The Attitudes of Physicians Toward Guideline Recommendations for the Management of Dyslipidemia in Clinical Practice - The VIPFARMA ISCP Project.

The aim of this study was to explore the different attitudes of physicians regarding international recommendations for the management of dyslipidemia in routine medical practice. Seven clusters of questions were designed to characterize the surveyed population. Eight hundred ninety-eight physicians answered the survey, 68.3% cardiologists and 40.0% had specialties related to cardiovascular prevention. 29.6% of physicians supported LDL goals above 70 mg/dL in secondary prevention. Acceptance of values lower than 70 mg/dL was associated with greater levels of continuing education (OR 0.64, 95% CI 0.45-0.91; P = 0.014), specialization in preventive cardiology (OR 0.49, 95% CI 0.28-0.88; P = 0.017) or diabetology (OR 0.48, 95% CI 0.24-0.98; P = 0.043). A less aggressive attitude toward the achievement of guideline goals were observed in physicians who considered LDL values higher than 70 mg/dL as the goal in secondary prevention. One-third of physicians in the survey do not follow goals recommended by international guidelines.

Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk.

BACKGROUND: High triglyceride levels are associated with increased cardiovascular risk, but whether reductions in these levels would lower the incidence of cardiovascular events is uncertain. Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, reduces triglyceride levels and improves other lipid levels. METHODS: In a multinational, double-blind, randomized, controlled trial, we assigned patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia (triglyceride level, 200 to 499 mg per deciliter), and high-density lipoprotein (HDL) cholesterol levels of 40 mg per deciliter or lower to receive pemafibrate (0.2-mg tablets twice daily) or matching placebo. Eligible patients were receiving guideline-directed lipid-lowering therapy or could not receive statin therapy without adverse effects and had low-density lipoprotein (LDL) cholesterol levels of 100 mg per deciliter or lower. The primary efficacy end point was a composite of nonfatal myocardial infarction, ischemic stroke, coronary revascularization, or death from cardiovascular causes. RESULTS: Among 10,497 patients (66.9% with previous cardiovascular disease), the median baseline fasting triglyceride level was 271 mg per deciliter, HDL cholesterol level 33 mg per deciliter, and LDL cholesterol level 78 mg per deciliter. The median follow-up was 3.4 years. As compared with placebo, the effects of pemafibrate on lipid levels at 4 months were -26.2% for triglycerides, -25.8% for very-low-density lipoprotein (VLDL) cholesterol, -25.6% for remnant cholesterol (cholesterol transported in triglyceride-rich lipoproteins after lipolysis and lipoprotein remodeling), -27.6% for apolipoprotein C-III, and 4.8% for apolipoprotein B. A primary end-point event occurred in 572 patients in the pemafibrate group and in 560 of those in the placebo group (hazard ratio, 1.03; 95% confidence interval, 0.91 to 1.15), with no apparent effect modification in any prespecified subgroup. The overall incidence of serious adverse events did not differ significantly between the groups, but pemafibrate was associated with a higher incidence of adverse renal events and venous thromboembolism and a lower incidence of nonalcoholic fatty liver disease. CONCLUSIONS: Among patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia, and low HDL and LDL cholesterol levels, the incidence of cardiovascular events was not lower among those who received pemafibrate than among those who received placebo, although pemafibrate lowered triglyceride, VLDL cholesterol, remnant cholesterol, and apolipoprotein C-III levels. (Funded by the Kowa Research Institute; PROMINENT ClinicalTrials.gov number, NCT03071692.).

Latin American Consensus on management of residual cardiometabolic risk. A consensus paper prepared by the Latin American Academy for the Study of Lipids and Cardiometabolic Risk (ALALIP) endorsed by the Inter-American Society of Cardiology (IASC), the International Atherosclerosis Society (IAS), and the Pan-American College of Endothelium (PACE).

