Multifaceted Strategy Based on Automated Text Messaging After a Recent Heart Failure Admission: The MESSAGE-HF Randomized Clinical Trial.

Importance: Readmissions after an index heart failure (HF) hospitalization are a major contemporary health care problem. Objective: To evaluate the feasibility and efficacy of an intensive telemonitoring strategy in the vulnerable period after an HF hospitalization. Design, Setting, and Participants: This randomized clinical trial was conducted in 30 HF clinics in Brazil. Patients with left ventricular ejection fraction less than 40% and access to mobile phones were enrolled up to 30 days after an HF admission. Data were collected from July 2019 to July 2022. Intervention: Participants were randomly assigned to a telemonitoring strategy or standard care. The telemonitoring group received 4 daily short message service text messages to optimize self-care, active engagement, and early intervention. Red flags based on feedback messages triggered automatic diuretic adjustment and/or a telephone call from the health care team. Main Outcomes and Measures: The primary end point was change in N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline to 180 days. A hierarchical win-ratio analysis incorporating blindly adjudicated clinical events (cardiovascular deaths and HF hospitalization) and variation in NT-proBNP was also performed. Results: Of 699 included patients, 460 (65.8%) were male, and the mean (SD) age was 61.2 (14.5) years. A total of 352 patients were randomly assigned to the telemonitoring strategy and 347 to standard care. Satisfaction with the telemonitoring strategy was excellent (net promoting score at 180 days, 78.5). HF self-care increased significantly in the telemonitoring group compared with the standard care group (score difference at 30 days, -2.21; 95% CI, -3.67 to -0.74; P = .001; score difference at 180 days, -2.08; 95% CI, -3.59 to -0.57; P = .004). Variation of NT-proBNP was similar in the telemonitoring group compared with the standard care group (telemonitoring: baseline, 2593 pg/mL; 95% CI, 2314-2923; 180 days, 1313 pg/mL; 95% CI, 1117-1543; standard care: baseline, 2396 pg/mL; 95% CI, 2122-2721; 180 days, 1319 pg/mL; 95% CI, 1114-1564; ratio of change, 0.92; 95% CI, 0.77-1.11; P = .39). Hierarchical analysis of the composite outcome demonstrated a similar number of wins in both groups (telemonitoring, 49 883 of 122 144 comparisons [40.8%]; standard care, 48 034 of 122 144 comparisons [39.3%]; win ratio, 1.04; 95% CI, 0.86-1.26). Conclusions and Relevance: An intensive telemonitoring strategy applied in the vulnerable period after an HF admission was feasible, well-accepted, and increased scores of HF self-care but did not translate to reductions in NT-proBNP levels nor improvement in a composite hierarchical clinical outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT04062461.

In-Hospital influenza vaccination to prevent cardiorespiratory events in the first 45 days after acute coronary syndrome: A prespecified analysis of the VIP-ACS trial.

BACKGROUND: Influenza vaccination prevents major cardiovascular events in individuals presenting a recent acute coronary syndrome (ACS), however the early effect of an in-hospital double-dose vaccination strategy remains uncertain. METHODS: The VIP-ACS was a randomized, pragmatic, multicenter, open-label trial with a blinded-adjudication endpoint. Patients with ACS ≤ 7 days of hospitalization were randomized to an in-hospital double-dose quadrivalent inactivated influenza vaccine (double-dose) or a standard-dose influenza vaccine at 30 days post-randomization. The primary endpoint was a hierarchical composite of death, myocardial infarction, stroke, hospitalization for unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory infections, analyzed with the win ratio (WR) method in short-term follow-up (45-days after randomization). RESULTS: The trial enrolled 1,801 patients (≥18 years old). Median participant age was 57 years, 70 % were male. There were no significant differences between groups on the primary hierarchical endpoint: there were 5.7 % wins in the double-dose in-hospital group and 5.5 % wins in the standard-dose delayed vaccination group (WR: 1.03; 95 % CI: 0.70---1.53; P = 0.85). In a sensitivity analysis including COVID-19 infection in the hospitalizations for respiratory infections endpoint, overall results were maintained (WR: 1.03; 95 % CI 0.71---1.51; P = 0.87). Results were consistent for major cardiovascular events only (WR: 0.82; 95 % CI: 0.48---1.39; P = 0.46). No serious adverse events were observed. CONCLUSION: In patients with recent ACS, in-hospital double-dose influenza vaccination did not significantly reduce cardiorespiratory events at 45 days compared with standard-dose vaccination at 30 days post-randomization.

