Association between Statin Therapy and Lower Incidence of Hyperglycemia in Patients Hospitalized with Acute Coronary Syndromes. / Associação entre Terapia com Estatinas e Menor Incidência de Hiperglicemia em Pacientes Internados com Síndromes Coronarianas Agudas.

BACKGROUND: Increased risk of new-onset diabetes with statins challenges the long-term safety of this drug class. However, few reports have analyzed this issue during acute coronary syndromes (ACS). OBJECTIVE: To explore the association between early initiation of statin therapy and blood glucose levels in patients admitted with ACS. METHODS: This was a retrospective analysis of patients hospitalized with ACS. Statin-naïve patients were included and divided according to their use or not of statins within the first 24 hours of hospitalization. The primary endpoint was incidence of in-hospital hyperglycemia (defined as peak blood glucose > 200 mg/dL). Multivariable linear and logistic regression models were used to adjust for confounders, and a propensity-score matching model was developed to further compare both groups of interest. A p-value of less than 0.05 was considered statistically significant. RESULTS: A total of 2,357 patients were included, 1,704 of them allocated in the statin group and 653 in the non-statin group. After adjustments, statin use in the first 24 hours was associated with a lower incidence of in-hospital hyperglycemia (adjusted OR=0.61, 95% CI 0.46-0.80; p < 0.001) and lower need for insulin therapy (adjusted OR = 0.56, 95% CI 0.41-0.76; p < 0.001). These associations remained similar in the propensity-score matching models, as well as after several sensitivity analyses, such as after excluding patients who developed cardiogenic shock, severe infection or who died during index-hospitalization. CONCLUSIONS: Among statin-naïve patients admitted with ACS, early statin therapy was independently associated with lower incidence of in-hospital hyperglycemia. (Arq Bras Cardiol. 2021; 116(2):285-294).

FUNDAMENTO: O maior risco de se desenvolver diabetes com o uso de estatinas é um desafio para a segurança do uso dessa classe de medicamentos em longo prazo. No entanto, poucos estudos analisaram essa questão durante síndromes coronarianas agudas (SCA). OBJETIVOS: Investigar a associação entre início precoce da terapia com estatina e níveis de glicemia em pacientes admitidos com SCA. MÉTODOS: Este foi um estudo retrospectivo de pacientes hospitalizados por SCA. Pacientes que nunca haviam usado estatinas foram incluídos e divididos segundo uso ou não de estatina nas primeiras 24 horas de internação. O desfecho primário foi a incidência de hiperglicemia na internação (definida como pico de glicemia > 200mg/dL). Modelos de regressão logística e modelos lineares multivariados foram usados para ajuste quanto a fatores de confusão e um modelo de pareamento por escore de propensão foi desenvolvido para comparações entre os dois grupos de interesses. Um valor de p menor que 0,05 foi considerado estatisticamente significativo. RESULTADOS: Um total de 2357 pacientes foram incluídos, 1704 deles alocados no grupo que receberam estatinas e 653 no grupo que não receberam estatinas nas primeiras 24 horas de internação. Após os ajustes, uso de estatina nas primeiras 24 horas foi associado com uma menor incidência de hiperglicemia durante a internação (OR ajustado = 0,61, IC95% 0,46-0,80; p < 0,001) e menor necessidade de uso de insulina (OR ajustado = 0,56, IC 95% 0,41-0,76; p < 0,001). Essas associações mantiveram-se similares nos modelos de pareamento por escore de propensão, bem como após análises de sensibilidade, como exclusão de pacientes que desenvolveram choque cardiogênico, infecção grave ou pacientes que foram a óbito durante a internação hospitalar. CONCLUSÕES: Entre os pacientes internados com SCA que não receberam estatinas previamente, a terapia precoce com estatina associou-se independentemente com menor incidência de hiperglicemia durante a internação. (Arq Bras Cardiol. 2021; 116(2):285-294).

