A Survey of Availability and Affordability of Polypills for Cardiovascular Disease in Selected Countries.

Background: The recent inclusion of polypills-fixed-dose combinations of antihypertensive medicines and a statin with or without aspirin-in the World Health Organization's Essential Medicines List (EML) reiterates the potential of this approach to improve global treatment coverage for cardiovascular diseases (CVDs). Although there exists extensive evidence on the effectiveness, safety and acceptability of polypills, there has been no research to date assessing the real-world availability and affordability of polypills globally. Methods: We conducted a cross-sectional survey, based on the WHO/Health Action International methodology, in 13 countries around the world. In the surveyed countries, we first ascertained whether any polypill was authorised for marketing and/or included in EMLs and clinical guidelines. In each country, we collected retail and price data for polypills from at least one public-sector facility and three private pharmacies using convenience sampling. Polypills were considered unaffordable if the lowest-paid worker spent more than a day's wage to purchase a monthly supply. Results: Polypills were approved for marketing in four of the 13 surveyed countries: Spain, India, Mauritius and Argentina. None of these countries included polypills in national guidelines, formularies, or EMLs. In the four countries, no surveyed public pharmacies stocked polypills. In the private sector, we identified seven unique polypill combinations, marketed by eight different companies. Private sector availability was 100% in Argentina and Spain. Most combinations (n = 5) identified were in India. Combinations found in India and Spain were affordable in the local context. A lowest-paid government worker would spend between 0.2 (India) and 2.8 (Mauritius) days' wages to pay the price for one month's supply of the polypills. Polypills were likely to be affordable if they were manufactured in the same country. Conclusion: Low availability and affordability of polypills in the public sector suggest that implementation remains poor globally. Context-specific multi-disciplinary health system research is required to understand factors affecting polypill implementation and to design and evaluate appropriate implementation strategies.

Análise do perfil lipídico de pacientes com diabetes tipo II com evento macrovascular estabelecido / Analysis of the lipid profile of patients with type II diabetes with predicted macrovascular event

Introdução: O termo diabetes mellitus (DM) descreve um distúrbio metabólico de etiologia múltipla caracterizado por hiperglicemia crônica decorrente de uma secreção deficiente de insulina e/ou incapacidade da mesma exercer adequadamente a sua função. Os efeitos desta enfermidade incluem danos a longo prazo, disfunção e falência de vários órgãos. Dentro deste contexto, a resistência à insulina e hiperinsulinemia são as principais forças motrizes no desenvolvimento da dislipidemia e representam um elo importante entre a obesidade e o desenvolvimento do diabetes tipo 2 e doenças cardiovasculares (DCV). Objetivo : Por conta da já determinada relação entre dislipidemia, DM e DCV, pretende se analisar os perfis lipídicos de pacientes com diabetes tipo II com eventos macrovasculares estabelecidos. Metodologia : Estudo observacional transversal, do tipo retrospectivo. Foram avaliados 60 pacientes atendidos no Ambulatório de Diabetes da especialidade de Endocrinologia e Metabologia do Hospital do Servidor Público Municipal de São Paulo , no período de janeiro a julho de 2022, através da análise de prontuários. Os pacientes foram divididos em dois grupos de acordo com os valores de triglicérides (TG): TG acima de 200 mg/dl e TG abaixo de 200 mg/dl, a fim de organizar e estabelecer os valores de colesterol de lipoproteína de baixa densidade (LDL) e colesterol de lipoproteína de não alta densidade (não HDL), preconizados como meta pela Sociedade Brasileira de Diabetes. Os pacientes também foram divididos de acordo com a medicação utilizada para o tratamento da dislipidemia. Resultados: A amostra foi composta majoritariamente por mulheres (56,7%), idosos (70%) e etnia caucasiana (6 6,7%). Nota se não alcance das metas lipídicas em 93,2% dos pacientes com níveis de TG menor es que 200mg/dL e em 100% dos pacientes com níveis de TG maior es que 200mg/dL, mesmo em uso , pela maioria, de medicação adequada (estatina de alta potência 71,7%). Dentre os 6 indivíduos que utilizavam fibrato, 2 obedeciam aos critérios do uso desta medicação, no determinado momento da coleta de dados, para redução do risco cardiovascular, que são: valores de TG maiores que 204 mg/dL e valores de HDL menores que 34 mg/d L . No estudo, os valores de LDL variaram de 39,0 a 249,0 mg/dL, com média 88,5 ± 36,7, enquanto os valores de não HDL variaram de 53,0 a 295,0 mg/dL, com média 117,3 ± 44,4. Triglicérides variou de 51,0 a 609,0 mg/dL, apresentando média 171,2 ± 101,8. Não houve associação significativa entre meta para colesterol e características sociodemográficas como sexo (p=0,076), idade (p=0,547) e etnia (p=0,582). Assim como também não houve associação significativa entre meta para colesterol e potência no uso das estatinas (p=0,903). Conclusão: O estudo exibiu um perfil lipídico desfavorável, a análise correta dos valores lipídicos e alcance das metas dos valores de colesterol em pacientes com diabetes classificados como muito alto risco cardiovascular é fundamental para evitar novos eventos macrovasculares. Neste trabalho, ficou evidente a quantidade de fatores que podem influenciar na obtenção dos níveis lipídicos desejados e preconizado s por diversas diretrizes. Palavras chave: Diabetes Mellitus. Hiperlipidemias. Doenças Cardiovasculares. Angiopatias Diabéticas.