Multifaceted strategy based on automated text messaging after a recent heart failure admission: the MESSAGE-HF Randomized Clinical Trial

IMPORTANCE: Readmissions after an index heart failure (HF) hospitalization are a major contemporary health care problem. OBJECTIVE: To evaluate the feasibility and efficacy of an intensive telemonitoring strategy in the vulnerable period after an HF hospitalization. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was conducted in 30 HF clinics in Brazil. Patients with left ventricular ejection fraction less than 40% and access to mobile phones were enrolled up to 30 days after an HF admission. Data were collected from July 2019 to July 2022. INTERVENTION: Participants were randomly assigned to a telemonitoring strategy or standard care. The telemonitoring group received 4 daily short message service text messages to optimize self-care, active engagement, and early intervention. Red flags based on feedback messages triggered automatic diuretic adjustment and/or a telephone call from the health care team. MAIN OUTCOMES AND MEASURES: The primary end point was change in N-terminal pro-brain natriuretic peptide (NT-proBNP) from baseline to 180 days. A hierarchical win-ratio analysis incorporating blindly adjudicated clinical events (cardiovascular deaths and HF hospitalization) and variation in NT-proBNP was also performed. RESULTS: Of 699 included patients, 460 (65.8%) were male, and the mean (SD) age was 61.2 (14.5) years. A total of 352 patients were randomly assigned to the telemonitoring strategy and 347 to standard care. Satisfaction with the telemonitoring strategy was excellent (net promoting score at 180 days, 78.5). HF self-care increased significantly in the telemonitoring group compared with the standard care group (score difference at 30 days, -2.21; 95% CI, -3.67 to -0.74; P = .001; score difference at 180 days, -2.08; 95% CI, -3.59 to -0.57; P = .004). Variation of NT-proBNP was similar in the telemonitoring group compared with the standard care group (telemonitoring: baseline, 2593 pg/mL; 95% CI, 2314-2923; 180 days, 1313 pg/mL; 95% CI, 1117-1543; standard care: baseline, 2396 pg/mL; 95% CI, 2122-2721; 180 days, 1319 pg/mL; 95% CI, 1114-1564; ratio of change, 0.92; 95% CI, 0.77-1.11; P = .39). Hierarchical analysis of the composite outcome demonstrated a similar number of wins in both groups (telemonitoring, 49 883 of 122 144 comparisons [40.8%]; standard care, 48 034 of 122 144 comparisons [39.3%]; win ratio, 1.04; 95% CI, 0.86-1.26). CONCLUSIONS and relevance: An intensive telemonitoring strategy applied in the vulnerable period after an HF admission was feasible, well-accepted, and increased scores of HF self-care but did not translate to reductions in NT-proBNP levels nor improvement in a composite hierarchical clinical outcome.

National Registry of Hypertension Control Evaluated by Office and Home Measurements: The LHAR National Registry. / Registro Nacional do Controle da Hipertensão Arterial Avaliado pela Medida de Consultório e Residencial no Brasil: Registro LHAR.

BACKGROUND: It is known that around 30% of patients have higher blood pressure (BP) values when examined at the office than at home. Worldwide, only 35% of patients with hypertension undergoing treatment have reached their BP targets. OBJECTIVE: To provide epidemiological data on BP control in the offices of a sample of Brazilian cardiologists, considering office and home BP measurement. METHODS: This is a cross-sectional analysis of patients with a hypertension diagnosis and undergoing antihypertensive treatment, with controlled BP or not. BP was assayed in the office by a medical professional and at home using home BP monitoring (HBPM). The association between categorical variables was verified using the chi-square test (p<0.05). RESULTS: The study included 2540 patients, with a mean age of 59.7 ± 15.2 years. Most patients were women (62%; n=1575). Prevalence rates of 15% (n=382) for uncontrolled white coat hypertension and 10% (n=253) for uncontrolled masked hypertension were observed. The rate of BP control in the office was 56.3% and at home, 61%. Meanwhile, 46.4% of the patients had controlled BP in and outside of the office. Greater control was observed in women and in the 49-61 years age group. Considering the new DBHA 2020 threshold for home BP control, the control rate was 42.4%. CONCLUSION: BP control in the offices of a sample of Brazilian cardiologists was 56.3%; this rate was 61% when BP was measured at home and 46.4% when considering both the office and home.

