Intracoronary Autologous CD34+ Stem Cell Therapy For Intractable Angina
Intracoronary Autologous CD34+ Stem Cell Therapy For Intractable Angina
Intracoronary Autologous CD34+ Stem Cell Therapy For Intractable Angina
Safety Analysis
No increase in angina frequency or usage of sublingual Table 2. Incidence of serious adverse events
NTG was observed in the patients of either group. There
were no cardiac enzyme elevations, myocardial infarc- Placebo CD34+ cells p
tions, acute coronary syndromes or deaths. Serious ad- (n = 56) (n = 56)
verse events (table 2) were distributed evenly between the
2 groups. No patients from either group developed ven- Atrial arrhythmia 2 (3) 1 (2) >0.05
Ventricular arrhythmia 1 (2) 0 (2) >0.05
tricular tachycardia during the cell or saline infusion pro- Angina exacerbation 3 (5) 2 (3) >0.05
cedure. No arrhythmias were detected by Holter monitor- Congestive heart failure 0 (0) 0 (0) >0.05
ing in any patient during or after the infusion process. Respiratory arrest 0 (0) 0 (0) >0.05
Cerebrovascular accident 0 (0) 1 (2) >0.05
Efficacy Analysis Peripheral vascular claudication 0 (0) 0 (0) >0.05
Bleeding/anemia 0 (0) 0 (0) >0.05
Angina Frequency Renal insufficiency 2 (3) 0 (0) >0.05
At baseline, patients in the control group experienced Gastrointestinal complication 1 (2) 0 (0) >0.05
20.5 8 3.5 episodes of angina per week compared to 21.2 Endocrine/electrolyte disorder 1 (2) 1 (2) >0.05
8 6.1 episodes of angina per week in the treatment group.
Three months after infusion, the frequency of angina had Values are numbers (percentages in parentheses).
decreased in both the placebo and treatment groups (16.0
8 3.2 episodes in the control group vs. 6.6 8 1.3 in the
treated group). Six months after infusion, the frequency
of angina was further reduced in both the control group NTG Use
and CD34+ cell-treated patients (15.5 8 3.3 vs. 5.6 8 2.1 Three and 6 months after infusion, NTG use in the
episodes). At both time points, the CD34+ stem cell- control group had decreased compared to baseline (–3.81
treated patients experienced a greater reduction of symp- 8 0.6 and –4.6 8 2.7 mg), and the CD34+ stem cell-
toms (change from baseline: controls, –4.5 8 0.3 epi- treated patients also used less NTG at both time points
sodes at 3 months and –3.0 8 1.2 at 6 months; CD34+ cell (–9.8 8 7.5 and –11.1 8 1.3 mg; table 3). The decrease in
treatment, –14.6 8 4.8 episodes at 3 months and –15.6 8 NTG use in the control population, in the context of a
4.0 episodes at 6 months; table 3). decrease in angina, may be a reflection of better utiliza-
Table 3. Angina frequency, NTG use, ETT time and CCS class at ercise time. Six months after infusion, exercise time on
baseline and 3 and 6 months after infusion the standard Bruce protocol was further improved in
control and treatment groups when compared with base-
Control CD34+ cells p
(n = 56) (n = 56) line (+2.5 8 2.1 and +4.5 8 1.3 min, respectively).
References
1 Wenaweser P, Windecker S: Acute coronary 4 Fukumoto Y, Miyamoto T, Okamura T, Gon- 7 Kawamoto A, Iwasaki H, Kusano K, Mu-
syndromes: management and secondary do H, Iwasaki H, Horiuchi T, Yoshizawa S, rayama T, Oyamada A, Silver M, Hulbert C,
prevention. Herz 2008;33:25–37. Inaba S, Harada M, Niho Y: Angina pectoris Gavin M, Hanley A, Ma H, Kearney M, Zak
2 Yang EH, Barsness GW, Gersh BJ, Chan- occurring during granulocyte colony-stim- V, Asahara T, Losordo DW: CD34-positive
drasekaran K, Lerman A: Current and future ulating factor-combined preparatory regi- cells exhibit increased potency and safety for
treatment strategies for refractory angina. men for autologous peripheral blood stem therapeutic neovascularization after myo-
Mayo Clin Proc 2004;79:1284–1292. cell transplantation in a patient with acute cardial infarction compared with total
3 Losordo DW, Schatz RA, White CJ, Udelson myelogenous leukaemia. Br J Haematol 1997; mononuclear cells. Circulation 2006; 114:
JE, Veereshwarayya V, Durgin M, Poh KK, 97:666–668. 2163–2169.
Weinstein R, Kearney M, Chaudhry M, Burg 5 Wilson RF, Henry TD: Granulocyte colony- 8 Manginas A, Goussetis E, Koutelou M, Kara-
A, Eaton L, Heyd L, Thorne T, Shturman L, stimulating factor and granulocyte-macro- tasakis G, Peristeri I, Theodorakos A, Leon-
Hoffmeister P, Story K, Zak V, Dowling D, phage colony-stimulating factor: double- tiadis E, Plessas N, Theodosaki M, Grapha-
Traverse JH, Olson RE, Flanagan J, Sodano edged swords. J Am Coll Cardiol 2005; 46: kos S, Cokkinos DV: Pilot study to evaluate
D, Murayama T, Kawamoto A, Kusano KF, 1649–1650. the safety and feasibility of intracoronary
Wollins J, Welt F, Shah P, Soukas P, Asahara 6 Iwasaki H, Kawamoto A, Ishikawa M, CD133(+) and CD133(–) CD34(+) cell thera-
T, Henry TD: Intramyocardial transplanta- Oyamada A, Nakamori S, Nishimura H, py in patients with nonviable anterior myo-
tion of autologous CD34+ stem cells for in- Sadamoto K, Horii M, Matsumoto T, Mu- cardial infarction. Catheter Cardiovasc In-
tractable angina: a phase I/IIa double-blind, rasawa S, Shibata T, Suehiro S, Asahara T: terv 2007;69:773–781.
randomized controlled trial. Circulation Dose-dependent contribution of CD34- 9 Brehm M, Darrelmann E, Strauer BE: Stem
2007;115:3165–3172. positive cell transplantation to concurrent cell therapy in acute myocardial infarction.
vasculogenesis and cardiomyogenesis for Internist 2008;49:1068–1078.
functional regenerative recovery after
myocardial infarction. Circulation 2006;
113:1311–1325.