BACKGROUND: Hypertension, hyperglycemia, dyslipidemia, overweight, obesity, and tobacco (smoking, chewing, and vaping), together with a pro-inflammatory and procoagulant state, are the main risk factors related to atherosclerotic cardiovascular disease. OBJECTIVE AND METHODS: A group of experts from the Americas, based on their clinical expertise in cardiology, cardiovascular prevention, and cardiometabolic (CM) diseases, joined together to develop these practical recommendations for the optimal evaluation and treatment of residual CM risk factors in Latin America, using a modified Delphi methodology (details in electronic TSI) to generate a comprehensive CM risk reduction guideline, and through personalized medicine and patient-centered decision, considering the cost-benefit ratio The process was well defined to avoid conflicts of interest that could bias the discussion and recommendations. RESULTS: Residual risk reduction should consider therapeutic options adapted to specific patient needs, based on five treatment objectives: triglyceride-rich lipoproteins, inflammation, impaired glucose metabolism, high blood pressure, and prothrombotic status. Comprehensive control of all CM risk factors should be a priority to deal with this important public health problem and prevent premature deaths. The recommendations in this paper address the evidence-based treatment of CM risk and are intended for clinical application in Latin American countries.

Antecedentes: Un grupo de factores de riesgo cardiometabólicos (hipertensión, hiperglucemia, dislipidemia, sobrepeso, obesidad y tabaco (fumado, masticado, vaporizado), junto con un estado proinflamatorio y procoagulante, son los principales factores de riesgo relacionados con la enfermedad cardiovascular aterosclerótica. Objetivo y métodos: Basándose en su experiencia en cardiología, prevención cardiovascular y enfermedades cardiometabólicas, un grupo de expertos de las Américas se unió para desarrollar estas recomendaciones prácticas para la evaluación y tratamiento óptimos de los factores de riesgo cardiometabólicos residuales en América Latina, utilizando una metodología Delphi modificada con el objetivo de generar una guía integral de pautas para la reducción del riesgo cardiometabólico, mediante la medicina personalizada y la decisión centrada en el paciente teniendo en cuenta la relación costo-beneficio. El proceso fue bien definido para evitar conflictos de intereses que podrían sesgar la discusión y las recomendaciones. Resultados: La reducción del riesgo residual debe considerar opciones terapéuticas adaptadas a las necesidades específicas del paciente, basadas en 5 objetivos de tratamiento: lipoproteínas ricas en triglicéridos inflamación, metabolismo de la glucosa, presión arterial alta y estado protrombótico. El Control integral de todos los factores de riesgo cardiometabólicos debe ser una prioridad para hacer frente a este importante problema de salud pública y prevenir las muertes prematuras. Las recomendaciones de este documento abordan el tratamiento basado en evidencia del riesgo cardiometabólico y están destinadas a la aplicación clínica en los países de América Latina.

Challenges in familial chylomicronemia syndrome diagnosis and management across Latin American countries: An expert panel discussion.

Familial chylomicronemia syndrome (FCS) is a rare genetic disorder characterized by extremely high triglyceride levels due to impaired clearance of chylomicrons from plasma. This paper is the result of a panel discussion with Latin American specialists who raised the main issues on diagnosis and management of FCS in their countries. Overall FCS is diagnosed late on the course of the disease, is characterized by heterogeneity on the occurrence of pancreatitis, and remains a long time in care of different specialists until reaching a lipidologist. Pancreatitis and secondary diabetes are frequently seen, often due to late diagnosis and inadequate care. Molecular diagnosis is unusual; however, loss of function variants on the lipoprotein lipase gene are apparently the most frequent etiology. A founder effect of the glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1 gene has been described in the northeast of Brazil. Low awareness of the disease amongst health professionals contributes to inadequate care and an inadequate patient journey.