Prescription of statins according to the ASCVD estimator at Pablo Arturo Suarez Hospital, March 2021 to February 2022 / Prescripción de estatinas según el estimador ASCVD en el Hospital Pablo Arturo Suárez, marzo 2021 a febrero 2022

Worldwide, the leading cause of death is cardiovascular disease. The study details the prescription of statins at the Pablo Arturo Suarez Hospital in Ecuador between March 2021 and February 2022 following the ASCVD risk scale of the American College of Cardiology and the American Heart Association. There are 563 people in this cross-sectional and retrospective study: 70% women, 30% men, 93.30% mestizos, 48.10% diabetics, 62.30% hypertensives, and 18.70% smokers. 26.10% of all patients received statins, with simvastatin being the most common (96.60%). The mean cardiovascular risk in the general population was 15.52 ± 14.51%, 44.99% of subjects had a risk lower than 7.50%, and 29% had a risk higher than 20%, with a statistically significant difference (p<0.001) according to sex. The study determined that 58.60% of the population received a statin or an inadequate dosage.

A nivel mundial, la principal causa de muerte es la enfermedad cardiovascular. El estudio detalla la prescripción de estatinas en el Hospital Pablo Arturo Suárez de Ecuador entre marzo de 2021 y febrero de 2022, siguiendo la escala de riesgo ASCVD del Colegio Americano de Cardiología y la Asociación Americana del Corazón. Son 563 personas en este estudio transversal y retrospectivo: 70% mujeres, 30% hombres, 93.30% mestizos, 48.10% diabéticos, 62.30% hipertensos y 18.70% fumadores. El 26.10% de los pacientes recibía estatinas, siendo la simvastatina la más frecuente (96.60%). El riesgo cardiovascular medio en la población general fue de 15.52 ± 14.51%, el 44.99% de los sujetos tenía un riesgo inferior al 7.50%, y el 29% tenía un riesgo superior al 20%, con una diferencia estadísticamente significativa (p<0.001) según el sexo. El estudio determinó que el 58.60% de la población recibía una estatina o una dosis inadecuada.

Are statins a risk factor in patients with atherosclerosis? / ¿Son las estatinas un factor de riesgo en pacientes con aterosclerosis?

SUMMARY: Statins inhibit cholesterol synthesis, but also have other pleiotropic effects. There are indications that they affect macrophage survival trough the regulation of apoptosis. We analyzed 50 samples of aortic wall, selected based on statins in patients' therapy (n=25, Th-S group) or statin-free therapy (n=25, Th-nonS group). Each group had 5 samples of healthy aortic tissue, 10 samples of mild and 10 samples of severe atherosclerotic changes in aortic wall. Tissue was stained with hematoxylin-eosin and immunohistochemical methods (anti-Bcl-2 antibody). Presence of Bcl2-positive macrophages (Bcl-2+ MP) was determined semiquantitatively, and data were processed in Microsoft Excell and IMB SPSS 23 Statistics. 60 % of patients in the Th-S group had a mild increase of Bcl-2+ MP The use of statins leads to a significantly more frequent increase in Bcl2+ macrophages in the intima of the healthy aortic tissue. Analysis of all aortic samples with pathohistological diagnosis showed that statin therapy was statistically significantly more often leading to a markedly increased presence of Bcl-2+ MP. In the media, all samples of the Th-S group have a mild increase of Bcl-2+ MP, and in adventitia 40 % of patients. The use of statins more often leads to a markedly increased presence of Bcl-2+ MP in aortic tissue with diagnosed mild and severe atherosclerosis. In samples of severe atherosclerosis, statins lead to a markedly increased presence of Bcl-2+ MP in the parts of the plaque towards the intima and towards the media. Statins lead to an increased presence of Bcl-2+ macrophages, prolong their life, both in healthy and atherosclerotic altered aortic tissue. This indicates potentiation of inflammation and damage to the aortic wall, and calls into question the positive effect of statins on the aortic wall with atherosclerosis.

