Treatment of patients with aortic atherosclerotic disease with paclitaxel-associated lipid nanoparticles

OBJECTIVE: The toxicity of anti-cancer chemotherapeutic agents can be reduced by associating these compounds, such as the anti-proliferative agent paclitaxel, with a cholesterol-rich nanoemulsion (LDE) that mimics the lipid composition of low-density lipoprotein (LDL). When injected into circulation, the LDE concentrates the carried drugs in neoplastic tissues and atherosclerotic lesions. In rabbits, atherosclerotic lesion size was reduced by 65% following LDE-paclitaxel treatment. The current study aimed to test the effectiveness of LDE-paclitaxel on inpatients with aortic atherosclerosis. METHODS: This study tested a 175 mg/m2 body surface area dose of LDE-paclitaxel (intravenous administration, 3/3 weeks for 6 cycles) in patients with aortic atherosclerosis who were aged between 69 and 86 yrs. A control group of 9 untreated patients with aortic atherosclerosis (72-83 yrs) was also observed. RESULTS: The LDE-paclitaxel treatment elicited no important clinical or laboratory toxicities. Images were acquired via multiple detector computer tomography angiography (64-slice scanner) before treatment and at 1-2 months after treatment. The images showed that the mean plaque volume in the aortic artery wall was reduced in 4 of the 8 patients, while in 3 patients it remained unchanged and in one patient it increased. In the control group, images were acquired twice with an interval of 6-8 months. None of the patients in this group exhibited a reduction in plaque volume; in contrast, the plaque volume increased in three patients and remained stable in four patients. During the study period, one death unrelated to the treatment occurred in the LDE-paclitaxel group and one death occurred in the control group. CONCLUSION: Treatment with LDE-paclitaxel was tolerated by patients with cardiovascular disease and showed the potential to reduce atherosclerotic lesion size.

Comparison between MDCT and Grayscale IVUS in a Quantitative Analysis of Coronary Lumen in Segments with or without Atherosclerotic Plaques / Comparação da TCMD e da USIV em escala de cinza na Análise Quantitativa da Luz Coronária em Segmentos com ou sem Placas Ateroscleróticas

Background: The diagnostic accuracy of 64-slice MDCT in comparison with IVUS has been poorly described and is mainly restricted to reports analyzing segments with documented atherosclerotic plaques. Objectives: We compared 64-slice multidetector computed tomography (MDCT) with gray scale intravascular ultrasound (IVUS) for the evaluation of coronary lumen dimensions in the context of a comprehensive analysis, including segments with absent or mild disease. Methods: The 64-slice MDCT was performed within 72 h before the IVUS imaging, which was obtained for at least one coronary, regardless of the presence of luminal stenosis at angiography. A total of 21 patients were included, with 70 imaged vessels (total length 114.6 ± 38.3 mm per patient). A coronary plaque was diagnosed in segments with plaque burden > 40%. Results: At patient, vessel, and segment levels, average lumen area, minimal lumen area, and minimal lumen diameter were highly correlated between IVUS and 64-slice MDCT (p < 0.01). However, 64-slice MDCT tended to underestimate the lumen size with a relatively wide dispersion of the differences. The comparison between 64-slice MDCT and IVUS lumen measurements was not substantially affected by the presence or absence of an underlying plaque. In addition, 64-slice MDCT showed good global accuracy for the detection of IVUS parameters associated with flow-limiting lesions. Conclusions: In a comprehensive, multi-territory, and whole-artery analysis, the assessment of coronary lumen by 64-slice MDCT compared with coronary IVUS showed a good overall diagnostic ability, regardless of the presence or absence of underlying atherosclerotic plaques. .

Fundamento: A comparação do rigor diagnóstico da TCMD e da USIV foi pouco descrita, estando restrita principalmente a estudos que avaliaram segmentos com placas ateroscleróticas já documentadas. Objetivos: Este estudo objetiva avaliar o desempenho diagnóstico da tomografia computadorizada com 64 colunas de detectores (tomografia computadorizada multidetector- TCMD) e da ultrassonografia intravascular (USIV) em escala de cinza na verificação das dimensões da luz coronária, em um contexto mais amplo, incluindo também segmentos coronários sadios e com patologia leve. Métodos: A TCMD foi realizada em todos os pacientes antes da realização da USIV, com um intervalo < 72 horas entre os dois exames. Imagens de USIV foram obtidas de pelo menos uma coronária, independente da presença de estenose luminal durante a angiografia. Um total de 21 pacientes foram incluídos, com imagens de 70 vasos (comprimento total 114,6 ± 38.3 mm por paciente). Placas coronárias foram diagnosticada em segmentos com carga de placas > 40%. Resultados: Uma alta correlação entre as medidas de TCMD e USIV para área luminar média, área luminar mínima e diâmetro luminar mínimo foi encontrada no nível de paciente, vaso e segmento (p-valor < 0,01 para todas as correlações). A TCMD, no entanto, tendeu a subestimar o tamanho luminar com uma dispersão de diferenças relativamente ampla. A comparação entre as medidas da luz por TCMD e USIV não foi substancialmente afetada pela presença ou ausência de placa subjacente. Além disso, a TCMD mostrou boa precisão geral na detecção de parâmetros associados a lesões limitantes de fluxo. Conclusão: Em uma análise compreensiva e multi-focal da luz coronária, demonstramos bom desempenho diagnóstico da TCMD, quando comparada a USIV, independente da presença de placas ateroscleróticas adjacentes. .