Cost-effectiveness in unstable economies: the case of sacubitril/valsartan in heart failure with reduced ejection fraction in Argentina.

BACKGROUND: Sacubitril/valsartan (an Angiotensin receptor-neprilysin inhibitor-ARNI) is one of the cornerstones in the management of patients with heart failure with reduced ejection fraction (HFrEF) having demonstrated significant reductions in both mortality and hospitalisations as compared with enalapril. It proved to be a cost-effective treatment in many countries with stable economies. In Argentina, a country with chronic financial instability and a fragmented health care system, the estimation of its cost-effectiveness requires to consider local financial data. OBJECTIVES: To estimate the cost-effectiveness of sacubitril/valsartan in HFrEF in Argentina. METHODS: We populated an Excel-based cost-effectiveness model, previously validated, using inputs from the pivotal phase-3 PARADIGM-HF trial and from local sources. As the main problem to consider was the financial instability, we adopted a differential approach to cost discounting based on the opportunity cost of capital. Thus, a discount rate for costs were set at 31.6%, using the BADLAR rate published by the Central Bank of Argentina. Discount for effects were set at 5% as is the current practice. Costs were expressed in Argentinian pesos (ARS). We used the perspective for both the social security and private payers at a 30-year horizon. The primary analysis was the incremental cost-effectiveness ratio (ICER) versus enalapril, the previous standard of care. Alternative scenarios performed included a 5% cost discount rate and 3 a 5-year horizon (as is usually used). RESULTS: In Argentina the cost-per quality adjusted life-year (QALY) gained for sacubitril/valsartan versus enalapril was 391,158 ARS and 376,665 ARS for a social security and a private payer, respectively, at a 30- year horizon. These ICERs were under the cost- effectiveness threshold of 520,405.79 ARS (1 Gross domestic product (GDP) per capita) suggested by Argentinian health technology assessment bodies. Probabilistic sensitivity analysis showed an acceptability of sacubitril/valsartan as a cost-effective alternative of 86.40% and 88.25% for social security and private payers, respectively. CONCLUSION: Sacubitril/valsartan is a cost-effective treatment in HFrEF using local inputs that considered the financial instability. For both payers considered the cost per QALY gained are under the cost-effectiveness threshold considered.

Direct Oral Anticoagulants: An Updated Systematic Review of Their Clinical Pharmacology and Clinical Effectiveness and Safety in Patients With Nonvalvular Atrial Fibrillation.

Direct oral anticoagulants have been an increasingly used class of drugs in the setting of nonvalvular atrial fibrillation, defying vitamin K antagonists' monopoly when it comes to anticoagulation due to its several limitations. Direct oral anticoagulants (DOACs) have entered the market as a noninferior and safer option in comparison with vitamin K antagonists, as their respective phase III clinical trials proved. The aim of this article was to update and summarize data on their clinical pharmacology and to review real-world data to know their comparative effectiveness and safety. We performed a systematic review using PubMed, Google Scholar, Embase, and Web of Science as search engines. Regarding pharmacodynamics, there were no substantial changes reported from their original profile. There were many advances in the knowledge about clinical pharmacokinetics of DOACs that have had a direct impact on their clinical use, mainly related to drug-drug interactions. In a real-world setting, DOACs have shown to be noninferior in preventing thromboembolic events compared to vitamin K antagonists. In regards to safety, DOACs have shown a lower bleeding risk relative to warfarin. Comparison between DOACs has demonstrated rivaroxaban to have the highest bleeding risk. Overall, the evidence gathered showed few changes from the original data presented in phase III clinical trials, concluding that their real-world use coincides greatly with them.

Real-world data meta-analysis: procedural success and clinical outcomes after radiofrequency ablation of atrial fibrillation in South America.