RACCOVID-19: primer Registro Argentino de Complicaciones Cardiovasculares en pacientes con COVID-19 / RACCOVID-19: First Argentine Registry of Cardiovascular Complications in COVID-19 Patients

RESUMEN Introducción: La enfermedad por coronavirus (COVID-19) ha causado una de las mayores pandemias conocidas al día de la fecha. La Sociedad Argentina de Cardiología (SAC) y la Federación Argentina de Cardiología (FAC) elaboraron el primer Registro Argentino de Complicaciones Cardiovasculares en pacientes con COVID-19 (RACCOVID-19), con el propósito de relevar, a nivel nacional, su impacto en la evolución hospitalaria de estos pacientes. Objetivos: Documentar la aparición de complicaciones cardiovasculares en pacientes internados por COVID-19 y evaluar predictores de riesgo de dichas complicaciones y su impacto pronóstico. Material y Métodos: Se incluyen datos de 2750 pacientes en 50 centros de 11 provincias del país, desde el 18 de mayo hasta el 31 de octubre de 2020. Resultados: La edad promedio fue de 57±18 años y hubo predominio de sexo masculino (60,2%). La tasa de complicaciones cardiovasculares fue del 15,3%. La insuficiencia cardíaca (43,5%), las arritmias (33,5%) y el daño miocárdico (31,1%) fueron las complicaciones más frecuentes. La mortalidad fue del 19,3%. Un modelo de predicción de sobrevida en la etapa hospitalaria incluyó las siguientes variables: edad, sexo masculino, valores de hematocrito y creatinina al ingreso, existencia de antecedentes patológicos, formas de presentación de COVID-19 graves y presencia de complicaciones cardiovasculares. Conclusiones: El registro RACCOVID-19 mostró una tasa de complicaciones cardiovasculares del 15,3%. La mortalidad total del registro fue del 19,3% y las complicaciones cardiovasculares junto con otras variables de presentación, así como la gravedad del cuadro clínico de COVID-19, forman parte de un perfil de riesgo clínico asociado a mayor mortalidad.

ABSTRACT Background: Coronavirus disease (COVID-19) has caused one of the largest pandemics known to date. The Argentine Society of Cardiology (SAC) and the Argentine Federation of Cardiology (FAC) have developed the First Argentine Registry of Cardiovascular Complications in COVID-19 patients (RACCOVID-19) with the purpose of performing a nationwide review of their impact in the in-hospital evolution of these patients. Objectives: The aim of this study was to record cardiovascular complications in hospitalized patients for COVID-19, and to evaluate risk predictors of these complications and their prognostic impact. Methods: A total of 2750 patients from 50 centers in 11 provinces of the country were included from May 18 to October 31, 2020. Results: Mean age was 57±18 years, with a prevalence of male gender (60.2%). Cardiovascular complications occurred in 15.3% of cases. Heart failure (43.5%), arrhythmias (33.5%) and myocardial injury (31.1%) were the most relevant complications. Mortality was 19.3%, and a predictive model of in-hospital survival included age, male gender, admission hematocrit and creatinine, history of previous diseases, severe forms of COVID-19 presentation and cardiovascular complications. Conclusions: The RACCOVID-19 registry showed 15.3% of cardiovascular complications. Overall mortality was 19.3% and cardiovascular complications together with other presentation variables as well as the clinical severity of COVID-19, are part of a clinical risk profile associated with higher mortality.

Management of Dyslipidaemia in Real-world Clinical Practice: Rationale and Design of the VIPFARMA ISCP Project.

Dyslipidaemia plays a major role in the pathogenesis of atherosclerosis. Every year, scientific institutions publish cardiovascular prevention guidelines with updated goals and recommendations based on new evidence. However, medical barriers exist that make achieving these goals difficult and gaps between guidelines and best daily clinical practice still persist. The International Society of Cardiovascular Pharmacotherapy designed the Surveillance of Prescription Drugs in the Real World Project (VIPFARMA ISCP), a survey for physicians who manage lipid disorders in high-risk patients. Seven clusters of questions will be analysed comprising demographics, institution profile, access to continuing medical education, clinical practice profile, attitude regarding use of statins, knowledge regarding proprotein convertase subtilisin/kexin type 9 inhibitors and attitudes regarding medical decisions about triglycerides. The present study will be the first part of a larger programme and aims to shed light on barriers between lipid-lowering drug therapy recommendations in the 2019 European Society of Cardiology guidelines and clinical practice in different countries.

