Sacubitril/Valsartan Versus Enalapril in Chronic Chagas Cardiomyopathy: Rationale and Design of the PARACHUTE-HF Trial.

Chronic Chagas cardiomyopathy (CCC) has unique pathogenic and clinical features with worse prognosis than other causes of heart failure (HF), despite the fact that patients with CCC are often younger and have fewer comorbidities. Patients with CCC were not adequately represented in any of the landmark HF studies that support current treatment guidelines. PARACHUTE-HF (Prevention And Reduction of Adverse outcomes in Chagasic Heart failUre Trial Evaluation) is an active-controlled, randomized, phase IV trial designed to evaluate the effect of sacubitril/valsartan 200 mg twice daily vs enalapril 10 mg twice daily added to standard of care treatment for HF. The study aims to enroll approximately 900 patients with CCC and reduced ejection fraction at around 100 sites in Latin America. The primary outcome is a hierarchical composite of time from randomization to cardiovascular death, first HF hospitalization, or relative change from baseline to week 12 in NT-proBNP levels. PARACHUTE-HF will provide new data on the treatment of this high-risk population. (Efficacy and Safety of Sacubitril/Valsartan Compared With Enalapril on Morbidity, Mortality, and NT-proBNP Change in Patients With CCC [PARACHUTE-HF]; NCT04023227).

Pharmacogenetics of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) in cardiovascular diseases.

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.

Renin-angiotensin system inhibitors positively impact on multiple aging regulatory pathways: Could they be used to protect against human aging?

The renin-angiotensin system (RAS)-a classical blood pressure regulator-largely contributes to healthy organ development and function. Besides, RAS activation promotes age-related changes and age-associated diseases, which are attenuated/abolished by RAS-blockade in several mammalian species. RAS-blockers also increase rodent lifespan. In previous work, we discussed how RAS-blockade downregulates mTOR and growth hormone/IGF-1 signaling, and stimulates AMPK activity (together with klotho, sirtuin, and vitamin D-receptor upregulation), and proposed that at least some of RAS-blockade's aging benefits are mediated through regulation of these intermediaries and their signaling to mitochondria. Here, we included RAS-blockade's impact on other aging regulatory pathways, that is, TGF-ß, NF-kB, PI3K, MAPK, PKC, Notch, and Wnt, all of which affect mitochondria. No direct evidence is available on RAS/RAS-blockade-aging regulatory pathway-mitochondria interactions. However, existing results allow to conjecture that RAS-blockers neutralize mitochondrial dysfunction by acting on the discussed pathways. The reviewed evidence led us to propose that the foundation is laid for conducting clinical trials aimed at testing whether angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB)-even at subclinical doses-offer the possibility to live longer and in better health. As ACEi and ARB are low cost and well-tolerated anti-hypertension therapies in use for over 35 years, investigating their administration to attenuate/prevent aging effects seems simple to implement.

Heart failure management with ß-blockers: can we do better?

Heart failure (HF) is associated with disabling symptoms, poor quality of life, and a poor prognosis with substantial excess mortality in the years following diagnosis. Overactivation of the sympathetic nervous system is a key feature of the pathophysiology of HF and is an important driver of the process of adverse remodelling of the left ventricular wall that contributes to cardiac failure. Drugs which suppress the activity of the renin-angiotensin-aldosterone system, including ß-blockers, are foundation therapies for the management of heart failure with reduced ejection fraction (HFrEF) and despite a lack of specific outcomes trials, are also widely used by cardiologist in patients with HF with preserved ejection fraction (HFpEF). Today, expert opinion has moved away from recommending that treatment for HF should be guided solely by the LVEF and interventions should rather address signs and symptoms of HF (e.g. oedema and tachycardia), the severity of HF, and concomitant conditions. ß-blockers improve HF symptoms and functional status in HF and these agents have demonstrated improved survival, as well as a reduced risk of other important clinical outcomes such as hospitalisation for heart failure, in randomised, placebo-controlled outcomes trials. In HFpEF, ß-blockers are anti-ischemic and lower blood pressure and heart rate. Moreover, ß-blockers also reduce mortality in the setting of HF occurring alongside common comorbid conditions, such as diabetes, CKD (of any severity), and COPD. Higher doses of ß-blockers are associated with better clinical outcomes in populations with HF, so that ensuring adequate titration of therapy to their maximal (or maximally tolerated) doses is important for ensuring optimal outcomes for people with HF. In principle, a patient with HF could have combined treatment with a ß-blocker, renin-angiotensin-aldosterone system inhibitor/neprilysin inhibitor, mineralocorticoid receptor antagonist, and a SGLT2 inhibitor, according to tolerability.