OBJECTIVE: To profile patients' characteristics, in-hospital results, and recurrence rates after radiofrequency ablation of atrial fibrillation (RAAF) in South America. METHODS: We comprehensively searched for single-center studies from South America with ≥10 patients receiving RAAF, published or presented from January 1, 2010, through June 29, 2020, excluding those reports aimed to specific populations such as permanent atrial fibrillation, structural cardiopathies, or re-do procedures. RESULTS: Main pooled estimates from a random-effects meta-analysis that included 3909 patients from 27 cohorts (from 5 countries): a) Patients characteristics: age 57.6 years (95% CI 55.7-59.5), male gender 71.5% (95% CI 67.0-75.6%), hypertension 54.2% (95% CI 45.4-62.8%), paroxysmal atrial fibrillation 79.8% (95% CI 71.3-94.5%), CHADS score 1.2 (95% CI 0.5-1.9), b) Acute procedural success 91.1% (95% CI 82.2-95.8%), c) In-hospital complications: stroke 0.6% (95% CI 0.3-1.2%), cardiac tamponade 2.3% (95% CI 1.4-3.7), hematoma 3.5% (95% CI 2.0-6.1), pseudoaneurysm 1.2% (95% CI 0.6-2.3), arteriovenous fistula 2.5% (95% CI 1.6-4.1). There were no cases of esophageal-atrial fistula nor death. Pooled estimate for arrhythmia recurrence (excluded 3-months blanking period) at 12 months was 19.9% (95% CI 17.0-23.1). CONCLUSION: In-hospital results of RAAF reported for South American centers were worse than published international registries, even when included populations profile was of lower risk, as reflected in younger age and less prevalence of non-paroxysmal AF. Late recurrence rates seemed appropriate. This study provides a real-life framework for the analysis of the performance of this technology in the region.

Temporal Trends in Self-Expandable Transcatheter Aortic Valve Replacement in South America: A Systematic Review and Meta-Analysis.

OBJECTIVES: This study aimed to estimate temporal trends in clinical presentation and short-term outcomes of transcatheter aortic valve replacement (TAVR) with self-expandable prostheses in South America through a systematic review and meta-analysis of observational data. METHODS: We comprehensively searched for articles published in peer-reviewed medical journals and for abstracts presented in medical conferences of the region from September 1, 2008, to June 29, 2020. We included single-center studies on self-expandable TAVR populations with ≥ 10 patients from South America. RESULTS: A total of 28 cohorts from 6 countries pooling 1780 patients were included in a random-effects meta-analysis. Pooled estimates of age changed during time (period 2011-2015, 81.6 years; 95% confidence interval [CI] 80.7-82.4; period 2016-2018, 80.6 years; 95% CI 79.8-81.3; period 2019: 78.5 years; 95% CI 77.0-80.0; P = .0003); no other temporal trends in patient characteristics were ascertained. Temporal trends in short-term mortality pooled estimates were in-hospital mortality (11.8% [95% CI 8.2-16.7] for the period 2011-2015, 6.6% [95% CI 4.5-9.6] for the period 2016-2018, and 4.4% [95% CI 1.9-9.8] for the period 2019 [P = .007]) and 30-day mortality (12.8% [95% CI 7.7-20.4], 9.7% [95% CI 7.0-13.3], and 5.7% [95% CI 2.8-11.3], respectively [P =.044]). These associations between reporting year of the study and lower mortality remained after adjusting by age and surgical risk (multivariate meta-regression). CONCLUSIONS: In studies reported between 2011 and 2019 in South America, we demonstrated a clear time trend toward reduction of short-term mortality after self-expandable TAVR, independently of age and surgical risk of populations. These findings are relevant to the local reassessment of cost-effectiveness of TAVR.

[Relación entre enfermedad cardiovascular y renal en una muestra de pacientes con diabetes del mundo real]. / Association between cardiovascular disease and kidney disease in a sample of real-world diabetes patients

Objectives: Kidney disease is one of the microvascular complications of diabetes mellitus (DM) with little research and a strong association with cardiovascular disease (CVD). The objective of this study is to characterize the prevalence of kidney disease in a population of patients with type 2 diabetes who attend outpatient control by cardiology, to evaluate its degree of investigation and whether its presence impacts on the achievement of therapeutic goals and use of antidiabetics with cardiovascular and kidney protective effect. Methods: Cross-sectional, observational and multicenter study, carried out in 44 centers in Argentina between May and July 2019. Results: A population with 693 patients with DM was included. The prevalence of CVD was 47.5% (329 patients) and that of microvascular disease was 42.3%. Albuminuria was evaluated only in 46.2% of the patients and was significantly higher in the group with renal impairment (RI). The presence of CVD in patients with RI was greater than in those without RI (64.8% vs. 42.2%; p = 0.0001). The presence of albuminuria was associated with a higher prevalence of CVD. The achievement of therapeutic goals was scarce and no differences were evidenced based on the presence of RI, except for the LDL goal. Low prescription of antidiabetic drugs with proven cardiovascular and kidney benefit was observed. Conclusions: This study highlights the importance of the active search for kidney disease in patients with DM, exposing the low scope of therapeutic goals and the prescription of antidiabetic drugs with cardiovascular and kidney benefit.

