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1.
Ars pharm ; 61(4): 253-257, oct.-dic. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-193586

RESUMO

INTRODUCCIÓN: La Enfermedad por coronavirus 2019 (COVID-19) causada por el virus SARS-CoV-2, con característica de infectar el tracto respiratorio causando un síndrome respiratorio agudo como paso inicial para ingresar a la célula huésped el virus usa los receptores ACE II y la proteína transmembrana TMPRSS2 para causar la infección, Por lo que se ha descrito diferentes tipos de fármacos para realizar su inhibición en la adhesión del paso inicial. METODOLOGÍA: Revisión no sistemática de artículos con la ayuda de palabras clave preestablecidas. RESULTADOS: En esta revisión presentaremos fármacos que inhiben este tipo de receptor, por lo tanto, estos medicamentos podrían considerarse candidatos potenciales para mitigar la propagación del SARS-CoV-2


INTRODUCTION: Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus with characteristic of infecting the respiratory tract, causing severe acute respiratory syndrome. The virus uses the ACE II receptors and the transmembrane protein TMPRSS2 initial step to enter the host cell, this contribution described different types of drug, to perform its inhibition in initial step adhesion. METHODOLOGY: Non-systematic review of articles with the help of preset keywords. RESULTS: In this review we will present drugs that inhibitors of this type of receptor therefore these drugs could be considered potential candidates to mitigate the spread of SARS-CoV-2


Assuntos
Humanos , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Serina Endopeptidases/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores de Serino Proteinase/farmacologia , Serina Endopeptidases/farmacologia
2.
Clin Sci (Lond) ; 134(21): 2851-2871, 2020 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-33146371

RESUMO

Angiotensin converting enzyme (ACE) is well-known for its role in blood pressure regulation via the renin-angiotensin aldosterone system (RAAS) but also functions in fertility, immunity, haematopoiesis and diseases such as obesity, fibrosis and Alzheimer's dementia. Like ACE, the human homologue ACE2 is also involved in blood pressure regulation and cleaves a range of substrates involved in different physiological processes. Importantly, it is the functional receptor for severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 responsible for the 2020, coronavirus infectious disease 2019 (COVID-19) pandemic. Understanding the interaction between SARS-CoV-2 and ACE2 is crucial for the design of therapies to combat this disease. This review provides a comparative analysis of methodologies and findings to describe how structural biology techniques like X-ray crystallography and cryo-electron microscopy have enabled remarkable discoveries into the structure-function relationship of ACE and ACE2. This, in turn, has enabled the development of ACE inhibitors for the treatment of cardiovascular disease and candidate therapies for the treatment of COVID-19. However, despite these advances the function of ACE homologues in non-human organisms is not yet fully understood. ACE homologues have been discovered in the tissues, body fluids and venom of species from diverse lineages and are known to have important functions in fertility, envenoming and insect-host defence mechanisms. We, therefore, further highlight the need for structural insight into insect and venom ACE homologues for the potential development of novel anti-venoms and insecticides.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/enzimologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/enzimologia , Receptores Virais/metabolismo , Internalização do Vírus , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Interações Hospedeiro-Patógeno , Humanos , Pandemias , Peptidil Dipeptidase A/química , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Conformação Proteica , Receptores Virais/química , Relação Estrutura-Atividade
3.
Biomed Pharmacother ; 131: 110748, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33152916

RESUMO

The severe form of COVID-19 has significant sex disparities, with high fatalities commonly reported among males than females. The incidence of COVID-19 has also been higher in males compared with their female counterparts. This trend could be attributed to a better responsive and robust immune system in females. Cytokine storm is one of the pathophysiological features of severe COVID-19, and it occurs as a result of over-activation of immune cells leading to severe inflammation and tissue damage. Nevertheless, it is well modulated in females compared to their male counterparts. Severe inflammation in males is reported to facilitate progression of mild to severe COVID-19. The sex hormones, estrogens and androgens which exist in varying functional levels respectively in females and males are cited as the underlying cause for the differential immune response to COVID-19. Evidence abounds that estrogen modulate the immune system to protect females from severe inflammation and for that matter severe COVID-19. On the contrary, androgen has been implicated in over-activation of immune cells, cytokine storm and the attendant severe inflammation, which perhaps predispose males to severe COVID-19. In this review efforts are made to expand understanding and explain the possible roles of the immune system, the sex hormones and the angiotensin-converting enzyme (ACE) systems in male bias to severe COVID-19. Also, this review explores possible therapeutic avenues including androgen deprivation therapy (ADT), estrogen-based therapy, and ACE inhibitors for consideration in the fight against COVID-19.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/farmacologia , Antagonistas de Androgênios/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Criança , Pré-Escolar , Infecções por Coronavirus/complicações , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Suscetibilidade a Doenças , Feminino , Hormônios Esteroides Gonadais/fisiologia , Humanos , Imunidade Inata , Lactente , Recém-Nascido , Inflamação , Masculino , Camundongos , Pessoa de Meia-Idade , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Neoplasias da Próstata/complicações , Neoplasias da Próstata/tratamento farmacológico , Isomerases de Dissulfetos de Proteínas/fisiologia , Receptores de Superfície Celular/fisiologia , Receptores Virais/fisiologia , Distribuição por Sexo , Fumar/efeitos adversos , Adulto Jovem
4.
Open Heart ; 7(2)2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33154144