FUNDAMENTO: Sabe-se que em torno de 30% dos pacientes apresentam valores de pressão arterial (PA) mais elevados quando examinados no consultório do que em suas residências. No mundo, admite-se que apenas 35% dos hipertensos já tratados tenham alcançado meta pressórica. OBJETIVO: Fornecer dados epidemiológicos sobre o controle da PA nos consultórios, em uma amostra de cardiologistas brasileiros, avaliado pela medida de consultório e monitorização residencial da pressão arterial (MRPA). MÉTODOS: Análise transversal. Observou-se pacientes com diagnóstico de hipertensão arterial, em tratamento anti-hipertensivo, podendo ou não estar com a PA controlada. A PA foi verificada no consultório por profissional médico, e no domicílio através da MRPA. A associação entre variáveis categóricas se deu por meio do teste do qui-quadrado (p < 0,05). RESULTADOS: Foram incluídos 2.540 pacientes, com idade média 59,7 ± 15,2 anos. A maioria dos pacientes eram mulheres (62%; n = 1.575). O estudo mostrou uma prevalência de 15% (n = 382) de hipertensão do avental branco não controlada, e 10% (n = 253) de hipertensão mascarada não controlada. A taxa de controle da PA no consultório foi 56,3%, e no domicílio, de 61%; 46,4% dos pacientes tiveram PA controlada no consultório e fora dele. Observou-se maior controle no sexo feminino e na faixa etária 49-61 anos. Observando o controle domiciliar com o novo ponto de corte das Diretrizes Brasileiras de Hipertensão Arterial de 2020, a taxa de controle foi de 42,4%. CONCLUSÃO: O controle pressórico nos consultórios em uma amostra de cardiologistas brasileiros foi de 56,3%; 61% quando a PA foi obtida no domicílio, e 46,4% quando o controle foi observado tanto no consultório como no domicílio.

P2Y12 inhibitor monotherapy versus dual antiplatelet therapy in patients with acute coronary syndromes undergoing coronary stenting: rationale and design of the NEOMINDSET Trial

Dual antiplatelet therapy (DAPT) is currently the standard of care after percutaneous coronary intervention (PCI). Recent studies suggest that reducing DAPT to 1-3 months followed by an aspirin-free single antiplatelet therapy (SAPT) strategy with a potent P2Y12 inhibitor is safe and associated with less bleeding. However, to date, no randomised trial has tested the impact of initiating SAPT immediately after PCI, particularly in patients with acute coronary syndromes (ACS). NEOMINDSET is a multicentre, randomised, open-label trial with a blinded outcome assessment designed to compare SAPT versus DAPT in 3,400 ACS patients undergoing PCI with the latest-generation drug-eluting stents (DES). After successful PCI and up to 4 days following hospital admission, patients are randomised to receive SAPT with a potent P2Y12 inhibitor (ticagrelor or prasugrel) or DAPT (aspirin plus a potent P2Y12 inhibitor) for 12 months. Aspirin is discontinued immediately after randomisation in the SAPT group. The choice between ticagrelor and prasugrel is at the investigator's discretion. The primary hypothesis is that SAPT will be non-inferior to DAPT with respect to the composite endpoint of all-cause mortality, stroke, myocardial infarction or urgent target vessel revascularisation, but superior to DAPT on rates of bleeding defined by Bleeding Academic Research Consortium 2, 3 or 5 criteria. NEOMINDSET is the first study that is specifically designed to test SAPT versus DAPT immediately following PCI with DES in ACS patients. This trial will provide important insights on the efficacy and safety of withdrawing aspirin in the early phase of ACS.