Objetivos: La enfermedad renal es una de las complicaciones microvasculares de la diabetes mellitus (DM) con escasa pesquisa y gran relación con enfermedad cardiovascular (ECV). El objetivo de este trabajo es caracterizar la prevalencia de enfermedad renal en una población de pacientes con diabetes tipo 2 que concurren a control ambulatorio por cardiología, determinar su grado de pesquisa y su posible efecto en el alcance de los objetivos terapéuticos y en el uso de los antidiabéticos con efecto protector cardiorrenal. Métodos: Estudio de corte transversal, observacional y multicéntrico realizado en 44 centros de Argentina entre mayo y julio de 2019. Resultados: Se incluyó a 693 pacientes con una prevalencia de ECV establecida de 47.5% (329 pacientes) y de enfermedad microvascular de 42.3%. La albuminuria se valoró sólo en el 46.2% de los pacientes y fue significativamente mayor en el grupo con IR. La ECV en pacientes con IR fue mayor que en aquéllos sin IR (64.8% vs. 42.2%; p = 0.0001). La presencia de albuminuria se acompañó de mayor prevalencia de ECV. El alcance de los objetivos terapéuticos fue escaso y no se reconocieron diferencias en función de la IR, a excepción del objetivo de LDL. Se observó baja prescripción de fármacos antidiabéticos con probado beneficio cardiorrenal. Conclusiones: El trabajo resalta la importancia de la búsqueda activa de la enfermedad renal en pacientes con diabetes, lo que revela el bajo alcance de los objetivos terapéuticos y la prescripción de fármacos antidiabéticos con beneficio cardiorrenal.

Clinical outcomes after transcatheter aortic valve replacement in South America: A centre-level systematic review and meta-analysis of observational data.

OBJECTIVES: To estimate in-hospital and 30-day outcomes after transcatheter aortic valve replacement (TAVR) in South America through a systematic review and meta-analysis of observational data. METHODS: We comprehensively searched for papers published in peer-reviewed medical journals and for abstracts presented in medical conferences of the region from 1 September 2008, through 29 June 2020, using predefined criteria. We included single-centre studies on TAVR populations with ≥10 patients from South America reporting any in-hospital or 30-day clinical outcome. RESULTS: Fifty-five cohorts from seven countries, pooling 3001 patients, were included in a random-effects meta-analysis. Self-expandable prostheses were the most frequently implanted. Pooled estimate of procedure success by VARC2 criteria was 90.0% (95%CI 81.8%-94.7%; I2 75.0%). The pooled estimate rates of the outcomes were as follow: post-procedure moderate or severe aortic regurgitation, 9.7% (95%CI 6.0%-15.4%; I2 65.4%), in-hospital cardiac tamponade, 4.0% (95%CI 2.5%-6.6%; I2 0%), in-hospital stroke, 4.1% (95%CI 2.9%-5.7%; I2 0%), in-hospital major vascular complication, 7.8% (95%CI 5.2%-11.5%; I2 22.3%), in-hospital permanent pacemaker implantation, 19.4% (95%CI 15.9%-23.4%; I2 53.8%), in-hospital mortality, 8.0% (95%CI 6.7%-9.6%; I2 0%), and 30-day mortality, 9.7% (95%CI 7.9%-11.8%; I2 26.4%). CONCLUSION: As compared with published international registries, the overall results of TAVR in South America seemed underrated. Significant heterogeneity was observed in procedural success, pacemaker requirement, and post-procedure moderate or severe aortic regurgitation. This study provides a real-life framework for the analysis of the performance of this technology in the region, intended to be a starting point for quality improvement.

Latin American Expert Consensus for Comprehensive Management of Type 2 Diabetes from a Metabolic-Cardio-Renal Perspective for the Primary Care Physician.

Growing scientific evidence from studies on type 2 diabetes (T2D) has recently led to a better understanding of the associated metabolic-cardio-renal risks. The large amount of available information makes it essential to have a practical guide that summarizes the recommendations for the initial management of patients with T2D, integrating different aspects of endocrinology, cardiology, and nephrology. The expert consensus presented here does not attempt to summarize all the evidence in this regard but rather attempts to define practical summary recommendations for the primary care physician to improve the clinical prognosis and management of patients with T2D, while ensuring economic sustainability of health systems, beyond glycemic control.

