Efficacy of stem cell in improvement of left ventricular function in acute myocardial infarction - MI3 Trial
Velu Nair1, Hemant Madan1, Sunil Sofat1, Prosenjit Ganguli1, MJ Jacob1, Rajat Datta2, Prashant Bharadwaj2, RS Sarkar2, AJ Pandit2, Soniya Nityanand3, Pravin K Goel3, Naveen Garg3, Sanjay Gambhir3, Paul V George4, Sunil Chandy4, Vikram Mathews4, Oomen K George4, KK Talwar5, Ajay Bahl5, Neelam Marwah5, Anish Bhatacharya5, Balram Bhargava6, Balram Airan6, Sujata Mohanty6, Chetan D Patel6, Alka Sharma7, Shinjini Bhatnagar8, A Mondal9, Jacob Jose4, A Srivastava4, MI3 Trial10
1 Army Hospital (Research and Referral), New Delhi, India
2 Military Hospital, Cardio Thoracic Centre, Pune, India
3 Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
4 Christian Medical College, Vellore, India
5 Postgraduate Institute of Medical Education & Research, Chandhigarh, India
6 All India Institute of Medical Sciences, New Delhi, India
7 Department of Biotechnology, Government of India, New Delhi, India
8 All India Institute of Medical Sciences, India
9 Institute of Nuclear Medicine & Allied Sciences, India
Department of Haematology & Bone Marrow Transplantation, Army Research and Referral Hospital, Dhaula Kuan, Delhi Cantt 110 010
Source of Support: None, Conflict of Interest: None
Background & objectives: Acute myocardial infarction (AMI) is characterized by irreparable and irreversible loss of cardiac myocytes. Despite major advances in the management of AMI, a large number of patients are left with reduced left ventricular ejection fraction (LVEF), which is a major determinant of short and long term morbidity and mortality. A review of 33 randomized control trials has shown varying improvement in left ventricular (LV) function in patients receiving stem cells compared to standard medical therapy. Most trials had small sample size and were underpowered. This phase III prospective, open labelled, randomized multicenteric trial was undertaken to evaluate the efficacy in improving the LVEF over a period of six months, after injecting a predefined dose of 5-10 Χ 10  autologous mononuclear cells (MNC) by intra-coronary route, in patients, one to three weeks post ST elevation AMI, in addition to the standard medical therapy.
Methods: In this phase III prospective, multicentric trial 250 patients with AMI were included and randomized into stem cell therapy (SCT) and non SCT groups. All patients were followed up for six months. Patients with AMI having left ventricular ejection fraction (LVEF) of 20-50 per cent were included and were randomized to receive intracoronary stem cell infusion after successfully completing percutaneous coronary intervention (PCI).
Results: On intention-to-treat analysis the infusion of MNCs had no positive impact on LVEF improvement of ≥ 5 per cent. The improvement in LVEF after six months was 5.17 ± 8.90 per cent in non SCT group and 4.82 ± 10.32 per cent in SCT group. The adverse effects were comparable in both the groups. On post hoc analysis it was noted that the cell dose had a positive impact when infused in the dose of ≥ 5 X 10  (n=71). This benefit was noted upto three weeks post AMI. There were 38 trial deviates in the SCT group which was a limitation of the study.
Interpretation & conclusions:Infusion of stem cells was found to have no benefit in ST elevation AMI. However, the procedure was safe. A possible benefit was seen when the predefined cell dose was administered which was noted upto three weeks post AMI, but this was not significant and needs confirmation by larger trials.