P2Y12 inhibitor monotherapy versus dual antiplatelet therapy in patients with acute coronary syndromes undergoing coronary stenting: rationale and design of the NEOMINDSET Trial.

Dual antiplatelet therapy (DAPT) is currently the standard of care after percutaneous coronary intervention (PCI). Recent studies suggest that reducing DAPT to 1-3 months followed by an aspirin-free single antiplatelet therapy (SAPT) strategy with a potent P2Y12 inhibitor is safe and associated with less bleeding. However, to date, no randomised trial has tested the impact of initiating SAPT immediately after PCI, particularly in patients with acute coronary syndromes (ACS). NEOMINDSET is a multicentre, randomised, open-label trial with a blinded outcome assessment designed to compare SAPT versus DAPT in 3,400 ACS patients undergoing PCI with the latest-generation drug-eluting stents (DES). After successful PCI and up to 4 days following hospital admission, patients are randomised to receive SAPT with a potent P2Y12 inhibitor (ticagrelor or prasugrel) or DAPT (aspirin plus a potent P2Y12 inhibitor) for 12 months. Aspirin is discontinued immediately after randomisation in the SAPT group. The choice between ticagrelor and prasugrel is at the investigator's discretion. The primary hypothesis is that SAPT will be non-inferior to DAPT with respect to the composite endpoint of all-cause mortality, stroke, myocardial infarction or urgent target vessel revascularisation, but superior to DAPT on rates of bleeding defined by Bleeding Academic Research Consortium 2, 3 or 5 criteria. NEOMINDSET is the first study that is specifically designed to test SAPT versus DAPT immediately following PCI with DES in ACS patients. This trial will provide important insights on the efficacy and safety of withdrawing aspirin in the early phase of ACS. (ClinicalTrials.gov: NCT04360720).

Registro Nacional do Controle da Hipertensão Arterial Avaliado pela Medida de Consultório e Residencial no Brasil: Registro LHAR / National Registry of Hypertension Control Evaluated by Office and Home Measurements: The LHAR National Registry

Resumo Fundamento Sabe-se que em torno de 30% dos pacientes apresentam valores de pressão arterial (PA) mais elevados quando examinados no consultório do que em suas residências. No mundo, admite-se que apenas 35% dos hipertensos já tratados tenham alcançado meta pressórica. Objetivo Fornecer dados epidemiológicos sobre o controle da PA nos consultórios, em uma amostra de cardiologistas brasileiros, avaliado pela medida de consultório e monitorização residencial da pressão arterial (MRPA). Métodos Análise transversal. Observou-se pacientes com diagnóstico de hipertensão arterial, em tratamento anti-hipertensivo, podendo ou não estar com a PA controlada. A PA foi verificada no consultório por profissional médico, e no domicílio através da MRPA. A associação entre variáveis categóricas se deu por meio do teste do qui-quadrado (p < 0,05). Resultados Foram incluídos 2.540 pacientes, com idade média 59,7 ± 15,2 anos. A maioria dos pacientes eram mulheres (62%; n = 1.575). O estudo mostrou uma prevalência de 15% (n = 382) de hipertensão do avental branco não controlada, e 10% (n = 253) de hipertensão mascarada não controlada. A taxa de controle da PA no consultório foi 56,3%, e no domicílio, de 61%; 46,4% dos pacientes tiveram PA controlada no consultório e fora dele. Observou-se maior controle no sexo feminino e na faixa etária 49-61 anos. Observando o controle domiciliar com o novo ponto de corte das Diretrizes Brasileiras de Hipertensão Arterial de 2020, a taxa de controle foi de 42,4%. Conclusão O controle pressórico nos consultórios em uma amostra de cardiologistas brasileiros foi de 56,3%; 61% quando a PA foi obtida no domicílio, e 46,4% quando o controle foi observado tanto no consultório como no domicílio.

