RESUMO
BACKGROUND: Patients who have undergone catheter ablation for atrial fibrillation (AF) may experience recurrence of this condition. The efficacy of sacubitril-valsartan (S/V) in preventing AF recurrence compared with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) is not established. This meta-analysis aimed to establish the best therapeutic choice for preventing AF recurrence after catheter ablation. METHOD: A systematic search of the PubMed, Embase, and Cochrane databases was conducted for randomized controlled trials (RCTs) and observational studies comparing the use of S/V with ACEI/ARB in patients who underwent catheter ablation. Results are presented as mean difference (MD) with 95% confidence interval (CI). Heterogeneity was assessed with the I2 statistic, and outcomes are expressed as relative risk (RR). R software version 4.2.3 was used for the analysis. RESULTS: Three RCTs and one cohort study, comprising 642 patients with 319 patients in the S/V group and 323 in the control group, were included. Follow-up ranged from 6 to 36 months, with mean ages ranging from 58.9 to 65.8 years. A significant reduction in persistent AF occurrence was demonstrated favoring the S/V group (RR: 0.54; 95% CI: [0.41, 0.70]; pâ¯= 0.000004; I2: 80%) over the ACEI/ARB group. There was no significant difference in left ventricular ejection fraction with S/V use (MD: 1.23; 95% CI: [-0.12, 2.60]; pâ¯= 0.076; I2: 0%) compared with ACEI/ARB. The analysis also showed a significant reduction in left atrial volume index (MD: -5.33; 95% CI: [-8.76, -1.90]; pâ¯= 0.002; I2: 57%) in the S/V group compared with the ACEI/ARB group. CONCLUSION: This meta-analysis demonstrated the efficacy of S/V in reducing the incidence of AF in patients undergoing catheter ablation compared with the use of ACEI/ARB. However, more RCTs are needed for a comprehensive evaluation of its efficacy in reducing AF recurrence after catheter ablation in clinical practice.
RESUMO
Cardiovascular diseases (CVDs) have a high mortality rate, and despite the several available therapeutic targets, non-response to antihypertensives remains a common problem. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are important classes of drugs recommended as first-line therapy for several CVDs. However, response to ACEIs and ARBs varies among treated patients. Pharmacogenomics assesses how an individual's genetic characteristics affect their likely response to drug therapy. Currently, numerous studies suggest that genetic polymorphisms may contribute to variability in drug response. Moreover, further studies evaluating gene-gene interactions within signaling pathways in response to antihypertensives might help to unravel potential genetic predictors for antihypertensive response. This review summarizes the pharmacogenetic data for ACEIs and ARBs in patients with CVD, and discusses the potential pharmacogenetics of these classes of antihypertensives in clinical practice. However, replication studies in different populations are needed. In addition, studies that evaluate gene-gene interactions that share signaling pathways in the response to antihypertensive drugs might facilitate the discovery of genetic predictors for antihypertensive response.
Assuntos
Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Doenças Cardiovasculares , Farmacogenética , Humanos , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/tratamento farmacológico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , AnimaisRESUMO
Hypertension is a risk factor for vascular dementia, which is the second most prevalent type of dementia, just behind Alzheimer's disease. This highlights the brain vulnerability due to hypertension, which may increase with aging. Thus, studying how hypertension affects neural cells and behavior, as well as the effects of antihypertensives on these alterations, it's important to understand the hypertension consequences in the brain. The spontaneously hypertensive rat (SHR) has been useful for the study of hypertension alterations in diverse organs, including the brain. Thus, we studied the losartan effects on cognitive and structural neuroplasticity impairments in SHR of 10 months of age. In the first instance, we evaluated the losartan effects on exploratory behavior and novel object recognition test (NORT) in the SHR. Then, we assessed the density and morphology of dendritic spines of pyramidal neurons from the prefrontal cortex (PFC) layers 3 and 5, and CA1 of the dorsal Hp (dHp). Our results indicate that in SHR, losartan treatment (2 months, 15 mg/Kg/day) reduces high blood pressure to age-matched vehicle-treated Wistar-Kyoto (WKY) rat levels. Moreover, losartan improved long-term memory in SHR compared with age-matched vehicle-treated WKY rats, without affecting the locomotor and anxiety behaviors. The behavioral improvement of the SHR can be associated with the increase in the number of dendritic spines and the mushroom spine population in the PFC and the dHp. In conclusion, losartan enhances cognitive impairments by controlling the high blood pressure and improving neuroplasticity in animals with chronic hypertension.
