Sex-Based Differences in Autologous Cell Therapy Trials in Patients With Acute Myocardial Infarction: Subanalysis of the ACCRUE Database

Abstract

Background: Sex-based differences are under-studied in cardiovascular trials as women are commonly underrepresented in dual sex studies, even though major sex-based differences in epidemiology, pathophysiology, and outcomes of cardiovascular disease have been reported. We examined sex-based differences in patient characteristics, outcome, and BM-CD34+ frequency of the ACCRUE (Meta-Analysis of Cell-based CaRdiac studies) database involving patients with acute myocardial infarction (AMI) randomized to autologous cell-based or control treatment.Methods: We compared baseline characteristics and 1-year follow-up clinical data: composite major adverse cardiac and cerebrovascular events (primary endpoint), and changes in left ventricular ejection fraction (LVEF), end-diastolic (EDV), and end-systolic volumes (ESV) (secondary efficacy endpoint) in women and men (N = 1,252; 81.4% men). Secondary safety endpoints included freedom from hard clinical endpoints.Results: In cell-treated groups, women but not men had a lower frequency of stroke, AMI, and mortality than controls. The frequency of BM-CD34+ cells was significantly correlated with baseline EDV and ESV and negatively correlated with baseline LVEF in both sexes; a left shift in regression curve in women indicated a smaller EDV and ESV was associated with higher BM-CD34+ cells in women.Conclusions: Sex differences were found in baseline cardiovascular risk factors and cardiac function and in outcome responses to cell therapy.

Epigenetic mechanisms regulate sex differences in cardiac reparative functions of bone marrow progenitor cells

“…Unfortunately, many of these clinical trials predominantly used male bone marrow stem cells. Based on the ACCRUE database (Meta-Analysis of Cell-based CaRdiac stUdiEs), the percentage of women in 13 different cell therapy studies for heart diseases ranged from 0 to 31% 24 , 25 . A subset analysis of cardiac function between women ( n = 233) and men ( n = 1019) who have undergone autologous stem cell therapy resulted in significant improvement in women 25 .…”

“…Based on the ACCRUE database (Meta-Analysis of Cell-based CaRdiac stUdiEs), the percentage of women in 13 different cell therapy studies for heart diseases ranged from 0 to 31% 24 , 25 . A subset analysis of cardiac function between women ( n = 233) and men ( n = 1019) who have undergone autologous stem cell therapy resulted in significant improvement in women 25 . Interestingly, the average age of women in these studies was higher than males (60 y for females vs. 56 y For males), suggesting that the therapeutic effects of cells were still evident during postmenopausal years in women 25 .…”

“…A subset analysis of cardiac function between women ( n = 233) and men ( n = 1019) who have undergone autologous stem cell therapy resulted in significant improvement in women 25 . Interestingly, the average age of women in these studies was higher than males (60 y for females vs. 56 y For males), suggesting that the therapeutic effects of cells were still evident during postmenopausal years in women 25 . While lack of information on the current hormonal status or possible hormone therapy in these women does not allow to claim sex hormone-independent mechanisms, nonetheless, data does suggest a better functional potency of female cells compared with age-match men.…”