Abstract Background It is known that around 30% of patients have higher blood pressure (BP) values when examined at the office than at home. Worldwide, only 35% of patients with hypertension undergoing treatment have reached their BP targets. Objective To provide epidemiological data on BP control in the offices of a sample of Brazilian cardiologists, considering office and home BP measurement. Methods This is a cross-sectional analysis of patients with a hypertension diagnosis and undergoing antihypertensive treatment, with controlled BP or not. BP was assayed in the office by a medical professional and at home using home BP monitoring (HBPM). The association between categorical variables was verified using the chi-square test (p<0.05). Results The study included 2540 patients, with a mean age of 59.7 ± 15.2 years. Most patients were women (62%; n=1575). Prevalence rates of 15% (n=382) for uncontrolled white coat hypertension and 10% (n=253) for uncontrolled masked hypertension were observed. The rate of BP control in the office was 56.3% and at home, 61%. Meanwhile, 46.4% of the patients had controlled BP in and outside of the office. Greater control was observed in women and in the 49-61 years age group. Considering the new DBHA 2020 threshold for home BP control, the control rate was 42.4%. Conclusion BP control in the offices of a sample of Brazilian cardiologists was 56.3%; this rate was 61% when BP was measured at home and 46.4% when considering both the office and home.

Lipoprotein(a) levels in a global population with established atherosclerotic cardiovascular disease.

OBJECTIVE: Lipoprotein(a) (Lp(a)) is an important genetically determined risk factor for atherosclerotic vascular disease (ASCVD). With the development of Lp(a)-lowering therapies, this study sought to characterise patterns of Lp(a) levels in a global ASCVD population and identify racial, ethnic, regional and gender differences. METHODS: A multicentre cross-sectional epidemiological study to estimate the prevalence of elevated Lp(a) in patients with a history of myocardial infarction, ischaemic stroke or peripheral artery disease conducted at 949 sites in 48 countries in North America, Europe, Asia, South America, South Africa and Australia between April 2019 and July 2021. Low-density lipoprotein cholesterol (LDL-C) and Lp(a) levels were measured either as mass (mg/dL) or molar concentration (nmol/L). RESULTS: Of 48 135 enrolled patients, 13.9% had prior measurements of Lp(a). Mean age was 62.6 (SD 10.1) years and 25.9% were female. Median Lp(a) was 18.0 mg/dL (IQR 7.9-57.1) or 42.0 nmol/L (IQR 15.0-155.4). Median LDL-C was 77 mg/dL (IQR 58.4-101.0). Lp(a) in women was higher, 22.8 (IQR 9.0-73.0) mg/dL, than in men, 17.0 (IQR 7.1-52.2) mg/dL, p<0.001. Black patients had Lp(a) levels approximately threefold higher than white, Hispanic or Asian patients. Younger patients also had higher levels. 27.9% of patients had Lp(a) levels >50 mg/dL, 20.7% had levels >70 mg/dL, 12.9% were >90 mg/dL and 26.0% of patients exceeded 150 nmol/L. CONCLUSIONS: Globally, Lp(a) is measured in a small minority of patients with ASCVD and is highest in black, younger and female patients. More than 25% of patients had levels exceeding the established threshold for increased cardiovascular risk, approximately 50 mg/dL or 125 nmol/L.

Multimodal exercise program contributes to balance and motor functions in men and women with Parkinson's disease differently: an intervention study

Abstract Aim: To verify the effects of a multimodal exercise program on balance and motor functions, and the differences by sex, in people with Parkinson's disease (PD). Methods: The intervention study, was composed of 16 people with PD, that were assessed before and after 16 weeks of interventions with the multimodal exercise program. The effects were analyzed generally and by sex, using the Wilcoxon Test. The significance level was established at 5%. Results: Overall, there was an improvement in the strength of the lower limbs (LL) (p = 0.035) and upper limbs (UL) (p = 0.009), functional mobility (p = 0.003), gait (p = 0.050), balance (p = 0.001) and in motor scores of UPDRS III (p = 0.005), which categorize motor symptoms of the disease. In regards to sex, women affected muscle strength (p = 0.044) and flexibility of LL (p = 0.028), gait (p = 0.018), and motor aspects of the UPDRS III (p = 0.042). The men presented effects in muscle strength of the UL (p = 0.042). Women and men had a significant increase in functional mobility (p = 0.046 and p = 0.027, respectively) and in balance (p = 0.012 and p = 0.042, respectively). There was no significant difference for both sexes, in body mass and the reach behind the backtest. Conclusion: the multimodal exercise program contributed to the improvement in motor function and balance in men and women with PD. Nevertheless, the effects were more significant in women. The comprehension of the differences between men and women grants us a more directional and efficient approach to their treatment.