RESUMO

OBJECTIVE: The association between the use of renin-angiotensin-aldosterone (RAAS) inhibitors and the risk of mortality from COVID-19 is unclear. We aimed to estimate the association of RAAS inhibitors, including ACE inhibitors (ACEi) and angiotensin II receptor blockers (ARBs) with COVID-19 mortality risk in patients with hypertension. METHODS: PubMed (MEDLINE) SCOPUS, OVID, Cochrane Library databases and medrxiv.org were searched from 1 January 2020 to 1 September 2020. Studies reporting the association of RAAS inhibitors (ACEi or ARBs) and mortality in patients with hypertension, hospitalised for COVID-19 were extracted. Two reviewers independently extracted appropriate data of interest and assessed the risk of bias. All analyses were performed using random-effects models on log-transformed risk ratio (RR) estimates, and heterogeneity was quantified. RESULTS: Fourteen studies were included in the systematic review (n=73,073 patients with COVID-19; mean age 61 years; 53% male). Overall, the between-study heterogeneity was high (I2=80%, p<0.01). Patients with hypertension with prior use of RAAS inhibitors were 35% less likely to die from COVID-19 compared with patients with hypertension not taking RAAS inhibitors (pooled RR 0.65, 95% CI 0.45 to 0.94). The quality of evidence by Grading of Recommendations, Assessment, Development and Evaluations was graded as 'moderate' quality. CONCLUSIONS: In this meta-analysis, with prior use of RAAS inhibitors was associated with lower risk mortality from COVID-19 in patients with hypertension. Our findings suggest a potential protective effect of RAAS-inhibitors in COVID-19 patients with hypertension. PROSPERO REGISTRATION NUMBER: The present study has been registered with PROSPERO (registration ID: CRD 42020187963).


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Infecções por Coronavirus/mortalidade , Hospitalização , Hipertensão/tratamento farmacológico , Pneumonia Viral/mortalidade , Sistema Renina-Angiotensina/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/mortalidade , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Fatores de Proteção , Medição de Risco , Fatores de Risco , Resultado do Tratamento
5.
Rev Med Liege ; 75(S1): 123-129, 2020.
Artigo em Francês | MEDLINE | ID: mdl-33211434

RESUMO

The breakthrough of the secrets of hypertension and the renin-angiotensin-aldosterone system (RAAS) is one of the legends of medicine. The first chapter is the one of Tigerstedt's experiments about renin, and Loesch and Gollblatt's model of renal hypertension. The race to elucidate the mechanisms of angiotensin, angiotensinogen and the angiotensin conversion enzyme cascade, by Braun Menéndez and Page teams, is a second chapter. The puzzle of this elegant cascade is completed by aldosterone isolation by the collaboration of Tait spouses and Tadeus Rechstein. As a corollary of these findings, Conn made the first description of primary hyperaldosteronism. The elucidation of RAAS pathophysiology naturally led to the synthesis of the antihypertensive captopril by Ondetti and Cushman, thereby opening the modern era of ACE inhibitors and ARII blockers. In March 2020, a viral pandemic caused by SARS-Cov-2 ignites the entire planet. This new coronavirus uses the RAAS angiotensin conversion enzyme type 2 (ACE-2) as a gateway. The SARS-CoV-2/ACE-2 signalling pathway and its pathological effects on the cardio-respiratory and renal system of these patients initiate a new chapter. The interaction of SARS-Cov-2/ACE-2 axis with anti-hypertensive agents, as well as with ACE-2 activators and ACE-2 homologs, takes a part of an active international study searching for therapeutic targets. This modern research, summarized in this article, will further develop our knowledge of RAAS and, hopefully, will improve the management of COVID-19 patients.


Assuntos
Infecções por Coronavirus , Pandemias , Pneumonia Viral , Sistema Renina-Angiotensina , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Betacoronavirus , Humanos
6.
J Am Med Dir Assoc ; 21(11): 1539-1545, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33138935