Características clínicas y control cardiometabólico de personas con diabetes en el consultorio de cardiología en la República Argentina / Clinical Characteristics and Cardiometabolic Control of Persons with Diabetes in the Cardiology Office in Argentina

RESUMEN Introducción: La cardiología tiene un rol protagónico en el control y el tratamiento de las personas con diabetes mellitus tipo 2 (DM2). No contamos con datos epidemiológicos locales acerca de los pacientes con DM2 asistidos por la especialidad. Objetivos: Evaluar las características clínicas, enfermedad cardiovascular (ECV) y tratamiento de personas con DM2 en el consultorio de cardiología. Material y métodos: Se realizó un estudio observacional en 17 provincias de la Argentina durante 3 meses. Resultados: Se incluyeron 694 pacientes. La edad media fue de 64.7 ± 10.5 años, con un tiempo de evolución de la DM2 de 10.7 ± 9.3 años, índice de masa corporal de 32 ± 5,9 kg/m2, HbA1c de 7,3 ± 1,6 % y tensión arterial 135/80 mmHg. El 70% de los pacientes presentaba 2 o más factores de riesgo. El 48,1% presentaba ECV y el 40,9% enfermedad microvascular (31,4% nefropatía, 10,5% retinopatía, 8,3% neuropatía, 3,3% pie diabético). El 57,3% se encontraban con antiagregantes, 84,3% con inhibidores del sistema renina/angiotensina/aldosterona (iECAS/ARAII), 79,5% con estatinas. Asimismo, el 85,9% recibía metformina, seguido de inhibidores de la dipeptidil peptidasa-4 (iDDP4) (24,1%), insulina (22,2%), sulfonilureas (SU) (14,3%), inhibidores del cotransportador sodio-glucosa tipo 2 (iSGLT2) (9,8%), agonistas del receptor glucagón like (arGLP1) (3%) y glitazonas (1,3%). El 55,9% tenía HbA1c < = 7%, 61,7% TA <140/90 mmHg, 58,5% LDL <100 mg/dl y 28,5% LDL <70 mg/dl. Conclusiones: La mayoría de los pacientes con DM2 presentaba dos o más factores de riesgo cardiovasculares y una elevada prevalencia de complicaciones asociadas. Observamos un bajo alcance de los objetivos terapéuticos, así como también un bajo uso de fármacos con beneficio cardiovascular.

ABSTRACT Background: Cardiology has a leading role in the control and treatment of persons with type 2 diabetes mellitus (DM2). We do not have local epidemiological data about patients with DM2 treated by cardiologists. Objectives: The aim of this study was to evaluate the clinical characteristics, cardiovascular disease (CVD) and treatment of patients with DM2 attending a cardiology office. Methods: We conducted and observational study in 17 provinces of Argentina during three months. Results: A total of 694 patients were included in the study. Mean age was 64.7±10.5 years, time of disease progression 10.7±9.3 years, body mass index 32±5.9 kg/m2, HbA1c 7.3%±1.6, and blood pressure 135/80 mm Hg. Seventy percent of the patients presented two or more risk factors, 48.1% had CVD and microvascular disease was present in 40.9% of cases (kidney disease in 31.4%, retinopathy in 10.5%, neuropathy in 8.3% and diabetic foot in 3.3%). Patients were receiving antiplatelet agents in 57.3% of cases, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) in 84.3% and 79.5% were treated with statins. Hypoglycemic agents included metformin in 85.9% of patients, dipeptidyl peptidase 4 (DPP4) inhibitors in 24.1%, sulfonylureas (SU) in 14.3%, sodium-glucose co-transporter 2 (SGLT2) inhibitors in 9.8%, glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in 3% and glitazones in 1.3%. HbA1C levels ≤7% were achieved by 55.9% of patients, BP <140/90 mm Hg by 61.7%, and LDL-C <100 mg/dL by 58.5% and <70 mg/dL by 28.5%. Conclusions: Most patients with DM2 presented two or more cardiovascular risk factors and a high prevalence of associated complications. Treatment goals were achieved by a low number of patients and the use of medications with demonstrated cardiovascular benefit was low.

Clinical Management Strategies in Mild COVID-19 cases in Latin-America: A Decision Model / Estrategias de manejo clínico de casos leves de COVID-19 en América Latina: Modelo de decisión

COVID-19 pandemic is challenging Latin American health systems, which could benefit from information to make appropriate decisions in contexts of constrained health resources.Objective: to evaluate, in adult patients with suspected mild clinical forms of COVID-19, the clinical effectiveness (life expectancy) and resource consumption (days of hospitalization) of different management strategies.Methods: stochastic decision tree comparing the conventional strategy recommended by WHO - PAHO (diagnostic test for COVID-19 and hospitalization of patients testing positive) versus two alternative strategies (immediate addition of a prognostic test with hospitalization according to its result, or follow-up with hospitalization only in case of clinical deterioration).Results: the alternative management strategies showed expected clinical utility similar to the conventional strategy in 80 years-old base cases, and slightly lower in 60 years- and 40 years-old base cases, with lower consumption of hospitalization days. In sensitivity analysis, alternative strategies comparatively improved their expected clinical utility given a lower sensitivity of the diagnostic test or a higher ability of the follow-up to detect clinical worsening.Conclusions: in cases of suspected COVID-19 without pneumonic infiltrate or signs of severity, alternative strategies can be considered to avoid hospitalization for the majority of patients, especially if efficient follow-up modalities can be implemented. This information is valuable for health decision-makers, to carefully weight clinical and epidemiological elements and design locally feasible strategies.