Liver transplantation: survival and indexes of donor-recipient matching.

OBJECTIVE: The aim of this study was to determine the prospective capacity and impact of donor risk index, preallocation survival outcomes following liver transplant, donor model for end-stage liver disease, and balance of risk on patients' 30-day survival after liver transplantation. METHODS: We prospectively analyzed patient survival in a multicentric observational cohort of adult liver transplantation through the year of 2019 at the state of Paraná, Brazil. The receiver operating characteristic curve, the area under the curve, and the best cutoff point (i.e., the Youden's index) were estimated to analyze the prognostic value of each index. RESULTS: In total, 252 liver transplants were included with an average model for end-stage liver disease score of 21.17 and a 30-day survival of 79.76%. The donor risk index was the only prognostic variable with no relation to patients' 30-day mortality model for end-stage liver disease and donor model for end-stage liver disease have no prognostic value on receiver operating characteristic curve, but preallocation survival outcomes following liver transplant, survival outcomes following liver transplant, and balance of risk presented good relationship with this observation. The cutoff value was estimated in 11-12 points for balance of risk and 9-12 for preallocation survival outcomes following liver transplant and survival outcomes following liver transplant. The 30-day survival for the group of transplants with scores up to 12 points (n=172) in all the three indexes was 87.79%, and for those transplants with scores higher than 12 it was 36.36%. CONCLUSIONS: The 30-day survival is 79.76%, and balance of risk, survival outcomes following liver transplant, and preallocation survival outcomes following liver transplant are the good prognostic indexes. The cutoff value of 12 points has clinical usefulness to predict the post-liver transplantation results.

Design of a multifaceted strategy based on automated text messaging in patients with recent heart failure admission.

AIMS: To evaluate a telemonitoring strategy based on automated text messaging and telephone support after heart failure (HF) hospitalization. METHODS AND RESULTS: The MESSAGE-HF study is a prospective multicentre, randomized, nationwide trial enrolling patients from 30 clinics in all regions of Brazil. HF patients with reduced left ventricular ejection fraction (<40%) and access to mobile phones are eligible after an acute decompensated HF hospitalization. Patients meeting eligibility criteria undergo an initial feasibility text messaging assessment and are randomized to usual care or telemonitoring intervention. All patients receive a HF booklet with basic information and recommendations about self-care. Patients in the intervention group receive four daily short text messages (educational and feedback) during the first 30 days of the protocol to optimize self-care; the feedback text messages from patients could trigger diuretic adjustments or a telephone call from the healthcare team. After 30 days, the frequency of text messages can be adjusted. Patients are followed up after 30, 90, and 180 days, with final status ascertained at 365 days by telephone. Our primary endpoint is the change in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels after 180 days. Secondary endpoints include changes in NT-proBNP after 30 days; health-related quality of life, HF self-care, and knowledge scales after 30 and 180 days; and a composite outcome of HF hospitalization and cardiovascular death, adjudicated by a blinded and independent committee. CONCLUSIONS: The MESSAGE-HF trial is evaluating an educational and self-care promotion strategy involving a simple, intensive, and tailored telemonitoring system. If proven effective, it could be applied to a broader population worldwide.

