Intracoronary Autologous Bone-Marrow Cell Transfer after Myocardial Infarction: A Double-Blind, Randomized, and Placebo-Controlled Clinical Trial Presented at American College of Cardiology Scientific Sessions 2005 Presented by Dr. Stefan Janssens Intracoronary Autologous Bone-Marrow Cell Transfer after Myocardial Infarction

www. Clinical trial results.org Endpoints (mean follow-up 4 months):  Global LVEF, LV mass index and infarct size Endpoints (mean follow-up 4 months):  Global LVEF, LV mass index and infarct size Intracoronary Autologous Bone-Marrow Cell Transfer after Myocardial Infarction Presented at ACC Scientific Sessions acute MI † patients; time after symptom onset > 2 hours; successful reperfusion post-PCI; documented LV dysfunction Placebo controlled. Randomized. Blinded. Mean age 56 years. 14% female. 66 acute MI † patients; time after symptom onset > 2 hours; successful reperfusion post-PCI; documented LV dysfunction Placebo controlled. Randomized. Blinded. Mean age 56 years. 14% female. Intracoronary autologous bone- marrow cell transfer** n=32 Intracoronary autologous bone- marrow cell transfer** n=32 † defined as cumulative ST segment elevation ≥ 6 mm ** bone marrow aspiration was performed and transferred to an open infarct-related artery. The transfer was performed intracoronary using over-the-wire balloon catheter during 3 coronary occlusions. Patients were monitored in-hospital for 7 days and underwent follow-up through 4 months. PET and MRI were performed at the initial hospitalization and at 4 month follow-up. Placebo n=34 Placebo n=34 24 hours later

www. Clinical trial results.org Presented at ACC Scientific Sessions 2005 Improvement in Global LV Ejection Fraction Over 4 Months Intracoronary Autologous Bone-Marrow Cell Transfer after Myocardial Infarction Bone marrow cell harvest volume averaged 130 mL, with 304 million total nucleated cells and 172 mononuclear cellsBone marrow cell harvest volume averaged 130 mL, with 304 million total nucleated cells and 172 mononuclear cells The infarct artery was in the left coronary in 62% of patients and the right coronary in 37%.The infarct artery was in the left coronary in 62% of patients and the right coronary in 37%. Post-PCI TIMI flow grade 3 was present in 91% of patients. All but one patient received aspirin, and glycoprotein IIb/IIIa inhibitors were used in 78% of the bone marrow group and 64% of the placebo groupPost-PCI TIMI flow grade 3 was present in 91% of patients. All but one patient received aspirin, and glycoprotein IIb/IIIa inhibitors were used in 78% of the bone marrow group and 64% of the placebo group Global LVEF increased by 2.1% in the bone marrow group and 3.9% in the placebo groupGlobal LVEF increased by 2.1% in the bone marrow group and 3.9% in the placebo group

www. Clinical trial results.org Presented at ACC Scientific Sessions 2005 There was no difference in change in systolic wall motion in either region End diastolic wall thickness reduction was larger in the bone marrow group compared with placebo in both the infarct region and the remote area There were no differences in the PET perfusion indices or metabolic indices in the infarct region or in the border zone Intracoronary Autologous Bone-Marrow Cell Transfer after Myocardial Infarction Infarct Region p=0.49 Border Zone p=0.94 Infarct Region p=0.04 Remote Area p=0.05 Systolic Wall Motion from baseline to 4 months End Diastolic Wall Thickness Reduction from baseline to 4 months BMC Placebo BMC Placebo BMC Placebo BMC Placebo

www. Clinical trial results.org At 4 months, LV mass index (p=0.018) and infarct size (p=0.036) were lower in the bone marrow group compared with the placebo groupAt 4 months, LV mass index (p=0.018) and infarct size (p=0.036) were lower in the bone marrow group compared with the placebo group Similar results were observed in infarct size in the subgroup of patients who underwent PCI within 6 hours and in patients with infarct size > 20% of LV mass indexSimilar results were observed in infarct size in the subgroup of patients who underwent PCI within 6 hours and in patients with infarct size > 20% of LV mass index There was no difference in adverse events during admission or at 4 month-follow-up, with atrial tachycardia on Holter in 19% of the bone marrow group and 15% of the placebo groupThere was no difference in adverse events during admission or at 4 month-follow-up, with atrial tachycardia on Holter in 19% of the bone marrow group and 15% of the placebo group Intracoronary Autologous Bone-Marrow Cell Transfer after Myocardial Infarction Presented at ACC Scientific Sessions 2005 Other Principle Findings:

www. Clinical trial results.org Among patients with recent reperfusion therapy following myocardial infarction, treatment with intracoronary autologous bone-marrow cell transfer was associated with reductions in infarct size compared with placebo but was not associated with changes in left ventricular systolic functional recovery. Bone marrow transfer was not associated with an increase in myocardial blood flow or oxidative metabolism on PET scan. While earlier studies have evaluated autologous bone-marrow cell transfer post-MI, the present study is the first to do so in a double-blind placebo controlled manner. Given the safety profile and the potential benefit in infarct size, larger randomized trials of autologous bone- marrow cell transfer are warranted. Among patients with recent reperfusion therapy following myocardial infarction, treatment with intracoronary autologous bone-marrow cell transfer was associated with reductions in infarct size compared with placebo but was not associated with changes in left ventricular systolic functional recovery. Bone marrow transfer was not associated with an increase in myocardial blood flow or oxidative metabolism on PET scan. While earlier studies have evaluated autologous bone-marrow cell transfer post-MI, the present study is the first to do so in a double-blind placebo controlled manner. Given the safety profile and the potential benefit in infarct size, larger randomized trials of autologous bone- marrow cell transfer are warranted. Presented at ACC Scientific Sessions 2005 Intracoronary Autologous Bone-Marrow Cell Transfer after Myocardial Infarction