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PurposeThe Balanced versus Saline Trialists (BEST) -Living Study is an ongoing living systematic review with aggregated and individual patient data meta-analysis (IPDMA) from eligible trials that assessed the effects of using balanced solutions compared with saline in critically ill adults. We herein present the search strategies for the BEST-Living Study and provide details for future analysis and presentation.MethodsThe report will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Individual Participant Data (PRISMA-IPD) recommendations. Search was performed in Pubmed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL). The primary endpoint will be hospital mortality, which will be analyzed using a Bayesian hierarchical model. Secondary endpoints include nurvival until longest follow-up available, use of kidney replacement therapy, and intensive care unit and hospital length-of-stay. Details on the analysis plan are provided in this statistical analysis plan.ConclusionThe study will provide the most up-to-date and comprehensive assessment using the best evidence available for the use of balanced solutions in critically ill patients.ApprovalsThe undersigned and all authors have reviewed this plan and approve it as final. They find it to be consistent with the requirements of the protocol as it applies to their respective areas. They also find it to be compliant with ICH-E9 principles and, in particular, confirm that this analysis plan was final prior to any analysis of the aggregated data.

Rationale: The effects of balanced crystalloid versus saline on clinical outcomes for ICU patients may be modified by the type of fluid that patients received for initial resuscitation and by the type of admission. Objectives: To assess whether the results of a randomized controlled trial could be affected by fluid use before enrollment and admission type. Methods: Secondary post hoc analysis of the BaSICS (Balanced Solution in Intensive Care Study) trial, which compared a balanced solution (Plasma-Lyte 148) with 0.9% saline in the ICU. Patients were categorized according to fluid use in the 24 hours before enrollment in four groups (balanced solutions only, 0.9% saline only, a mix of both, and no fluid before enrollment) and according to admission type (planned, unplanned with sepsis, and unplanned without sepsis). The association between 90-day mortality and the randomization group was assessed using a hierarchical logistic Bayesian model. Measurements and Main Results: A total of 10,520 patients were included. There was a low probability that the balanced solution was associated with improved 90-day mortality in the whole trial population (odds ratio [OR], 0.95; 89% credible interval [CrI], 0.66–10.51; probability of benefit, 0.58); however, probability of benefit was high for patients who received only balanced solutions before enrollment (regardless of admission type, OR, 0.78; 89% CrI, 0.56–1.03; probability of benefit, 0.92), mostly because of a benefit in unplanned admissions due to sepsis (OR, 0.70; 89% CrI, 0.50–0.97; probability of benefit, 0.96) and planned admissions (OR, 0.79; 89% CrI, 0.65–0.97; probability of benefit, 0.97). Conclusions: There is a high probability that balanced solution use in the ICU reduces 90-day mortality in patients who exclusively received balanced fluids before trial enrollment. Clinical trial registered with www.clinicaltrials.gov (NCT 02875873).

The effects of rivaroxaban in patients with atrial fibrillation and a bioprosthetic mitral valve remain uncertain.In this randomized trial, we compared rivaroxaban (20 mg once daily) with dose-adjusted warfarin (target international normalized ratio, 2.0 to 3.0) in patients with atrial fibrillation and a bioprosthetic mitral valve. The primary outcome was a composite of death, major cardiovascular events (stroke, transient ischemic attack, systemic embolism, valve thrombosis, or hospitalization for heart failure), or major bleeding at 12 months.A total of 1005 patients were enrolled at 49 sites in Brazil. A primary-outcome event occurred at a mean of 347.5 days in the rivaroxaban group and 340.1 days in the warfarin group (difference calculated as restricted mean survival time, 7.4 days; 95% confidence interval [CI], -1.4 to 16.3; P0.001 for noninferiority). Death from cardiovascular causes or thromboembolic events occurred in 17 patients (3.4%) in the rivaroxaban group and in 26 (5.1%) in the warfarin group (hazard ratio, 0.65; 95% CI, 0.35 to 1.20). The incidence of stroke was 0.6% in the rivaroxaban group and 2.4% in the warfarin group (hazard ratio, 0.25; 95% CI, 0.07 to 0.88). Major bleeding occurred in 7 patients (1.4%) in the rivaroxaban group and in 13 (2.6%) in the warfarin group (hazard ratio, 0.54; 95% CI, 0.21 to 1.35). The frequency of other serious adverse events was similar in the two groups.In patients with atrial fibrillation and a bioprosthetic mitral valve, rivaroxaban was noninferior to warfarin with respect to the mean time until the primary outcome of death, major cardiovascular events, or major bleeding at 12 months. (Funded by PROADI-SUS and Bayer; RIVER ClinicalTrials.gov number, NCT02303795.).