La pandemia COVID-19 desafía los sistemas de salud de Latinoamérica, que podrían beneficiarse de información para tomar decisiones apropiadas, en contextos de escasez de recursos sanitarios.Objetivo: evaluar, en pacientes adultos con sospecha de formas clínicas leves de COVID-19, la efectividad clínica (expectativa de vida) y el consumo de recursos (días de hospitalización) de distintas estrategias de manejo. Métodos: árbol de decisión estocástico, comparando la estrategia convencional recomendada por OMS - OPS (prueba diagnóstica para COVID-19 y hospitalización ante resultado positivo) versus dos estrategias alternativas (agregado inmediato de una prueba pronóstica con hospitalización según ese resultado, y seguimiento con hospitalización sólo ante empeoramiento clínico). Resultados: las estrategias de manejo alternativas mostraron utilidad clínica esperada similar a la estrategia convencional en casos base de 80 años de edad, y ligeramente inferior en casos base de 60 años y 40 años de edad, con menor consumo de días de hospitalización. En el análisis de sensibilidad, las estrategias alternativas mejoraron comparativamente su utilidad clínica esperada si la sensibilidad de la prueba diagnóstica fuera menor o la capacidad del seguimiento para detectar empeoramiento clínico fuera mayor. Conclusiones: ante casos sospechosos de COVID-19 sin infiltrado neumónico ni signos de gravedad, pueden considerarse estrategias que eviten la hospitalización de la mayoría de los pacientes, en especial si pueden implementarse modalidades de seguimiento eficientes. Esta información es valiosa para los decisores en salud, para analizar ponderadamente elementos clínicos y epidemiológicos y diseñar estrategias factibles localmente.

[Argentine Presidential Medical Unit. Survey of the Argentine hospital network and resources for golden hour pathologies.] / Unidad Médica Presidencial Argentina. Relevamiento de la red hospitalaria Argentina y recursos para patologías de hora de oro.

Introduction: Presidential medical units are intended to protect the dignitary's health in multiple aspects and work in close relationship with security. There are three central areas of coverage: myocardial infarction, stroke and trauma. By 2016 we had not found information about the resources on medical centers in Argentina and their integration into healthcare networks. Objective: Describe the relevant medical centers and their available resources for the medical coverage areas mentioned. Methods: It is a descriptive, cross-sectional study between 12/2016 and 8/2019. The sampling was not probabilistic and for convenience. Variables were reported as proportions and comparisons were made using the chi-square test or Fischer. Results: 232 centers were entered, 66.8% in capital cities and 67% in the public sector. Capitals were associated with a greater presence of resources: category 3 centers (OR 7.85; 95% CI 3.66-16.84; p <0.000001), angiography (OR 5.94; 95% CI 3.24-10.28; p <0.000001 ), tomography (OR 3.41; 95% CI 1.51-7.69; p=0.002), thrombolytics (OR 3.24; 95% CI 1.37-7.76; p=0.005); except trauma surgery (OR 1.83; 95% CI 0.75-4.46; p=0.17). Private centers were associated with greater resources for reperfusion; and public centers for trauma treatment. Conclusions: There is an unbalanced distribution of key resources between capital and non-capital cities in large geographical areas that makes it impossible to develop an adequate network for the treatment of heart attack, stroke and trauma. The best quality of care requires combining public and private networks.