Associação entre Terapia com Estatinas e Menor Incidência de Hiperglicemia em Pacientes Internados com Síndromes Coronarianas Agudas / Association between Statin Therapy and Lower Incidence of Hyperglycemia in Patients Hospitalized with Acute Coronary Syndromes

Resumo Fundamento O maior risco de se desenvolver diabetes com o uso de estatinas é um desafio para a segurança do uso dessa classe de medicamentos em longo prazo. No entanto, poucos estudos analisaram essa questão durante síndromes coronarianas agudas (SCA). Objetivos Investigar a associação entre início precoce da terapia com estatina e níveis de glicemia em pacientes admitidos com SCA. Métodos Este foi um estudo retrospectivo de pacientes hospitalizados por SCA. Pacientes que nunca haviam usado estatinas foram incluídos e divididos segundo uso ou não de estatina nas primeiras 24 horas de internação. O desfecho primário foi a incidência de hiperglicemia na internação (definida como pico de glicemia > 200mg/dL). Modelos de regressão logística e modelos lineares multivariados foram usados para ajuste quanto a fatores de confusão e um modelo de pareamento por escore de propensão foi desenvolvido para comparações entre os dois grupos de interesses. Um valor de p menor que 0,05 foi considerado estatisticamente significativo. Resultados Um total de 2357 pacientes foram incluídos, 1704 deles alocados no grupo que receberam estatinas e 653 no grupo que não receberam estatinas nas primeiras 24 horas de internação. Após os ajustes, uso de estatina nas primeiras 24 horas foi associado com uma menor incidência de hiperglicemia durante a internação (OR ajustado = 0,61, IC95% 0,46-0,80; p < 0,001) e menor necessidade de uso de insulina (OR ajustado = 0,56, IC 95% 0,41-0,76; p < 0,001). Essas associações mantiveram-se similares nos modelos de pareamento por escore de propensão, bem como após análises de sensibilidade, como exclusão de pacientes que desenvolveram choque cardiogênico, infecção grave ou pacientes que foram a óbito durante a internação hospitalar. Conclusões Entre os pacientes internados com SCA que não receberam estatinas previamente, a terapia precoce com estatina associou-se independentemente com menor incidência de hiperglicemia durante a internação. (Arq Bras Cardiol. 2021; 116(2):285-294)

Abstract Background Increased risk of new-onset diabetes with statins challenges the long-term safety of this drug class. However, few reports have analyzed this issue during acute coronary syndromes (ACS). Objective To explore the association between early initiation of statin therapy and blood glucose levels in patients admitted with ACS. Methods This was a retrospective analysis of patients hospitalized with ACS. Statin-naïve patients were included and divided according to their use or not of statins within the first 24 hours of hospitalization. The primary endpoint was incidence of in-hospital hyperglycemia (defined as peak blood glucose > 200 mg/dL). Multivariable linear and logistic regression models were used to adjust for confounders, and a propensity-score matching model was developed to further compare both groups of interest. A p-value of less than 0.05 was considered statistically significant. Results A total of 2,357 patients were included, 1,704 of them allocated in the statin group and 653 in the non-statin group. After adjustments, statin use in the first 24 hours was associated with a lower incidence of in-hospital hyperglycemia (adjusted OR=0.61, 95% CI 0.46-0.80; p < 0.001) and lower need for insulin therapy (adjusted OR = 0.56, 95% CI 0.41-0.76; p < 0.001). These associations remained similar in the propensity-score matching models, as well as after several sensitivity analyses, such as after excluding patients who developed cardiogenic shock, severe infection or who died during index-hospitalization. Conclusions Among statin-naïve patients admitted with ACS, early statin therapy was independently associated with lower incidence of in-hospital hyperglycemia. (Arq Bras Cardiol. 2021; 116(2):285-294)

Performance of acute coronary syndrome approaches in Brazil: a report from the BRACE (Brazilian Registry in Acute Coronary SyndromEs).

