title: Long-Term and Sustained Therapeutic Results of a Specific Promonocyte Cell Formulation in Refractory Angina: ReACT(®) (Refractory Angina Cell Therapy) Clinical Update and Cost-Effective Analysis.
abstract: Mononuclear stem cells have been studied for their potential in myocardial ischemia. In our previous published article, ReACT(®) phase I/II clinical trial, our results suggest that a certain cell population, promonocytes, directly correlated with the perceived angiogenesis in refractory angina patients. This study is ReACT's clinical update, assessing long-term sustained efficacy. The ReACT phase IIA/B noncontrolled, open-label, clinical trial enrolled 14 patients with refractory angina and viable ischemic myocardium, without ventricular dysfunction, who were not suitable for myocardial revascularization. The procedure consisted of direct myocardial injection of a specific mononuclear cell formulation, with a certain percentage of promonocytes, in a single series of multiple injections (24-90; 0.2 ml each) into specific areas of the left ventricle. Primary endpoints were Canadian Cardiovascular Society Angina Classification (CCSAC) improvement at the 12-month follow-up and ischemic area reduction (scintigraphic analysis) at the 12-month follow-up, in correlation with ReACT's formulation. A recovery index (for patients with more than 1 year follow-up) was created to evaluate CCSAC over time, until April 2011. Almost all patients presented progressive improvement in CCSAC beginning 3 months (p=0.002) postprocedure, which was sustained at the 12-month follow-up (p=0.002), as well as objective myocardium ischemic area reduction at 6 months (decrease of 15%, p<0.024) and 12 months (decrease of 100%, p<0.004) The recovery index (n=10) showed that the patients were graded less than CCSAC 4 for 73.9 ± 24.2% over a median follow-up time of 46.8 months. After characterization, ReACT's promonocyte concentration suggested a positive correlation with CCSAC improvement (r=-0.575, p=0.082). Quality of life (SF-36 questionnaire) improved significantly in almost all domains. Cost-effectiveness analysis showed decrease in angina-related direct costs. Refractory angina patients presented a sustained long-term improvement in CCSAC and myocardium ischemic areas after the procedure. The long-term follow-up and strong improvement in quality of life reinforce effectiveness. Promonocytes may play a key role in myocardial neoangiogenesis. ReACT dramatically decreased direct costs.
authors.affiliation: Cardiovascular Surgery Division, Surgery Department, Paulista School of Medicine, Federal University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Nelson Americo
authors.initials: NA
authors.lastname: Hossne
authors.forename: Eduardo
authors.initials: E
authors.lastname: Cruz
authors.forename: Enio
authors.initials: E
authors.lastname: Buffolo
authors.forename: Anna Carolina Teixeira de Siqueira Mac Dowell
authors.initials: AC
authors.lastname: Coimbra
authors.forename: Janaina
authors.initials: J
authors.lastname: Machado
authors.forename: Regina Coeli Dos Santos
authors.initials: RC
authors.lastname: Goldenberg
authors.forename: Germana
authors.initials: G
authors.lastname: Regazzi
authors.forename: Silvia
authors.initials: S
authors.lastname: Azevedo
authors.forename: Adriana Luckow
authors.initials: AL
authors.lastname: Invitti
authors.forename: João Nelson
authors.initials: JN
authors.lastname: Rodrigues Branco
authors.forename: José Salvador
authors.initials: JS
authors.lastname: Rodrigues de Oliveira
authors.forename: Noedir Antonio Groppo
authors.initials: NA
authors.lastname: Stolf
authors.forename: Leslie W
authors.initials: LW
authors.lastname: Miller
authors.forename: Paul R
authors.initials: PR
authors.lastname: Sanberg
mesh_terms: D000368:Aged; D000787:Angina Pectoris / Q000000981:diagnostic imaging / Q000191:economics* / Q000628:therapy*; D003362:Cost-Benefit Analysis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D055017:Monocyte-Macrophage Precursor Cells / Q000637:transplantation*; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging / Q000191:economics / Q000628:therapy; D009206:Myocardium / Q000473:pathology; D062645:Percutaneous Coronary Intervention; D011788:Quality of Life; D011877:Radionuclide Imaging; D018709:Statistics, Nonparametric; D011795:Surveys and Questionnaires; D013997:Time Factors