Apolipoprotein A1 Infusions and Cardiovascular Outcomes after Acute Myocardial Infarction.

BACKGROUND: Cardiovascular events frequently recur after acute myocardial infarction, and low cholesterol efflux - a process mediated by apolipoprotein A1, which is the main protein in high-density lipoprotein - has been associated with an increased risk of cardiovascular events. CSL112 is human apolipoprotein A1 derived from plasma that increases cholesterol efflux capacity. Whether infusions of CSL112 can reduce the risk of recurrent cardiovascular events after acute myocardial infarction is unclear. METHODS: We conducted an international, double-blind, placebo-controlled trial involving patients with acute myocardial infarction, multivessel coronary artery disease, and additional cardiovascular risk factors. Patients were randomly assigned to receive either four weekly infusions of 6 g of CSL112 or matching placebo, with the first infusion administered within 5 days after the first medical contact for the acute myocardial infarction. The primary end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes from randomization through 90 days of follow-up. RESULTS: A total of 18,219 patients were included in the trial (9112 in the CSL112 group and 9107 in the placebo group). There was no significant difference between the groups in the risk of a primary end-point event at 90 days of follow-up (439 patients [4.8%] in the CSL112 group vs. 472 patients [5.2%] in the placebo group; hazard ratio, 0.93; 95% confidence interval [CI], 0.81 to 1.05; P = 0.24), at 180 days of follow-up (622 patients [6.9%] vs. 683 patients [7.6%]; hazard ratio, 0.91; 95% CI, 0.81 to 1.01), or at 365 days of follow-up (885 patients [9.8%] vs. 944 patients [10.5%]; hazard ratio, 0.93; 95% CI, 0.85 to 1.02). The percentage of patients with adverse events was similar in the two groups; a higher number of hypersensitivity events was reported in the CSL112 group. CONCLUSIONS: Among patients with acute myocardial infarction, multivessel coronary artery disease, and additional cardiovascular risk factors, four weekly infusions of CSL112 did not result in a lower risk of myocardial infarction, stroke, or death from cardiovascular causes than placebo through 90 days. (Funded by CSL Behring; AEGIS-II ClinicalTrials.gov number, NCT03473223.).

Effect of Reconstituted Human Apolipoprotein A-I on Recurrent Ischemic Events in Survivors of Acute MI.

BACKGROUND: The AEGIS-II trial hypothesized that CSL112, an intravenous formulation of human apoA-I, would lower the risk of plaque disruption, decreasing the risk of recurrent events such as myocardial infarction (MI) among high-risk patients with MI. OBJECTIVES: This exploratory analysis evaluates the effect of CSL112 therapy on the incidence of cardiovascular (CV) death and recurrent MI. METHODS: The AEGIS-II trial was an international, multicenter, randomized, double-blind, placebo-controlled trial that randomized 18,219 high-risk acute MI patients to 4 weekly infusions of apoA-I (6 g CSL112) or placebo. RESULTS: The incidence of the composite of CV death and type 1 MI was 11% to 16% lower in the CSL112 group over the study period (HR: 0.84; 95% CI: 0.7-1.0; P = 0.056 at day 90; HR: 0.86; 95% CI: 0.74-0.99; P = 0.048 at day 180; and HR: 0.89; 95% CI: 0.79-1.01; P = 0.07 at day 365). Similarly, the incidence of CV death or any MI was numerically lower in CSL112-treated patients throughout the follow-up period (HR: 0.92; 95% CI: 0.80-1.05 at day 90, HR: 0.89; 95% CI: 0.79-0.996 at day 180, HR: 0.91; 95% CI: 0.83-1.01 at day 365). The effect of CSL112 treatment on MI was predominantly observed for type 1 MI and type 4b (MI due to stent thrombosis). CONCLUSIONS: Although CSL112 did not significantly reduce the occurrence of the primary study endpoints, patients treated with CSL112 infusions had numerically lower rates of CV death and MI, type-1 MI, and stent thrombosis-related MI compared with placebo. These findings could suggest a role of apoA-I in reducing subsequent plaque disruption events via enhanced cholesterol efflux. Further prospective data would be needed to confirm these observations.

Heparin Dose Intensity and Organ Support-Free Days in Patients Hospitalized for COVID-19.