RESUMEN: Las estatinas inhiben la síntesis de colesterol, pero también tienen otros efectos pleiotrópicos. Hay indicios de que afectan la supervivencia de los macrófagos a través de la regulación de la apoptosis.Se analizaron 50 muestras de pared aórtica, seleccionadas en base a estatinas en tratamiento de pacientes (n=25, grupo Th-S) o en tratamiento libre de estatinas (n=25, grupo Th- nonS). Cada grupo tenía 5 muestras de tejido aórtico sano, 10 muestras de cambios ateroscleróticos leves y 10 muestras de cambios ateroscleróticos severos en la pared aórtica. El tejido se tiñó con hematoxilina-eosina y métodos inmunohistoquímicos (anticuerpo anti-Bcl-2). La presencia de macrófagos positivos para Bcl2 (Bcl- 2+ MP) se determinó semicuantitativamente y los datos se procesaron en Microsoft Excell e IMB SPSS 23 Statistics. El 60 % de los pacientes del grupo Th-S tuvo un aumento leve de Bcl-2+ MP. El uso de estatinas conduce a un aumento significativamente más frecuente de macrófagos Bcl2+ en la íntima del tejido aórtico sano. El análisis de todas las muestras aórticas con diagnóstico anatomopatológico mostró que la terapia con estatinas fue significativamente más frecuente desde el punto de vista estadístico, lo que condujo a una presencia marcadamente mayor de Bcl-2+ MP. En los medios, todas las muestras del grupo Th-S tienen un leve aumento de Bcl-2+ MP, y en adventicia en el 40 % de los pacientes. El uso de estatinas con mayor frecuencia conduce a una presencia marcadamente mayor de MP Bcl-2+ en el tejido aórtico con aterosclerosis leve y grave diagnosticada. En muestras de aterosclerosis severa, las estatinas conducen a una presencia aumentada de Bcl-2+ MP en las partes de la placa hacia la íntima y hacia la media. Las estatinas conducen a una mayor presencia de macrófagos Bcl-2+, prolongan su vida, tanto en tejido aórtico sano como aterosclerótico alterado. Esto indica la potenciación de la inflamación y el daño a la pared aórtica y pone en duda el efecto positivo de las estatinas en la pared aórtica con aterosclerosis.

Prescription of statins and pharmacokinetic interactions in Colombian patients.

Background: Statins have extensive hepatic metabolism and can have multiple pharmacological interactions. The aim was to identify the main pharmacokinetic interactions between statins and their comedications in a group of patients from Colombia.Research design and methods: A cross-sectional study of pharmacokinetic interactions in patients treated with statins who were identified from a population database. The interactions were documented using the Lexicomp® database.Results: A total of 123,026 patients with statin prescriptions were identified, with a mean age of 68.4 ± 11.5 years; 57.1% were women, and 81.6% received atorvastatin. A total of 19.4% (n = 23.831) of patients presented pharmacological interactions. Some 15,474 (12.6%) had interactions classified as category C, 7.4% (n = 9077) as category D, and 0.5% (n = 660) as category X. 36.8% of the patients with lovastatin prescriptions had some interaction. Age older than 65 years, male sex, residence in capital cities, comorbidities, endocrine pathologies and HIV were associated with an increase in the probability of having contraindicated or risky interactions.Conclusions: Important interactions between statins and other medications were more common in adults over 65 years of age and those with endocrine comorbidities or HIV infection. This knowledge should help when proposing solutions that reduce the risk of adverse reactions.

Safety of Chronic Simvastatin Treatment in Patients with Decompensated Cirrhosis: Many Adverse Events but No Liver Injury.

BACKGROUND: The high mortality rate of decompensated cirrhosis underlines the need for new treatments. Experimental models of cirrhosis and its reported relationship with atherosclerotic cardiovascular disease have provided data supporting the rational use of statins in these patients. However, little is known about the safety of statins in this setting. AIM: We evaluate the safety of chronic simvastatin treatment in patients with decompensated cirrhosis. METHODS: We conducted a prospective, open, uncontrolled, phase 2a trial in 30 patients with Child-Pugh class A (n = 6), B (n = 22), and C (n = 2) decompensated cirrhosis. The patients received standard treatment throughout the trial plus simvastatin 20 mg/day for 2 weeks and thereafter simvastatin 40 mg/day up to 1 year. RESULTS: Sixteen out of 30 patients (53.3%) showed adverse events, including gastrointestinal toxicity (36.7%), muscle injury (MI) (36.7%), and headache (13.3%). No liver injury was registered. Due to MI alone, simvastatin dosage was reduced in 23.4% of cases and transiently interrupted in 13.3%. Once these adverse events were overcome, simvastatin was resumed until the end of the trial. MI was associated with baseline MELD score > 12 (p = 0.035) and with baseline Child-Pugh class C. No MI was associated with final Child-Pugh score ≤ 6 (p = 0.030) or final Child-Pugh class A (p = 0.020). CONCLUSIONS: Chronic treatment with simvastatin 40 mg/day in patients with decompensated cirrhosis was associated with several adverse events, being MI the only clinically significant one, which appears to be related to the simvastatin dosage and the degree of cirrhosis severity. Noticeably, no liver injury was recorded.

