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Introduction: Studies in cholesterol-fed rabbits showed that anti-proliferative chemotherapeutic agents such as paclitaxel associated with solid lipid nanoparticles (LDE) have marked anti-atherosclerotic effects. In addition, association with LDE nearly abolishes paclitaxel toxicity. We investigated whether treatment with LDE-paclitaxel changes plaque progression by coronary CT angiography and is safe in patients with chronic coronary artery disease. Methods: We conducted a prospective, randomized, double-blind, placebo-controlled pilot study in patients with multi-vessel chronic coronary artery disease. Patients were randomized to receive IV infusions of LDE-paclitaxel (paclitaxel dose: 175â mg/m2 body surface) or LDE alone (placebo group), administered every 3 weeks for 18 weeks. All participants received guideline-directed medical therapy. Clinical and laboratory safety evaluations were made at baseline and every 3 weeks until the end of the study. Analysis of inflammatory biomarkers and coronary CTA was also performed at baseline and 4 weeks after treatment. Results: Forty patients aged 65.6 ± 8 years, 20 in LDE-paclitaxel and 20 in placebo group were enrolled. Among those, 58% had diabetes, 50% had myocardial infarction, and 91% were in use of statin and aspirin. Baseline demographics, risk factors, and laboratory results were not different between groups. In all patients, no clinical or laboratory toxicities were observed. From the baseline to the end of follow-up, there was a non-significant trend toward a decrease in IL-6 levels and hsCRP in the LDE-paclitaxel group (-16% and -28%, respectively), not observed in placebo. Regarding plaque progression analysis, variation in plaque parameter values was wide, and no difference between groups was observed. Conclusion: In patients with multivessel chronic coronary artery disease and optimized medical therapy, LDE-paclitaxel was safe and showed clues of potential benefits in reducing inflammatory biomarkers. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT04148833, identifier (NCT04148833).
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The incidence of cardiovascular events in patients with chronic ischemic heart disease (CIHD) may vary significantly among countries. Although populous, Brazil is often underrepresented in international records. This study aimed to describe the quality of care and the two-year incidence of cardiovascular events and associated prognostic factors in CIHD patients in a tertiary public health care center in Brazil. Patients with CIHD who reported for clinical evaluation at Instituto do Coração (São Paulo, Brazil) were registered and followed for two years. The primary endpoint was a composite of myocardial infarction (MI), stroke, or death. A significance level of 0.05 was adopted. From January 2016 to December 2018, 625 participants were included in the study. Baseline characteristics show that 33.1% were women, median age 66.1 [59.6 - 71.9], 48.6% had diabetes, 83.1% had hypertension, 62.6% had previous MI, and 70.4% went through some revascularization procedure. At a median follow-up (FU) of 881 days, we noted 37 (7.05%) primary endpoints. After adjustments, age, previous stroke, and LDL-cholesterol were independently associated with the primary endpoint. Comparing baseline versus FU, participants experienced relief of angina based on the Canadian Cardiovascular Society (CCS) scale according to the following percentages: 65.7% vs. 81.7% were asymptomatic and 4.2% vs. 2.9% CCS 3 or 4 (p < 0.001). They also experienced better quality of medication prescription: 65.8% vs. 73.6% (p < 0.001). However, there was no improvement in LDL-cholesterol or blood pressure control. This study shows that CIHD patients had a two-year incidence of the primary composite endpoint of 7.05%, and the reduction of LDL-cholesterol was the only modifiable risk factor associated with prognosis.