Background: Clinical trials suggest that therapeutic-dose heparin may prevent critical illness and vascular complications due to COVID-19, but knowledge gaps exist regarding the efficacy of therapeutic heparin including its comparative effect relative to intermediate-dose anticoagulation. Objectives: The authors performed 2 complementary secondary analyses of a completed randomized clinical trial: 1) a prespecified per-protocol analysis; and 2) an exploratory dose-based analysis to compare the effect of therapeutic-dose heparin with low- and intermediate-dose heparin. Methods: Patients who received initial anticoagulation dosed consistently with randomization were included. The primary outcome was organ support-free days (OSFDs), a combination of in-hospital death and days free of organ support through day 21. Results: Among 2,860 participants, 1,761 (92.8%) noncritically ill and 857 (89.1%) critically ill patients were treated per-protocol. Among noncritically ill per-protocol patients, the posterior probability that therapeutic-dose heparin improved OSFDs as compared with usual care was 99.3% (median adjusted OR: 1.36; 95% credible interval [CrI]: 1.07-1.74). Therapeutic heparin had a high posterior probability of efficacy relative to both low- (94.6%; adjusted OR: 1.26; 95% CrI: 0.95-1.64) and intermediate- (99.8%; adjusted OR: 1.80; 95% CrI: 1.22-2.62) dose thromboprophylaxis. Among critically ill per-protocol patients, the posterior probability that therapeutic heparin improved outcomes was low. Conclusions: Among noncritically ill patients hospitalized for COVID-19 who were randomized to and initially received therapeutic-dose anticoagulation, heparin, compared with usual care, was associated with improved OSFDs, a combination of in-hospital death and days free of organ support. Therapeutic heparin appeared superior to both low- and intermediate-dose thromboprophylaxis.

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)

Factors associated with actively working in the very long-term following acute coronary syndrome

OBJECTIVES: Returning to work after an episode of acute coronary syndrome (ACS) is challenging for many patients, and has both personal and social impacts. There are limited data regarding the working status in the very long-term after ACS. METHODS: We retrospectively analyzed 1,632 patients who were working prior to hospitalization for ACS in a quaternary hospital and were followed-up for up to 17 years. Adjusted models were developed to analyze the variables independently associated with actively working at the last contact, and a prognostic predictive index for not working at follow-up was developed. RESULTS: The following variables were significantly and independently associated with actively working at the last contact: age>median (hazard-ratio [HR], 0.76, p<0.001); male sex (HR, 1.52, p<0.001); government health insurance (HR, 1.36, p<0.001); history of angina (HR, 0.69, p<0.001) or myocardial infarction (MI) (HR, 0.76, p=0.005); smoking (HR, 0.81, p=0.015); ST-elevation MI (HR, 0.81, p=0.021); anterior-wall MI (HR, 0.75, p=0.001); non-primary percutaneous coronary intervention (PCI) (HR, 0.77, p=0.002); fibrinolysis (HR, 0.61, p<0.001); cardiogenic shock (HR, 0.60, p=0.023); statin (HR, 3.01, p<0.001), beta-blocker (HR, 1.26, p=0.020), angiotensin-converting enzyme (ACE) inhibitor/angiotensin II receptor blocker (ARB) (HR, 1.37, p=0.001) at hospital discharge; and MI at follow-up (HR, 0.72, p=0.001). The probability of not working at the last contact ranged from 24.2% for patients with no variables, up to 80% for patients with six or more variables. CONCLUSIONS: In patients discharged after ACS, prior and in-hospital clinical variables, as well as the quality of care at discharge, have a great impact on the long-term probability of actively working.

Cardiomiopatia de takotsubo como causa de disfunção ventricular transitória / Takotsubo cardiomyopathy causing transitory ventricular dysfunction

Relato do caso de mulher de 74 anos, com hipertensão arterial sistêmica e insuficiência vascular periférica, que apresentou sintomas de síndrome coronariana aguda. A angiografia coronariana demonstrou artérias sem obstruções significativas. A ventriculografia e a ecocardiografia demonstraram acinesia dos segmentos médios e apicais, e hipercinesia dos segmentos basais do ventrículo esquerdo. A paciente evoluiu com recuperação completa da função global e motilidade segmentar em ecocardiografia realizada duas semanas após o início dos sintomas. Esse padrão incomum e reversível de disfunção sistólica e comprometimento segmentar dando ao ventrículo esquerdo forma semelhante a um takotsubo é hoje conhecido como cardiomiopatia do estresse.

