title: Impact of Cell Therapy on Myocardial Perfusion and Cardiovascular Outcomes in Patients With Angina Refractory to Medical Therapy: A Systematic Review and Meta-Analysis.
abstract: BACKGROUND
  The effect of stem/progenitor cells on myocardial perfusion and clinical outcomes in patients with refractory angina remains unclear because studies published to date have been small phase I-II trials.
  
  
  OBJECTIVE
  We performed a meta-analysis of randomized controlled trials to evaluate the effect of cell-based therapy in patients with refractory angina who were ineligible for coronary revascularization.
  
  
  RESULTS
  Several data sources were searched from inception to September 2015, which yielded 6 studies. The outcomes pooled were indices of angina (anginal episodes, Canadian Cardiovascular Society angina class, exercise tolerance, and antianginal 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 (major adverse cardiac events). Mean difference (MD), standardized mean differences, or odds ratio were calculated to assess relevant outcomes. Our analysis shows an improvement in anginal episodes (MD, -7.81; 95% confidence interval [CI], -15.22 to -0.41), use of antianginal medications (standardized MD, -0.59; 95% CI, -1.03 to -0.14), Canadian Cardiovascular Society class (MD, -0.58; 95% CI, -1.00 to -0.16), exercise tolerance (standardized MD, 0.331; 95% CI, 0.08 to 0.55), and myocardial perfusion (standardized MD, -0.49; 95% CI, -0.76 to -0.21) and a decreased risk of major adverse cardiac events (odds ratio, 0.49; 95% CI, 0.25 to 0.98) and arrhythmias (odds ratio, 0.25; 95% CI, 0.06 to 0.98) in cell-treated patients when 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 refractory angina. These encouraging results suggest that larger, phase III randomized controlled trials are in order to conclusively determine the effect of stem/progenitor cells in refractory angina.
authors.affiliation: From the Institute of Molecular Cardiology, University of Louisville, KY.
authors.forename: Abdur Rahman
authors.initials: AR
authors.lastname: Khan
authors.affiliation: From the Institute of Molecular Cardiology, University of Louisville, KY.
authors.forename: Talha A
authors.initials: TA
authors.lastname: Farid
authors.affiliation: From the Institute of Molecular Cardiology, University of Louisville, KY.
authors.forename: Asif
authors.initials: A
authors.lastname: Pathan
authors.affiliation: From the Institute of Molecular Cardiology, University of Louisville, KY.
authors.forename: Avnish
authors.initials: A
authors.lastname: Tripathi
authors.affiliation: From the Institute of Molecular Cardiology, University of Louisville, KY.
authors.forename: Shahab
authors.initials: S
authors.lastname: Ghafghazi
authors.affiliation: From the Institute of Molecular Cardiology, University of Louisville, KY.
authors.forename: Marcin
authors.initials: M
authors.lastname: Wysoczynski
authors.affiliation: From the Institute of Molecular Cardiology, University of Louisville, KY. rbolli@louisville.edu.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bolli
mesh_terms: D000787:Angina Pectoris / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy*; D002317:Cardiovascular Agents / Q000494:pharmacology / Q000627:therapeutic use; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D017079:Exercise Tolerance / Q000187:drug effects / Q000502:physiology; D006801:Humans; D062645:Percutaneous Coronary Intervention / Q000379:methods*; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D016896:Treatment Outcome
chemical_list: D002317:Cardiovascular Agents
keywords: cell- and tissue-based therapy; meta-analysis; perfusion; randomized controlled trial; stem cells
references.citation: JAMA. 2009 May 20;301(19):1997-2004
references.pmid: 19454638
references.citation: Am Heart J. 2008 Mar;155(3):435-44
references.pmid: 18294475
references.citation: Cochrane Database Syst Rev. 2010;(2):CD007219
references.pmid: 20166092
references.citation: Catheter Cardiovasc Interv. 2010 May 1;75(6):886-91
references.pmid: 20432394
references.citation: Cochrane Database Syst Rev. 2015;(2):CD003712
references.pmid: 25721946
references.citation: J Cardiovasc Transl Res. 2010 Apr;3(2):160-8
references.pmid: 20560030
references.citation: Cardiology. 2010;117(2):140-7
references.pmid: 20975266
references.citation: Am Heart J. 2011 Jun;161(6):1078-87.e3
references.pmid: 21641354
references.citation: Circ Res. 2011 Aug 5;109(4):428-36
references.pmid: 21737787
references.citation: BMJ. 2011;343:d5928
references.pmid: 22008217
references.citation: Am Heart J. 2012 Mar;163(3):415-21, 421.e1
references.pmid: 22424012
references.citation: Can J Cardiol. 2012 Mar-Apr;28(2 Suppl):S20-41
references.pmid: 22424281
references.citation: JAMA. 2012 Apr 25;307(16):1717-26
references.pmid: 22447880
references.citation: Cell Transplant. 2013;22(3):521-8
references.pmid: 22472086
references.citation: Can J Cardiol. 2013 Aug;29(8):908-14
references.pmid: 23465346
references.citation: Circ Res. 2013 Aug 30;113(6):810-34
references.pmid: 23989721
references.citation: Eur Heart J. 2013 Sep;34(34):2683-8
references.pmid: 23671156
references.citation: Cell Death Differ. 2014 Feb;21(2):216-25
references.pmid: 24185619
references.citation: Nat Rev Cardiol. 2014 Feb;11(2):78-95
references.pmid: 24366073
references.citation: Circ Res. 2014 Nov 7;115(11):950-60
references.pmid: 25231095
references.citation: J Am Heart Assoc. 2015 Feb;4(2). pii: e001287. doi: 10.1161/JAHA.114.001287
references.pmid: 25637344
references.citation: Circ Res. 2009 Oct 9;105(8):724-36
references.pmid: 19815827
references.citation: Arterioscler Thromb Vasc Biol. 2003 Jul 1;23(7):1185-9
references.pmid: 12714439
references.citation: BMJ. 2003 Sep 6;327(7414):557-60
references.pmid: 12958120
references.citation: Circ Res. 2004 Mar 19;94(5):678-85
references.pmid: 14739163
references.citation: Circulation. 2004 Mar 30;109(12):1543-9
references.pmid: 15023891
references.citation: Biometrics. 1994 Dec;50(4):1088-101
references.pmid: 7786990
references.citation: Circulation. 1998 Feb 17;97(6):535-43
references.pmid: 9494023
references.citation: Am J Cardiol. 1999 Sep 1;84(5):598-600, A8
references.pmid: 10482164
references.citation: Circulation. 2006 Mar 14;113(10):1311-25
references.pmid: 16534028
references.citation: Circulation. 2006 Nov 14;114(20):2163-9
references.pmid: 17075009
references.citation: Circulation. 2007 Jun 26;115(25):3165-72
references.pmid: 17562958
references.citation: Eur Heart J. 2007 Dec;28(24):2998-3005
references.pmid: 17984132
references.citation: Am Heart J. 2008 Mar;155(3):418-34
references.pmid: 18294474