Introducción: Las unidades médicas presidenciales están destinadas a proteger la salud del dignatario en múltiples aspectos y en íntima relación con la seguridad. Existen tres áreas centrales de cobertura: el infarto de miocardio, el accidente cerebrovascular y trauma. Hacia el año 2016 no hemos hallado información sobre los recursos de los centros médicos en Argentina y su integración en redes de atención. Objetivo: Describir los centros médicos relevados y sus recursos para las áreas médicas de cobertura mencionadas. Métodos: Es un estudio descriptivo, de corte trasversal entre 12/2016 y 8/2019. El muestreo fue no probabilístico y por conveniencia. Las variables se reportaron como proporciones y las comparaciones se realizaron mediante el test de chi cuadrado o Fischer. Resultados: Ingresaron 232 centros, 66.8% en ciudades capitales y 67% del ámbito público. Las capitales se asociaron con mayor presencia de recursos: centros categoría 3 (OR 7.85; IC del 95% 3.66-16.84; p<0,000001), angiografía (OR 5.94; IC del 95% 3.24-10.28; p<0,000001), tomografía (OR 3.41; IC del 95% 1.51-7.69; p=0,002), trombolíticos (OR 3.24; IC del 95% 1.37-7.76; p=0,005); excepto cirugía de trauma (OR 1.83; IC del 95% 0.75-4.46; p=0,17). Los centros privados se asociaron con mayores recursos para la reperfusión; y los centros públicos para el tratamiento del trauma. Conclusiones: Se observa una desbalanceada distribución de recursos claves entre ciudades capitales y no capitales en extensas áreas geográficas que imposibilita el desarrollo de una adecuada red para el tratamiento del infarto, accidente cerebrovascular y trauma. La mejor calidad de atención requiere combinar redes públicas y privadas.

Eficacia, seguridad y aplicabilidad clínica de los inhibidores de la PCSK9 / Efficacy, Safety and Clinical Applicability of PCSK9 Inhibitors

RESUMEN Los inhibidores de la proproteína convertasa subtilisina kexina tipo 9 (iPCSK9) representan un nuevo grupo de fármacos hipolipemiantes, que han generado un cambio sustancial en el manejo clínico de los lípidos. En pocos años, una gran cantidad de estudios han evaluado la eficacia antilipídica y la seguridad de estos fármacos. Más recientemente, grandes ensayos clínicos aleatorizados demostraron que el descenso del C-LDL alcanzado con estos fármacos se asoció con una menor incidencia de eventos cardiovasculares. Dicha evidencia dio lugar a la aprobación y comercialización de los iPCSK9 en muchos países. En consecuencia, diversas sociedades científicas y organismos de referencia en salud incorporaron estos fármacos en el arsenal terapéutico de la dislipidemia, con el objetivo de reducir el riesgo cardiovascular residual. En esta revisión describiremos la eficacia y la seguridad de estos fármacos, analizaremos la evidencia disponible acerca del beneficio cardiovascular y discutiremos en qué población podría ser más efectiva su utilización.

SUMMARY Proprotein convertase subtilisin kexin type 9 (iPCSK9) inhibitors represent a new group of lipid-lowering drugs that have generated a substantial change in lipid management. In a few years, a large number of studies have evaluated the lipid efficacy and safety of these drugs. More recently, large randomized clinical trials showed that the decrease in LDL-C achieved with these drugs was associated with a lower incidence of cardiovascular events. Such evidence resulted in the approval and commercialization of iPCSK9 in many countries. Consequently, various scientific societies and health reference agencies incorporated these drugs into the therapeutic arsenal of dyslipidemia, with the aim of reducing residual cardiovascular risk. In this review, we will describe the efficacy and safety of these drugs, analyze the available evidence about cardiovascular benefit, and discuss in which population their use might be most effective.

Agent-based computational models to explore diffusion of medical innovations among cardiologists.

BACKGROUND: Diffusion of medical innovations among physicians rests on a set of theoretical assumptions, including learning and decision-making under uncertainty, social-normative pressures, medical expert knowledge, competitive concerns, network performance effects, professional autonomy or individualism and scientific evidence. OBJECTIVES: The aim of this study was to develop and test four real data-based, agent-based computational models (ABM) to qualitatively and quantitatively explore the factors associated with diffusion and application of innovations among cardiologists. METHODS: Four ABM were developed to study diffusion and application of medical innovations among cardiologists, considering physicians' network connections, leaders' opinions, "adopters' categories", physicians' autonomy, scientific evidence, patients' pressure, affordability for the end-user population, and promotion from companies. RESULTS: Simulations demonstrated that social imitation among local cardiologists was sufficient for innovation diffusion, as long as opinion leaders did not act as detractors of the innovation. Even in the absence of full scientific evidence to support innovation, up to one-fifth of cardiologists could accept it when local leaders acted as promoters. Patients' pressure showed a large effect size (Cohen's d > 1.2) on the proportion of cardiologists applying an innovation. Two qualitative patterns (speckled and granular) appeared associated to traditional Gompertz and sigmoid cumulative distributions. CONCLUSIONS: These computational models provided a semiquantitative insight on the emergent collective behavior of a physician population facing the acceptance or refusal of medical innovations. Inclusion in the models of factors related to patients' pressure and accesibility to medical coverage revealed the contrast between accepting and effectively adopting a new product or technology for population health care.