Considerations and Guidance for the Structure, Organisation, and Operation of Cardiometabolic Prevention Units: A Consensus Statement of the Inter-American Society of Cardiology.

Cardiovascular diseases (CVDs) remain the leading cause of death worldwide, particularly in low- and middle-income regions such as Latin America. This is because of the combination and interaction in different proportions of a high prevalence of cardiometabolic risk factors and socio-economic and cultural characteristics. This reality brings about the need to change paradigms to consistently and systematically boost cardiovascular prevention as the most cost-effective medium- to long-term strategy to reduce their prevalence in medium- and low-resource countries, not only in Latin America but also in other global regions. To achieve the therapeutic goals in various diseases, including CVD, the current literature demonstrates that the most effective way is to carry out the patient's diagnosis and treatment in multidisciplinary units. For this reason, the Inter American Society of Cardiology (IASC) proposes the creation of cardiometabolic prevention units (CMPUs) as a regional initiative exportable throughout the world to standardise cardiovascular prevention based on the best available evidence. This ensures homogeneity in the global management of cardiometabolic risk factors and access to quality medicine independently of the population's social situation. These guidelines, written by a panel of experts in cardiovascular prevention, defines what a CMPU is, its objectives and the minimum requirements for it, as well as proposing three categories and suggesting an operational scheme. It must be used as a guide for all individuals or centres that, aware of the need for multidisciplinary and standardised work, want to create a unit for the comprehensive management of cardiometabolic risk established as an international research network. Lastly, the document makes meaningful points on the determination of cardiovascular risk and its importance. These guidelines do not cover specific targets and therapeutic schemes, as these topics will be extensively discussed in another SIAC publication, namely a statement on residual cardiometabolic risk.

Anti-inflammatory Treatment and Cardiovascular Outcomes: Results of Clinical Trials.

Atherosclerosis is a chronic inflammatory disorder of the vasculature where cholesterol accumulates in the arterial wall stimulating infiltration of immune cells. This plays an important role in plaque formation, as well as complications caused by its build up. Pro-inflammatory cytokines and chemokines are implicated throughout the progression of the disease and different therapies that aim to resolve this chronic inflammation, reduce cardiovascular (CV) events and improve clinical outcomes have been tested. The results from the pivotal CANTOS trial show that targeting the pro-inflammatory cytokine IL-1ß successfully reduces the incidence of secondary CV events. This review briefly assesses the role of inflammation in atherosclerosis, providing a picture of the multiple players involved in the process and offering a perspective on targeting inflammation to prevent atherosclerotic CV events, as well as focusing on the results of the latest Phase III clinical trials.

Effects of evolocumab in individuals with type 2 diabetes with and without atherogenic dyslipidemia: An analysis from BANTING and BERSON.