AIMS: Diagnostic and therapeutic tools have a significant impact on morbidity and mortality associated with acute coronary syndromes (ACS). Data about ACS performance measures are scarce in Brazil, and improving its collection is an objective of the Brazilian Registry in Acute Coronary syndromEs (BRACE). METHODS AND RESULTS: The BRACE is a cross-sectional, observational epidemiological registry of ACS patients. Stratified 'cluster sampling' methodology was adopted to obtain a representative picture of ACS. A performance score (PS) varying from 0 to 100 was developed to compare studied parameters. Performance measures alone and the PS were compared between institutions, and the relationship between the PS and outcomes was evaluated. A total of 1150 patients, median age 63 years, 64% male, from 72 hospitals were included in the registry. The mean PS for the overall population was 65.9% ± 20.1%. Teaching institutions had a significantly higher PS (71.4% ± 16.9%) compared with non-teaching hospitals (63.4% ± 21%; P < 0.001). Overall in-hospital mortality was 5.2%, and the variables that correlated independently with in-hospital mortality included: PS-per point increase (OR = 0.97, 95% CI 0.95-0.98, P < 0.001), age-per year (OR = 1.06, 95% CI 1.03-1.09, P < 0.001), chronic kidney disease (OR = 3.12, 95% CI 1.08-9.00, P = 0.036), and prior angioplasty (OR = 0.25, 95% CI 0.07-0.84, P = 0.025). CONCLUSIONS: In BRACE, the adoption of evidence-based therapies for ACS, as measured by the performance score, was independently associated with lower in-hospital mortality. The use of diagnostic tools and therapeutic approaches for the management of ACS is less than ideal in Brazil, with high variability especially among different regions of the country.

Cardiology Training in Brazil and Developed Countries: Some Ideas for Improvement.

Huge variations exist in cardiology training programs across the world. In developing (middle-income) countries, such as Brazil, to find the right balance between training improvements and social and economic conditions of the country may be a difficult task. Adding more training years or different mandatory rotations, for instance, may be costly and not have an immediate direct impact on enhancing patient care or public health. In this text, we compare the Brazilian cardiology training system with other proposals implemented in developed countries from North America and Europe, aiming to point out issues worth of future discussion. Factors such as training rotations and competencies, and program duration and distribution across the countries are presented. The number of first year cardiology trainees per inhabitants is similar between Brazil and the United States (0.24 medical residents/100,000 inhabitants in Brazil and 0.26 medical residents/100,000 inhabitants in the USA). These numbers should be analyzed considering the inequality in training program distribution across Brazil, since most centers are located in the Southeast and South regions. Having more residency programs in distant areas could improve cardiovascular care in these areas. Duration of cardiology Residency Training is shorter in Brazil (two years) in comparison with developed countries (> 3 years). Brazilian residency programs give less emphasis to scientific research and diagnostic methods. Unifying minimum training requirements across the globe would facilitate the development of international learning opportunities and even professional exchange around the world.

Cardiology training in Brazil and developed countries: some ideas for improvement / Residência em cardiologia no Brasil e em países desenvolvidos: ideias para melhoria

ABSTRACT: Huge variations exist in cardiology training programs across the world. In developing (middle-income) countries, such as Brazil, to find the right balance between training improvements and social and economic conditions of the country may be a difficult task. Adding more training years or different mandatory rotations, for instance, may be costly and not have an immediate direct impact on enhancing patient care or public health. In this text, we compare the Brazilian cardiology training system with other proposals implemented in developed countries from North America and Europe, aiming to point out issues worth of future discussion. Factors such as training rotations and competencies, and program duration and distribution across the countries are presented. The number of first year cardiology trainees per inhabitants is similar between Brazil and the United States (0.24 medical residents/100,000 inhabitants in Brazil and 0.26 medical residents/100,000 inhabitants in the USA). These numbers should be analyzed considering the inequality in training program distribution across Brazil, since most centers are located in the Southeast and South regions. Having more residency programs in distant areas could improve cardiovascular care in these areas. Duration of cardiology Residency Training is shorter in Brazil (two years) in comparison with developed countries (> 3 years). Brazilian residency programs give less emphasis to scientific research and diagnostic methods. Unifying minimum training requirements across the globe would facilitate the development of international learning opportunities and even professional exchange around the world.