Effect of statins on development of post thrombotic syndrome: cohort study. / Efecto de las estatinas en el desarrollo de síndrome postrombótico: estudio de cohorte

Objetivo: Explorar la asociación entre consumo de estatinas (CE) y desarrollo de síndrome postrombótico (SPT). Método: Cohorte retrospectiva con pacientes con primer episodio de trombosis venosa profunda (TVP) entre el 06/2006 y el 12/2017, incluidos en el Registro Institucional de Enfermedad TromboEmbólica (RIET) del Hospital Italiano de Buenos Aires. Se consideró exposición al CE entre los 30 días previos y hasta 180 días posterior al diagnóstico de TVP. Se definió SPT según constaba este dato en la base de seguimiento del RIET. Se evaluó el desarrollo de SPT con un modelo de riesgos proporcionales de Cox, reportando hazard ratios (HR) crudas y ajustadas. Se consideró la confusión por indicación del CE y se utilizó un propensity score (PS) para el ajuste del riesgo estimado, reportando los HR con sus intervalos de confianza del 95% (IC 95%). Resultados: Se incluyeron 905 pacientes, de los cuales 273 fueron CE y 632 no consumidor de estatinas (NCE). Al seguimiento, la incidencia de SPT fue: 6.59% (18) en el grupo CE y 8.07% (51) en el grupo NCE, con p = 0.412. La razón de riesgo para el desarrollo de SPT de CE resultó no significativa (HR cruda: 0.78; IC 95%: 0.43-1.41; p = 0.414). La HR de CE ajustada por edad, sexo, antiinflamatorios no esteroideos, corticosteroides, inmovilidad, anticoagulante, hipertensión arterial, diabetes, dislipidemia, insuficiencia renal crónica, enfermedad coronaria, accidente cerebrovascular, insuficiencia cardiaca y enfermedad oncológica fue 0.45 (IC 95%: 0.13-1.5; p = 0.196). La HR del CE ajustado por edad, sexo, antiinflamatorios no esteroideos, corticosteroides, inmovilidad, tratamiento anticoagulante, enfermedad oncológica y PS fue de 0.52 (IC 95%: 0.17-1.66; p = 0.272). Conclusiones: El CE no se asoció con menor SPT, aunque hubo escaso número de eventos detectados. Objective: To evaluate the association between statin consumption and development of post-thrombotic syndrome (PTS). Methods: Retrospective cohort study which included patients with a first episode of deep vein thrombosis (DVT) between 06/2006 and 12/2017, included in the Institutional Registry of ThromboEmbolic Disease of the Italian Hospital of Buenos Aires, Argentina. Exposure to statin use (SU) was considered between the 30 days before and up to 180 days after the diagnosis of DVT. PTS was defined as recorded dataset on registry. The development of PTS was evaluated with Cox proportional hazards model, raw and adjusted hazard ratios (HR) were reported. Confusion was considered by indication of SU and a propensity score (PS) was used for adjustment. We reported HR with their 95% confidence interval (CI); p value < 0.05 was considered statistically significant. Results: Of 1393 patients, 905 were included for the analysis, of which 273 were SU and 632 non-statin users (NSU). At follow-up, incidence of PTS was: 6.59% (18) in the SU group and 8.07% (51) in the NSU group, with p = 0.412. Crude HR for PTS for SU was not significant (0.78; 95% CI: 0.43-1.41; p = 0.414). Adjusted HR of SU by age, sex, non-steroidal anti-inflammatory drugs, corticosteroids, immobility, anticoagulant, high blood pressure, diabetes, dyslipidemia, chronic renal failure, coronary heart disease, stroke, heart failure and cancer disease was 0.45 (95% CI: 0.13-1.5; p = 0.196) for PTS. While HR for the development of PTS adjusted by age, sex, non-steroidal anti-inflammatory drugs, corticosteroids, immobility, anticoagulant treatment, cancer disease and PS of the SU was 0.52 (95% CI: 0.17-1.66; p = 0.272). Conclusion: No statistically significant association was found between CE and the development of SPT, although there were a small number of events detected in both groups.

Efecto de las estatinas en el desarrollo de síndrome postrombótico: estudio de cohorte / Effect of statins on development of post thrombotic syndrome: cohort study

Resumen Objetivo: Explorar la asociación entre consumo de estatinas (CE) y desarrollo de síndrome postrombótico (SPT). Método: Cohorte retrospectiva con pacientes con primer episodio de trombosis venosa profunda (TVP) entre el 06/2006 y el 12/2017, incluidos en el Registro Institucional de Enfermedad TromboEmbólica (RIET) del Hospital Italiano de Buenos Aires. Se consideró exposición al CE entre los 30 días previos y hasta 180 días posterior al diagnóstico de TVP. Se definió SPT según constaba este dato en la base de seguimiento del RIET. Se evaluó el desarrollo de SPT con un modelo de riesgos proporcionales de Cox, reportando hazard ratios (HR) crudas y ajustadas. Se consideró la confusión por indicación del CE y se utilizó un propensity score (PS) para el ajuste del riesgo estimado, reportando los HR con sus intervalos de confianza del 95% (IC 95%). Resultados: Se incluyeron 905 pacientes, de los cuales 273 fueron CE y 632 no consumidor de estatinas (NCE). Al seguimiento, la incidencia de SPT fue: 6.59% (18) en el grupo CE y 8.07% (51) en el grupo NCE, con p = 0.412. La razón de riesgo para el desarrollo de SPT de CE resultó no significativa (HR cruda: 0.78; IC 95%: 0.43-1.41; p = 0.414). La HR de CE ajustada por edad, sexo, antiinflamatorios no esteroideos, corticosteroides, inmovilidad, anticoagulante, hipertensión arterial, diabetes, dislipidemia, insuficiencia renal crónica, enfermedad coronaria, accidente cerebrovascular, insuficiencia cardiaca y enfermedad oncológica fue 0.45 (IC 95%: 0.13-1.5; p = 0.196). La HR del CE ajustado por edad, sexo, antiinflamatorios no esteroideos, corticosteroides, inmovilidad, tratamiento anticoagulante, enfermedad oncológica y PS fue de 0.52 (IC 95%: 0.17-1.66; p = 0.272). Conclusiones: El CE no se asoció con menor SPT, aunque hubo escaso número de eventos detectados.