RESUMO

OBJECTIVE: The role of treatment with renin-angiotensin-aldosterone system blockers at the onset of COVID-19 infection is not known in the geriatric population. The aim of this study was to assess the relationship between angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitor (ACEI) use and in-hospital mortality in geriatric patients hospitalized for COVID-19. DESIGN: This observational retrospective study was conducted in a French geriatric department. Patients were included between March 17 and April 18, 2020. SETTING AND PARTICIPANTS: All consecutive 201 patients hospitalized for COVID-19 (confirmed by reverse-transcriptase polymerase chain reaction methods) were included. All nondeceased patients had 30 days of follow-up and no patient was lost to follow-up. METHODS: Demographic, clinical, and biological data and medications were collected. In-hospital mortality of patients treated or not by ACEI/ARB was analyzed using multivariate Cox models. RESULTS: Mean age of the population was 86.3 (8.0) years, 62.7% of patients were institutionalized, 88.6% had dementia, and 53.5% had severe disability (activities of daily living [ADL] score <2). Sixty-three patients were treated with ACEI/ARB and 138 were not. Mean follow-up was 23.4 (10.0) days, 66 (33.8%) patients died after an average of 10.0 days (6.0). Lower mortality rate was observed in patients treated with ACEI/ARB compared with patients not treated with ARB or ACEI (22.2% [14] vs 37.7% [52], hazard ratio [HR] 0.54; 95% confidence interval 0.30-0.97; P = .03). In a multivariate Cox regression model including age, sex, ADL score, Charlson index, renal function, dyspnea, C-reactive protein, and white blood cell count, use of ACEI/ARB was significantly associated with lower in-hospital mortality (HR 0.52 (0.27-0.99), P = .048). CONCLUSION AND IMPLICATIONS: In very old subjects hospitalized in geriatric settings for COVID-19, mortality was significantly lower in subjects treated with ARB or ACEI before the onset of infection. The continuation of ACEI/ARB therapy should be encouraged during periods of coronavirus outbreak in older subjects.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Infecções por Coronavirus/mortalidade , Mortalidade Hospitalar/tendências , Pneumonia Viral/mortalidade , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Feminino , França/epidemiologia , Enfermagem Geriátrica , Humanos , Masculino , Pandemias , Estudos Retrospectivos
7.
J Diabetes Res ; 2020: 8205261, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33134395

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic continues to cause havoc to many countries of the globe, with no end in sight, due to nonavailability of a given vaccine or treatment regimen. The pandemic has so far had a relatively limited impact on the African continent, which contributes more than 93% of global malaria burden. However, the limited burden of COVID-19 pandemic on the African region could have long-term implications on the health and wellbeing of affected inhabitants due to its malaria-endemic status. Malaria causes recurrent insulin resistance with episodes of infection at relatively low parasitaemia. Angiotensin-converting enzyme 2 (ACE2) which is widely distributed in the human body is implicated in the pathogenesis of malaria, type 2 diabetes mellitus (T2DM), and COVID-19. Use of ACE2 by the COVID-19 virus induces inflammation and oxidative stress, which can lead to insulin resistance. Although COVID-19 patients in malaria-endemic African region may not exhibit severe signs and symptoms of the disease, their risk of exhibiting heightened insulin resistance and possible future development of T2DM is high due to their prior exposure to malaria. African governments must double efforts at containing the continued spread of the virus without neglecting existing malarial control measures if the region is to avert the plausible long-term impact of the pandemic in terms of future development of T2DM.


Assuntos
Infecções por Coronavirus/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/patologia , Doenças Endêmicas , Malária/epidemiologia , Pneumonia Viral/epidemiologia , África/epidemiologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Betacoronavirus/fisiologia , Infecções por Coronavirus/complicações , Diabetes Mellitus Tipo 2/complicações , Progressão da Doença , Humanos , Resistência à Insulina/fisiologia , Malária/complicações , Pandemias , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/complicações , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/patologia , Estado Pré-Diabético/virologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia
8.
Clin Sci (Lond) ; 134(21): 2791-2805, 2020 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-33135725

RESUMO

Angiotensin-converting enzyme II (ACE2) is a homologue of angiotensin-converting enzyme discovered in 2000. From the initial discovery, it was recognized that the kidneys were organs very rich on ACE2. Subsequent studies demonstrated the precise localization of ACE2 within the kidney and the importance of this enzyme in the metabolism of Angiotensin II and the formation of Angiotensin 1-7. With the recognition early in 2020 of ACE2 being the main receptor of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), the interest in this protein has dramatically increased. In this review, we will focus on kidney ACE2; its localization, its alterations in hypertension, diabetes, the effect of ACE inhibitors and angiotensin type 1 receptor blockers (ARBs) on ACE2 and the potential use of ACE2 recombinant proteins therapeutically for kidney disease. We also describe the emerging kidney manifestations of COVID-19, namely the frequent development of acute kidney injury. The possibility that binding of SARS-CoV-2 to kidney ACE2 plays a role in the kidney manifestations is also briefly discussed.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/enzimologia , Nefropatias/enzimologia , Rim/enzimologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/enzimologia , Receptores Virais/metabolismo , Lesão Renal Aguda/enzimologia , Lesão Renal Aguda/virologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Diabetes Mellitus/enzimologia , Diabetes Mellitus/fisiopatologia , História do Século XXI , Interações Hospedeiro-Patógeno , Humanos , Hipertensão/enzimologia , Hipertensão/fisiopatologia , Rim/fisiopatologia , Nefropatias/tratamento farmacológico , Nefropatias/fisiopatologia , Pandemias , Peptidil Dipeptidase A/história , Peptidil Dipeptidase A/uso terapêutico , Pneumonia Viral/virologia , Receptores Virais/história
9.
BMC Nephrol ; 21(1): 449, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33109103

RESUMO

The pandemic of coronavirus disease 2019 (CoVID-19) has been an unprecedented period. The disease afflicts multiple organ systems, with acute kidney injury (AKI) a major complication in seriously ill patients. The incidence of AKI in patients with CoVID-19 is variable across numerous international studies, but the high incidence of AKI and its associated worse outcomes in the critical care setting are a consistent finding. A multitude of patterns and mechanisms of AKI have been elucidated, and novel strategies to address shortage of renal replacement therapy equipment have been implemented. The disease also has had consequences on longitudinal management of patients with chronic kidney disease and end stage kidney disease. Kidney transplant recipients may be especially susceptible to CoVID-19 as a result of immunosuppression, with preliminary studies demonstrating high mortality rates. Increased surveillance of disease with low threshold for testing and adjustment of immunosuppression regimen during acute periods of illness have been recommended.