Rationale: Coated devices may reduce biofilm formation and reduce the occurrence of device-related infections in critically ill patients. A bundle of coated devices (an endotracheal tube [ETT], central venous catheter [CVC], and urinary catheter [UC]) simultaneously inserted may optimize benefits of coated devices in patients with the most severe illness. Objectives: To assess the feasibility of a randomized controlled trial on simultaneous insertion of gold/silver/palladium-coated devices versus uncoated devices in severely ill patients, which required sequential insertion of all three devices (an ETT, CVC, and UC) for support in the intensive care unit (ICU). Methods: This was a multicenter randomized controlled pilot trial. Patients who required simultaneous insertion of an ETT, CVC, and UC were randomized to treatment with coated versus uncoated devices, which were used as necessary for up to 28 days. The primary endpoint was feasibility, defined as the trial being able to enroll enough participants to have the sample size necessary for its secondary primary endpoint (estimating sepsis incidence in this population) in less than 1 year and for estimating the number of admitted patients who require simultaneous insertion of all three devices. Secondary endpoints included the incidence of sepsis and device-associated infections (ventilator-associated pneumonia, catheter-related bloodstream infection, and catheter-related urinary-tract infection) within each group as well as the number of days alive and free of antibiotics during the ICU stay. All events were adjudicated. Results: One hundred and three patients (48 in the coated-device group and 55 in the uncoated-device group) were included in the perprotocol analysis. The inclusion period was 8 months. There were 13 septic events in each group (26 in total), with an approximate incidence of sepsis of 32.3 (95% credible interval [CrI], 22.4-44.9) per 100 patient-days. The overall incidences of ventilator-associated pneumonia, catheter-related urinary-tract infection, and catheterrelated bloodstream infection were 15.2 (95% CrI, 7.8-26.4), 6.3 (95% CrI, 2.4-13.7), and 7.9 (95% CrI, 3.6-15.1) per 1,000 patient-days, and incidence rates were not statistically different between groups. Patients in the coated-device group had more days alive and free of antibiotics in the ICU (28.97 d vs. 19.62 d per 100 patient-days; mean ratio, 1.48; 95% CrI, 1.16-1.89). Conclusions: Use of a bundle of coated devices as the initial treatment for of severely ill patients is feasible. Coated devices may be associated with more days alive and free of antibiotics. Clinical trial registered with www.clinicaltrials.gov (NCT 03868241).

The effect of high-flow oxygen therapy vs conventional oxygen therapy has not been established in the setting of severe COVID-19.To determine the effect of high-flow oxygen therapy through a nasal cannula compared with conventional oxygen therapy on need for endotracheal intubation and clinical recovery in severe COVID-19.Randomized, open-label clinical trial conducted in emergency and intensive care units in 3 hospitals in Colombia. A total of 220 adults with respiratory distress and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of less than 200 due to COVID-19 were randomized from August 2020 to January 2021, with last follow-up on February 10, 2021.Patients were randomly assigned to receive high-flow oxygen through a nasal cannula (n = 109) or conventional oxygen therapy (n = 111).The co-primary outcomes were need for intubation and time to clinical recovery until day 28 as assessed by a 7-category ordinal scale (range, 1-7, with higher scores indicating a worse condition). Effects of treatments were calculated with a Cox proportional hazards model adjusted for hypoxemia severity, age, and comorbidities.Among 220 randomized patients, 199 were included in the analysis (median age, 60 years; n = 65 women [32.7%]). Intubation occurred in 34 (34.3%) randomized to high-flow oxygen therapy and in 51 (51.0%) randomized to conventional oxygen therapy (hazard ratio, 0.62; 95% CI, 0.39-0.96; P = .03). The median time to clinical recovery within 28 days was 11 (IQR, 9-14) days in patients randomized to high-flow oxygen therapy vs 14 (IQR, 11-19) days in those randomized to conventional oxygen therapy (hazard ratio, 1.39; 95% CI, 1.00-1.92; P = .047). Suspected bacterial pneumonia occurred in 13 patients (13.1%) randomized to high-flow oxygen and in 17 (17.0%) of those randomized to conventional oxygen therapy, while bacteremia was detected in 7 (7.1%) vs 11 (11.0%), respectively.Among patients with severe COVID-19, use of high-flow oxygen through a nasal cannula significantly decreased need for mechanical ventilation support and time to clinical recovery compared with conventional low-flow oxygen therapy.ClinicalTrials.gov Identifier: NCT04609462.