Abstract Objective: To evaluate the association between statin consumption and development of post-thrombotic syndrome (PTS). Methods: Retrospective cohort study which included patients with a first episode of deep vein thrombosis (DVT) between 06/2006 and 12/2017, included in the Institutional Registry of ThromboEmbolic Disease of the Italian Hospital of Buenos Aires, Argentina. Exposure to statin use (SU) was considered between the 30 days before and up to 180 days after the diagnosis of DVT. PTS was defined as recorded dataset on registry. The development of PTS was evaluated with Cox proportional hazards model, raw and adjusted hazard ratios (HR) were reported. Confusion was considered by indication of SU and a propensity score (PS) was used for adjustment. We reported HR with their 95% confidence interval (CI); p value < 0.05 was considered statistically significant. Results: Of 1393 patients, 905 were included for the analysis, of which 273 were SU and 632 non-statin users (NSU). At follow-up, incidence of PTS was: 6.59% (18) in the SU group and 8.07% (51) in the NSU group, with p = 0.412. Crude HR for PTS for SU was not significant (0.78; 95% CI: 0.43-1.41; p = 0.414). Adjusted HR of SU by age, sex, non-steroidal anti-inflammatory drugs, corticosteroids, immobility, anticoagulant, high blood pressure, diabetes, dyslipidemia, chronic renal failure, coronary heart disease, stroke, heart failure and cancer disease was 0.45 (95% CI: 0.13-1.5; p = 0.196) for PTS. While HR for the development of PTS adjusted by age, sex, non-steroidal anti-inflammatory drugs, corticosteroids, immobility, anticoagulant treatment, cancer disease and PS of the SU was 0.52 (95% CI: 0.17-1.66; p = 0.272). Conclusion: No statistically significant association was found between CE and the development of SPT, although there were a small number of events detected in both groups.

Dyslipidaemias and their treatment in high complexity centres in Colombia. / Las dislipidemias y su tratamiento en centros de alta complejidad en Colombia.

BACKGROUND AND OBJECTIVE: Data is scarce on the distribution of different types of dyslipidaemia in Colombia. The primary objective was to describe the frequency of dyslipidaemias. The secondary objectives were: frequency of cardiovascular comorbidity, statins and other lipid-lowering drugs use, frequency of statins intolerance, percentage of patients achieving c-LDL goals, and distribution of cardiovascular risk (CVR). MATERIALS AND METHODS: Cross-sectional study with retrospective data collection from 461 patients diagnosed with dyslipidaemia and treated in 17 highly specialised centres distributed into six geographic and economic regions of Colombia. RESULTS: Mean (SD) age was 66.4 (±12.3) years and 53.4% (246) were women. Dyslipidaemias were distributed as follows in order of frequency: mixed dyslipidaemia (51.4%), hypercholesterolaemia (41.0%), hypertriglyceridaemia (5.4%), familial hypercholesterolaemia (3.3%), and low c-HDL (0.7%). The most prescribed drugs were atorvastatin (75.7%) followed by rosuvastatin (24.9%). As for lipid control, 55% of all patients, and 28.6% of those with coronary heart disease, did not achieve their personal c-LDL goal despite treatment. The frequency of statin intolerance was 2.6% in this study. CONCLUSIONS: Mixed dyslipidaemia and hypercholesterolaemia are the most frequent dyslipidaemias in Colombia. A notable percentage of patients under treatment with lipid-lowering drugs, including those with coronary heart disease, did not achieve specific c-LDL goals. This poor lipid control may worsen patient's CVR, so that therapeutic strategies need to be changed, either with statin intensification or addition of new drugs in patients with higher CVR.

Combination of statin/vitamin D and metastatic castration-resistant prostate cancer (CRPC): a post hoc analysis of two randomized clinical trials.