A incidência de eventos cardiovasculares em pacientes com doença cardíaca isquêmica crônica (DCIC) pode variar significativamente entre os países. Embora populoso, o Brasil é frequentemente sub-representado nos registros internacionais. Este estudo teve como objetivo descrever a qualidade do atendimento e a incidência de eventos cardiovasculares em dois anos, além de fatores prognósticos associados em pacientes com DCIC em um centro terciário de saúde pública no Brasil. Pacientes com DCIC que compareceram para avaliação clínica no Instituto do Coração (São Paulo, Brasil) foram cadastrados e acompanhados por dois anos. O desfecho primário foi um composto de infarto do miocárdio (IM), acidente vascular encefálico ou morte. Um nível de significância de 0,05 foi adotado. De janeiro de 2016 a dezembro de 2018, 625 participantes foram incluídos no estudo. As características basais mostram que 33,1% eram mulheres, a idade mediana era de 66,1 [59,6 71,9], 48,6% tinham diabetes, 83,1% tinham hipertensão, 62,6% tinham IM prévio e 70,4% passaram por algum procedimento de revascularização. Em um acompanhamento mediano de 881 dias, 37 (7,05%) desfechos primários foram observados. Após ajustes, idade, acidente vascular encefálico prévio e colesterol LDL foram independentemente associados ao desfecho primário. Comparando a linha de base com o acompanhamento, os participantes relataram alívio da angina com base na escala da Sociedade Cardiovascular Canadense (SCC) de acordo com as seguintes porcentagens: 65,7% vs. 81,7% eram assintomáticos e 4,2% vs. 2,9% eram SCC 3 ou 4 (p < 0,001). Eles também relataram melhor qualidade na prescrição de medicamentos: 65,8% vs. 73,6% (p < 0,001). No entanto, não houve melhora no colesterol LDL ou no controle da pressão arterial. O presente estudo mostra que pacientes com DCIC apresentaram uma incidência de 7,05% do desfecho primário composto em um período de dois anos, sendo a diminuição do colesterol LDL o único fator de risco modificável associado ao prognóstico.
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Infarto del Miocardio , Isquemia Miocárdica , Accidente Cerebrovascular , Humanos , Femenino , Anciano , Masculino , Estudios de Seguimiento , Brasil/epidemiología , Canadá , Isquemia Miocárdica/epidemiología , LDL-Colesterol , Accidente Cerebrovascular/epidemiologíaRESUMEN
Atherosclerosis is the biological basis of ischemic heart disease and ischemic stroke, the leading causes of death in the world. After decades of studies, the understanding of atherosclerosis has evolved dramatically, and inflammation has been recognized as one of the most relevant pillars in all phases of atherosclerotic disease. Nevertheless, only recently, the trial CANTOS, and subsequent outcome studies with colchicine, finally provided proof-of-concept evidence that anti-inflammatory therapies were able to reduce cardiovascular events with no influence on lipid levels. These landmark studies inaugurated an era of clinical and pre-clinical studies of immunomodulatory strategies focused on reduction of cardiovascular risk. Although there are promising results in the field, selection of the most appropriate immunomodulatory therapy and identification of patients who could benefit the most, are still enormous challenges. Further research is imperative before we can finally advance towards regular use of anti-inflammatory agents to reduce atherosclerotic events in our clinical practice.
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Resumo Fundamento A incidência de eventos cardiovasculares em pacientes com doença cardíaca isquêmica crônica (DCIC) pode variar significativamente entre os países. Embora populoso, o Brasil é frequentemente sub-representado nos registros internacionais. Objetivos Este estudo teve como objetivo descrever a qualidade do atendimento e a incidência de eventos cardiovasculares em dois anos, além de fatores prognósticos associados em pacientes com DCIC em um centro terciário de saúde pública no Brasil. Métodos Pacientes com DCIC que compareceram para avaliação clínica no Instituto do Coração (São Paulo, Brasil) foram cadastrados e acompanhados por dois anos. O desfecho primário foi um composto de infarto do miocárdio (IM), acidente vascular encefálico ou morte. Um nível de significância de 0,05 foi adotado. Resultados De janeiro de 2016 a dezembro de 2018, 625 participantes foram incluídos no estudo. As características basais mostram que 33,1% eram mulheres, a idade mediana era de 66,1 [59,6 - 71,9], 48,6% tinham diabetes, 83,1% tinham hipertensão, 62,6% tinham IM prévio e 70,4% passaram por algum procedimento de revascularização. Em um acompanhamento mediano de 881 dias, 37 (7,05%) desfechos primários foram observados. Após ajustes, idade, acidente vascular encefálico prévio e colesterol LDL foram independentemente associados ao desfecho primário. Comparando a linha de base com o acompanhamento, os participantes relataram alívio da angina com base na escala da Sociedade Cardiovascular Canadense (SCC) de acordo com as seguintes porcentagens: 65,7% vs. 81,7% eram assintomáticos e 4,2% vs. 2,9% eram SCC 3 ou 4 (p < 0,001). Eles também relataram melhor qualidade na prescrição de medicamentos: 65,8% vs. 73,6% (p < 0,001). No entanto, não houve melhora no colesterol LDL ou no controle da pressão arterial. Conclusão O presente estudo mostra que pacientes com DCIC apresentaram uma incidência de 7,05% do desfecho primário composto em um período de dois anos, sendo a diminuição do colesterol LDL o único fator de risco modificável associado ao prognóstico.