Despite the need for targeting specific therapeutic options for coronavirus disease 2019 (COVID-19), there has been no evidence of effectiveness of any specific treatment for the outpatient clinical setting. There are few randomized studies evaluating hydroxychloroquine (HCQ) in non-hospitalized patients. These studies indicate no benefit from the use of HCQ, but they assessed different primary outcomes and presented important biases for outcome evaluation.To evaluate if HCQ may prevent hospitalization due to COVID-19 compared to a matching placebo.The COVID-19 Outpatient Prevention Evaluation (COPE) study is a pragmatic, randomized, double-blind, placebo-controlled clinical trial evaluating the use of HCQ (800 mg on day 1 and 400 mg from day 2 to day 7) or matching placebo for the prevention of hospitalization due to COVID-19 in early non-hospitalized confirmed or suspected cases. Inclusion criteria are adults (≥ 18 years) seeking medical care with mild symptoms of COVID-19, with randomization ≤ 7 days after symptom onset, without indication of hospitalization at study screening, and with at least one risk factor for complication (65 years; hypertension; diabetes mellitus; asthma; chronic obstructive pulmonary disease or other chronic lung diseases; smoking; immunosuppression; or obesity). All hypothesis tests will be two-sided. A p-value0.05 will be considered statistically significant in all analyses. Clinicaltrials.gov: NCT04466540.Clinical outcomes will be centrally adjudicated by an independent clinical event committee blinded to the assigned treatment groups. The primary efficacy endpoint will be assessed following the intention-to-treat principle.This study has the potential to reliably answer the scientific question of HCQ use in outpatients with COVID-19. To our knowledge, this is the largest trial evaluating HCQ in non-hospitalized individuals with COVID-19.Apesar da necessidade de opções terapêuticas específicas para a doença do coronavírus 2019 (covid-19), ainda não há evidências da eficácia de tratamentos específicos no contexto ambulatorial. Há poucos estudos randomizados que avaliam a hidroxicloroquina (HCQ) em pacientes não hospitalizados. Esses estudos não indicaram benefício com o uso da HCQ; no entanto, avaliaram desfechos primários diferentes e apresentaram vieses importantes na avaliação dos desfechos.Investigar se a HCQ possui o potencial de prevenir hospitalizações por covid-19 quando comparada ao placebo correspondente.O estudo COVID-19 Outpatient Prevention Evaluation (COPE) é um ensaio clínico randomizado, pragmático, duplo-cego, multicêntrico e controlado por placebo que avalia o uso da HCQ (800 mg no dia 1 e 400 mg do dia 2 ao dia 7) ou placebo correspondente na prevenção de hospitalizações por covid-19 em casos precoces confirmados ou suspeitos de pacientes não hospitalizados. Os critérios de inclusão são adultos (≥ 18 anos) que procuraram atendimento médico com sintomas leves de covid-19, com randomização ≤ 7 dias após o início dos sintomas, sem indicação de hospitalização na triagem do estudo e com pelo menos um fator de risco para complicações (65 anos, hipertensão, diabetes melito, asma, doença pulmonar obstrutiva crônica ou outras doenças pulmonares crônicas, tabagismo, imunossupressão ou obesidade). Todos os testes de hipótese serão bilaterais. Um valor de p0,05 será considerado estatisticamente significativo em todas as análises. Clinicaltrials.gov: NCT04466540.Os desfechos clínicos serão avaliados centralmente por um comitê de eventos clínicos independente cegado para a alocação dos grupos de tratamento. O desfecho primário de eficácia será avaliado de acordo com o princípio da intenção de tratar.Este estudo apresenta o potencial de responder de forma confiável a questão científica do uso da HCQ em pacientes ambulatoriais com covid-19. Do nosso conhecimento, este é o maior estudo avaliando o uso de HCQ em indivíduos com covid-19 não hospitalizados.

