Effects of Transendocardial Delivery of Bone Marrow-Derived CD133⁺ Cells on Left Ventricle Perfusion and Function in Patients With Refractory Angina: Final Results of Randomized, Double-Blinded, Placebo-Controlled REGENT-VSEL Trial.

Abstract

New therapies for refractory angina are needed. Assessment of transendocardial delivery of bone marrow CD133⁺ cells in patients with refractory angina. Randomized, double-blinded, placebo-controlled trial enrolled 31 patients with recurrent Canadian Cardiovascular Society II-IV angina, despite optimal medical therapy, ≥1 myocardial segment with inducible ischemia in Tc-99m SPECT who underwent bone marrow biopsy and were allocated to cells (n=16) or placebo (n=15). Primary end point was absolute change in myocardial ischemia by SPECT. Secondary end points were left ventricular function and volumes by magnetic resonance imaging and angina severity. After 4 months, there were no significant differences in extent of inducible ischemia between groups (summed difference score mean [±SD]: 2.60 [2.6] versus 3.63 [3.6], <i>P</i>=0.52; total perfusion deficit: 3.60 [3.6] versus 5.01 [4.3], <i>P</i>=0.32; absolute changes of summed difference score: -1.38 [5.2] versus -0.73 [1.9], <i>P</i>=0.65; and total perfusion deficit: -1.33 [3.3] versus -2.19 [6.6], <i>P</i>=0.65). There was a significant reduction of left ventricular volumes (end-systolic volume: -4.3 [11.3] versus 7.4 [11.8], <i>P</i>=0.02; end-diastolic volume: -9.1 [14.9] versus 7.4 [15.8], <i>P</i>=0.02) and no significant change of left ventricular ejection fraction in the cell group. There was no difference in number of patients showing improvement of ≥1 Canadian Cardiovascular Society class after 1 (41.7% versus 58.3%; <i>P</i>=0.68), 4 (50% versus 33.3%; <i>P</i>=0.63), 6 (70% versus 50.0%; <i>P</i>=0.42), and 12 months (55.6% versus 81.8%; <i>P</i>=0.33) and use of nitrates after 12 months. Transendocardial CD133⁺ cell therapy was safe. Study was underpowered to conclusively validate the efficacy, but it did not show a significant reduction of myocardial ischemia and angina versus placebo. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01660581.