This is the report of a 74-year-old female patient with a history of systemic hypertension and peripheral vascular disease who presented acute coronary syndrome symptoms. Coronary angiography showed coronary arteries with no significant obstructions. Ventriculography and echocardiography showed akinesia in mid and apical segments; and hyperkinesia of left ventricle basal segments. Two weeks after the onset of symptoms, a new echocardiogram demonstrated normal global and regional systolic function. The uncommon, reversible pattern for systolic dysfunction and segmental compromising that gives left ventricle a takostubo-like shape is known today as stress cardiomyopathy.

Vasoespasmo coronariano induzido pela ecocardiografia sob estresse pela dobutamina-atropina / Coronary spasm induced by dobutamine-atropine stress echocardiography

Relatamos caso de mulher de 45 anos de idade, com antecedentes de hipertensão arterial sistêmica e tabagismo, submetida a ecocardiografia sob estresse pela dobutamina-atropina para investigação de doença arterial coronariana. No pico do estresse, a paciente apresentou dor precordial súbita e de forte intensidade. O eletrocardiograma de doze derivações revelou elevação do segmento ST nas derivações DII, DIII, aVF, V5 e V6 e depressão do segmento ST nas derivações DI, aVL, V2 e V3. Pela monitoração das imagens ecocardiográficas foi observado aparecimento de discinesia do septo inferior e acinesia da parede inferior do ventrículo esquerdo. O exame foi interrompido imediatamente, a paciente foi medicada e evoluiu com melhora da dor precordial e das alterações de motilidade segmentar. A angiografia coronariana revelou lesões coronarianas irregulares com menos de 50 por cento de obstrução do diâmetro luminal. Trata-se de um caso de vasoespasmo coronariano induzido por estimulação alfa-adrenérgica durante a ecocardiografia sob estresse pela dobutamina-atropina.

This is the report on a 45-year-old female, with a history of systemic arterial hypertension and cigarette smoking, submitted to dobutamine-atropine stress echocardiography for the investigation of coronary artery disease. At stress peak, the patient reported sudden, highly intense precordial pain. The 12-lead electrocardiogram showed ST segment elevation in DII, DIII, aVF, V5 and V6, and depression in DI, aVL, V2 and V3. Echocardiographic imaging monitoring showed dyskinesia of inferior septum and akinesia of inferior wall. The test was interrupted immediately. The patient was medicated and improved her precordial pain condition as well as wall motion abnormalities. Coronary angiography showed irregular coronary lesions with <50 percent luminal diameter obstruction. It is a case of coronary spasm induced by alpha-adrenergic stimulation during dobutamine-atropine stress echocardiography.

Programa de Avaliaçäo Nacional do Conhecimento sobre Prevençäo da Aterosclerose (PANDORA): um questionário entre cardiologistas brasileiros sobre reduçäo do colesterol / PANDORA: survey of Brazilian cardiologists about cholesterol reduction

OBJECTIVE: To report about a group of physicians' understanding of the recommendations of the II Brazilian Guidelines Conference on Dyslipidemias, and about the state of the art of primary and secondary prevention of atherosclerosis. METHODS: Through the use of a questionnaire on dyslipidemia, atherosclerosis prevention, and recommendations for lipid targets established by the II Brazilian Guidelines Conference on Dyslipidemias, 746 physicians, 98 percent cardiologists, were evaluated. RESULTS:Eighty-seven percent of the respondents stated that the treatment of dyslipidemia changes the natural history of coronary disease. Although most of the participants followed the total cholesterol recommendations (<200mg/dL for atherosclerosis prevention), only 55.8 percent would adopt the target of LDL-C <100 mg/dL for secondary prevention. Between 30.5 and 36.7 percent answered, in different questions, that the recommended level for HDL-C should be <35mg/dL. Only 32.7 percent would treat their patients indefinitely with lipid- lowering drugs. If the drug treatment did not reach the proposed target, only 35.5 percent would increase the dosage, and 29.4 percent would change the medication. Participants did not know the targets proposed for diabetics. CONCLUSION: Although the participating physicians valued the role played by lipids in the prevention of atherosclerosis, serious deficiencies exist in their knowledge of the recommendations given during the II Brazilian Guidelines Conference on Dyslipidemias