Dapagliflozin in patients with cardiometabolic risk factors hospitalised with COVID-19 (DARE-19): a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: COVID-19 can lead to multiorgan failure. Dapagliflozin, a SGLT2 inhibitor, has significant protective benefits for the heart and kidney. We aimed to see whether this agent might provide organ protection in patients with COVID-19 by affecting processes dysregulated during acute illness. METHODS: DARE-19 was a randomised, double-blind, placebo-controlled trial of patients hospitalised with COVID-19 and with at least one cardiometabolic risk factor (ie, hypertension, type 2 diabetes, atherosclerotic cardiovascular disease, heart failure, and chronic kidney disease). Patients critically ill at screening were excluded. Patients were randomly assigned 1:1 to dapagliflozin (10 mg daily orally) or matched placebo for 30 days. Dual primary outcomes were assessed in the intention-to-treat population: the outcome of prevention (time to new or worsened organ dysfunction or death), and the hierarchial composite outcome of recovery (change in clinical status by day 30). Safety outcomes, in patients who received at least one study medication dose, included serious adverse events, adverse events leading to discontinuation, and adverse events of interest. This study is registered with ClinicalTrials.gov, NCT04350593. FINDINGS: Between April 22, 2020 and Jan 1, 2021, 1250 patients were randomly assigned with 625 in each group. The primary composite outcome of prevention showed organ dysfunction or death occurred in 70 patients (11·2%) in the dapagliflozin group, and 86 (13·8%) in the placebo group (hazard ratio [HR] 0·80, 95% CI 0·58-1·10; p=0·17). For the primary outcome of recovery, 547 patients (87·5%) in the dapagliflozin group and 532 (85·1%) in the placebo group showed clinical status improvement, although this was not statistically significant (win ratio 1·09, 95% CI 0·97-1·22; p=0·14). There were 41 deaths (6·6%) in the dapagliflozin group, and 54 (8·6%) in the placebo group (HR 0·77, 95% CI 0·52-1·16). Serious adverse events were reported in 65 (10·6%) of 613 patients treated with dapagliflozin and in 82 (13·3%) of 616 patients given the placebo. INTERPRETATION: In patients with cardiometabolic risk factors who were hospitalised with COVID-19, treatment with dapagliflozin did not result in a statistically significant risk reduction in organ dysfunction or death, or improvement in clinical recovery, but was well tolerated. FUNDING: AstraZeneca.

Mudança no padrão demográfico dos doadores de órgãos no Estado do Paraná de 2011 a 2019 / Change in the demographic pattern of organ donors in the State of Paraná from 2011 to 2019

A demanda de órgãos para transplante necessita de um sistema eficaz na identificação de potenciais doadores. Estudo transversal com objetivo de avaliar o perfil epidemiológico dos doadores e o reflexo nos órgãos disponíveis para transplante. A expansão da base de doadores no Paraná, atingindo 43,8 doadores/pmp em 2019, ocorreu pelo aumento da média de idade (46,3±1,68), principalmente da faixa etária dos 50 aos 79 anos. Houve mudança na principal etiologia de morte encefálica, modificada dos traumatismos crânio-encefálicos (28,10%), para os acidentes vasculares cerebrais (46,35%). A média do número de transplantes realizados por cada doador efetivo foi de 2,14±0,37, com média de 52,24±18,48 transplantes pmp. A queda da razão transplantes/doador efetivo é contrastada com o comportamento da linha dos transplantes/pmp. Perfil de doadores ideais foi modificado para doadores de critérios expandidos. A ampliação da base de doadores consegue beneficiar um número cada vez maior de pacientes. (AU)

The demand for organs for transplantation requires an effective system in the identification of potential donors. Transversal study with the objective to evaluate the epidemiological profile of donors and the impact on the organs available for transplantation. The expansion of the donor base in Paraná, reaching 43.8 donors/pmp in 2019, occurred due to the increase in the mean age (46.3±1.68), mainly from the age group 50 to 79 years. There was a change in the main etiology of brain death, modified from traumatic brain injuries (28.10%), to strokes (46.35). The average number of transplants performed by each effective donor was 2.14 ± 0.37, with an average of 52.24 ± 18.48 pmp transplants. The drop in the transplant / effective donor ratio is contrasted with the behavior of the transplant / pmp line. Ideal donor profile has been modified for expanded criteria donors. The expansion of the donor base can benefit an increasing number of patients. (AU)

Doadores de órgãos efetivos no Paraná e correlação com o Índice de Desenvolvimento Humano Municipal / Effective organ donors in Paraná and correlation with the Municipal Human Development Index

