RESUMO
OBJECTIVES: To evaluate the effect of sildenafil as add-on therapy on the microvascular blood flow in patients with Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc). METHODS: In this double-blind, placebo-controlled study, 41 patients with RP secondary to SSc were randomly assigned to receive oral sildenafil 100 mg/day (21 patients, mean age 47.2 years) or placebo (20 patients, mean age 41.6 years) for 8 weeks. Patients were evaluated at baseline, 8 weeks after treatment, and 2 weeks after the end of the treatment. The primary outcome measures were the mean changes in finger blood flow (FBF) measured using laser Doppler imaging before and after cold stimulus at 8 weeks of treatment. Secondary endpoints included frequency and duration of RP attacks, Visual Analog Scale (VAS) score for RP severity, Raynaud's condition score, and serum levels of VEGF and endothelial progenitor cells (EPCs). RESULTS: After 8 weeks of treatment, the sildenafil group presented a significantly higher mean percentage change from baseline in FBF before cold stimulus (p=0.026), and in FBF after cold stimulus (p=0.028) compared with the placebo group. There was a significant improvement in the duration of RP and in the percentage change from baseline to week 8 in the RP VAS score in sildenafil compared with placebo. There were no changes in EPCs and VEGF levels after treatment in either group. CONCLUSIONS: Sildenafil improved digital blood flow and RP symptoms in SSc patients after 8 weeks of treatment, and might be a good therapeutic option for secondary RP.
Assuntos
Escleroderma Sistêmico/tratamento farmacológico , Citrato de Sildenafila/uso terapêutico , Adulto , Método Duplo-Cego , Células Progenitoras Endoteliais/fisiologia , Dedos/irrigação sanguínea , Humanos , Microcirculação/efeitos dos fármacos , Pessoa de Meia-Idade , Doença de Raynaud , Escleroderma Sistêmico/fisiopatologia , Citrato de Sildenafila/farmacologia , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
INTRODUCTION: Microangiopathy and endothelial dysfunction are present in the early stages of systemic sclerosis (SSc). Defective vasculogenesis mediated by bone marrow-derived endothelial progenitor cells (EPCs) might be involved in the vascular abnormalities found in SSc. OBJECTIVES: To evaluate the circulating EPC levels and EPC subtypes via flow cytometry and early outgrowth colony-forming units (CFUs) in patients with SSc compared to healthy subjects. METHODS: Thirty-nine female SSc patients (30 in the early stages of SSc) and 44 age-matched healthy women were included. Peripheral blood EPCs were quantified using flow cytometry and by counting the early outgrowth CFUs. RESULTS: The EPCs quantified with flow cytometry and the CFU numbers were significantly lower in SSc patients than in control subjects (155.1 ± 95.1 vs. 241.3 ± 184.2 EPC/10(6) lymphomononuclear cells, p=0.011; 15.4 ± 8.6 vs. 23.5 ± 10.9 CFU, p<0.001; respectively), as well as in the group of patients in the early stages of SSc compared to the controls. Patients with digital ulcers had significantly higher CFU counts than those without ulcers (p=0.013). Among patients with the scleroderma pattern on nailfold capillaroscopy, patients with the late pattern had significantly lower EPC levels than those with the early and active patterns (p=0.046). There were no significant correlations of EPCs or CFU levels with RP duration. CONCLUSIONS: The present study revealed decreased EPCs in SSc patients, including those with early disease onset. These findings suggest that defective vasculogenesis occurs in the early phases of the disease. Therefore, EPCs might be an important therapeutic target for the prevention of vascular complications in SSc patients.