Association between LDL-C, Non HDL-C, and Apolipoprotein B Levels with Coronary Plaque Regression / Associação entre Níveis De LDL-C, Não-HDL-C E Apolipoproteína B com Regressão de Placa Coronariana

Previous reports have inferred a linear relationship between LDL-C and changes in coronary plaque volume (CPV) measured by intravascular ultrasound. However, these publications included a small number of studies and did not explore other lipid markers.

Estudos prévios sugerem uma relação linear entre o LDL-C e mudanças no volume de placa coronariana (VPC) medido por ultrassonografia intravascular. No entanto, estas publicações incluíram um número pequeno de estudos e não exploraram outros marcadores lipídicos.

Estimation of the cost-effectiveness of apixaban versus vitamin K antagonists in the management of atrial fibrillation in Argentina.

Apixaban, a novel oral anticoagulant which has been approved for the prevention of stroke and systemic embolism in non-valvular atrial fibrillation, reduces both ischemic and haemorrhagic stroke and produces fewer bleedings than vitamin K antagonist warfarin. These clinical results lead to a decrease in health care resource utilization and, therefore, have a positive impact on health economics of atrial fibrillation. The cost-effectiveness of apixaban has been assessed in a variety of clinical settings and countries. However, data from emergent markets, as is the case of Argentina, are still scarce.We performed a cost-effectiveness analysis of apixaban versus warfarin in non-valvular atrial fibrillation (NVAF) in patients suitable for oral anticoagulation in Argentina. A Markov-based model including both costs and effects were used to simulate a cohort of patients with NVAF. Local epidemiological, resource utilization and cost data were used and all inputs were validated by a Delphi Panel of local experts. We adopted the payer's perspective with costs expressed in 2012 US Dollars.The study revealed that apixaban is cost-effective compared with warfarin using a willingness to pay threshold ranging from 1 to 3 per capita Gross Domestic Product (11558 - 34664 USD) with an incremental cost-effectiveness ratio of 786.08 USD per QALY gained. The benefit is primarily a result of the reduction in stroke and bleeding events.The study demonstrates that apixaban is a cost-effective alternative to warfarin in Argentina.

Estudio TAMARA II. Tabaquismo en médicos de la República Argentina II / The tamara ii trial. smoking among physicians in argentina

background: Smoking is the leading cause of preventable morbidity and death. It is important to know the characteristics of smoking habits among physicians and their attitude toward patients who smoke. Objective: The aim of this study is to investigate the prevalence of smoking among physicians in Argentina, the factors associated with tobacco consumption and their attitude toward their patients who smoke. Methods: An observational cross- sectional study was performed between June and December 2013 in Argentine physicians of dif-ferent specialties. Using a structured survey, the following variables were analyzed: associated cardiovascular risk factors, charac-teristics of tobacco consumption, smoking cessation training and the attitude toward the patient who smokes. results: 3,033 physicians were surveyed, ; 57% were men, and mean age was 41.3±12 years; 19.7% were current smokers and 21.7% were former smokers. The probability of being a smoker was higher among surgeons (OR 1.29) or physicians working at the emergency room (OR 1.41). Undergraduate and postgraduate tobacco cessation training was achieved by 36.6% and 40.8% of physicians, respectively. Young physicians, clinical specialties or private practice were associated with higher level of training. Tobacco cessation counseling was more frequent in physicians with higher level of training than physicians who smoked or surgeons. Former smokers presented higher prevalence of risk factors and cardiovascular events. Family history of smoking habit was more common in former smokers and current smokers. Conclusions: The prevalence of smoking among Argentine physicians is high. Different factors are involved in the probability of smoking, tobacco cessation training or the possibility of medical counseling. Higher level of training in smoking cessation must be provided.

Association between LDL-C, Non HDL-C, and Apolipoprotein B Levels with Coronary Plaque Regression.