Assuntos
Lesão Renal Aguda/etiologia , Betacoronavirus , Infecções por Coronavirus/complicações , Falência Renal Crônica/terapia , Transplante de Rim , Pneumonia Viral/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Lesão Renal Aguda/epidemiologia , Lesão Renal Aguda/terapia , Fatores Etários , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/mortalidade , Cuidados Críticos , Disparidades em Assistência à Saúde , Humanos , Imunossupressão/efeitos adversos , Imunossupressão/métodos , Incidência , Falência Renal Crônica/complicações , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Transplante de Rim/mortalidade , Pandemias , Peptidil Dipeptidase A , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Insuficiência Renal Crônica/complicações , Terapia de Substituição Renal/instrumentação , Fatores de Risco , Fatores Sexuais , Transplantados , Populações Vulneráveis
10.
Geriatr Psychol Neuropsychiatr Vieil ; 18(2): 141-148, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33064080

RESUMO

Coronavirus disease 2019 (COVID-19) is a secondary infectious disease caused by severe acute respiratory syndrome coronavirus 2. The link between cardiovascular disease and COVID-19 appears to be twofold. First, some reports indicate that certain groups of patients are at greater risk of COVID-19, including patients with cardiovascular risk factors, pre-existing cardiovascular conditions and older patients. In addition, the outcomes these patients face are disproportionately more severe. Second, SARS-CoV-2 infection can be complicated by life-threatening acute cardiovascular diseases. Despite the rapid ongoing evolution of information about this pandemic, this review aims to highlight cardiovascular pathologies related to COVID-19 as either comorbidities, including concerns and uncertainty regarding the effect of renin-angiotensin-aldosterone system (RAAS) inhibitors on angiotensin conversion enzyme 2, or cardiovascular complications.


Assuntos
Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/terapia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Comorbidade , Humanos , Pandemias , Peptidil Dipeptidase A/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos
11.
PLoS Comput Biol ; 16(10): e1008235, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33031368

RESUMO

Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) are frequently prescribed for a range of diseases including hypertension, proteinuric chronic kidney disease, and heart failure. There is evidence indicating that these drugs upregulate ACE2, a key component of the renin-angiotensin system (RAS) and is found on the cells of a number of tissues, including the epithelial cells in the lungs. While ACE2 has a beneficial role in many diseases such as hypertension, diabetes, and cardiovascular disease, it also serves as a receptor for both SARS-CoV and SARS-CoV-2 via binding with the spike protein of the virus, thereby allowing it entry into host cells. Thus, it has been suggested that these therapies can theoretically increase the risk of SARS- CoV-2 infection and cause more severe COVID-19. Given the success of ACEi and ARBs in cardiovascular diseases, we seek to gain insights into the implications of these medications in the pathogenesis of COVID-19. To that end, we have developed a mathematical model that represents the RAS, binding of ACE2 with SARS-CoV-2 and the subsequent cell entry, and the host's acute inflammatory response. The model can simulate different levels of SARS-CoV-2 exposure, and represent the effect of commonly prescribed anti-hypertensive medications, ACEi and ARB, and predict tissue damage. Model simulations indicate that whether the extent of tissue damage may be exacerbated by ACEi or ARB treatment depends on a number of factors, including the level of existing inflammation, dosage, and the effect of the drugs on ACE2 protein abundance. The findings of this study can serve as the first step in the development of appropriate and more comprehensive guidelines for the prescription of ACEi and ARB in the current and future coronavirus pandemics.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Infecções por Coronavirus , Hipertensão , Modelos Biológicos , Pandemias , Pneumonia Viral , Betacoronavirus , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Síndrome do Desconforto Respiratório do Adulto , Carga Viral/imunologia
13.
ESC Heart Fail ; 7(5): 3119-3123, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33121220

RESUMO

The present Perspective examined the latest evidence on the association between the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) and the incidence/mortality of coronavirus disease 2019 (COVID-19). Our critical appraisal from existing literature does not support discontinuation of ACEIs/ARBs in clinical practice as there is absence of solid evidence. However, we do recommend future research perspective in formulation and implementation of practice-changing guidelines.


