RESUMO
OBJECTIVES: COVID-19, caused by SARS-CoV-2, has spread around the world since 2019. In severe cases, COVID-19 can lead to hospitalization and death. Systemic arterial hypertension and other comorbidities are associated with serious COVID-19 infection. Literature is unclear whether antihypertensive therapy with angiotensin receptor blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors affect COVID-19 outcomes. We aim to assess whether ACEI/ARB therapy is a risk factor for worse respiratory outcomes related to COVID-19 in hospitalized patients. METHODS: Retrospective study enrolling admitted COVID-19-diagnosed patients by RT-PCR at the Hospital Geral de Fortaleza, Brazil, during 2021. Patient medical records, sociodemographic, and clinical data were analyzed. Chest CT images were analyzed using CAD4COVID-CT/Thirona™ software. RESULTS: A total of 294 patients took part in the study. A cut-off point of 66% of pulmonary involvement was found by ROC curve, with patients having higher risk of death and intubation and lower 60-day survival. Advanced age (RR 1.025, P=0.001) and intubation (RR 16.747, P<0.001) were significantly associated with a higher risk of death. Advanced age (RR 1.023, P=0.001) and the use of noninvasive ventilation (RR 1.548, P=0.037) were associated with a higher risk of intubation. Lung involvement (>66%) increased the risk of death by almost 2.5-fold (RR 2.439, P<0.001) and by more than 2.3-fold the risk of intubation (RR 2.317, P<0.001). CONCLUSIONS: Altogether, our findings suggest that ACEI or ARB therapy does not affect the risk of death and disease course during hospitalization.
Assuntos
COVID-19 , Hipertensão , Humanos , COVID-19/complicações , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/efeitos adversos , SARS-CoV-2 , Estudos Retrospectivos , Receptores de Angiotensina/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologiaRESUMO
INTRODUCTION: COVID-19 related mortality is about 2%, and it increases with comorbidities, like hypertension. Regarding management, there is debatable evidence about the benefits of continuation vs. discontinuation of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACEI/ARB). AIM: We performed a systematic review to assess the effects and safety of in-hospital discontinuation compared to continuation of ACEI/ARB in COVID-19 patients. METHODS: We systematically searched on PubMed, Scopus, and EMBASE from inception to June 19, 2021. We included observational studies and trials that compared the effects and safety of continuing ACEI/ARB compared to discontinuing it in COVID-19 patients. Effects sizes for dichotomous variables were expressed as risk ratios (RR) and 95% confidence intervals. For continuous variables, effects were expressed as mean difference (MD). We used random effect models with the inverse variance method. We assessed certainty of evidence using the GRADE approach. RESULTS: We included three open-label randomized controlled trials and five cohort studies. We found that the continuation group had lower risk of death compared with the discontinuation group only in the cohort group (RR: 0.46, 95% CI: 0.24-0.90), but not in the RCT group (RR: 1.22, 95% CI: 0.75-2.00). The ICU admission rate was significantly lower in the continuation group (RR: 0.46, 95% CI: 0.31-0.68) in the cohort group, but not in RCT group (RR: 1.03, 95% CI: 0.67-1.59). We did not find significant differences between groups regarding hospitalization length, hypotension, AKI needing renal replacement therapy, mechanical ventilation, new or worsening heart failure, myocarditis, renal replacement therapy, arrhythmias, thromboembolic events and SOFA AUC. The GRADE approach revealed that the certainty ranged from moderate to high level. CONCLUSIONS: There is no significant difference in mortality and other outcomes between continuation and discontinuation groups.