Abstract Background The incidence of cardiovascular events in patients with chronic ischemic heart disease (CIHD) may vary significantly among countries. Although populous, Brazil is often underrepresented in international records. Objectives This study aimed to describe the quality of care and the two-year incidence of cardiovascular events and associated prognostic factors in CIHD patients in a tertiary public health care center in Brazil. Methods Patients with CIHD who reported for clinical evaluation at Instituto do Coração (São Paulo, Brazil) were registered and followed for two years. The primary endpoint was a composite of myocardial infarction (MI), stroke, or death. A significance level of 0.05 was adopted. Results From January 2016 to December 2018, 625 participants were included in the study. Baseline characteristics show that 33.1% were women, median age 66.1 [59.6 - 71.9], 48.6% had diabetes, 83.1% had hypertension, 62.6% had previous MI, and 70.4% went through some revascularization procedure. At a median follow-up (FU) of 881 days, we noted 37 (7.05%) primary endpoints. After adjustments, age, previous stroke, and LDL-cholesterol were independently associated with the primary endpoint. Comparing baseline versus FU, participants experienced relief of angina based on the Canadian Cardiovascular Society (CCS) scale according to the following percentages: 65.7% vs. 81.7% were asymptomatic and 4.2% vs. 2.9% CCS 3 or 4 (p < 0.001). They also experienced better quality of medication prescription: 65.8% vs. 73.6% (p < 0.001). However, there was no improvement in LDL-cholesterol or blood pressure control. Conclusion This study shows that CIHD patients had a two-year incidence of the primary composite endpoint of 7.05%, and the reduction of LDL-cholesterol was the only modifiable risk factor associated with prognosis.
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INTRODUCTION: Moderate daily consumption of alcohol (MDCA) is associated with cardiovascular risk (CVR) reduction in observational studies. Some researches have suggested that this benefit may be associated not only with red wine consumption but also with other beverages. However, there are no clinical trials evaluating the possible CVR benefit of Brazilian spirit (cachaça) in humans. METHODS: This is a prospective, randomized, crossover study including healthy individuals initially assigned to a MDCA of cachaça or red wine for a period of 4 weeks. After a one-week abstinence period, the type of drink was changed for another 4 weeks of intervention. The MDCA for both beverages was determined as a dose equivalent to 28 g of ethanol per day for men and 14 g for women. CVR biomarkers analyses were performed before and after each intervention to assess the serologic status of C-reactive protein, lipid profile, platelet aggregation and glycemic profile. This study is registered on the ISRCTN platform under number 15978506. RESULTS: Of the 42 subjects initially randomized, 2 refused to continue in the study. The median age was 44.3 ± 10.3 years and 19 were male (47.5%). Adherence to the protocol was considered ideal with 100% regular use in both interventions and only 3 individuals in each intervention group reported alcohol abuse. There was no significant variation in anthropometric measurements during the study, except for weight gain (0.7 kg) in the red wine group (p = 0.005). The median of the delta of platelet aggregation for MDCA of cachaça was 1.2% (-1.1 to 5.3) and the median of the delta to the MDCA of wine was -1.6% (-4.5 to 2) (p = 0.02). The other biomarkers didn't show any statistically significant variation. CONCLUSION: Moderate consumption of wine and cachaça was related to variation in laboratory biomarkers of CVR related to atherosclerosis. There was significant weight gain during the period of wine consumption and there was observed a difference between platelet aggregation values after both interventions.