Assuntos
Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Infecções por Coronavirus/tratamento farmacológico , Pandemias/estatística & dados numéricos , Pneumonia Viral/tratamento farmacológico , Síndrome Respiratória Aguda Grave/mortalidade , Adulto , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Causas de Morte , Infecções por Coronavirus/mortalidade , Feminino , Mortalidade Hospitalar/tendências , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/mortalidade , Prognóstico , Medição de Risco , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Análise de Sobrevida
14.
J Am Heart Assoc ; 9(19): e017297, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-32998607

RESUMO

Background Angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) may worsen the prognosis of coronavirus disease 2019, but any association could be confounded by the cardiometabolic conditions indicating ACE-I/ARB use. We therefore examined the impact of ACE-Is/ARBs on respiratory tract infection outcomes. Methods and Results This cohort study included all adult patients hospitalized with influenza or pneumonia from 2005 to 2018 in Denmark using population-based medical databases. Thirty-day mortality and risk of admission to the intensive care unit in ACE-Is/ARBs users was compared with nonusers and with users of calcium channel blockers. We used propensity scores to handle confounding and computed propensity score-weighted risks, risk differences (RDs), and risk ratios (RRs). Of 568 019 patients hospitalized with influenza or pneumonia, 100 278 were ACE-I/ARB users and 37 961 were users of calcium channel blockers. In propensity score-weighted analyses, ACE-I/ARB users had marginally lower 30-day mortality than users of calcium channel blockers (13.9% versus 14.5%; RD, -0.6%; 95% CI, -1.0 to -0.1; RR, 0.96; 95% CI, 0.93-0.99), and a lower risk of admission to the intensive care unit (8.0% versus 9.6%; RD, -1.6%; 95% CI, -2.0 to -1.2; RR, 0.83; 95% CI, 0.80-0.87). Compared with nonusers, current ACE-I/ARB users had lower mortality (RD, -2.4%; 95% CI, -2.8 to -2.0; RR, 0.85; 95% CI, 0.83-0.87), but similar risk of admission to the intensive care unit (RD, 0.4%; 95% CI, 0.0-0.7; RR, 1.04; 95% CI, 1.00-1.09). Conclusions Among patients with influenza or pneumonia, ACE-I/ARB users had no increased risk of admission to the intensive care unit and slightly reduced mortality after controlling for confounding.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Influenza Humana/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Pneumonia/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Dinamarca/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Influenza Humana/epidemiologia , Masculino , Razão de Chances , Pandemias , Pneumonia/epidemiologia , Pontuação de Propensão , Estudos Retrospectivos , Taxa de Sobrevida/tendências
15.
Front Immunol ; 11: 552925, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072093

RESUMO

Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) induced Coronavirus Disease - 19 (COVID-19) cases have been increasing at an alarming rate (7.4 million positive cases as on June 11 2020), causing high mortality (4,17,956 deaths as on June 11 2020) and economic loss (a 3.2% shrink in global economy in 2020) across 212 countries globally. The clinical manifestations of this disease are pneumonia, lung injury, inflammation, and severe acute respiratory syndrome (SARS). Currently, there is no vaccine or effective pharmacological agents available for the prevention/treatment of SARS-CoV2 infections. Moreover, development of a suitable vaccine is a challenging task due to antibody-dependent enhancement (ADE) and Th-2 immunopathology, which aggravates infection with SARS-CoV-2. Furthermore, the emerging SARS-CoV-2 strain exhibits several distinct genomic and structural patterns compared to other coronavirus strains, making the development of a suitable vaccine even more difficult. Therefore, the identification of novel small molecule inhibitors (NSMIs) that can interfere with viral entry or viral propagation is of special interest and is vital in managing already infected cases. SARS-CoV-2 infection is mediated by the binding of viral Spike proteins (S-protein) to human cells through a 2-step process, which involves Angiotensin Converting Enzyme-2 (ACE2) and Transmembrane Serine Protease (TMPRSS)-2. Therefore, the development of novel inhibitors of ACE2/TMPRSS2 is likely to be beneficial in combating SARS-CoV-2 infections. However, the usage of ACE-2 inhibitors to block the SARS-CoV-2 viral entry requires additional studies as there are conflicting findings and severe health complications reported for these inhibitors in patients. Hence, the current interest is shifted toward the development of NSMIs, which includes natural antiviral phytochemicals and Nrf-2 activators to manage a SARS-CoV-2 infection. It is imperative to investigate the efficacy of existing antiviral phytochemicals and Nrf-2 activators to mitigate the SARS-CoV-2-mediated oxidative stress. Therefore, in this review, we have reviewed structural features of SARS-CoV-2 with special emphasis on key molecular targets and their known modulators that can be considered for the development of NSMIs.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/imunologia , Infecções por Coronavirus , Sistemas de Liberação de Medicamentos , Pandemias , Pneumonia Viral , Internalização do Vírus/efeitos dos fármacos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Humanos , Peptidil Dipeptidase A/imunologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Serina Endopeptidases/imunologia , Inibidores de Serino Proteinase/uso terapêutico , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores , Glicoproteína da Espícula de Coronavírus/imunologia , Células Th2/imunologia , Vacinas Virais/imunologia , Vacinas Virais/uso terapêutico
16.
Pharmacol Res Perspect ; 8(6): e00666, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33084232