Assuntos
COVID-19 , Hipertensão , Humanos , Anti-Hipertensivos/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/efeitos adversos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológicoRESUMO
Abstract Background: Sarcopenia is a disease that involves skeletal muscle mass loss and is highly prevalent in the older adult population. Moreover, the incidence of sarcopenia is increased in patients with hypertension. Objectives: The study aimed to evaluate the association between the classes of the drugs used for arterial hypertension treatment and the presence or absence of sarcopenia. Methods: 129 older adults with hypertension were evaluated by the researchers who registered the participants medication for arterial hypertension treatment. Sarcopenia level was measured by anthropometric parameters, muscular strength, and functional capacity. The data were analyzed by one-way ANOVA followed by post-hoc test and Fisher's exact test; statistical significance was set at 0.05. Results: Age was not different between women with different levels of sarcopenia, but significant differences were observed between men with absent sarcopenia (66.8±4.2 years) and men with probable sarcopenia (77.0±10.2 years). Individuals with absent sarcopenia showed higher handgrip strength (men: 33.8±7.4, women: 23.2±4.6 Kgf) in comparison with those with sarcopenia (men with probable sarcopenia: 9.5±3.3 Kgf, women with probable, confirmed, and severe sarcopenia: 11.7±2.5, 12.2±3.0, 11.8±1.8 Kgf, respectively). The analysis showed an association between the type of medication and degree of sarcopenia; diuretics were significantly associated with probable sarcopenia, and angiotensin II receptor blockers (alone or in combination with diuretics) was associated with absence of sarcopenia. Conclusion: In conclusion, handgrip strength was a good method to diagnose sarcopenia, and diuretics were associated with increased risk of sarcopenia in older adults with hypertension.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Diuréticos/uso terapêutico , Sarcopenia/complicações , Hipertensão/complicações , Envelhecimento , Estudos Transversais , Diuréticos/efeitos adversos , Sarcopenia/etiologia , Antagonistas de Receptores de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/uso terapêuticoRESUMO
BACKGROUND: IgA nephropathy (IgAN) is one of the most prevalent primary glomerulopathies in children. There are various studies investigating the efficacy of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) in adults with IgAN. However, only few studies evaluated the efficacy of these medications in pediatric patients. OBJECTIVE: To evaluate the efficacy and safety of ACEI/ARB in children with IgAN. DATA SOURCES: Databases including PubMed, Web of Science, Cochrane, Scopus, and Google Scholar were searched between the 1st of April and 20th of July of 2021 using the keywords "IgA Nephropathy," "Berger's Disease," "Angiotensin-Converting Enzyme Inhibitors," "Angiotensin Receptor Antagonists," "Angiotensin II Type 1 Receptor Blockers," and similar entry terms collected from the Medical Subject Headings (MeSH). STUDY ELIGIBILITY CRITERIA: Observational studies (case series, case-control, cohort, and cross-sectional) and clinical trials with descriptions of pediatric patients (under 19 years old) with histopathological diagnosis of IgA nephropathy and who received ACEI and/or ARB. PARTICIPANTS AND INTERVENTIONS: Pediatric patients (under 19 years old) with histopathological diagnosis of IgA nephropathy and who received ACEI and/or ARB. STUDY APPRAISAL: For quality assessment, the Risk of Bias 2 tool (RoB 2), the Risk Of Bias In Non-randomized Studies of Interventions tool (ROBINS-I), the National Institutes of Health (NIH) quality assessment tool, and the Newcastle-Ottawa Scale (NOS) were used. RESULTS: After recovering 1,471 studies, only eight, published between 2003 and 2019, met the eligibility criteria and were included in this systematic review. Of the 737 included children in the studies, 202 (25.8%) used ACEI/ARB and were compared with placebo and other therapy regimens. Of the seven studies that evaluated proteinuria, six reported an efficacy of ACEI/ARB in reducing this marker. ACEI/ARB also showed a possible effect in reducing hematuria and oxidative stress. The most common side effect was dizziness. LIMITATIONS: The number of studies about the treatment with ACEI/ARB in children with IgAN is scarce. In addition, the studies are very heterogeneous. There are few studies that compared ACEI/ARB with placebo. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: The use of ACEI and/or ARB appears to be safe and to reduce proteinuria in pediatric patients with IgAN. Nonetheless, further randomized controlled trials, with greater methodological rigor and longer follow-up time, are required to establish the efficacy and safety of this therapy in this population. SYSTEMATIC REVIEW REGISTRATION NUMBER: The protocol of this systematic literature review was registered in PROSPERO under the number CRD42021245375, and in the OSF registries ( https://osf.io/qft4z/ ) with the registration https://doi.org/10.17605/OSF.IO/VADYR . A higher resolution version of the Graphical abstract is available as Supplementary information.
Assuntos
Antagonistas de Receptores de Angiotensina , Glomerulonefrite por IGA , Adulto , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Criança , Estudos Transversais , Feminino , Glomerulonefrite por IGA/tratamento farmacológico , Humanos , Masculino , Proteinúria/tratamento farmacológico , Adulto JovemRESUMO
Among the multiple uncertainties surrounding the novel coronavirus disease (COVID-19) pandemic, a research letter published in The Lancet implicated drugs that antagonize the renin-angiotensin-aldosterone system (RAAS) in an unfavorable prognosis of COVID-19. This report prompted investigations to identify mechanisms by which blocking angiotensin-converting enzyme 2 (ACE2) could lead to serious consequences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The possible association between RAAS inhibitors use and unfavorable prognosis in this disease may have been biased by the presence of underlying cardiovascular diseases. As the number of COVID-19 cases has increased worldwide, it has now become possible to investigate the association between RAAS inhibitors and unfavorable prognosis in larger cohorts. Observational studies and one randomized clinical trial failed to identify any consistent association between the use of these drugs and unfavorable prognosis in COVID-19. In view of the accumulated clinical evidence, several scientific societies recommend that treatment with RAAS inhibitors should not be discontinued in patients diagnosed with COVID-19 (unless contraindicated). This recommendation should be followed by clinicians and patients.