In castration-resistant prostate cancer (CRPC) patients, observational studies have reported that statins may boost the antitumor activity of abiraterone (AA) and data suggest an improvement in efficacy; conclusions with vitamin D are less clear but an eventual benefit has been pointed. We conducted a post hoc analysis of individual patient data of CRPC patients treated with prednisone and/or AA with or without statins/vitamin D on randomized clinical trials. In the COU-AA-301 trial, use of AA with statin and vitamin D reduced the risk of death by 38% (p = 0.0007) while AA alone was associated with a decrease of 10% (p = 0.025), compared to prednisone alone. Meanwhile, in the COU-AA-302 trial, use of AA plus statin plus vitamin D was associated with a reduced risk of death of 26% (p = 0.0054). In this data analysis from two prospective randomized clinical trials, statin and vitamin D use was associated with superior overall survival in metastatic CRPC patients treated with AA and prednisone. To our knowledge, this is the first report suggesting the impact of statin plus vitamin D in this population. New strategies using big data may help to clarify these questions easily and in a most cost-effective approach.

Multicap to improve adherence after acute coronary syndromes: results of a randomized controlled clinical trial.

BACKGROUND: Adherence to treatment after a myocardial infarction (MI) is poor, even in the early postinfarction period. Combining evidence-based drugs into a multicap could improve adherence in this population. No previous randomized trial assessing fixed-dose combination therapy has included patients early after a MI. We aimed to assess if a multicap containing four secondary prevention drugs increases adherence to treatment at 6 months after MI hospitalization. The study was designed as a randomized, parallel, open-label, controlled trial. METHODS: Patients were randomized within 7 days of a MI to either multicap or control group. The multicap group received a capsule containing aspirin, atenolol, ramipril, and simvastatin. The control group received each drug in separate pills. The primary outcome was adherence at 6 months. We also measured blood pressure, heart rate, serum cholesterol levels, C-reactive protein, and platelet aggregation. RESULTS: The study was stopped prematurely when 100 patients were included for futility. At 6 months, 92 (95.8%) patients were adherent to medical treatment: 98.0% in the multicap group and 93.5% in the control group [relative risk (RR) 1.05; 95% confidence interval (CI) 0.96-1.14; p = 0.347]. There were no differences between groups in systolic blood pressure (p = 0.662), diastolic blood pressure (p = 0.784), heart rate (p = 0.533), total cholesterol (p = 0.760), LDL-c (p = 0.979), C-reactive protein (p = 0.399), or in the proportion of patients with adequate platelet aggregation inhibition (p = 0.600). CONCLUSIONS: The study did not find any improvement in the adherence at 6 months after a MI with a multicap-based strategy (Multicap for Increase Adherence After Acute Myocardial Infarction; [ ClinicalTrials.gov identifier: NCT02271178]).

Statin Use in the Early Phase of ST-Segment Elevation Myocardial Infarction Is Associated With Decreased QTc Dispersion.

BACKGROUND: Although there is strong evidence supporting the use of statin therapy after myocardial infarction (MI), some mechanistic gaps exist regarding the benefits of this therapy at the very onset of MI. Among the potential beneficial mechanisms, statins may improve myocardial electrical stability and reduce life-threatening ventricular arrhythmia, as reported in stable clinical conditions. This study was designed to evaluate whether this mechanism could also occur during the acute phase of MI. METHODS: Consecutive patients with ST-segment elevation MI were treated without statin (n = 57) or with a simvastatin dose of 20 to 80 mg (n = 87) within the first 24 hours after MI symptom onset. Patients underwent digital electrocardiography within the first 24 hours and at the third and fifth days after MI. The QTC dispersion (QTcD) was measured both with and without the U waves. RESULTS: Although QTcD values were equivalent between the groups at the first day (80.6 ± 36.0 vs 80.0 ± 32.1; P = 0.36), they were shorter among individuals using simvastatin than in those receiving no statins on the third (90.4 ± 38.6 vs 86.5 ± 36.9; P = .036) and fifth days (73.1 ± 31 vs 69.2 ± 32.6; P = .049). We obtained similar results when analyzing the QTcD duration including the U wave. All values were adjusted by an ANCOVA model after propensity-score matching. CONCLUSIONS: Statins administered within 24 hours of ST-segment elevation MI reduced QTc dispersion, which may potentially attenuate the substrate for life-threatening ventricular arrhythmias.

Plasma mevalonic acid exposure as a pharmacodynamic biomarker of fluvastatin/atorvastatin in healthy volunteers.