RESUMO

Conflicting evidence exists about the effect of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) on COVID-19 clinical outcomes. We aimed to provide a comprehensive/updated evaluation of the effect of ACEIs/ARBs on COVID-19-related clinical outcomes, including exploration of interclass differences between ACEIs and ARBs, using a systematic review/meta-analysis approach conducted in Medline (OVID), Embase, Scopus, Cochrane library, and medRxiv from inception to 22 May 2020. English studies that evaluated the effect of ACEIs/ARBs among patients with COVID-19 were included. Studies' quality was appraised using the Newcastle-Ottawa Scale. Data were analyzed using the random-effects modeling stratified by exposure (ACEIs/ARBs, ACEIs, and ARBs). Heterogeneiity was assessed using I2 statistic. Several subgroup analyses were conducted to explore the impact of potential confounders. Overall, 27 studies were eligible. The pooled analyses showed nonsignificant associations between ACEIs/ARBs and death (OR:0.97, 95%CI:0.75,1.27), ICU admission (OR:1.09;95%CI:0.65,1.81), death/ICU admission (OR:0.67; 95%CI:0.52,0.86), risk of COVID-19 infection (OR:1.01; 95%CI:0.93,1.10), severe infection (OR:0.78; 95%CI:0.53,1.15), and hospitalization (OR:1.15; 95%CI:0.81,1.65). However, the subgroup analyses indicated significant association between ACEIs/ARBs and hospitalization among USA studies (OR:1.59; 95%CI:1.03,2.44), peer-reviewed (OR:1.93, 95%CI:1.38,2.71), good quality and studies which reported adjusted measure of effect (OR:1.30, 95%CI:1.10,1.50). Significant differences were found between ACEIs and ARBs with the latter being significantly associated with lower risk of acquiring COVID-19 infection (OR:0.24; 95%CI: 0.17,0.34). In conclusion, high-quality evidence exists for the effect of ACEIs/ARBs on some COVID-19 clinical outcomes. For the first time, we provided evidence, albeit of low quality, on interclass differences between ACEIs and ARBs for some of the reported clinical outcomes.


Assuntos
Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Betacoronavirus/efeitos dos fármacos , Doenças Cardiovasculares/tratamento farmacológico , Infecções por Coronavirus/mortalidade , Pneumonia Viral/mortalidade , Adulto , Idoso , Antagonistas de Receptores de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Doenças Cardiovasculares/complicações , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Feminino , Mortalidade Hospitalar/tendências , Hospitalização/estatística & dados numéricos , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Avaliação de Resultados em Cuidados de Saúde , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Medição de Risco , Ventiladores Mecânicos/efeitos adversos , Ventiladores Mecânicos/estatística & dados numéricos
17.
Nat Commun ; 11(1): 5453, 2020 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-33116139

RESUMO

The coronavirus SARS-CoV-2 is the causative agent of the ongoing severe acute respiratory disease pandemic COVID-19. Tissue and cellular tropism is one key to understanding the pathogenesis of SARS-CoV-2. We investigate the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of human donors using a diverse panel of banked tissues. Here, we report our discovery that the ACE2 receptor protein robustly localizes within the motile cilia of airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during host respiratory transmission. We further determine whether ciliary ACE2 expression in the upper airway is influenced by patient demographics, clinical characteristics, comorbidities, or medication use, and show the first mechanistic evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) does not increase susceptibility to SARS-CoV-2 infection through enhancing the expression of ciliary ACE2 receptor. These findings are crucial to our understanding of the transmission of SARS-CoV-2 for prevention and control of this virulent pathogen.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Infecções por Coronavirus/patologia , Expressão Gênica/efeitos dos fármacos , Peptidil Dipeptidase A/genética , Pneumonia Viral/patologia , Sistema Respiratório/patologia , Fatores Etários , Cílios/metabolismo , Infecções por Coronavirus/virologia , Células Endoteliais , Células Caliciformes/metabolismo , Humanos , Pulmão/patologia , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/virologia , Sistema Respiratório/metabolismo , Sistema Respiratório/virologia , Fatores Sexuais , Sinusite/metabolismo , Fumar
18.
Ann Cardiol Angeiol (Paris) ; 69(5): 247-254, 2020 Nov.
Artigo em Francês | MEDLINE | ID: mdl-33039120

RESUMO

BACKGROUND AND AIM: Angiotensin converting enzyme (ACE) type 2 is the receptor of SARSCoV-2 for cell entry into lung cells. Because ACE-2 may be modulated by ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs), there are concern that patients treated with ACEIs and ARBs are at higher risk for COVID-19 infection or severity. This study sought to analyse the association of severe forms of COVID-19 and mortality with hypertension and a previous treatment with ACEI and ARB. METHODS: Prospective follow-up of 433 consecutive patients hospitalised for COVID-19 pneumonia confirmed by PCR or highly probable on clinical, biological, and radiological findings, and included in the COVHYP study. Mortality and severe COVID-19 (criteria: death, intensive care unit, or hospitalisation >30 days) were compared in patients receiving or not ACEIs and ARBs. Follow-up was 100% at hospital discharge, and 96.5% at >1month. RESULTS: Age was 63.6±18.7 years, and 40%) were female. At follow-up (mean 78±50 days), 136 (31%) patients had severity criteria (death, 64 ; intensive care unit, 73; hospital stay >30 days, 49). Hypertension (55.1% vs 36.7%, P<0.001) and antihypertensive treatment were associated with severe COVID-19 and mortality. The association between ACEI/ARB treatment and COVID-19 severity criteria found in univariate analysis (Odds Ratio 1.74, 95%CI [1.14-2.64], P=0.01) was not confirmed when adjusted on age, gender, and hypertension (adjusted OR1.13 [0.59-2.15], P=0.72). Diabetes and hypothyroidism were associated with severe COVID-19, whereas history of asthma was not. CONCLUSION: This study suggests that previous treatment with ACEI and ARB is not associated with hospital mortality, 1- and 2-month mortality, and severity criteria in patients hospitalised for COVID-19. No protective effect of ACEIs and ARBs on severe pneumonia related to COVID-19 was demonstrated.