Assuntos
COVID-19 , Coronavirus , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Humanos , Peptidil Dipeptidase A/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema Renina-Angiotensina , SARS-CoV-2RESUMO
Among the multiple uncertainties surrounding the novel coronavirus disease (COVID-19) pandemic, a research letter published in The Lancet implicated drugs that antagonize the renin-angiotensin-aldosterone system (RAAS) in an unfavorable prognosis of COVID-19. This report prompted investigations to identify mechanisms by which blocking angiotensin-converting enzyme 2 (ACE2) could lead to serious consequences in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The possible association between RAAS inhibitors use and unfavorable prognosis in this disease may have been biased by the presence of underlying cardiovascular diseases. As the number of COVID-19 cases has increased worldwide, it has now become possible to investigate the association between RAAS inhibitors and unfavorable prognosis in larger cohorts. Observational studies and one randomized clinical trial failed to identify any consistent association between the use of these drugs and unfavorable prognosis in COVID-19. In view of the accumulated clinical evidence, several scientific societies recommend that treatment with RAAS inhibitors should not be discontinued in patients diagnosed with COVID-19 (unless contraindicated). This recommendation should be followed by clinicians and patients.
Assuntos
Humanos , Coronavirus , COVID-19 , Sistema Renina-Angiotensina , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Peptidil Dipeptidase A/metabolismo , Antagonistas de Receptores de Angiotensina/efeitos adversos , SARS-CoV-2RESUMO
The first case of COVID-19 was reported on 31 December 2019 in Wuhan, China. Ever since there has been unprecedented and growing interest in learning about all aspects of this new disease. Debate has been generated as to the association between antihypertensive therapy with renin-angiotensin-aldosterone system (RAAS) inhibitors and SARS-CoV-2 infection. While many questions as yet remain unanswered, the aim of this report is to inform health professionals about the current state of knowledge. Because this is an ever-evolving topic, the recommendation is that it be updated as new evidence becomes available. Below, we provide a review of pre-clinical and clinical studies that link coronavirus to the RAAS.
Assuntos
Betacoronavirus , Infecções por Coronavirus/fisiopatologia , Pandemias , Pneumonia Viral/fisiopatologia , Sistema Renina-Angiotensina/fisiologia , Proteína ADAM17/fisiologia , Angiotensina II/fisiologia , Antagonistas de Receptores de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Enzima de Conversão de Angiotensina 2 , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , COVID-19 , Vacinas contra COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Pulmão/fisiopatologia , Modelos Biológicos , Pandemias/prevenção & controle , Peptidil Dipeptidase A/efeitos dos fármacos , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Receptores Virais/efeitos dos fármacos , Sistema Renina-Angiotensina/efeitos dos fármacos , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/fisiopatologia , SARS-CoV-2 , Serina Endopeptidases/fisiologia , Vacinas Virais , Internalização do Vírus/efeitos dos fármacosRESUMO
Based on some publications that associate SARS-CoV-2 infection with the use of anti-hypertensive drug groups such as angiotensin-converting-enzyme inhibitors (e.g. enalapril) or angiotensin II receptor blockers (e.g. losartan), many patients from South America, Central America or Spain, have stopped or intend to interrupt their treatments with these drugs. Hence, it may exist ominous consequences due to this drop out. For this reason, it is necessary to quickly warn about this situation and the risks associated with it.
Assuntos
Anti-Hipertensivos/efeitos adversos , Infecções por Coronavirus/complicações , Hipertensão/complicações , Pneumonia Viral/complicações , Antagonistas de Receptores de Angiotensina/efeitos adversos , Enzima de Conversão de Angiotensina 2 , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Betacoronavirus/fisiologia , COVID-19 , Enalapril/efeitos adversos , Humanos , Hipertensão/tratamento farmacológico , Losartan/efeitos adversos , Pandemias , Peptidil Dipeptidase A , SARS-CoV-2 , Internalização do VírusRESUMO
OBJECTIVE: The effect of dual renin-angiotensin system (RAS) inhibition in heart failure (HF) is still controversial. Systematic reviews have shown that dual RAS blockade may reduce mortality and hospitalizations, yet it has been associated with the increased risk of renal dysfunction (RD). Surprisingly, although RD in patients with HF is frequent, the effect of combining RAS inhibitors in HF patients with RD has never been studied in a meta-analysis. METHODS: A systematic review and meta-analysis of randomized clinical trials involving HF patients with RD who received dual blockade analyzing death, cardiovascular (CV) death or HF hospitalization, and adverse events. RESULTS: Out of 2258 screened articles, 12 studies were included (34,131 patients). Compared with monotherapy, dual RAS inhibition reduced hazard ratio of death to 0.94 (p=0.07) and significantly reduced CV death or HF hospitalization to 0.89 (p=0.0006) in all individuals, and to 0.86 (p=0.005) in patients with RD and to 0.91 (p=0.04) without RD. Nevertheless, dual RAS blockade significantly increased the risk of renal impairment (40%), hyperkalemia (44%), and hypotension (42%), although discontinuation of treatment occurs only in 3.68% versus 2.19% (p=0.00001). CONCLUSIONS: Dual RAS inhibition therapy reduces the risk of CV death or HF hospitalization. However, cautions monitoring for specific adverse events may be warranted.