Pressure control and treatment interact in the deterioration of incidental visuospatial memory in hypertensive patients.

BACKGROUND: Systemic hypertension (SH) is the main risk factor to cognitive deterioration, whereas visuospatial memory is more vulnerable to ageing. Some antihypertensive agents have a neuroprotector effect, however, such effects could be masked by comorbidities and/or the lack of effective control on the arterial pressure of patients. OBJECTIVE: To assess this, the evaluation of incidental visuospatial memory of SH patients and the relation to the treatment received and the effective control of pressure were made. METHOD: 80 patients (46 woman) were included grouped by the received medication: angiotensin 2 receptor blockers (ARB) or angiotensin converting enzyme inhibitors (ACEI). A multiple correlation analysis between visuospatial scores and clinical variables was made; also, a mixed model analysis (fixed factors: treatment, pressure control, diabetes comorbidity; aleatory factors: age, schooling, months from SH diagnoses). RESULTS: Half of the patients had a controlled pressure, from them the higher proportion received ARB, and a minor number of patients received ACEI. The normotensive patients receiving ACEI were inefficient whereas the hypertensive patients were more efficient. The systolic pressure was negatively related with the visuospatial scores in spite of no correlations occurred with MoCA and Raven tests. CONCLUSIONS: The visuospatial incidental/intentional scores were negatively correlated with systolic pressure. The efficiency in the visuospatial ability depends on the interaction of treatment and effective control of blood pressure. The interaction between treatment and effective pressure control must be taken in count when cognitive deterioration is studied.

ANTECEDENTES: La hipertensión arterial sistémica (HAS) es el principal factor de riesgo para el deterioro cognitivo; por otro lado, la memoria visuoespacial es más vulnerable al envejecimiento. Algunos fármacos antihipertensivos tienen un efecto neuroprotector, pero tal efecto puede enmascararse o bien no manifestarse por comorbilidad o por falta de control efectivo de la presión arterial. OBJETIVO: Evaluar las alteraciones en la memoria visuoespacial incidental de pacientes con HAS en relación con su tratamiento antihipertensivo y su control de la presión. MÉTODO: Se incluyeron 80 pacientes con HAS (46 mujeres), agrupados por su medicación en bloqueadores de los receptores de la angiotensina II (BRA) o inhibidores de la enzima convertidora de angiotensina (IECA). Se realizó un análisis de correlaciones múltiples para los puntajes obtenidos en la prueba de memoria visuoespacial incidental/intencional y un análisis de modelos mixtos (factores fijos: tratamiento, control de la presión y comorbilidad con diabetes; factores aleatorios: edad, escolaridad, meses desde el diagnóstico de HAS y coeficiente intelectual). RESULTADOS: De los pacientes controlados, la mayoría de los que recibían BRA fueron eficientes y los que recibían IECA fueron deficientes. De los que recibían IECA, los descontrolados hipertensos fueron más eficientes que los normotensos. La memoria visuoespacial se correlacionó negativamente con la presión sistólica a pesar de no haber diferencias en MoCA y Raven. CONCLUSIONES: La eficiencia en la memoria visuoespacial dependió de la interacción del tratamiento y el control de la presión. Ambos factores, tratamiento y control efectivo de la presión, deben considerarse en la evaluación del deterioro cognitivo asociado a la HAS.

Adherence to Treatment Guidelines in Ambulatory Heart Failure Patients with Reduced Ejection Fraction in a Latin-American Country: Observational Study of the Colombian Heart Failure Registry (RECOLFACA).

