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Refractory angina pectoris is a chronic disabling condition affecting ≈850 000 patients in the United States.1 It is characterized by frequent angina attacks unresponsive to maximal medical therapy and obstructive coronary artery disease not amenable to coronary revascularization.2 Although major progress has been made in medical therapy and cardiovascular interventions,1 up to 43% of patients continue to experience symptoms and 33% have positive exercise tests after angioplasty.3 It is now well recognized that these patients have concomitant microvascular disease, with reduced coronary and systemic flow reserve at a microvascular level and impaired endothelium-mediated vasorelaxation, that is, endothelial dysfunction.4 Currently, the treatment of these patients remains a major clinical challenge.Article, see p 984 To address this large unmet therapeutic need, research has focused on biological strategies for refractory angina. A key effort is the use of cell therapy, which has the potential to restore the microcirculation and improve myocardial tissue perfusion by stimulating neoangiogenesis.5 In this regard, accumulating evidence supports the idea that cell-based therapy can improve clinical outcomes, including frequency of angina episodes, myocardial infarction (MI) rate, and exercise tolerance, in patients with refractory angina5,6 and, thus, should be subject to further trials to evaluate this treatment option for this patient population.In this issue of Circulation Research , Khan et al present a comprehensive meta-analysis of cell-based therapy for refractory angina. Importantly, their analysis addresses the heterogeneity of the included trials, the problem of missing data, and limitations of the study.5 Six single- and double-blinded, randomized clinical trials were included in this meta-analysis, comprising a patient population that had class III-IV Canadian Cardiovascular Society angina, were refractory to medical therapy, and were not coronary revascularization candidates (Table). The study included 192 patients who received cell therapy plus standard …

Cell Therapy Augments Myocardial Perfusion and Improves Quality of Life in Patients With Refractory Angina