O Paraná se destaca na oferta de órgãos para transplante. O processo é inserido no Sistema Único de Saúde, portanto, influenciado por desigualdades regionais. O índice de desenvolvimento humano municipal (IDHM) é utilizado para análise e compreensão do desenvolvimento e sua relação com a doação de órgãos é desconhecida. Objetivo é analisar a correlação do IDHM com a doação de órgãos no estado no período de 2011 a 2019. Ocorreram 2875 doações efetivas em 7,27% dos municípios, com diferença do IDHM daqueles com (0,7514±0,03) e sem (0,6981±0,03) doação. Municípios com IDHM alto e muito alto (59,65% do total), foram responsáveis por 97,46% das doações. O agrupamento por Regionais de Saúde demonstra correlação linear positiva entre o IDHM e as doações efetivas por milhão de população, porém sem diferença do IDHM médio entre elas. Há correlação entre o IDHM e os doadores efetivos, não sendo o único fator de influência. (AU)

Paraná stands out in the offer of organs for transplantation. The process is inserted in the Unified Health System, thus influenced by regional inequalities. The municipal human development index (MHDI) is used for analysis and understanding of development and its relationship with organ donation is unknown. The objective is to analyze the correlation of MHDI with organ donation in the state from 2011 to 2019. There were 2875 effective donations in 7.27% of the municipalities, with a difference in the MHDI of those with (0.7514±0.03) and without (0.6981±0.03) donation. Municipalities with high and very high MHDI (59.65% of the total) accounted for 97.46% of the donations. The grouping by Regional Health shows a positive linear correlation between the MHDI and the effective donations per million population, but with no difference from the mean MHDI between them. There is a correlation between the MHDI and the effective donors, and it is not the only factor of influence. (AU)

A randomized clinical trial to evaluate the efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valve and atrial fibrillation or flutter: rationale and design of the RIVER trial

Background The efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valves and atrial fibrillation or flutter remain uncertain. Design RIVER was an academic-led, multicenter, open-label, randomized, non-inferiority trial with blinded outcome adjudication that enrolled 1005 patients from 49 sites in Brazil. Patients with a bioprosthetic mitral valve and atrial fibrillation or flutter were randomly assigned (1:1) to rivaroxaban 20 mg once daily (15 mg in those with creatinine clearance <50 mL/min) or dose-adjusted warfarin (target international normalized ratio 2.0-30.); the follow-up period was 12 months. The primary outcome was a composite of all-cause mortality, stroke, transient ischemic attack, major bleeding, valve thrombosis, systemic embolism, or hospitalization for heart failure. Secondary outcomes included individual components of the primary composite outcome, bleeding events, and venous thromboembolism. Summary RIVER represents the largest trial specifically designed to assess the efficacy and safety of a direct oral anticoagulant in patients with bioprosthetic mitral valves and atrial fibrillation or flutter. The results of this trial can inform clinical practice and international guidelines.

A randomized clinical trial to evaluate the efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valve and atrial fibrillation or flutter: Rationale and design of the RIVER trial.

The efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valves and atrial fibrillation or flutter remain uncertain. DESIGN: RIVER was an academic-led, multicenter, open-label, randomized, non-inferiority trial with blinded outcome adjudication that enrolled 1005 patients from 49 sites in Brazil. Patients with a bioprosthetic mitral valve and atrial fibrillation or flutter were randomly assigned (1:1) to rivaroxaban 20 mg once daily (15 mg in those with creatinine clearance <50 mL/min) or dose-adjusted warfarin (target international normalized ratio 2.0-30.); the follow-up period was 12 months. The primary outcome was a composite of all-cause mortality, stroke, transient ischemic attack, major bleeding, valve thrombosis, systemic embolism, or hospitalization for heart failure. Secondary outcomes included individual components of the primary composite outcome, bleeding events, and venous thromboembolism. SUMMARY: RIVER represents the largest trial specifically designed to assess the efficacy and safety of a direct oral anticoagulant in patients with bioprosthetic mitral valves and atrial fibrillation or flutter. The results of this trial can inform clinical practice and international guidelines.