INTRODUCTION: Although several guidelines recommend that patients with heart failure with reduced ejection fraction (HFrEF) be treated with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEIs/ARBs) or angiotensin receptor-neprilysin inhibitors (ARNIs), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and sodium-glucose cotransporter-2 inhibitor (SGLT2i), there are still several gaps in their prescription and dosage in Colombia. This study aimed to describe the use patterns of HFrEF treatments in the Colombian Heart Failure Registry (RECOLFACA). METHODS: Patients with HFrEF enrolled in RECOLFACA during 2017-2019 were included. Heart failure (HF) medication prescription and daily dose were assessed using absolute numbers and proportions. Therapeutic schemes of patients treated by internal medicine specialists were compared with those treated by cardiologists. RESULTS: Out of 2,528 patients in the registry, 1,384 (54.7%) had HFrEF. Among those individuals, 88.9% were prescribed beta-blockers, 72.3% with ACEI/ARBs, 67.9% with MRAs, and 13.1% with ARNIs. Moreover, less than a third of the total patients reached the target doses recommended by the European HF guidelines. No significant differences in the therapeutic schemes or target doses were observed between patients treated by internal medicine specialists or cardiologists. CONCLUSION: Prescription rates and target dose achievement are suboptimal in Colombia. Nevertheless, RECOLFACA had one of the highest prescription rates of beta-blockers and MRAs compared to some of the most recent HF registries. However, ARNIs remain underprescribed. Continuous registry updates can improve the identification of patients suitable for ARNI and SGLT2i therapy to promote their use in clinical practice.

Systematic analysis of the scientific-technological production on the use of the UV, H2O2, and/or Cl2 systems in the elimination of bacteria and associated antibiotic resistance genes.

This study presents a systematic review of the scientific and technological production related to the use of systems based on UV, H2O2, and Cl2 for the elimination of antibiotic-resistant bacteria (ARB) and genes associated with antibiotic resistance (ARGs). Using the Pro Know-C (Knowledge Development Process-Constructivist) methodology, a portfolio was created and analyzed that includes 19 articles and 18 patents published between 2011 and 2022. The results show a greater scientific-technological production in UV irradiation systems (8 articles and 5 patents) and the binary combination UV/H2O2 (9 articles and 4 patents). It was emphasized that UV irradiation alone focuses mainly on the removal of ARB, while the addition of H2O2 or Cl2, either individually or in binary combinations with UV, enhances the removal of ARB and ARG. The need for further research on the UV/H2O2/Cl2 system is emphasized, as gaps in the scientific-technological production of this system (0 articles and 2 patents), especially in its electrochemically assisted implementation, have been identified. Despite the gaps identified, there are promising prospects for the use of combined electrochemically assisted UV/H2O2/Cl2 disinfection systems. This is demonstrated by the effective removal of a wide range of contaminants, including ARB, fungi, and viruses, as well as microorganisms resistant to conventional disinfectants, while reducing the formation of toxic by-products.

American Registry of Ambulatory or acutely decompensated heart failure (AMERICCAASS Registry): First 1000 patients.

BACKGROUND: About 80% of cardiovascular diseases (including heart failure [HF]) occur in low-income and developing countries. However, most clinical trials are conducted in developed countries. HYPOTHESIS: The American Registry of Ambulatory or Acutely Decompensated Heart Failure (AMERICCAASS) aims to describe the sociodemographic characteristics of HF, comorbidities, clinical presentation, and pharmacological management of patients with ambulatory or acutely decompensated HF in America. METHODOLOGY: Descriptive, observational, prospective, and multicenter registry, which includes patients >18 years with HF in an outpatient or hospital setting. Collected information is stored in the REDCap electronic platform. Quantitative variables are defined according to the normality of the variable using the Shapiro-Wilk test. RESULTS: This analysis includes data from the first 1000 patients recruited. 63.5% were men, the median age of 66 years (interquartile range 56.7-75.4), and 77.6% of the patients were older than 55 years old. The percentage of use of the four pharmacological pillars at the time of recruitment was 70.7% for beta-blockers (BB), 77.4% for angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB II)/angiotensin receptor-neprilysin inhibitor (ARNI), 56.8% for mineralocorticoid receptor antagonists (MRA), and 30.7% for sodium-glucose cotransporter type-2 inhibitors (SGLT2i). The main cause of decompensation in hospitalized patients was HF progression (64.4%), and the predominant hemodynamic profile was wet-warm (68.3%). CONCLUSIONS: AMERICCAASS is the first continental registry to include hospitalized or outpatient patients with HF. Regarding optimal medical therapy, approximately a quarter of the patients still need to receive BB and ACEI/ARB/ARNI, less than half do not receive MRA, and more than two-thirds do not receive SGLT2i.

