240 likes | 367 Views
Myocardial Recovery: Stem Cell Therapy - are we getting there?. Professor Anthony Mathur Queen Mary University of London Barts and the London NHS Trust. Yes. efficacy. preclinical promise?. Source and Administration in AMI Trials.
E N D
Myocardial Recovery:Stem Cell Therapy - are we getting there? Professor Anthony Mathur Queen Mary University of London Barts and the London NHS Trust
Source and Administration in AMI Trials Dimmeler S, Zeiher AM, Schneider MD J Clin Invest 2005:115;572.
RCT using BMC post MI Effect on LVEF MI Size CHF TOPCARE-CHF +2.9% (p<0.01) ND BOOST ND +6.0% (p<0.01) +2.8% (p=ns)* ASTAMI p=ns +0.6% (p=ns) AMI REPAIR-AMI +2.5% (p=0.01) ND -28% (p=0.03) LEUVEN-AMI +1.2% (p=ns) 1 10 100 1000 Timing of BMC Transfer post MI [Days post MI] * 18 months follow-up
Meta-analysis of randomised placebo control trials 3% Martin-Rendon et al., 2008, Eur Heart J, 29, 1807-18
Discrepancy? • Not enough cells injected in man • Wrong cells • Wrong timing relative to infarct age • Wrong delivery method • Animal models not representative
RCT using BMC post MI MI Size Effect on LVEF TOPCARE-CHF +2.9% (p<0.01) ND CHF REGENERATE-IHD ******* BOOST ND +6.0% (p<0.01) +2.8% (p=ns)* ASTAMI p=ns +0.6% (p=ns) AMI REPAIR-AMI +2.5% (p=0.01) ND -28% (p=0.03) LEUVEN-AMI +1.2% (p=ns) REGENERATE-AMI ******* 0 1 10 100 1000 10000 Timing of BMC Transfer post MI [Days post MI] * 18 months follow-up
REGENERATE-IHD P=0.2 P=0.006 * p = 0.0057 p = 0.1887
0 1.0 12 24 36 48 60 0.8 0.6 0.4 0.2 0.0 NYHA class vs. prognosis Log rank test P<0.001 NYHA IV NYHA III Cumulative risk of all-cause mortality (%) NYHA II NYHA I Follow up in months
Primary PCI Lancet. 2007 Jun 30;369(9580):2142-3
Epicardium Intravenous Intra-arterial Mobilised intramyocardium Coronary artery Coronary sinus Delivery Routes INDIRECT DIRECT
REGENERATE-IHD P=0.2 P=0.006 * p = 0.0057 p = 0.1887
Summary • Stem cells for myocardial recovery - we could already be there • Results of more outcome studies needed • Important questions for translational research • Clinicians need to agree on acceptable outcome measures
Clinical importance vs statistical significance? ‘……..in contrast to the well-established standards for statistical significance (p values), no guidelines exist for deciding what magnitude of difference is clinically significant or practically important.’ J Am Coll Cardiol 2010; 55:415-27.