Impacto da pandemia da COVID-19 sobre o tratamento medicamentoso dos pacientes com doença arterial periférica: um estudo observacional transversal / Impact of the COVID-19 pandemic on drug treatment of patients with peripheral arterial disease: an observational cross-sectional study

Resumo Contexto A pandemia do Coronavírus 2019 (COVID-19) tem afetado negativamente o comportamento da população. Nesse contexto, o impacto da pandemia da COVID-19 no tratamento medicamentoso dos pacientes com doença arterial periférica (DAP) e claudicação intermitente (CI) permanece obscuro. Objetivos Analisar o impacto da pandemia da COVID-19 no tratamento medicamentoso dos pacientes com DAP e CI. Métodos Neste estudo observacional transversal, 136 pacientes com DAP e CI, recrutados do nosso banco de dados, responderam por telefone um questionário envolvendo as seguintes questões: a) cuidados com a COVID-19; b) saúde global; c) tratamento das doenças. Posteriormente, os pacientes foram divididos em dois grupos, de acordo com a dificuldade para a aquisição dos medicamentos (DAM: dificuldade e SDAM: sem dificuldade), para a comparação da saúde global entre os dois grupos. Resultados Dezessete porcento dos pacientes reportaram dificuldades para a aquisição dos medicamentos durante a pandemia. Uma maior prevalência desses pacientes reportou estar mais triste (56,5% versus 24,8%, p < 0,01) e com mais dificuldades para dormir (56,5% versus 24,8%, p < 0,01) em relação aos pacientes do grupo SDAM. Os grupos não apresentaram diferenças para o declínio na capacidade de caminhada, ansiedade, estresse e depressão (p > 0,05). Conclusões Uma maior prevalência de pacientes do grupo DAM reportou estar mais triste e com mais dificuldade para dormir em comparação ao grupo SDAM durante a pandemia da COVID-19.

Abstract Background The Coronavirus 2019 (COVID-19) pandemic has had a negative impact on the population's behavior. In this context, the effect of the COVID-19 pandemic on drug treatment of patients with peripheral arterial disease (PAD) and intermittent claudication (IC) remains unclear. Objectives To analyze the impact of the COVID-19 pandemic on drug treatment of patients with PAD and IC. Methods In this cross-sectional, observational study, 136 patients with PAD and IC were recruited from our database and answered a questionnaire by telephone involving the following questions: a) precautions related to COVID-19; b) general health status; and c) treatment of diseases. Subsequently, patients were divided into two groups according to difficulty in obtaining their drugs (DOD: difficulty obtaining drugs, or NDOD: no difficulty obtaining drugs) and overall health was compared between groups. Results Seventeen percent of patients reported difficulties with obtaining drugs during the pandemic. A higher proportion of these patients reported being sadder (56.5% vs. 24.8%, P < 0.01) and having more difficulty sleeping (56.5% vs. 24.8%, P < 0.01) than of the patients in the NDOD group (P <0.01). The groups did not differ in terms of impairment of walking capability, anxiety, stress, or depression (P> 0.05). Conclusions A higher proportion of patients in the DOD group reported being sadder and having greater difficulty sleeping compared to the NDOD group during the COVID-19 pandemic.

Coexistence of proangiogenic potential and increased MMP-9, TIMP-1, and TIMP-2 levels in the plasma of patients with critical limb ischemia / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The objective of this study was to assess the angiogenic potential expressed as a quotient of vascular endothelial growth factor A (VEGF-A), as an indicator of proangiogenic activity, and the circulating receptors (soluble VEGF receptor protein R1 (sVEGFR-1) and sVEGFR-2), as indicators of the effect of angiogenic inhibition, depending on the concentrations of matrix metalloproteinase 2 (MMP-2) and MMP-9 and their tissue inhibitor 1 (TIMP-1) and TIMP-2 in the plasma of patients with lower extremity artery disease (LEAD). These blood parameters in patients with intermittent claudication (IC) and critical limb ischemia (CLI) were compared for select clinical and biochemical features. Stimulation of angiogenesis in the plasma of individuals with LEAD was evident as indicated by the significant increase in VEGF-A concentration along with reduced inhibition depending on circulating receptors sVEGFR-1 and sVEGFR-2. Critical ischemia was associated with higher VEGF-A, MMP-9, TIMP-1, and TIMP-2 concentrations than in the case of IC.

Riesgos y beneficios del uso de beta bloqueantes en pacientes con enfermedad vascular periférica / Risk and benefits of beta blockers in patients with peripheral arterial disease

La claudicación intermitente es una manifestación clínica de la enfermedad arterial periférica aterosclerótica en los miembros inferiores. El uso de beta bloqueantes en estos casos estaba limitado por la creencia de que aumentaban los síntomas funcionales y podian aumentar el riesgo de amputación. La revisión de la literatura parece sugerir que, si bien disminuye marginalmente la distancia caminada por los pacientes tratados, también disminuye la mortalidad a largo plazo y este efecto debería prevalecer. No parece apropiado privar a este grupo de pacientes de un tratamiento que reduce la mortalidad simplemente porque podrían ver afectada su capacidad de caminar mayores distancias.