Influence of angiotensin receptor and converting enzyme blockers therapy in the respiratory outcome of COVID-19 hospitalized patients.

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.

Application of eligibility criteria from DAPA-HF, EMPEROR-Reduced, and PARADIGM-HF trials to a population with heart failure with reduced ejection fraction at a specialized cardiology Clinic in Medellin, Colombia: A retrospective cohort study.

INTRODUCTION: The evidence supporting pharmacological heart failure treatment relies on randomized clinical trials with stringent inclusion and exclusion criteria. OBJECTIVES: Assess the eligibility of outpatients with chronic heart failure for the trials DAPA-HF, EMPEROR-reduced, and PARADIGM-HF, while exploring potential differences among study populations. METHODS: By reviewing medical records, we determined the eligibility rate for each study and evaluated the incidence of heart failure hospitalizations and all-cause mortality during this period. RESULTS: A total of 446 patients were included in the cohort. Approximately 75% would be ineligible for the trials, mainly because of their comorbidities. Ineligible patients had a higher all-cause mortality, but a similar incidence of hospitalization. CONCLUSION: Approximately 1 in 4 patients from a heart failure clinic in Medellin, Colombia would meet the eligibility criteria for the DAPA-HF, EMPEROR-reduced, and PARADIGM-HF trials. These findings highlight the need to complement randomized clinical trials with real-world data.

A Nationwide Initiative to Improve Cardiology Quality: The Best Practice in Cardiology Program in Brazil. / Uma Iniciativa Nacional de Melhoria da Qualidade em Cardiologia: O Programa de Boas Práticas em Cardiologia no Brasil.

BACKGROUND: A Nationwide Initiative to Improve Cardiology Quality: The Best Practice in Cardiology Program in Brazil ACEI/ARB: angiotensin-converting enzyme inhibitor/angiotensin receptor blocker; LVEF: left ventricular ejection fraction; LVSD: left ventricular systolic dysfunction; AF: atrial fibrillation; PT/INR: prothrombin time/international normalized ratio. BACKGROUND: Despite significant progress in improving the quality of cardiovascular care, persistent gaps remain in terms of inconsistent adherence to guideline recommendations. OBJECTIVE: This study evaluates the effects of implementing a quality improvement program adapted from the American Heart Association's Get with the Guidelines™ initiative on adherence to guideline-directed medical therapy for acute coronary syndrome (ACS), atrial fibrillation (AF), and heart failure (HF). METHODS: We examined demographics, quality measures, and short-term outcomes in patients hospitalized with ACS, AF, and HF enrolled in the Best Practice in Cardiology (BPC) Program from 2016 to 2022. RESULTS: This study included 12,167 patients in 19 hospitals in Brazil. Mean age was 62.5 [53.8-71] y/o; 61.1% were male, 68.7% had hypertension, 32.0% diabetes mellitus, and 24.1% had dyslipidemia. Composite score had a sustainable performance in the period from baseline to the last quarter: 65.8±36.2% to 73± 31.2% for AF (p=0.024), 81.0± 23.6% to 89.9 ± 19.3% for HF (p<0.001), and from 88.0 ± 19.1 to 91.2 ±14.9 for ACS (p<0.001). CONCLUSIONS: The BPC program is a quality improvement program in Brazil in which real-time data, obtained using cardiology guideline metrics, were implemented in a quality improvement program resulting in an overall sustained improvement in AF, HF, and ACS management.

Use of sacubitril/valsartan in patients with heart failure: evidence from the real world.