BACKGROUND: Previous reports have inferred a linear relationship between LDL-C and changes in coronary plaque volume (CPV) measured by intravascular ultrasound. However, these publications included a small number of studies and did not explore other lipid markers. OBJECTIVE: To assess the association between changes in lipid markers and regression of CPV using published data. METHODS: We collected data from the control, placebo and intervention arms in studies that compared the effect of lipidlowering treatments on CPV, and from the placebo and control arms in studies that tested drugs that did not affect lipids. Baseline and final measurements of plaque volume, expressed in mm3, were extracted and the percentage changes after the interventions were calculated. Performing three linear regression analyses, we assessed the relationship between percentage and absolute changes in lipid markers and percentage variations in CPV. RESULTS: Twenty-seven studies were selected. Correlations between percentage changes in LDL-C, non-HDL-C, and apolipoprotein B (ApoB) and percentage changes in CPV were moderate (r = 0.48, r = 0.47, and r = 0.44, respectively). Correlations between absolute differences in LDL-C, non­HDL-C, and ApoB with percentage differences in CPV were stronger (r = 0.57, r = 0.52, and r = 0.79). The linear regression model showed a statistically significant association between a reduction in lipid markers and regression of plaque volume. CONCLUSION: A significant association between changes in different atherogenic particles and regression of CPV was observed. The absolute reduction in ApoB showed the strongest correlation with coronary plaque regression.

Adaptación para la Argentina y evaluación de las propiedades psicométricas del Cuestionario sobre la Dieta Restrictiva de Sodio en pacientes con insuficiencia cardíaca / Evaluation of Psychometric Properties in the Argentine-Adapted Dietary Sodium Restriction Questionnaire in Heart Failure Patients

Introducción: El Cuestionario sobre la Dieta Restrictiva de Sodio [Dietary Sodium Restriction Questionnaire (DSRQ)] está basado en la teoría del comportamiento planificado. Originalmente desarrollado en inglés, este instrumento, compuesto por tres subescalas (en 16 ítems que evalúan los parámetros vinculados con la actitud en relación con el comportamiento, la norma subjetiva y el control comportamental percibido), identifica los factores que afectan la adhesión a la dieta hiposódica en pacientes con insuficiencia cardíaca congestiva (ICC). Objetivos: Realizar la adaptación transcultural del DSRQ en idioma español para su utilización en la Argentina y evaluar las propiedades psicométricas (validez y confiabilidad). Material y métodos: La adaptación transcultural se realizó con la metodología recomendada (traducción, síntesis, revisión y retrotraducción). La validez se determinó mediante análisis de forma y factorial de componentes principales con la extracción de factores y rotación Varimax. El análisis de la confiabilidad se efectuó mediante el cálculo de la consistencia interna (alfa de Cronbach) y la correlación ítem-total de la escala. Resultados: En la adaptación transcultural se adaptaron los encabezados y solamente una pregunta tuvo alteraciones semánticas relevantes. Para el análisis de las propiedades psicométricas se incluyeron 230 pacientes con ICC. La proporción de datos faltantes fue muy baja (0,20%). En el análisis de componentes principales se extrajeron tres factores. Luego de la rotación Varimax, los ítems se agruparon con los factores seleccionados, coincidiendo con las tres subescalas originales. En el análisis ítem-total, ninguna correlación mostró un valor < 0,30. El alfa de Cronbach global fue de 0,86 (0,89, 0,71 y 0,89 para las tres subescalas, de actitud en relación con el comportamiento, norma subjetiva y control comportamental percibido, respectivamente). Conclusiones: En nuestro trabajo se realizó por primera vez la adaptación transcultural del DSRQ al español para su utilización en la Argentina; la confiabilidad y la validez de esta versión del instrumento fueron adecuadas.

Background: The Dietary Sodium Restriction Questionnaire (DSRQ) is based on the theory of planned behavior. Originally developed in English, this instrument, consisting of three subscales (divided in 16 items evaluating the parameters associated with attitude relative to behavior, the subjective norm and the perceived behavioral control), identifies the factors affecting adherence to low-sodium diet in patients with congestive heart failure (CHF). Objectives: The purpose of this study was to perform the DSRQ transcultural adaptation into Spanish to be used in Argentina and assess its psychometric properties (validity and reliability). Methods: The transcultural adaptation was done with the recommended methodology (translation, synthesis, revision and back translation). Its validity was explored by principal component structure and factor analysis with factor extraction and Varimax rotation. Reliability was analyzed by internal consistency calculation (Cronbach's alpha) and the item-total scale correlation. Results: Headlines were adjusted and one question only had relevant semantic changes in the transcultural adaptation. A total of 230 CHF patients were included for the psychometric analysis. The proportion of missing data was very low (0.20%). Three factors were extracted from the main component analysis. After Varimax rotation, the items were grouped with the selected factors, matching the three original subscales. In the item-total analysis, no correlation showed a value < 0.30. Global Cronbach's alpha was 0.86 (0.89, 0.71 and 0.89 for the three subscales, of attitude relative to behavior, subjective norm and perceived behavioral control, respectively). Conclusions: We performed for the first time the DSRQ transcultural adaptation into Spanish for its use in Argentina. This version of the instrument showed adequate validity and reliability.