Efficacy and safety of cilostazol, a novel phosphodiesterase inhibitor in patients with intermittent claudication.

Pharmacotherapy is limited for the relief of intermittent claudication (IC), a common manifestation of peripheral arterial disease (PAD). Pentoxyfylline, the only current pharmacological therapy for IC, has been shown to have similar efficacy as placebo. Cilostazol, a new phosphodiesterase III (PDE III) inhibitor, is a potent inhibitor of platelet aggregation with vasodilatory, antithrombotic, antiproliferative and positive lipid-altering effects. To evaluate the efficacy and safety of cilostazol for the treatment of IC in Indian patients, 123 patients were selected from 6 centres in India. The patients, aged 58-73 years, with the diagnosis of stable moderate-to-severe IC received cilostazol 100/50 mg twice daily for a period of 12 weeks. Primary efficacy measures included initial claudication distance (ICD) and absolute walking distance (ACD) by treadmill testing and ankle-brachial index (ABI) using Doppler ultrasonography-measured systolic pressures. Secondary efficacy outcomes included subjective assessment of symptom improvement by patient and investigator and estimation of lipid values. Adverse events were monitored throughout the study. Laboratory investigations were carried out at baseline and end of study. At the end of week 12 of cilostazol therapy, there was a significant improvement in the raw walking distances (ICD and ACD). Percentage change in ICD and ACD was 46.77% and 64.5%, respectively, at the end of study. There was a significant increase (32.7%) in the ABI by the end of study period. According to patient and investigator assessment of symptoms, 58-60% of the subjects showed significant improvement to complete resolution of claudication symptoms by the end of 12 weeks of therapy. In addition, there was a significant increase of 20.24% in the mean plasma HDL-cholesterol levels and a decrease of 29.55% in the mean plasma triglyceride concentrations by the end of study period. Headache, diarrhoea, palpitation and dizziness were the commonly reported adverse effects during the study. No adverse effect led to discontinuation of therapy. The present study suggests that cilostazol is an effective therapeutic option with an acceptable tolerability profile for the treatment of IC in patients with PAD.

Utilizaçäo clínica do cloridrato de buflomedil na síndrome isquêmica crônica de membros superiores / Clinical use of buflomedil hydrochloride in the chronic ischemic syndrome of the lower limbs

Foram estudados 25 pacientes portadores de síndrome isquêmica crônica de membros inferiores com queixas clínicas de claudicaçäo intermitente. Avaliou-se nesses pacientes a atividade terapêutica do cloridrato de buflomedil per os (600 mg ao dia, por 90 dias), através da evoluçäo clínica, da dopplerometria e da ergometria, com acompanhamento aos 30, 60 e 90 dias. Resultados bastante positivos foram obtidos nos testes ergométricos (esteira rolante), através da determinaçäo da distância percorrida até o início da dor (capacidade funcional útil) e até a impotência funcional (capacidade funcional máxima). A análise estatística mostrou que houve um aumento significativo (p < 0,001) da distância percorrida (CFU e CFM), ao longo do tratamento, e que a significância desses resultados teve início no 1§ mês. Podemos concluir, a partir desse estudo, que o cloridrato de buflomedil é uma efetiva e segura droga no tratamento da claudicaçäo intermitente, melhorando acentuadamente a capacidade laborativa dos pacientes e sua qualidade de vida

Pentoxifylline--a new drug for the treatment of intermittent claudication.

Pentoxifylline, a xanthine analogue was evaluated for efficacy, safety and tolerance in the treatment of intermittent claudication in a pilot study. Evaluation was performed in 35 cases. 20 patients were given Pentoxifylline in doses of 1200 mg daily, and 15 patients were given placebo for a period of 8 weeks respectively. Pentoxifylline given in doses of 1200 mg was significantly more effective than the placebo in increasing both the initial and absolute claudication distance (ICD & ACD) in patients with chronic occlusive arterial disease. The subjective parameters, such as paraesthesias, muscular cramps and sensation of heaviness in the legs paralleled the course of walking parameters. These results support the hypothesis that Pentoxifylline in doses of 400 mg TDS reduces blood viscosity by improving red cell flexibility, and thereby enhances blood flow in patients with COAD (Fontaine Stage II or Stage III). Pentoxifylline is thus regarded as a promising drug for circulatory ischaemic disorders, especially in intermittent claudication. It was well tolerated with minimal untoward effects.