BACKGROUND: To characterize the use of sacubitril/valsartan in a group of patients with heart failure in Colombia. RESEARCH DESIGN AND METHODS: Follow-up study of patients with heart failure who started sacubitril/valsartan and were affiliated with the Colombian health system between 2019 and 2021. Sociodemographic, clinical, and pharmacological variables and adherence and persistence of use were identified. RESULTS: A total of 514 patients were identified, with a mean age of 65.7 years, 73.7% of whom started sacubitril/valsartan at low doses, and only 12.5% reached the maximum dose. Adherence was 78.2% and persistence was 56.8% at 1 year of follow-up. The increase in systolic blood pressure (odds ratio (OR): 1.01; 95% CI: 1.00-1.03) and the use of ß-blockers (OR: 2.63; 95% CI: 1.42-4.85) were correlated with a greater persistence, while receiving furosemide (OR: 0.59; 95% CI: 0.39-0.89) and not having received renin - angiotensin - aldosterone system inhibitors in the 3 months before starting sacubitril/valsartan (OR: 0.48; 95% CI: 0.31-0.76) were associated with lower persistence. CONCLUSIONS: The persistence of treatment 1 year after starting sacubitril/valsartan was not high, and a small proportion of patients reached the target dose of the drug. Nontitration of the drug dose was common.

Consensus document on the use of sacubitril/valsartan in patients with heart failure: Consejo Interamericano de Falla Cardiaca e Hipertensión Pulmonar (CIFACAH) of the Inter-American Society of Cardiology (IASC).

Heart failure (HF) is a significant event for public health. It has a prevalence between 1-2%, mortality rate between 7-17%, and hospitalization between 32-44%. This implies a risk to health and quality of life, but also great financial efforts for health systems. Sacubitril/valsartan is a medication recognized for its efficacy, and this consensus seeks to synthesize the available information regarding its use for the benefit of patients. This document consists of a description of the epidemiology of HF, pharmacology of the drug, clinical trials, use of the drug in cases with reduced ejection fraction, mildly reduced ejection fraction and preserved ejection fraction, available literature on HF guidelines, recommendations and conclusions.

La insuficiencia cardiaca (IC) es un evento significativo para la salud pública. Tiene una prevalencia entre el 1 y 2%, tasa de mortalidad entre el 7 y 17% y de hospitalización entre el 32 y 44%. Esto implica un riesgo a la salud y calidad de vida, pero también grandes esfuerzos financieros para los sistemas de salud. El sacubitrilo/valsartán es un medicamento reconocido por su eficacia, y este consenso busca sintetizar la información disponible respecto a su uso en búsqueda del beneficio de los pacientes. El presente documento se compone de una descripción de la epidemiología de la IC, farmacología del medicamento, estudios clínicos sobre este, uso del medicamento en casos con fracción de eyección reducida, fracción de eyección ligeramente reducida y fracción de eyección preservada, literatura disponible en guías de IC, recomendaciones y conclusiones.

Effect on the Quality of Life of Patients with Heart Failure and Reduced/Preserved Ejection Fraction Using Sacubitril/Valsartan. / Efeito na Qualidade de Vida de Pacientes com Insuficiência Cardíaca e Fração de Ejeção Reduzida/Preservada em Uso de Sacubitril/Valsartan.

BACKGROUND: Heart failure (HF) management has markedly improved, but a clinically meaningful improvement in functional capacity and quality of life is perhaps more important for patients than living longer. OBJECTIVE: This study aimed to review the improvement in quality of life with sacubitril/valsartan in patients with HF and reduced/preserved ejection fraction (EF) from prospective clinical trials. METHODS: PubMed, Embase, and the Cochrane Library were searched for randomized controlled trials (RCTs) and prospective cohort studies published from inception to July 2021. A total of 6 clinical trials and 16854 patients with HF were included. The primary outcome was the change from baseline in KCCQ clinical summary score. The secondary outcomes were scores in other domains of KCCQ, the occurrence of serious adverse events (AEs), and overall mortality. P-values <0.05 were considered statistically significant. RESULTS: Treatment of sacubitril/valsartan showed significantly higher KCCQ-CSS compared to the control (WMD=0.975, 95% CI: 0.885, 1.064, p<0.001; I2=94.8%, pheterogeneity<0.001). A significant decrease in the mortality rate was observed in the sacubitril/valsartan group compared to the control group (RR=0.895, 95%CI:0.831, 0.965, p=0.004; I2=43.6%, pheterogeneity=0.150). Nevertheless, no significant reduction in the occurrence of serious AEs was found among HF patients treated with sacubitril/valsartan compared to the control group (RR=0.950, 95%CI: 0.879, 1.027, p<0.001; I2=68.1%, pheterogeneity=0.024). CONCLUSIONS: Our study demonstrated that sacubitril/valsartan might significantly improve the HRQL compared to other treatments according to the results in KCCQ-CSS and some subdomains in the KCCQ index during the follow-up in patients with HF.