Fluvastatin and atorvastatin are inhibitors of hydroxy-methylglutaryl-CoA (HMG-CoA) reductase, the enzyme that converts HMG-CoA to mevalonic acid (MVA). The present study reports for the first time the analysis of mevalonolactone (MVL) in plasma samples by UPLC-MS/MS as well as the use of MVA, analyzed as MVL, as a pharmacodynamics parameter of fluvastatin in multiple oral doses (20, 40 or 80 mg/day for 7 days) and atorvastatin in a single oral dose (20, 40 or 80 mg) in healthy female volunteers. this study presents the use of MVL exposure as a pharmacodynamics biomarker of fluvastatin in multiple oral doses (20, 40 or 80 mg/day for 7 days) or atorvastatin in a single oral dose (20, 40 or 80 mg) in healthy volunteers (n = 30). The administration of multiple doses of fluvastatin (n = 15) does not alter the values (geometric mean and 95 % CI) of AUC0-24 h of MVL [72.00 (57.49-90.18) vs 65.57 (51.73-83.12) ng∙h/mL], but reduces AUC0-6 h [15.33 (11.85-19.83) vs 8.15 (6.18-10.75) ng∙h/mL] by approximately 47 %, whereas single oral dose administration of atorvastatin (n = 15) reduces both AUC0-24 h [75.79 (65.10-88.24) vs 32.88 (27.05-39.96) ng∙h/mL] and AUC0-6 h [17.07 (13.87-21.01) vs 7.01 (5.99-8.22) ng∙h/mL] values by approximately 57 % and 59 %, respectively. In conclusion, the data show that the plasma exposure of MVL represents a reliable pharmacodynamic parameter for PK-PD (pharmacokinetic-pharmacodynamic) studies of fluvastatin in multiple doses and atorvastatin in a single dose.

Rosuvastatin reduced brain parasite burden in a chronic toxoplasmosis in vivo model and influenced the neuropathological pattern of ME-49 strain.

This study evaluated the effects of rosuvastatin in vivo on toxoplasmosis chronic infection. Thirty-five Swiss mice were orally infected (ME-49 strain). After 50 days, the mice were separated into five groups: GI - non-infected, GII - infected, GIII - infected and treated with pyrimethamine and sulfadiazine (12.5 + 50 mg kg-1 body weight day-1), GIV and GV - infected and treated with rosuvastatin 10 and 40 mg kg-1 body weight day-1, respectively. After 21 days, we collected blood, liver, lungs, femoral biceps and brain were removed for Toxoplasma gondii DNA quantification by qPCR and histopathological analysis. GIV and GV did not present premature death or clinical changes, and the hepatic enzyme levels were lower compared to GI. Toxoplasma gondii DNA was detected mainly in brain and muscle, but the parasite load was significantly lower in GV compared to GII brains (P < 0.05). Histopathological changes were observed in brains, with T. gondii cysts as well as an inflammatory condition, including necrosis areas in GII and GIII. These data confirm active infection with tissue injury. This inflammatory condition was attenuated in the groups treated with rosuvastatin, especially R40 (GV). Our findings demonstrated the in vivo action of rosuvastatin in reducing cerebral parasitic load and indicate that this drug may interfere in chronic toxoplasmosis.

FACTORS INFLUENCING ACHIEVEMENT OF LOW-DENSITY LIPOPROTEIN CHOLESTEROL GOALS IN MEXICO: THE INTERNATIONAL CHOLESTEROL MANAGEMENT PRACTICE STUDY.

BACKGROUND: The International Cholesterol Management Practice Study is a multinational collaborative effort to describe the effectiveness of the lipid-lowering therapy (LLT) as well as the main barriers to achieve the low-density lipoprotein cholesterol (LDL-C) goals. OBJECTIVE: The objective of the study was to investigate factors associated with the achievement of LDL-C goals in Mexico using real-life data. METHODS: This was a cross-sectional observational study from 18 physicians across different health facilities in Mexico, who provided information about their practices between August 2015 and August 2016. We included patients treated for ≥3 months with any LLT in whom LDL-C measurement on stable LLT was available for the previous 12 months. RESULTS: We included 623 patients with a mean age of 59.3 ± 12.7 years; 55.6% were women. The mean LDL-C value on LLT was 141.8 ± 56.1 mg/dL. At enrollment, 97.4% of patients were receiving statin therapy (11.3% on high-intensity treatment). Only 24.8% of the very-high cardiovascular (CV) risk patients versus 26.4% of the high risk and 52.4% of the moderate risk patients achieved their LDL-C goals. Independent factors associated with non-achievement of LDL-C goal were statin intolerance, overweight and obesity, abdominal obesity, female sex, high CV risk, use of public health-care service, metabolic syndrome, type 2 diabetes, and hypertriglyceridemia. Higher-level of education was associated with a lower risk of not achieving LDL-C goals. CONCLUSIONS: Achievement of LDL-C goals is suboptimal in Mexico, especially in patients with the highest CV risk. The main barriers to achieve the goal are easily detectable. Implementation of LLT should be adapted to the patient's needs and profile.