Most of the evidence on bariatric surgery on obstructive sleep apnea (OSA) is based on observational studies and/or short-term follow-up in patients with obesity grade 3.This randomized study compared the effects of roux-en-Y gastric bypass (RYGB) or usual care (UC) on OSA severity in patients with obesity grade 1-2. Mild, moderate, and severe OSA was defined by the apnea-hypopnoea index (AHI): 5-14.9; 15-29.9, and ≥30 events/h, respectively. OSA remission was defined by converting any form of OSA into normal AHI (5 events/h).After 3-year of follow-up, the body-mass index increased in the UC while decreased in the RYGB group: +1.7 (-1.9; 2.7) versus -10.6 (-12.7; -9.2) kg/mRYGB is an attractive strategy for mid-term OSA remission or decrease moderate-to-severe forms of OSA in patients with obesity grade 1-2.

Rationale: Although proposed as a clinical prompt to sepsis based on predictive validity for mortality, the Quick Sepsis-related Organ Failure Assessment (qSOFA) score is often used as a screening tool, which requires high sensitivity.Objectives: To assess the predictive accuracy of qSOFA for mortality in Brazil, focusing on sensitivity.Methods: We prospectively collected data from two cohorts of emergency department and ward patients. Cohort 1 included patients with suspected infection but without organ dysfunction or sepsis (22 hospitals: 3 public and 19 private). Cohort 2 included patients with sepsis (54 hospitals: 24 public and 28 private). The primary outcome was in-hospital mortality. The predictive accuracy of qSOFA was examined considering only the worst values before the suspicion of infection or sepsis.Measurements and Main Results: Cohort 1 contained 5,460 patients (mortality rate, 14.0%; 95% confidence interval [CI], 13.1-15.0), among whom 78.3% had a qSOFA score less than or equal to 1 (mortality rate, 8.3%; 95% CI, 7.5-9.1). The sensitivity of a qSOFA score greater than or equal to 2 for predicting mortality was 53.9% and the 95% CI was 50.3 to 57.5. The sensitivity was higher for a qSOFA greater than or equal to 1 (84.9%; 95% CI, 82.1-87.3), a qSOFA score greater than or equal to 1 or lactate greater than 2 mmol/L (91.3%; 95% CI, 89.0-93.2), and systemic inflammatory response syndrome plus organ dysfunction (68.7%; 95% CI, 65.2-71.9). Cohort 2 contained 4,711 patients, among whom 62.3% had a qSOFA score less than or equal to 1 (mortality rate, 17.3%; 95% CI, 15.9-18.7), whereas in public hospitals the mortality rate was 39.3% (95% CI, 35.5-43.3).Conclusions: A qSOFA score greater than or equal to 2 has low sensitivity for predicting death in patients with suspected infection in a developing country. Using a qSOFA score greater than or equal to 2 as a screening tool for sepsis may miss patients who ultimately die. Using a qSOFA score greater than or equal to 1 or adding lactate to a qSOFA score greater than or equal to 1 may improve sensitivity.Clinical trial registered with www.clinicaltrials.gov (NCT03158493).

To the Editor: Cavalcanti et al (Nov 19 issue)(1) stated in the originally published Supplementary Appendix of their article (a corrected version is available at NEJM org) that the use of "hydroxychloroquine and macrolides rapidly became part of the routine care of patients with Covid-19 [coronavirus disease 2019] in Brazil" during their trial, such that, as they stated in the originally published version of their article, "enrollment of patients with no previous use of these medications was challenging "(2) Preenrollment use of these medications was not an exclusion criterion until a change in their trial protocol (available at NEJM org) was made 5

Bariatric surgery is an effective strategy for blood pressure (BP) reduction, but most of the evidence relies on office BP measurements. In this study, we evaluated the impact of bariatric surgery on 24-hour BP profile, BP variability, and resistant hypertension prevalence. This is a randomized trial including obese patients with grade 1 and 2 using at least 2 antihypertensive drugs at maximal doses or2 at moderate doses. Patients were allocated to either Roux-en-Y Gastric Bypass (RYGB) combined with medical therapy or medical therapy alone for 12 months. The primary outcome was the 24-hour BP profile and variability (average real variability of daytime and night time BP). We evaluated the nondipping status and prevalence of resistant hypertension as secondary end points. We included 100 patients (76% female, body mass index, 36.9±2.7 kg/m