FUNDAMENTO: O manejo da insuficiência cardíaca (IC) tem melhorado acentuadamente, mas uma melhora clinicamente significativa na capacidade funcional e na qualidade de vida talvez seja mais importante para os pacientes do que viver mais. OBJETIVO: Este estudo teve como objetivo revisar a melhora na qualidade de vida com sacubitril/valsartan em pacientes com IC e fração de ejeção (FE) reduzida/preservada a partir de ensaios clínicos prospectivos. MÉTODOS: PubMed, Embase e Cochrane Library foram pesquisados em busca de ensaios clínicos randomizados (ECRs) e estudos de coorte prospectivos publicados desde o início até julho de 2021. Um total de 6 ensaios clínicos e 16.854 pacientes com IC foram incluídos. O desfecho primário foi a alteração da linha de base na pontuação do resumo clínico do KCCQ. Os desfechos secundários foram pontuações em outros domínios do KCCQ, ocorrência de eventos adversos graves (EAs) e mortalidade geral. Valores de p < 0,05 foram considerados estatisticamente significativos. RESULTADOS: O tratamento de sacubitril/valsartan mostrou KCCQ-CSS significativamente maior em comparação com o controle (DMP=0,975, IC 95%:0,885, 1,064, p<0,001; I2=94,8%, pheterogeneidade<0,001). Uma diminuição significativa na taxa de mortalidade foi observada no grupo sacubitril/valsartan em comparação com o grupo controle (RR=0,895, IC 95%: 0,831, 0,965, p=0,004; I2=43,6%, pheterogeneidade=0,150). No entanto, nenhuma redução significativa na ocorrência de EAs graves foi encontrada entre pacientes com IC tratados com sacubitril/valsartan em comparação com o grupo controle (RR=0,950, IC 95%: 0,879, 1,027, p<0,001; I2=68,1%, pheterogeneidade= 0,024). CONCLUSÕES: Nosso estudo demonstrou que o sacubitril/valsartan pode melhorar significativamente a QVRS em comparação com outros tratamentos de acordo com os resultados do KCCQ-CSS e alguns subdomínios do índice KCCQ durante o acompanhamento em pacientes com IC.

Leveraging the COVID-19 pandemic as a natural experiment to assess changes in antibiotic use and antibiotic-resistant E. coli carriage in semi-rural Ecuador.

The coronavirus 2019 (COVID-19) pandemic has had significant impacts on health systems, population dynamics, public health awareness, and antibiotic stewardship, which could affect antibiotic resistant bacteria (ARB) emergence and transmission. In this study, we aimed to compare knowledge, attitudes, and practices (KAP) of antibiotic use and ARB carriage in Ecuadorian communities before versus after the COVID-19 pandemic began. We leveraged data collected for a repeated measures observational study of third-generation cephalosporin-resistant E. coli (3GCR-EC) carriage among children in semi-rural communities in Quito, Ecuador between July 2018 and September 2021. We included 241 households that participated in surveys and child stool sample collection in 2019, before the pandemic, and in 2021, after the pandemic began. We estimated adjusted Prevalence Ratios (aPR) and 95% Confidence Intervals (CI) using logistic and Poisson regression models. Child antibiotic use in the last 3 months declined from 17% pre-pandemic to 5% in 2021 (aPR: 0.30; 95% CI 0.15, 0.61) and 3GCR-EC carriage among children declined from 40 to 23% (aPR: 0.48; 95% CI 0.32, 0.73). Multi-drug resistance declined from 86 to 70% (aPR: 0.32; 95% CI 0.13; 0.79), the average number of antibiotic resistance genes (ARGs) per 3GCR-EC isolate declined from 9.9 to 7.8 (aPR of 0.79; 95% CI 0.65, 0.96), and the diversity of ARGs was lower in 2021. In the context of Ecuador, where COVID-19 prevention and control measures were strictly enforced after its major cities experienced some of the world's the highest mortality rates from SARS-CoV-2 infections, antibiotic use and ARB carriage declined in semi-rural communities of Quito from 2019 to 2021.