BACKGROUND: Atherogenic dyslipidemia (AD), characterized by increased concentrations of apolipoprotein B (ApoB)-containing particles, is often present in individuals with type 2 diabetes mellitus (T2DM). Non-high-density lipoprotein cholesterol (non-HDL-C), cholesterol transported by apolipoprotein B (ApoB)-containing particles), and total apoB are considered secondary goals of lipid-lowering therapy to guide treatment of residual cardiovascular risk. The BANTING and BERSON studies demonstrated that evolocumab added to statin therapy reduced atherogenic lipid and lipoproteins concentrations in patients with T2DM. METHODS: This post-hoc analysis combined data from two randomized, placebo-controlled trials, BANTING and BERSON, to investigate the effect of evolocumab (140 mg every two weeks [Q2W] or 420 mg monthly [QM]) on atherogenic lipid (LDL-C, non-HDL-C, VLDL-C, remnant cholesterol) and lipoproteins (ApoB, lipoprotein(a) (Lp[a])), and achievement of 2019 European Society of Cardiology/European Atherosclerosis Society lipid treatment goals in individuals with and without AD. RESULTS: In individuals with high TGs with (n = 389) and without (n = 196) AD receiving background statin therapy, evolocumab, compared with placebo, substantially reduced the cholesterol levels from all ApoB atherogenic lipoproteins (least squares (LS) mean LDL-C by 66.7% to 74.3%, non-HDL-C by 53.4% to 65.8%, median remnant cholesterol by 28.9% to 34.2%, VLDL-C by 16.1% to 19.6%) and median TGs levels (by 17.5% to 19.6%) at the mean of weeks 10 and 12. LS mean ApoB was significantly reduced by 41.5% to 56.6% at week 12. Results were consistent in diabetic individuals with normal TGs (n = 519). Evolocumab was also associated with a significant reduction in median Lp(a) by 35.0% to 53.9% at the mean of weeks 10 and 12. A majority (74.7% to 79.8%) of evolocumab-treated individuals achieved the goal of both an LDL-C < 1.4 mmol/L and an LDL-C reduction of at least 50%, > 75% achieved non-HDL-C < 2.2 mmol/L at the mean of weeks 10 and 12, and > 67% achieved ApoB < 65 mg/dL at week 12. CONCLUSIONS: Evolocumab effectively reduced LDL-C, non-HDL-C, ApoB, Lp(a), and remnant cholesterol in individuals with T2DM with and without AD. Evolocumab Q2W or QM enabled most individuals at high/very-high cardiovascular disease risk to achieve their LDL-C, non-HDL-C, and ApoB recommended goals.

Results of an international crowdsourcing survey on the treatment of non-ST segment elevation ACS patients at high-bleeding risk undergoing percutaneous intervention.

AIMS: Choosing an antiplatelet strategy in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) at high bleeding risk (HBR), undergoing post-percutaneous coronary intervention (PCI), is complex. We used a unique open-source approach (crowdsourcing) to document if practices varied across a small, global cross-section of antiplatelet prescribers in the post-PCI setting. METHODS AND RESULTS: Five-hundred and fifty-nine professionals from 70 countries (the 'crowd') completed questionnaires containing single- or multi-option and free form questions regarding antiplatelet clinical practice in post-PCI NSTE-ACS patients at HBR. A threshold of 75% defined 'agreement'. There was strong agreement favouring monotherapy with either aspirin or a P2Y12 inhibitor following initial DAPT, within the first year (94%). No agreement was reached on the optimal duration of DAPT or choice of monotherapy: responses were in equipoise for shorter (≤3 months, 51%) or longer (≥6 months, 46%) duration, and monotherapy choice (45% aspirin; 53% P2Y12 inhibitor). Most respondents stated use of guideline-directed tools to assess risk, although clinical judgement was preferred by 32% for assessing bleeding risk and by 46% for thrombotic risk. CONCLUSION: The crowdsourcing methodology showed potential as a tool to assess current practice and variation on a global scale and to achieve a broad demographic representation. These preliminary results indicate a high degree of variation with respect to duration of DAPT, monotherapy drug of choice following DAPT and how thrombotic and bleeding risk are assessed. Further investigations should concentrate on interrogating practice variation between key demographic groups.

Ambulatory Patients with Cardiometabolic Disease and Without Evidence of COVID-19 During the Pandemic. The CorCOVID LATAM Study.

