLUSION: These data suggest that PROX1 SNP rs340874, discovered in fasting glucose GWAS, may also be a pharmacogenetic risk factor for antihypertensive-induced hyperglycemia. ß-blockers and thiazides may interact with genetic risk factors to increase risk for dysglycemia and diabetes.


Assuntos
Anti-Hipertensivos/efeitos adversos , Glicemia/efeitos dos fármacos , Proteínas de Homeodomínio/genética , Hipertensão/tratamento farmacológico , Proteínas Supressoras de Tumor/genética , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/efeitos adversos , Adulto , Anti-Hipertensivos/administração & dosagem , Atenolol/administração & dosagem , Atenolol/efeitos adversos , Glicemia/genética , Quimioterapia Combinada , Jejum , Feminino , Humanos , Hidroclorotiazida/administração & dosagem , Hidroclorotiazida/efeitos adversos , Hiperglicemia/induzido quimicamente , Hiperglicemia/genética , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Farmacogenética , Polimorfismo de Nucleotídeo Único , Fatores de Risco , População Branca/genética
16.
Anesthesiology ; 119(4): 777-87, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23820187

RESUMO

BACKGROUND: Perioperative metoprolol increases postoperative stroke. Animal studies indicate that the mechanism may be related to attenuated ß(2)-adrenoreceptor-mediated cerebral vasodilatation. The authors therefore conducted a cohort to study whether the highly ß(1)-specific ß-blocker (bisoprolol) was associated with a reduced risk of postoperative stroke compared with less selective ß-blockers (metoprolol or atenolol). METHODS: The authors conducted a single-center study on 44,092 consecutive patients with age 50 yr or more having noncardiac, nonneurologic surgery. The primary outcome was stroke within 7 days of surgery. The secondary outcome was a composite of all-cause mortality, postoperative myocardial injury, and stroke. A propensity score-matched cohort was created to assess the independent association between bisoprolol and less ß(1)-selective agents metoprolol or atenolol. A secondary analysis using logistic regression, based on previously identified confounders, also compared selective ß(1)-antagonism. RESULTS: Twenty-four percent (10,756) of patients were exposed to in-hospital ß-blockers. A total of 88 patients (0.2%) suffered a stroke within 7 days of surgery. The matched cohort consisted of 2,462 patients, and the pairs were well matched for all variables. Bisoprolol was associated with fewer postoperative strokes than the less selective agents (odds ratio = 0.20; 95% CI, 0.04-0.91). Multivariable risk-adjustment in the ß-blockers-exposed patients comparing bisoprolol with the less selective agents was associated with a similarly reduced stroke rate. CONCLUSIONS: The use of metoprolol and atenolol is associated with increased risks of postoperative stroke, compared with bisoprolol. These findings warrant confirmation in a pragmatic randomized trial.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/efeitos adversos , Atenolol/efeitos adversos , Bisoprolol/efeitos adversos , Metoprolol/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Ontário , Estudos Retrospectivos
17.
Anesthesiology ; 119(6): 1340-6, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23612244

RESUMO

BACKGROUND: Numerous risk factors have been identified for perioperative stroke, but there are conflicting data regarding the role of ß adrenergic receptor blockade in general and metoprolol in particular. METHODS: The authors retrospectively screened 57,218 consecutive patients for radiologic evidence of stroke within 30 days after noncardiac procedures at a tertiary care university hospital. Incidence of perioperative stroke within 30 days of surgery and associated risk factors were assessed. Patients taking either metoprolol or atenolol were matched based on a number of risk factors for stroke. Parsimonious logistic regression was used to generate a preoperative risk model for perioperative stroke in the unmatched cohort. RESULTS: The incidence of perioperative stroke was 55 of 57,218 (0.09%). Preoperative metoprolol was associated with an approximately 4.2-fold increase in perioperative stroke (P < 0.001; 95% CI, 2.2-8.1). Analysis of matched cohorts revealed a significantly higher incidence of stroke in patients taking preoperative metoprolol compared with atenolol (P = 0.016). However, preoperative metoprolol was not an independent predictor of stroke in the entire cohort, which included patients who were not taking ß blockers. The use of intraoperative metoprolol was associated with a 3.3-fold increase in perioperative stroke (P = 0.003; 95% CI, 1.4-7.8); no association was found for intraoperative esmolol or labetalol. CONCLUSIONS: Routine use of preoperative metoprolol, but not atenolol, is associated with stroke after noncardiac surgery, even after adjusting for comorbidities. Intraoperative metoprolol but not esmolol or labetalol, is associated with increased risk of perioperative stroke. Drugs other than metoprolol should be considered during the perioperative period if ß blockade is required.