The Pivotal Role of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Hypertension Management and Cardiovascular and Renal Protection: A Critical Appraisal and Comparison of International Guidelines.

Arterial hypertension is the main preventable cause of premature mortality worldwide. Across Latin America, hypertension has an estimated prevalence of 25.5-52.5%, although many hypertensive patients remain untreated. Appropriate treatment, started early and continued for the remaining lifespan, significantly reduces the risk of complications and mortality. All international and most regional guidelines emphasize a central role for renin-angiotensin-aldosterone system inhibitors (RAASis) in antihypertensive treatment. The two main RAASi options are angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs). Although equivalent in terms of blood pressure reduction, ACEis are preferably recommended by some guidelines to manage other cardiovascular comorbidities, with ARBs considered as an alternative when ACEis are not tolerated. This review summarizes the differences between ACEis and ARBs and their place in the international guidelines. It provides a critical appraisal of the guidelines based on available evidence from randomized controlled trials (RCTs) and meta-analyses, especially considering that hypertensive patients in daily practice often have other comorbidities. The observed differences in cardiovascular and renal outcomes in RCTs may be attributed to the different mechanisms of action of ACEis and ARBs, including increased bradykinin levels, potentiated bradykinin response, and stimulated nitric oxide production with ACEis. It may therefore be appropriate to consider ACEis and ARBs as different antihypertensive drugs classes within the same RAASi group. Although guideline recommendations only differentiate between ACEis and ARBs in patients with cardiovascular comorbidities, clinical evidence suggests that ACEis provide benefits in many hypertensive patients, as well as those with other cardiovascular conditions.

Pharmacogenetics of angiotensin modulators according to APOE-ϵ4 alleles and the ACE insertion/deletion polymorphism in Alzheimer's disease.

OBJECTIVE: In Alzheimer's disease (AD), angiotensin II receptor blockers (ARBs) could reduce cerebrovascular dysfunction, while angiotensin-converting enzyme inhibitors (ACEis) might increase brain amyloid-ß by suppressing effects of the angiotensin-converting enzyme 1, an amyloid-ß-degrading enzyme. However, ACEis could benefit patients with AD by reducing the amyloidogenic processing of the amyloid precursor protein, by central cholinergic and anti-inflammatory mechanisms, and by peripheral modulation of glucose homeostasis. We aimed to investigate whether the ACE insertion/deletion polymorphism is associated with clinical changes in patients with AD, while considering apolipoprotein E (APOE)-ϵ4 carrier status and blood pressure response to angiotensin modulators. METHODS: Consecutive outpatients with late-onset AD were screened with cognitive tests and anthropometric measurements, while their caregivers were queried for functional and caregiver burden scores. Prospective pharmacogenetic associations were estimated for 1 year, taking APOE-ϵ4 carrier status and genotypes of the ACE insertion/deletion polymorphism into account, along with treatment with ACEis or ARBs. RESULTS: For 193 patients (67.4% women, 53.4% APOE-ϵ4 carriers), the ACE insertion/deletion polymorphism was in Hardy-Weinberg equilibrium (p = 0.281), while arterial hypertension was prevalent in 80.3% (n = 124 used an ACEi, n = 21 used an ARB). ARBs benefitted mostly APOE-ϵ4 carriers concerning caregiver burden variations, cognitive and functional decline. ACEis benefitted APOE-ϵ4 non-carriers concerning cognitive and functional decline due to improved blood pressure control in addition to possible central mechanisms. The ACE insertion/deletion polymorphism led to variable response to angiotensin modulators concerning neurological outcomes and blood pressure variations. CONCLUSION: Angiotensin modulators may be disease-modifiers in AD, while genetic stratification of samples is recommended in clinical studies.

Discontinuation of Antihypertensive Drug Use Compared to Continuation in COVID-19 Patients: A Systematic Review with Meta-analysis and Trial Sequential Analysis.

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.