Assuntos
Losartan , Plasticidade Neuronal , Animais , Pressão Sanguínea , Cognição , Losartan/farmacologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
Background: The pharmacological response and the therapeutic efficacy of a drug depends on the interactions with plasma proteins. Methodology: The interaction of bovine serum albumin (BSA) with the metal complexes of antihypertensive drugs, Zn(II)/sartan complexes (candesartan, valsartan and losartan), was investigated using fluorescence quenching determinations at different temperatures. Results: The binding studies of the compounds with BSA showed static quenching and moderate binding with calculated constants in the range of 104-106 M-1, indicating potent serum distribution via albumins. In all cases, negative values of free energy are indicative of spontaneous processes and the stabilization of BSA/compound complexes through hydrogen bonding and van der Waals forces. The results for the sartans agree with the reported pharmacokinetics studies. Conclusion: It has been determined that the three sartans and the Zn complexes could be transported and distributed by albumin.
Assuntos
Benzimidazóis/química , Compostos de Bifenilo/química , Complexos de Coordenação/metabolismo , Losartan/química , Soroalbumina Bovina/metabolismo , Tetrazóis/química , Valsartana/química , Zinco/química , Animais , Bovinos , Complexos de Coordenação/química , Cinética , Ligação Proteica , Soroalbumina Bovina/química , Espectrofotometria , Temperatura , TermodinâmicaRESUMO
OBJECTIVE: This living systematic review aims to provide a timely, rigorous, and continuously updated summary of the evidence available on the role of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) in the treatment of patients with COVID-19. DATA SOURCES: We conducted searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), grey literature and in a centralized repository in L·OVE (Living OVerview of Evidence), which retrieves articles from multiple sources such as PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase, among other pre-print and protocols repositories. In response to the COVID-19 emergency, L·OVE (Living OVerview of Evidence) was adapted to expand the range of evidence and customized to group all COVID-19 evidence in one place on a daily search basis. The search covered a period of time up to July 31, 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES AND METHODS: We adapted an already published standard protocol for multiple parallel living systematic reviews to this question's specificities. We included randomized trials evaluating the effect of either suspension or indication of angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers as monotherapy, or in combination versus placebo or no treatment in patients with COVID-19. We searched for randomized trials evaluating the effect of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers versus placebo or no treatment in patients with COVID-19. Two reviewers independently screened each study for eligibility, extracted data, and assessed the risk of bias. We pooled the results using meta-analysis and applied the GRADE system to assess the certainty of the evidence for each outcome. We will resubmit results every time the conclusions change or whenever there are substantial updates. RESULTS: We screened 772 records, but none was considered for eligibility. We identified 55 ongoing studies, including 41 randomized trials evaluating angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers for patients with COVID-19. CONCLUSIONS: We did not find a randomized clinical trial meeting our inclusion criteria, and hence there is no evidence for supporting the role of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in the treatment of patients with COVID-19. A substantial number of ongoing studies would provide valuable evidence to inform researchers and decision-makers in the near future. PROSPERO REGISTRATION NUMBER: CRD42020182495. PROTOCOL PREPRINT DOI: 10.31219/osf.io/vp9nj.