Background: SARS-CoV-2 pandemic has modified the cardiovascular care of ambulatory patients. The aim of this survey was to study changes in lifestyle habits, treatment adherence, and mental health status in patients with cardiometabolic disease, but no clinical evidence of COVID-19. Methods: A cross-sectional survey was conducted in ambulatory patients with cardiometabolic disease using paper/digital surveys. Variables investigated included socioeconomic status, physical activity, diet, tobacco use, alcohol intake, treatment discontinuation, and psychological symptoms. Results: A total of 4,216 patients (50.9% males, mean age 60.3 ± 15.3 years old) from 13 Spanish-speaking Latin American countries were enrolled. Among the study population, 46.4% of patients did not have contact with a healthcare provider, 31.5% reported access barriers to treatments and 17% discontinued some medication. Multivariate analysis showed that non-adherence to treatment was more prevalent in the secondary prevention group: peripheral vascular disease (OR 1.55, CI 1.08-2.24; p = 0.018), heart failure (OR 1.36, CI 1.05-1.75; p = 0.017), and coronary artery disease (OR 1.29 CI 1.04-1.60; p = 0.018). No physical activity was reported by 38% of patients. Only 15% of patients met minimum recommendations of physical activity (more than 150 minutes/week) and vegetable and fruit intake. Low/very low income (45.5%) was associated with a lower level of physical activity (p < 0.0001), less fruit and vegetables intake (p < 0.0001), more tobacco use (p < 0.001) and perception of depression (p < 0.001). Low educational level was also associated with the perception of depression (OR 1.46, CI 1.26-1.70; p < 0.01). Conclusions: Patients with cardiometabolic disease but without clinical evidence of COVID-19 showed significant medication non-adherence, especially in secondary prevention patients. Deterioration in lifestyle habits and appearance of depressive symptoms during the pandemic were frequent and related to socioeconomic status.

New Perspectives on Atherogenic Dyslipidaemia and Cardiovascular Disease.

Over the past few decades, atherogenic dyslipidaemia has become one of the most common phenotypic presentations of lipid abnormalities, being strongly and unequivocally associated with an increased risk of cardiovascular (CV) disease. Despite the excellent results achieved from statin and non-statin management of LDL cholesterol and CV events prevention, there still remains a significant residual risk, associated with the prevalence of non-LDL cholesterol lipid patterns characterised by elevated triglyceride levels, low HDL cholesterol, a preponderance of small and dense LDL particles, accumulation of remnant lipoproteins and postprandial hyperlipidaemia. These qualitative and quantitative lipid modifications are largely associated with insulin resistance, type 2 diabetes and obesity, the prevalence of which has grown to epidemic proportions throughout the world. In this review, we analyse the pathophysiology of this particular dyslipidaemia, its relationship with the development of atherosclerotic CV disease and, finally, briefly describe the therapeutic approaches, including changes in lifestyle and current pharmacological interventions to manage these lipid alterations aimed at preventing CV events.

The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMα) paradigm: conceptual framework and therapeutic potential : A consensus statement from the International Atherosclerosis Society (IAS) and the Residual Risk Reduction Initiative (R3i) Foundation.

In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARMα) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARMα agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARMα agonist safely reduces residual cardiovascular risk.

New evidence on the role of inflammation in CVD risk.

PURPOSE OF REVIEW: Based on compelling data from animal and human studies, over the past few decades, the viewpoint of atherosclerosis as an exclusively lipid-driven disease, has been gradually replaced by the concept of a chronic low-grade inflammatory process of the arterial wall. This review presents a brief description on the role of inflammation in atherosclerosis, and examines selected anti-inflammatory interventions that have been tested in clinical trials designed to prevent adverse cardiovascular disease (CVD) events and excess CVD risk. RECENT FINDINGS: The Canakinumab Anti-inflammatory Thrombosis Outcomes Study trial has provided convincing evidence that neutralization of the interleukin (IL)-1ß inflammatory pathway by the selective antibody canakinumab reduces major CVD events and significantly lowers IL-1ß, IL-6 and high-sensitivity C-reactive protein, without affecting low-density lipoprotein cholesterol levels. In contrast, in the latest Cardiovascular Inflammation Reduction Trial, low-dose methotrexate compared with placebo did not reduce CVD events, probably because there was no reduction in IL-1ß, or in downstream inflammatory biomarker levels either. SUMMARY: Notwithstanding the utilization of effective medical treatments including statins and proprotein convertase subtilisin/kexin type 9 inhibitors or precise revascularizations, the recurrence of CVD events remains unacceptably high. Canakinumab is, at present, the only anti-inflammatory agent that has been proven to reduce cardiovascular events in patients with elevated markers of inflammation without modifying cholesterol levels. Nevertheless, clinical application related to this new evidence and associated knowledge has not yet been implemented in daily practice.