The relative contributions of intraoperative and postoperative hypotension to perioperative morbidity remain unclear. We determined the association between hypotension and a composite of 30-day myocardial infarction and death over three periods: (1) intraoperative, (2) remaining day of surgery, and (3) during the initial four postoperative days.This was a substudy of POISE-2, a 10,010-patient factorial-randomized trial of aspirin and clonidine for prevention of myocardial infarction. Clinically important hypotension was defined as systolic blood pressure less than 90 mmHg requiring treatment. Minutes of hypotension was the exposure variable intraoperatively and for the remaining day of surgery, whereas hypotension status was treated as binary variable for postoperative days 1 to 4. We estimated the average relative effect of hypotension across components of the composite using a distinct effect generalized estimating model, adjusting for hypotension during earlier periods.Among 9,765 patients, 42% experienced hypotension, 590 (6.0%) had an infarction, and 116 (1.2%) died within 30 days of surgery. Intraoperatively, the estimated average relative effect across myocardial infarction and mortality was 1.08 (98.3% CI, 1.03, 1.12; P0.001) per 10-min increase in hypotension duration. For the remaining day of surgery, the odds ratio was 1.03 (98.3% CI, 1.01, 1.05; P0.001) per 10-min increase in hypotension duration. The average relative effect odds ratio was 2.83 (98.3% CI, 1.26, 6.35; P = 0.002) in patients with hypotension during the subsequent four days of hospitalization.Clinically important hypotension-a potentially modifiable exposure-was significantly associated with a composite of myocardial infarction and death during each of three perioperative periods, even after adjustment for previous hypotension.

The effectiveness and safety of balanced crystalloid fluids compared with saline (0.9% sodium chloride) as a fluid of choice in critically ill patients remain unclear. The effects of different fluid infusion rates on outcomes are also unknown.To test the hypothesis that a balanced crystalloid solution, compared with saline, decreases 90-day all-cause mortality among critically ill patients; and to test the hypothesis that slow, compared with rapid, infusion rate decreases 90-day mortality in this population of patients.The Balanced Solution versus Saline in Intensive Care Study (BaSICS) is a pragmatic, 2 ??2 factorial, randomised controlled trial. A total of 11 000 patients will be recruited from at least 100 Brazilian intensive care units. Patients will be randomised to receive Plasma-Lyte 148 or saline, and to rapid infusion (999 mL/h) or slow infusion (333 mL/h). Study fluids will be used for resuscitation episodes (at rapid or slow infusion rates), dilution of compatible medications and maintenance solutions. Patients, health care providers and investigators will be blinded to the solutions being tested. The rate of bolus infusion will not be blinded.The primary outcome is 90-day all-cause mortality. Secondary outcomes are: incidence of renal failure requiring renal replacement therapy within 90 days, incidence of acute kidney injury (Kidney Disease: Improving Global Outcomes stages 2 and 3), incidence of non-renal organ dysfunction assessed by Sepsis-related Organ Failure Assessment score at Days 3 and 7, and number of mechanical ventilationfree days within the first 28 days after randomisation.The BaSICS trial will provide robust evidence on whether a balanced crystalloid, compared with saline, improves important patient outcomes in critically ill patients. BaSICS will also provide relevant information on whether bolus infusion rate affects outcomes in this population.ClinicalTrials.gov NCT02875873.

The Checklist During Multidisciplinary Visits for Reduction of Mortality in Intensive Care Units (Checklist- ICU) trial is a pragmatic, two-arm, cluster-randomised trial involving 118 intensive care units in Brazil, with the primary objective of determining if a multifaceted qualityimprovement intervention with a daily checklist, definition of daily care goals during multidisciplinary daily rounds and clinician prompts can reduce inhospital mortality.To describe our trial statistical analysis plan (SAP).This is an ongoing trial conducted in two phases. In the preparatory observational phase, we collect three sets of baseline data: ICU characteristics; patient characteristics, processes of care and outcomes; and completed safety attitudes questionnaires (SAQs). In the randomised phase, ICUs are assigned to the experimental or control arms and we collect patient data and repeat the SAQ.Our SAP includes the prespecified model for the primary and secondary outcome analyses, which account for the cluster-randomised design and availability of baseline data. We also detail the multiple mediation models that we will use to assess our secondary hypothesis (that the effect of the intervention on inhospital mortality is mediated not only through care processes targeted by the checklist, but also through changes in safety culture). We describe our approach to sensitivity and subgroup analyses and missing data.We report our SAP before closing our study database and starting analysis. We anticipate that this should prevent analysis bias and enhance the utility of results.