Assuntos
Antagonistas Adrenérgicos beta/efeitos adversos , Metoprolol/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Adolescente , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Atenolol/efeitos adversos , Atenolol/uso terapêutico , Estudos de Coortes , Interpretação Estatística de Dados , Feminino , Humanos , Incidência , Labetalol/efeitos adversos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Razão de Chances , Propanolaminas/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
18.
Mediciego ; 18(n.esp)dic. 2012. tab
Artigo em Espanhol | LILACS | ID: lil-710869

RESUMO

Se realizó un estudio cuantitativo, retrospectivo y descriptivo para determinar el la incorrecta prescripción del atenolol en el área sur de Morón, se distribuyeron los pacientes según sexo, edad, criterio de prescripción, se precisó la dosis indicada, se determinó el tiempo de duración de la terapia y se describieron las interacciones y reacciones medicamentosas encontradas. Se determinó que el sexo más afectado fue el masculino con un 50,87 por ciento, el grupo de edad más afectado fue el de 25 a 59 con un 54, 31%, el criterio que prevaleció fue la epilepsia con un total de 70 pacientes y un 60,74 por ciento, la dosis que con mayor frecuencia se usó fue la de 3 tabletas diarias, la interacción medicamentosa más frecuente fue con el fenobarbital en un 70,69 por ciento y la reacción medicamentosa más común fue el ras cutáneo para un 14, 65 por ciento.


Assuntos
Humanos , Masculino , Feminino , Atenolol/administração & dosagem , Atenolol , Atenolol/efeitos adversos , Epidemiologia Descritiva , Estudos de Avaliação como Assunto , Estudos Retrospectivos
20.
Clinics ; 67(1): 41-48, 2012. ilus, tab
Artigo em Inglês | LILACS | ID: lil-610622

RESUMO

OBJECTIVE: Hypertension is a major issue in public health, and the financial costs associated with hypertension continue to increase. Cost-effectiveness studies focusing on antihypertensive drug combinations, however, have been scarce. The cost-effectiveness ratios of the traditional treatment (hydrochlorothiazide and atenolol) and the current treatment (losartan and amlodipine) were evaluated in patients with grade 1 or 2 hypertension (HT1-2). For patients with grade 3 hypertension (HT3), a third drug was added to the treatment combinations: enalapril was added to the traditional treatment, and hydrochlorothiazide was added to the current treatment. METHODS: Hypertension treatment costs were estimated on the basis of the purchase prices of the antihypertensive medications, and effectiveness was measured as the reduction in systolic blood pressure and diastolic blood pressure (in mm Hg) at the end of a 12-month study period. RESULTS: When the purchase price of the brand-name medication was used to calculate the cost, the traditional treatment presented a lower cost-effectiveness ratio [US$/mm Hg] than the current treatment in the HT1-2 group. In the HT3 group, however, there was no difference in cost-effectiveness ratio between the traditional treatment and the current treatment. The cost-effectiveness ratio differences between the treatment regimens maintained the same pattern when the purchase price of the lower-cost medication was used. CONCLUSIONS: We conclude that the traditional treatment is more cost-effective (US$/mm Hg) than the current treatment in the HT1-2 group. There was no difference in cost-effectiveness between the traditional treatment and the current treatment for the HT3 group.


Assuntos
Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anlodipino/economia , Anti-Hipertensivos/economia , Atenolol/economia , Hidroclorotiazida/economia , Hipertensão/tratamento farmacológico , Losartan/economia , Anlodipino/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Atenolol/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Custos de Medicamentos , Quimioterapia Combinada/economia , Enalapril/administração & dosagem , Enalapril/economia , Hidroclorotiazida/efeitos adversos , Hipertensão/classificação , Losartan/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto
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