Randomised study of evolocumab in patients with type 2 diabetes and dyslipidaemia on background statin: Primary results of the BERSON clinical trial.

AIM: To evaluate the lipid-lowering efficacy and safety of evolocumab combined with background atorvastatin in patients with type 2 diabetes mellitus (T2DM) and hyperlipidaemia or mixed dyslipidaemia. MATERIALS AND METHODS: BERSON was a double-blind, 12-week, phase 3 study (NCT02662569) conducted in 10 countries. Patients ≥18 to ≤80 years with type T2DM received atorvastatin 20 mg/d and were randomised 2:2:1:1 to evolocumab 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM) or placebo Q2W or QM. Co-primary endpoints were the percentage change in low-density lipoprotein cholesterol (LDL-C) from baseline to week 12 and from baseline to the mean of weeks 10 and 12. Additional endpoints included atherogenic lipids, glycaemic measures, and adverse events (AEs). RESULTS: Overall, 981 patients were randomised and received ≥1 dose of study drug. Evolocumab significantly reduced LDL-C versus placebo at week 12 (Q2W, -71.8%; QM, -74.9%) and at the mean of weeks 10 and 12 (Q2W, -70.3%; QM, -70.0%; adjusted P < 0.0001 for all) when administered with atorvastatin. Non-high-density lipoprotein cholesterol, apolipoprotein B100, total cholesterol, lipoprotein (a), triglycerides, high-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol improved significantly with evolocumab versus placebo. The overall incidence of AEs was similar between evolocumab and placebo-treated patients, and there were no clinically meaningful differences in changes over time in glycaemic variables (fasting serum glucose and HbA1c) between the two groups. CONCLUSIONS: In patients with T2DM and hyperlipidaemia or mixed dyslipidaemia on statin, evolocumab significantly reduced LDL-C and other atherogenic lipids, was well tolerated, and had no notable impact on glycaemic measures.

Randomized study of evolocumab in patients with type 2 diabetes and dyslipidaemia on background statin: Pre-specified analysis of the Chinese population from the BERSON clinical trial.

AIM: The aim of this study was to evaluate the efficacy and safety of evolocumab with background atorvastatin in Chinese patients with type 2 diabetes mellitus (T2DM) and hyperlipidaemia or mixed dyslipidaemia. MATERIALS AND METHODS: This is a pre-specified analysis of patients in the BERSON study (ClinicalTrials.gov, NCT02662569) in China. Patients initiated background atorvastatin 20 mg/d, after which they were randomized 2:2:1:1 to evolocumab 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM) or to placebo Q2W or QM. Co-primary endpoints were percentage change in LDL cholesterol (LDL-C) from baseline to week 12 and from baseline to the mean of weeks 10 and 12. Additional endpoints included atherogenic lipids, glycaemic measures and adverse events (AEs). RESULTS: Among 453 patients randomized in China, 451 received at least one dose of study drug (evolocumab or placebo). Evolocumab significantly reduced LDL-C compared with placebo at week 12 (Q2W, -85.0%; QM, -74.8%) and at the mean of weeks 10 and 12 (Q2W, -80.4%; QM, -81.0%) (adjusted P < 0.0001 for all) when administered with background atorvastatin. Non-HDL-C, ApoB100, total cholesterol, Lp(a), triglycerides, HDL-C and VLDL-C significantly improved with evolocumab vs placebo. No new safety findings were observed with evolocumab. The incidence of diabetes AEs was higher with evolocumab compared with placebo. There were no differences over time between evolocumab and placebo in measures of glycaemic control. CONCLUSIONS: In patients in China with T2DM and hyperlipidaemia or mixed dyslipidaemia receiving background atorvastatin, evolocumab significantly reduced LDL-C and other atherogenic lipids, was well tolerated, and had no notable impact on glycaemic measures.

Role of Anti-inflammatory Interventions in Coronary Artery Disease: Understanding the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS).