This article reports the rationale for the Brazilian Cardioprotective Nutritional Program (BALANCE Program) Trial. This pragmatic, multicenter, nationwide, randomized, concealed, controlled trial was designed to investigate the effects of the BALANCE Program in reducing cardiovascular events. The BALANCE Program consists of a prescribed diet guided by nutritional content recommendations from Brazilian national guidelines using a unique nutritional education strategy, which includes suggestions of affordable foods. In addition, the Program focuses on intensive follow-up through one-on-one visits, group sessions, and phone calls. In this trial, participants 45 years or older with any evidence of established cardiovascular disease will be randomized to the BALANCE or control groups. Those in the BALANCE group will receive the afore mentioned program interventions, while controls will be given generic advice on how to follow a low-fat, low-energy, low-sodium, and low-cholesterol diet, with a view to achieving Brazilian nutritional guideline recommendations. The primary outcome is a composite of death (any cause), cardiac arrest, acute myocardial infarction, stroke, myocardial revascularization, amputation for peripheral arterial disease, or hospitalization for unstable angina. A total of 2468 patients will be enrolled in 34 sites and followed up for up to 48 months. If the BALANCE Program is found to decrease cardiovascular events and reduce risk factors, this may represent an advance in the care of patients with cardiovascular disease.

Context Studies have found that patients with acute coronary syndromes (ACS) often do not receive evidence-based therapies in community practice. This is particularly true in low- and middle-income countries. Objective To evaluate whether a multifaceted quality improvement (QI) intervention can improve the use of evidence-based therapies and reduce the incidence of major cardiovascular events among patients with ACS in a middle-income country. Design, Setting, and Participants The BRIDGE-ACS (Brazilian Intervention to Increase Evidence Usage in Acute Coronary Syndromes) trial, a cluster-randomized (concealed allocation) trial conducted among 34 clusters (public hospitals) in Brazil and enrolling a total of 1150 patients with ACS from March 15, 2011, through November 2, 2011, with follow-up through January 27, 2012. Intervention Multifaceted QI intervention including educational materials for clinicians, reminders, algorithms, and case manager training, vs routine practice (control). Main Outcome Measures Primary end point was the percentage of eligible patients who received all evidence-based therapies (aspirin, clopidogrel, anticoagulants, and statins) during the first 24 hours in patients without contraindications. Results Mean age of the patients enrolled was 62 (SD, 13) years; 68.6% were men, and 40% presented with ST-segment elevation myocardial infarction, 35.6% with non–ST-segment elevation myocardial infarction, and 23.6% with unstable angina. The randomized clusters included 79.5% teaching hospitals, all from major urban areas and 41.2% with 24-hour percutaneous coronary intervention capabilities. Among eligible patients (923/1150 [80.3%]), 67.9% in the intervention vs 49.5% in the control group received all eligible acute therapies (population average odds ratio [OR PA ], 2.64 [95% CI, 1.28-5.45]). Similarly, among eligible patients (801/1150 [69.7%]), those in the intervention group were more likely to receive all eligible acute and discharge medications (50.9% vs 31.9%; OR PA , , 2.49 [95% CI, 1.08-5.74]). Overall composite adherence scores were higher in the intervention clusters (89% vs 81.4%; mean difference, 8.6% [95% CI, 2.2%-15.0%]). In-hospital cardiovascular event rates were 5.5% in the intervention group vs 7.0% in the control group (OR PA , 0.72 [95% CI, 0.36-1.43]); 30-day all-cause mortality was 7.0% vs 8.4% (OR PA , 0.79 [95% CI, 0.46-1.34]). Conclusion Among patients with ACS treated in Brazil, a multifaceted educational intervention resulted in significant improvement in the use of evidence-based therapies. Trial Registration clinicaltrials.gov Identifier: NCT00958958