Lipid-lowering drug prescriptions in a group of Colombian patients. / Patrones de prescripción de hipolipemiantes en pacientes de Colombia

INTRODUCTION: Lipid-lowering drugs, especially statins, have shown great relevance in preventing and treating cardiovascular diseases. OBJECTIVE: To determine the prescription patterns of lipid-lowering drugs and the variables associated with their use in a Colombian population. MATERIALS AND METHODS: This is a cross-sectional descriptive study. From a drug dispensing database of approximately 4.5 million Colombian health system affiliates, patients of all ages and both sexes treated with lipid-lowering agents (statins, fibrates, ezetimibe) were identified between January and March, 2017. Demographic, pharmacological and co-medication variables were included. RESULTS: In total, 103,624 patients were identified as being treated with lipid-lowering agents. The average age was 67.5 years, and 49.8% were 65 years or older. Women comprised 58.0% of the patients. Statins were the most used (n=96,910; 93.5%), and atorvastatin (n=80,812; 78.0%) and lovastatin (n=12,621; 12.2%) were the most frequent. The mean atorvastatin dose was 30.3 mg/day, and 49.9% of its users received presentations of 40 mg or more. A total of 9,258 (8.9%) patients received fibrates, and only 780 (0.8%) were taking ezetimibe. Of this population, 94.9% were treated with lipid-lowering monotherapy, and 97.3% (n=100,813) had co-medication for their comorbidities, with the most frequent being antihypertensive (89.1%), antiplatelet (57.8%), antidiabetic (31.5%) and antiulcerative agents (34.2%). CONCLUSIONS: Atorvastatin is currently the most frequently used lipid-lowering drug in this group of Colombian patients, especially in monotherapy and at doses close to the defined daily dose. Only half received high-intensity doses. New studies are required to verify the efficacy of these therapies.

Introducción. Los fármacos hipolipemiantes, especialmente las estatinas, han demostrado gran relevancia para la prevención y el tratamiento de las enfermedades cardiovasculares. Objetivo. Determinar los patrones de prescripción de los fármacos hipolipemiantes y las variables asociadas con su uso en una población de Colombia. Materiales y métodos. Se trata de un estudio descriptivo y transversal. A partir de una base de datos de dispensación de medicamentos de 4,5 millones de afiliados al sistema de salud de Colombia, se identificaron los pacientes de cualquier edad y sexo en tratamiento con hipolipemiantes (estatinas, fibratos, ezetimibe), entre enero y marzo de 2017. Se incluyeron variables demográficas, farmacológicas y de comedicaciones. Resultados. Se identificaron 103.624 pacientes en tratamiento con hipolipemiantes. La edad promedio fue de 67,5 años y el 49,8 % tenía 65 o más años. El 58,0 % eran mujeres. Las estatinas fueron los más utilizados (n=96.910; 93,5 %), siendo la atorvastatina (n=80.812; 78,0 %) y la lovastatina (n=12.621; 12,2 %) las más frecuentes. La dosis promedio de atorvastatina fue de 30,3 mg/día y el 49,9 % de sus usuarios recibía presentaciones de 40 mg o más. Un total de 9.258 (8,9 %) pacientes recibían fibratos y solo 780 (0,8 %) tomaban ezetimibe. El 94,9 % de casos recibió tratamiento en monoterapia hipolipemiante y el 97,3 % (n=100.813) tenía comedicaciones para comorbilidades, siendo las más frecuentes antihipertensivos (89,1 %), antiagregantes plaquetarios (57,8 %), antidiabéticos (31,5 %) y antiulcerosos (34,2 %). Conclusiones. La atorvastatina es actualmente el medicamento hipolipemiante más utilizado en este grupo de pacientes de Colombia, especialmente en monoterapia y a dosis cercanas a las definidas, aunque solo la mitad recibían dosis recibían dosis de alta intensidad. Se requieren nuevos estudios que verifiquen la efectividad de estos tratamientos.

Factors influencing achievement of low-density lipoprotein cholesterol goals in mexico: the international cholesterol management practice study

ABSTRACT Background The International Cholesterol Management Practice Study is a multinational collaborative effort to describe the effectiveness of the lipid-lowering therapy (LLT) as well as the main barriers to achieve the low-density lipoprotein cholesterol (LDL-C) goals Objective The objective of the study was to investigate factors associated with the achievement of LDL-C goals in Mexico using real-life data Methods This was a cross-sectional observational study from 18 physicians across different health facilities in Mexico, who provided information about their practices between August 2015 and August 2016. We included patients treated for ≥3 months with any LLT in whom LDL-C measurement on stable LLT was available for the previous 12 months Results We included 623 patients with a mean age of 59.3 ± 12.7 years; 55.6% were women. The mean LDL-C value on LLT was 141.8 ± 56.1 mg/dL. At enrollment, 97.4% of patients were receiving statin therapy (11.3% on high-intensity treatment). Only 24.8% of the very-high cardiovascular (CV) risk patients versus 26.4% of the high risk and 52.4% of the moderate risk patients achieved their LDL-C goals. Independent factors associated with non-achievement of LDL-C goal were statin intolerance, overweight and obesity, abdominal obesity, female sex, high CV risk, use of public health-care service, metabolic syndrome, type 2 diabetes, and hypertriglyceridemia. Higher-level of education was associated with a lower risk of not achieving LDL-C goals Conclusions Achievement of LDL-C goals is suboptimal in Mexico, especially in patients with the highest CV risk. The main barriers to achieve the goal are easily detectable. Implementation of LLT should be adapted to the patient’s needs and profile.