Assuntos
Bloqueadores do Receptor Tipo 2 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/mortalidade , Hipertensão/tratamento farmacológico , Pneumonia Viral/mortalidade , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Bloqueadores do Receptor Tipo 2 de Angiotensina II/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Infecções por Coronavirus/epidemiologia , Cuidados Críticos/estatística & dados numéricos , Diabetes Mellitus , Feminino , França/epidemiologia , Hospitalização , Humanos , Hipotireoidismo/complicações , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Pandemias , Peptidil Dipeptidase A , Pneumonia Viral/epidemiologia , Estudos Prospectivos , Estudos Retrospectivos , Índice de Gravidade de Doença
19.
Cochrane Database Syst Rev ; 10: CD012569, 2020 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-33089502

RESUMO

BACKGROUND: Renin inhibitors (RIs) reduce blood pressure more than placebo, with the magnitude of this effect thought to be similar to that for angiotensin converting enzyme (ACE) inhibitors. However, a drug's efficacy in lowering blood pressure cannot be considered as a definitive indicator of its effectiveness in reducing mortality and morbidity. The effectiveness and safety of RIs compared to ACE inhibitors in treating hypertension is unknown. OBJECTIVES: To evaluate the benefits and harms of renin inhibitors compared to ACE inhibitors in people with primary hypertension. SEARCH METHODS: The Cochrane Hypertension Group Information Specialist searched the following databases for randomized controlled trials up to August 2020: the Cochrane Hypertension Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted authors of relevant papers about further published and unpublished work. The searches had no language restrictions. SELECTION CRITERIA: We included randomized, active-controlled, double-blinded studies (RCTs) with at least four weeks follow-up in people with primary hypertension, which compared renin inhibitors with ACE inhibitors and reported morbidity, mortality, adverse events or blood pressure outcomes. We excluded people with proven secondary hypertension. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the included trials, evaluated the risks of bias and entered the data for analysis. MAIN RESULTS: We include 11 RCTs involving 13,627 participants, with a mean baseline age from 51.5 to 74.2 years. Follow-up duration ranged from four weeks to 36.6 months. There was no difference between RIs and ACE inhibitors for the outcomes: all-cause mortality: risk ratio (RR) 1.05, 95% confidence interval (CI) 0.93 to 1.18; 5 RCTs, 5962 participants; low-certainty evidence; total myocardial infarction: RR 0.86, 95% CI 0.22 to 3.39; 2 RCTs, 957 participants; very low-certainty evidence; adverse events: RR 0.98, 95% CI 0.93 to 1.03; 10 RTCs, 6007 participants;  moderate-certainty evidence; serious adverse events: RR 1.21, 95% CI 0.89 to 1.64; 10 RTCs, 6007 participants; low-certainty evidence; and withdrawal due to adverse effects: RR 0.85, 95% CI 0.68 to 1.06; 10 RTCs, 6008 participants; low-certainty evidence. No data were available for total cardiovascular events, heart failure, stroke, end-stage renal disease or change in heart rate. Low-certainty evidence suggested that RIs reduced systolic blood pressure: mean difference (MD) -1.72, 95% CI -2.47 to -0.97; 9 RCTs, 5001 participants;  and diastolic blood pressure: MD -1.18, 95% CI -1.65 to -0.72; 9 RCTs, 5001 participants,  to a greater extent than ACE inhibitors, but we judged this to be more likely due to bias than a true effect.  AUTHORS' CONCLUSIONS: For the treatment of hypertension, we have low certainty that renin inhibitors (RI) and angiotensin converting enzyme (ACE) inhibitors do not differ for all-cause mortality and myocardial infarction. We have low to moderate certainty that they do not differ for adverse events. Small reductions in blood pressure with renin inhibitors compared to ACE inhibitors are of low certainty.  More independent, large, long-term trials are needed to compare RIs with ACE inhibitors, particularly assessing morbidity and mortality outcomes, but also on blood pressure-lowering effect.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Renina/antagonistas & inibidores , Idoso , Amidas/efeitos adversos , Amidas/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Causas de Morte , Feminino , Fumaratos/efeitos adversos , Fumaratos/uso terapêutico , Frequência Cardíaca/efeitos dos fármacos , Humanos , Irbesartana/uso terapêutico , Falência Renal Crônica/epidemiologia , Lisinopril/uso terapêutico , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Ramipril/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
Cochrane Database Syst Rev ; 10: CD007004, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33107592