Coronary artery disease (CAD) is the leading cause of death worldwide. Despite notable advances in understanding the nature of atherosclerotic processes and the use of effective medications such as statins, there remains a significant residual risk. Even after optimal medical treatments and precise revascularisations, the recurrence of MI remains at approximately one-third for 5 years after an acute coronary syndrome (ACS). Over the past two decades, compelling data from animal and human studies has clearly identified atherosclerosis as an inflammatory disease of the arterial wall, but clinical applications related to this accumulated knowledge are still scarce. Recently, the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) has provided convincing evidence that an anti-inflammatory intervention with the monoclonal antibody canakinumab reduces cardiovascular events in well-treated CAD patients without affecting LDL cholesterol levels. This article presents a brief description of the role of inflammation in atherogenesis and examines selected anti-inflammatory interventions and their potential use in CAD-affected individuals.

Attitudes and Recommendations of Physicians towards Alcohol Consumption and Cardiovascular Health: A Perspective from Argentina.

Despite epidemiological findings of improvements in cardiovascular risk factors with a light-to-moderate intake of alcohol, many misconceptions remain regarding alcohol intake and the risks and benefits of consumption. We sought to examine physician attitudes and recommendations regarding alcohol intake in a cohort of Argentine physicians and to establish their sources of knowledge. An online national survey was distributed through the Argentine Federation of Cardiology (FAC) to cardiologists, internal medicine specialists, general and other subspecialty physicians in Argentina. The survey was completed by 745 physicians, of whom 671 (90%) were cardiologists. In total, 35% of physicians viewed moderate alcohol intake to be beneficial for cardiovascular health, 36% believed only wine offered such benefits, 24% viewed any intake to be harmful, and 5% had other opinions. More than half (57%) self-reported their knowledge came from academic sources. Regarding knowledge of drinking guidelines, only 41% of physicians were aware of the concept of "standard drink". Physicians were generally not comfortable converting standard drinks into other metric units, however men tended to be more comfortable than women (p = 0.052). Physicians were not satisfied with their knowledge of drinking guidelines (3.01 ± 2.73, on a 0⁻10 scale). Physicians were generally comfortable in counselling patients regarding safe limits of consumption (6.22 ± 3.20, on a 0⁻10 scale). Argentine physicians were not satisfied with their knowledge of alcohol consumption guidelines or their understanding of the reported metrics. Only one-third of study participants viewed moderate alcohol intake as beneficial for cardiovascular health. This study shows the necessity to optimize the sources of knowledge.

Rationale and design of a randomized study to assess the efficacy and safety of evolocumab in patients with diabetes and dyslipidemia: The BERSON clinical trial.

Type 2 diabetes mellitus (T2DM) is a major independent risk factor for cardiovascular disease, and diabetic dyslipidemia is a major contributor to cardiovascular risk in these patients. Here we report the rationale and design of a phase 3, double-blind study specifically designed to evaluate the lipid-lowering efficacy of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab in patients with T2DM and hyperlipidemia or mixed dyslipidemia who are on background statin therapy. In the BERSON (evolocumaB Efficacy for LDL-C Reduction in subjectS with T2DM On background statiN) trial, patients with T2DM, a screening low-density lipoprotein cholesterol (LDL-C) level of ≥ 2.6 mmol/L (≥100 mg/dL) or ≥ 3.4 mmol/L (≥130 mg/dL), and with or without statin treatment at screening, respectively, were enrolled and started on atorvastatin 20 mg/day for a lipid stabilization period of at least 4 weeks. Then, patients were randomly assigned in a 2:2:1:1 ratio to receive atorvastatin 20 mg once daily plus either evolocumab 140 mg every 2 weeks (Q2W), evolocumab 420 mg every month (QM), placebo Q2W, or placebo QM. The co-primary outcome measures were the percentage change from baseline in LDL-C at week 12 and the percentage change from baseline in LDL-C at the mean of weeks 10 and 12. The BERSON trial has completed enrollment. The study completed in the first half of 2018, and will provide information on the efficacy and safety of evolocumab in patients with T2DM and dyslipidemia.