Impact of Cell Therapy on Myocardial Perfusion and Cardiovascular Outcomes in Patients With Angina Refractory to Medical Therapy

Abstract

Rationale The effect of stem/progenitor cells on myocardial perfusion and clinical outcomes in patients with refractory angina (RFA) remains unclear because studies published to date have been small phase I-II trials. Objective We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of cell-based therapy in patients with RFA who were ineligible for coronary revascularization. Methods and Results Several data sources were searched from inception till September 2015, which yielded six studies. The outcomes pooled were indices of angina (anginal episodes, Canadian Cardiovascular Society [CCS] angina class, exercise tolerance, anti-anginal medications), myocardial perfusion, and clinical end-points. We combined the reported clinical outcomes (myocardial infarction, cardiac-related hospitalization, and mortality) into a composite end-point (MACE). Mean difference (MD), standardized mean differences (SMD), or odds ratio (OR) were calculated to assess relevant outcomes. Our analysis shows an improvement in anginal episodes (MD -7.81;95% CI, -15.22−-0.-41), use of anti-anginal medications (SMD -0.59;CI, -1.03−-0.14), CCS class (MD -0.58;CI, -1.00−-0.16), exercise tolerance (SMD 0.331;CI, 0.08−0.55), and myocardial perfusion (SMD -0.49;CI, -0.76−-0.21) and a decreased risk of MACE (OR 0.49;CI, 0.25−0.98) and arrhythmias (OR 0.25; 95% CI, 0.06−0.98) in cell-treated patients compared with patients on maximal medical therapy. Conclusions The present meta-analysis indicates that cell-based therapies are not only safe but also lead to an improvement in indices of angina, relevant clinical outcomes, and myocardial perfusion in patients with RFA. These encouraging results suggest that larger, phase III RCTs are in order to conclusively determine the effect of stem/progenitor cells in RFA.

Alternative interventions for refractory angina

“…Meta-analysis has suggested that bone marrow cell therapy may result in a significant improvement in CCS class (mean difference −0.55, 95% CI −1.00 to −0.10, p<0.02) and reduced frequency of weekly angina episodes (mean difference −5.21, 95% CI −7.35 to −3.07, p<0.00001)75 in symptomatic patients with no option coronary disease. A more recent meta-analysis76 has confirmed these findings and further suggested that cellular therapies significantly combined primary endpoint of myocardial infarction, hospitalisation for a cardiac cause and death (OR 0.49, 95% CI 0.25 to 0.98), exercise tolerance, myocardial perfusion and arrhythmia occurrence. Importantly, no significant safety concerns related to cellular products have been observed to date.…”

Challenges to success in heart failure: Cardiac cell therapies in patients with heart diseases

“…Although the study design varied among reports, overall results revealed that bone marrow cell infusion might provide functional benefits in patients with myocardial infarction or refractory angina [23][24][25][26][27]. The promising nature of these findings has encouraged clinicians to continue the use of cardiac cell therapies in patients, at least until any contradictory evidence is reported.…”

The (Translational) Road Less Traveled

“…Furthermore, multiple meta-analyses in trials of "no option" patients with or without left ventricular dysfunction have documented significant improvements in a variety of end points. [17][18][19] To summarize the current status of CD34 + cell therapy for refractory angina, preclinical studies in small and large animals have clearly demonstrated improvement in vascularity and myocardial perfusion, and the cell type, CD34 + cells, has been clearly shown to be important for angiogenesis and vascular repair, thereby providing a mechanism of action. Therefore, contrary to the pronouncements of the anonymous editorial, "sound scientific evidence and a well-characterized mechanism of action" have been established, and "much more preclinical work defining a mechanism of action and demonstrating a strong rationale for exposing humans to these procedures" is not needed.…”