RESUMO

BACKGROUND: Treatment with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) is used to reduce proteinuria and retard the progression of chronic kidney disease (CKD). However, resolution of proteinuria may be incomplete with these therapies and the addition of an aldosterone antagonist may be added to further prevent progression of CKD. This is an update of a Cochrane review first published in 2009 and updated in 2014. OBJECTIVES: To evaluate the effects of aldosterone antagonists (selective (eplerenone), non-selective (spironolactone or canrenone), or non-steroidal mineralocorticoid antagonists (finerenone)) in adults who have CKD with proteinuria (nephrotic and non-nephrotic range) on: patient-centred endpoints including kidney failure (previously know as end-stage kidney disease (ESKD)), major cardiovascular events, and death (any cause); kidney function (proteinuria, estimated glomerular filtration rate (eGFR), and doubling of serum creatinine); blood pressure; and adverse events (including hyperkalaemia, acute kidney injury, and gynaecomastia). SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 13 January 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs that compared aldosterone antagonists in combination with ACEi or ARB (or both) to other anti-hypertensive strategies or placebo in participants with proteinuric CKD. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. Data were summarised using random effects meta-analysis. We expressed summary treatment estimates as a risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, or standardised mean difference (SMD) when different scales were used together with their 95% confidence interval (CI). Risk of bias were assessed using the Cochrane tool. Evidence certainty was evaluated using GRADE. MAIN RESULTS: Forty-four studies (5745 participants) were included. Risk of bias in the evaluated methodological domains were unclear or high risk in most studies. Adequate random sequence generation was present in 12 studies, allocation concealment in five studies, blinding of participant and investigators in 18 studies, blinding of outcome assessment in 15 studies, and complete outcome reporting in 24 studies. All studies comparing aldosterone antagonists to placebo or standard care were used in addition to an ACEi or ARB (or both). None of the studies were powered to detect differences in patient-level outcomes including kidney failure, major cardiovascular events or death. Aldosterone antagonists had uncertain effects on kidney failure (2 studies, 84 participants: RR 3.00, 95% CI 0.33 to 27.65, I² = 0%; very low certainty evidence), death (3 studies, 421 participants: RR 0.58, 95% CI 0.10 to 3.50, I² = 0%; low certainty evidence), and cardiovascular events (3 studies, 1067 participants: RR 0.95, 95% CI 0.26 to 3.56; I² = 42%; low certainty evidence) compared to placebo or standard care. Aldosterone antagonists may reduce protein excretion (14 studies, 1193 participants: SMD -0.51, 95% CI -0.82 to -0.20, I² = 82%; very low certainty evidence), eGFR (13 studies, 1165 participants, MD -3.00 mL/min/1.73 m², 95% CI -5.51 to -0.49, I² = 0%, low certainty evidence) and systolic blood pressure (14 studies, 911 participants: MD -4.98 mmHg, 95% CI -8.22 to -1.75, I² = 87%; very low certainty evidence) compared to placebo or standard care. Aldosterone antagonists probably increase the risk of hyperkalaemia (17 studies, 3001 participants: RR 2.17, 95% CI 1.47 to 3.22, I² = 0%; moderate certainty evidence), acute kidney injury (5 studies, 1446 participants: RR 2.04, 95% CI 1.05 to 3.97, I² = 0%; moderate certainty evidence), and gynaecomastia (4 studies, 281 participants: RR 5.14, 95% CI 1.14 to 23.23, I² = 0%; moderate certainty evidence) compared to placebo or standard care. Non-selective aldosterone antagonists plus ACEi or ARB had uncertain effects on protein excretion (2 studies, 139 participants: SMD -1.59, 95% CI -3.80 to 0.62, I² = 93%; very low certainty evidence) but may increase serum potassium (2 studies, 121 participants: MD 0.31 mEq/L, 95% CI 0.17 to 0.45, I² = 0%; low certainty evidence) compared to diuretics plus ACEi or ARB. Selective aldosterone antagonists may increase the risk of hyperkalaemia (2 studies, 500 participants: RR 1.62, 95% CI 0.66 to 3.95, I² = 0%; low certainty evidence) compared ACEi or ARB (or both). There were insufficient studies to perform meta-analyses for the comparison between non-selective aldosterone antagonists and calcium channel blockers, selective aldosterone antagonists plus ACEi or ARB (or both) and nitrate plus ACEi or ARB (or both), and non-steroidal mineralocorticoid antagonists and selective aldosterone antagonists. AUTHORS' CONCLUSIONS: The effects of aldosterone antagonists when added to ACEi or ARB (or both) on the risks of death, major cardiovascular events, and kidney failure in people with proteinuric CKD are uncertain. Aldosterone antagonists may reduce proteinuria, eGFR, and systolic blood pressure in adults who have mild to moderate CKD but may increase the risk of hyperkalaemia, acute kidney injury and gynaecomastia when added to ACEi and/or ARB.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Falência Renal Crônica/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Proteinúria/tratamento farmacológico , Viés , Bloqueadores dos Canais de Cálcio/uso terapêutico , Canrenona/uso terapêutico , Progressão da Doença , Eplerenona/uso terapêutico , Humanos , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/prevenção & controle , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Naftiridinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Espironolactona/efeitos adversos , Espironolactona/análogos & derivados , Espironolactona/uso terapêutico
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