RESUMEN
RATIONALE: Refractory angina constitutes a clinical problem. OBJECTIVE: The aim of this study was to assess the safety and the feasibility of transendocardial injection of CD133(+) cells to foster angiogenesis in patients with refractory angina. METHODS AND RESULTS: In this randomized, double-blinded, multicenter controlled trial, eligible patients were treated with granulocyte colony-stimulating factor, underwent an apheresis and electromechanical mapping, and were randomized to receive treatment with CD133(+) cells or no treatment. The primary end point was the safety of transendocardial injection of CD133(+) cells, as measured by the occurrence of major adverse cardiac and cerebrovascular event at 6 months. Secondary end points analyzed the efficacy. Twenty-eight patients were included (n=19 treatment; n=9 control). At 6 months, 1 patient in each group had ventricular fibrillation and 1 patient in each group died. One patient (treatment group) had a cardiac tamponade during mapping. There were no significant differences between groups with respect to efficacy parameters; however, the comparison within groups showed a significant improvement in the number of angina episodes per month (median absolute difference, -8.5 [95% confidence interval, -15.0 to -4.0]) and in angina functional class in the treatment arm but not in the control group. At 6 months, only 1 simple-photon emission computed tomography (SPECT) parameter: summed score improved significantly in the treatment group at rest and at stress (median absolute difference, -1.0 [95% confidence interval, -1.9 to -0.1]) but not in the control arm. CONCLUSIONS: Our findings support feasibility and safety of transendocardial injection of CD133(+) cells in patients with refractory angina. The promising clinical results and favorable data observed in SPECT summed score may set up the basis to test the efficacy of cell therapy in a larger randomized trial.
Asunto(s)
Angina de Pecho/terapia , Antígenos CD/metabolismo , Células Progenitoras Endoteliales/trasplante , Glicoproteínas/metabolismo , Neovascularización Fisiológica , Péptidos/metabolismo , Trasplante de Células Madre/métodos , Antígeno AC133 , Anciano , Angina de Pecho/diagnóstico por imagen , Antígenos CD/genética , Método Doble Ciego , Células Progenitoras Endoteliales/citología , Células Progenitoras Endoteliales/metabolismo , Femenino , Glicoproteínas/genética , Humanos , Masculino , Persona de Mediana Edad , Péptidos/genética , Estudios Prospectivos , Trasplante de Células Madre/efectos adversos , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
Atherosclerotic cardiovascular disease is the leading cause of death and a major part of its pathophysiology remains obscure. Some hematological targets have been related to the development and clinical outcome of this disease, especially soluble cytokines, leukocytes, red blood cells, hemostatic factors and platelets, and bone-marrow vascular progenitors. These emerging factors may be modulated by current antiatherosclerotic pharmacotherapy, target-designed novel drugs or progenitor cell therapy. The aim of current review article is to comprehensively review the role of these antiatherosclerotic targets and therapy.