RESUMO: Existe enorme variação nos programas de residência em cardiologia no mundo. Em países em desenvolvimento, tal como o Brasil, encontrar o equilíbrio correto entre melhorias nos programas de residência e condições socioeconômicas do país pode ser uma tarefa difícil. Aumentar a duração dos programas ou o número de estágios obrigatórios, por exemplo, pode ter um custo elevado e não ter um impacto imediato na melhoria do cuidado do paciente ou na saúde pública. Neste texto, comparamos o sistema de residência em cardiologia brasileiro com outras propostas implementadas em países desenvolvidos da América do Norte e Europa, com objetivo de indicar questões para discussões futuras. Apresentamos fatores como rodízios por estágios e competências, duração e distribuição dos programas pelos países. O número de alunos no primeiro ano de Residência em cardiologia por número de habitantes é similar entre o Brasil e os Estados Unidos (0,24 médicos residentes/100 mil habitantes no Brasil e 0,26 médicos residentes/100 mil habitantes nos EUA). Esses números devem ser analisados considerando a desigualdade na distribuição dos programas pelo país, uma vez que a maioria dos centros localiza-se nas regiões sul e sudeste do país. A existência de mais programas de residência em áreas distantes melhoraria o cuidado cardiovascular nessas áreas. O período de treinamento é menor no Brasil (dois anos) em comparação a países desenvolvidos (>3 anos). Os programas de residência no Brasil dão menos ênfase em pesquisa científica e métodos diagnósticos. O estabelecimento de exigências mínimas que sejam padronizadas a todos os países facilitaria o desenvolvimento de oportunidades de aprendizagem e mesmo o intercâmbio de profissionais pelo mundo.

Is There Safety in the Use of Clopidogrel Loading Dose in Patients Over 75 Years of Age with Acute Coronary Syndrome?

There is limited evidence in the literature regarding the administration of clopidogrel to acute coronary syndrome (ACS) in patients over 75 years of age. Most studies excluded this age group, making the subject controversial due to the increased risk of bleeding in this population. Objective: This is a retrospective, unicentric, and observational study aimed at assessing whether the administration of clopidogrel loading dose increases bleeding rates in patients over 75 years of age. Methods: Patients were divided into two groups: group I: 75 mg of clopidogrel; group II: 300-to 600-mg loading dose of clopidogrel. A total of 174 patients (129 in group I and 45 in group II) were included between May 2010 and May 2015. Statistical analysis: The primary outcome was bleeding (major and/or minor). The secondary outcome was combined events (cardiogenic shock, reinfarction, death, stroke and bleeding). The comparison between groups was performed through Q-square and T-test. The multivariate analysis was performed by logistic regression, being considered significant p < 0.05. Results: Comparisons between groups I and II showed differences in the prevalence of diabetes (46.5% vs. 24.4%, p = 0.01), arterial hypertension (90.7% vs. 75, p = 0.01), dyslipidemia (62% vs. 42.2%, p = 0.021), ST segment elevation (11.6% vs. 26.6%, p = 0.016) and coronary intervention percutaneous (16.5% vs. 62.2%, p < 0.0001), respectively. In the multivariate analysis, significant differences were observed between groups I and II in relation to the occurrence of bleeding (8.5% vs. 20%, OR = 0.173, 95% CI: 0.049 - 0.614, p = 0.007). Conclusion: A loading dose of 300 mg or more of clopidogrel

SYNTAX Score in Patients With Diabetes Undergoing Coronary Revascularization in the FREEDOM Trial.