OBJETIVO: Esta revisión sistemática viva tiene como objetivo proporcionar un resumen oportuno, riguroso y continuamente actualizado de la evidencia disponible sobre el rol de los inhibidores de la enzima convertidora de angiotensina (iECA) y los bloqueadores del receptor de angiotensina II (ARA-II) en el tratamiento de pacientes con COVID-19. FUENTES DE DATOS: Realizamos búsquedas en PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), literatura gris y en el repositorio centralizado L·OVE (Living OVerview of Evidence) que recupera artículos de múltiples fuentes como PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase, entre otros repositorios de preprints y protocolos. En respuesta a la emergencia de COVID-19, L·OVE (Living OVerview of Evidence) se adaptó para ampliar el rango de información que cubre y se personalizó para agrupar toda la evidencia en torno a COVID-19 en un solo lugar, en una base de búsqueda diaria. La búsqueda cubrió el período hasta el 31 de julio de 2020. CRITERIOS DE ELEGIBILIDAD PARA LA SELECCIÓN DE ESTUDIOS Y MÉTODOS: Adaptamos un protocolo común ya publicado para múltiples revisiones sistemáticas vivas paralelas a las especificidades de esta pregunta. Se incluyeron ensayos aleatorizados que evaluaban el efecto de la suspensión o la indicación de inhibidores de la enzima convertidora de angiotensina o bloqueadores de los receptores de angiotensina II, como monoterapia o en combinación, versus placebo o ningún tratamiento, en pacientes con COVID-19. Se buscaron ensayos aleatorizados que evaluaran el efecto de los inhibidores de la enzima convertidora de angiotensina/bloqueadores del receptor de angiotensina II versus placebo o ningún tratamiento en pacientes con COVID-19. Dos revisores examinaron de forma independiente la elegibilidad de cada estudio, extrajeron los datos y evaluaron el riesgo de sesgo. Los resultados se agruparon mediante un metanálisis y se aplicó GRADE para evaluar la certeza de la evidencia para cada resultado. Cada vez que cambien las conclusiones o hayan actualizaciones sustanciales, volveremos a enviar un reporte. RESULTADOS: Analizamos 772 artículos, pero ninguno cumplió con los criterios de inclusión. Identificamos 55 estudios en curso, incluidos 41 ensayos aleatorizados que evaluaban inhibidores de la enzima convertidora de angiotensina/bloqueadores del receptor de angiotensina II para pacientes con COVID-19. CONCLUSIONES: No encontramos ningún ensayo clínico aleatorizado que cumpliera con nuestros criterios de inclusión y, por lo tanto, no hay pruebas que respalden el papel de los inhibidores de la enzima convertidora de angiotensina y los bloqueadores de los receptores de angiotensina II en el tratamiento de pacientes con COVID-19. Identificamos un número considerable de estudios en curso que podría proporcionar evidencia valiosa para informar a los investigadores y a los responsables de la toma de decisiones en un futuro próximo.
Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Tratamento Farmacológico da COVID-19 , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de PesquisaRESUMO
BACKGROUND: Telmisartan is an antihypertensive angiotensin II receptor blocker. This antihypertensive shows antiinflammatory activity. PURPOSE: In this study, the antiinflammatory activity of telmisartan was tested in an acetic acid (10%) model of ulcerative colitis (UC) in rats. METHODS: Rats were given 1, 3, and 5mg/kg/day of telmisartan orally for 3 days before induction of UC. The same doses were also administered 2 and 24h after induction. Rats from the non-colitis and non-treated colitis groups were administered vehicle (saline, 5 ml/kg) orally and another group received sulfasalazine (50mg/kg/day). Colons tissue was analyzed by macroscopic, by histopathology, by the immunohistochemical examination of RANKL/RANK pathway; by ELISA analysis of the levels of IL-10, TNF-α, myeloperoxidase (MPO) and malonaldehyde (MDA). RESULTS: Telmisartan at 5mg/kg reduced levels of MPO, MDA, TNF-α and increased of IL-10 (p<0.05). Additionally, telmisartan reduced macroscopic damage, number of ulcers, and inflammatory and histopathological processes such as neutrophil infiltration, changes in cytoarchitecture, and necrosis. Immunohistochemistry revealed down-regulation of nuclear factor-kappaB receptor/nuclear factor-kappaB ligand (RANK/RANKL) in groups treated with sulfasalazine or telmisartan. CONCLUSION: Telmisartan exerts beneficial effects in an acetic acid model of colitis in rats. These effects may be due to accelerated termination of the acute inflammatory phase, indicated by decreased TNF-α and increased production of IL-10 and low expression of RANKL and RANK.
Assuntos
Benzimidazóis/uso terapêutico , Benzoatos/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Interleucina-10/fisiologia , Ligante RANK/fisiologia , Receptor Ativador de Fator Nuclear kappa-B/fisiologia , Fator de Necrose Tumoral alfa/fisiologia , Animais , Colite Ulcerativa/metabolismo , Colite Ulcerativa/patologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Ratos , Ratos Wistar , TelmisartanRESUMO
In a systematic review and random-effects meta-analysis, we evaluated whether obesity is associated with postoperative atrial fibrillation (POAF) in patients undergoing cardiac operations. We selected 18 observational studies until December 2011 that excluded patients with preoperative AF (n=36,147). Obese patients had a modest higher risk of POAF compared with nonobese (odds ratio, 1.12; 95% confidence interval, 1.04 to 1.21; p=0.002). The association between obesity and POAF did not vary substantially by type of cardiac operation, study design, or year of publication. POAF was significantly associated with a higher risk of stroke, respiratory failure, and operative death.