BACKGROUND: Diabetes mellitus (DM) is associated with complex coronary artery disease (CAD), which in turn results in increased morbidity and mortality from cardiovascular disease. OBJECTIVES: This study sought to evaluate the utility of SYNTAX score (SS) for predicting future cardiovascular events in patients with DM and complex CAD undergoing either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI). METHODS: The FREEDOM (Future REvascularization Evaluation in patients with Diabetes mellitus: Optimal management of Multivessel disease) trial randomized patients with DM and multivessel CAD to undergo either PCI with drug-eluting stents or CABG. The SS was calculated retrospectively by a core laboratory. The endpoint of hard cardiovascular events (HCE) was a composite of death from any cause, nonfatal myocardial infarction, and nonfatal stroke, while the endpoint of major adverse cardiac and cerebrovascular events (MACCE) was a composite of HCE and repeat revascularization. RESULTS: A total of 1,900 patients were randomized to PCI (n = 953) or CABG (n = 947). The SS was considered an independent predictor of 5-year MACCE (hazard ratio per unit of SS: 1.02; 95% confidence interval: 1.00 to 1.03; p = 0.014) and HCE (hazard ratio per unit of SS: 1.03; 95% confidence interval: 1.01 to 1.04; p = 0.002) in the PCI cohort, but not in the CABG group. There was a higher incidence of MACCE in PCI patients with low, intermediate, and high SS compared with those who underwent CABG (36.6% vs. 25.9%, p = 0.02; 43.9% vs. 26.8%, p < 0.001; 48.7% vs. 29.7%, p = 0.003, respectively). CONCLUSIONS: In DM patients with multivessel CAD, the complexity of CAD evaluated by the SS is an independent risk factor for MACCE and HCE only in patients undergoing PCI. The SS should not be utilized to guide the choice of coronary revascularization in patients with DM and multivessel CAD. (Comparison of Two Treatments for Multivessel Coronary Artery Disease in Individuals With Diabetes [FREEDOM]; NCT00086450).

Cost-effectiveness of on-pump and off-pump coronary artery bypass grafting for patients with coronary artery disease: Results from the MASS III trial.

BACKGROUND: Recent trials have reported similar clinical outcomes between on-pump and off-pump coronary artery bypass graft (CABG). However, long-term cost-effectiveness of these strategies is unknown. METHODS: A prespecified economic study was performed based on the MASS III trial. Costs were estimated for all patients based on observed healthcare resource usage over a 5-year follow-up. Health state utilities were evaluated with the SF-6D questionnaire. Cost-effectiveness was assessed as cost per quality-adjusted life-year (QALY) gained using a Markov model. Probabilistic sensitivity analysis with the Monte-Carlo simulation and cost-effectiveness acceptability curve were used to address uncertainty. RESULTS: Quality of life improved significantly in both groups during follow-up compared with baseline. At 5 years, when comparing on-pump and off-pump CABG groups, no differences were found in cumulative life-years (4.851 and 4.766 years, P = .319) and QALY gained (4.150 and 4.105 QALYs, P = .332). Mean cost in US dollars per patient during the trial did not differ significantly between the on-pump and off-pump groups ($5890.29 and $5674.75, respectively, P = .409). Over a lifetime horizon, the incremental cost-effectiveness ratio of on-pump versus off-pump CABG was $12,576 per QALY gained, which is above the suggested cost-effectiveness threshold range (from $3210 to 10,122). In the sensitivity analysis, the probability that on-pump CABG is cost-effective compared to off-pump surgery for a willingness-to-pay threshold of $3212 per QALY gained was <1%. For the $10,122 per QALY threshold, the same probability was 35%. CONCLUSION: This decision-analytic model suggests that on-pump CABG is not cost-effective when compared to off-pump CABG from a public health system perspective.

Diabetes and multivessel disease: coronary artery bypass grafting remains king.

PURPOSE OF REVIEW: Review the recently published scientific evidence to support the decision-making process of revascularization strategy in patients with diabetes mellitus (DM) and multivessel coronary artery disease (MVD). RECENT FINDINGS: Recently published observational analyses have proven the superiority of coronary artery bypass grafting (CABG) in patients presenting with other comorbidities together with DM, such as renal disease or heart failure. SUMMARY: Significant challenges and controversies surrounded the choice of the appropriate revascularization method in patients with DM and MVD over the last decades. FREEDOM trial was the first adequately powered randomized study to directly compare percutaneous coronary intervention (PCI) versus CABG in the DM population, showing the superiority of CABG in the long-term follow-up. Subsequently, other studies confirmed that CABG is also preferable over PCI in diabetic patients with particular comorbidities, such as renal failure and left ventricular dysfunction, and also in patients with type 1 DM and in the setting of an early acute coronary syndrome. Finally, in 2018, an individual level data meta-analysis reported an expressive reduction in all-cause mortality when comparing CABG versus PCI in patients with DM and MVD enrolled in the most recent clinical trials (hazard ratio 1.44, 95% confidence interval 1.20-1.74, P = 0.0001).