S M O Peeters Weem1, M Teraa1, G J de Borst2, M C Verhaar3, F L Moll1. 1. Department of Vascular Surgery, University Medical Center Utrecht, Heidelberglaan 100, 3584CX, Utrecht, The Netherlands. 2. Department of Vascular Surgery, University Medical Center Utrecht, Heidelberglaan 100, 3584CX, Utrecht, The Netherlands. Electronic address: G.J.deBorst-2@umcutrecht.nl. 3. Department of Nephrology and Hypertension, University Medical Center Utrecht, Heidelberglaan 100, 3584CX, Utrecht, The Netherlands.
Abstract
OBJECTIVE/ BACKGROUND: Critical limb ischemia (CLI) is the most advanced stage of peripheral artery disease (PAD), and many patients with CLI are not eligible for conventional revascularization. In the last decade, cell based therapies have been explored as an alternative treatment option for CLI. A meta-analysis was conducted of randomized placebo controlled trials investigating bone marrow (BM) derived cell therapy in patients with CLI. METHODS: The MEDLINE, Embase, and the Cochrane Controlled Trials Register databases were systematically searched, and all included studies were critically appraised by two independent reviewers. The meta-analysis was performed using a random effects model. RESULTS: Ten studies, totaling 499 patients, were included in this meta-analysis. No significant differences were observed in major amputation rates (relative risk [RR] 0.91; 95% confidence interval [CI] 0.65-1.27), survival (RR 1.00; 95% CI 0.95-1.06), and amputation free survival (RR 1.03; 95% CI 0.86-1.23) between the cell treated and placebo treated patients. The ankle brachial index (mean difference 0.11; 95% CI 0.07-0.16), transcutaneous oxygen measurements (mean difference 11.88; 95% CI 2.73-21.02), and pain score (mean difference -0.72; 95% CI -1.37 to -0.07) were significantly better in the treatment group than in the placebo group. CONCLUSIONS: This meta-analysis of placebo controlled trials showed no advantage of stem cell therapy on the primary outcome measures of amputation, survival, and amputation free survival in patients with CLI. The potential benefit of more sophisticated cell based strategies should be explored in future randomized placebo controlled trials.
OBJECTIVE/ BACKGROUND:Critical limb ischemia (CLI) is the most advanced stage of peripheral artery disease (PAD), and many patients with CLI are not eligible for conventional revascularization. In the last decade, cell based therapies have been explored as an alternative treatment option for CLI. A meta-analysis was conducted of randomized placebo controlled trials investigating bone marrow (BM) derived cell therapy in patients with CLI. METHODS: The MEDLINE, Embase, and the Cochrane Controlled Trials Register databases were systematically searched, and all included studies were critically appraised by two independent reviewers. The meta-analysis was performed using a random effects model. RESULTS: Ten studies, totaling 499 patients, were included in this meta-analysis. No significant differences were observed in major amputation rates (relative risk [RR] 0.91; 95% confidence interval [CI] 0.65-1.27), survival (RR 1.00; 95% CI 0.95-1.06), and amputation free survival (RR 1.03; 95% CI 0.86-1.23) between the cell treated and placebo treated patients. The ankle brachial index (mean difference 0.11; 95% CI 0.07-0.16), transcutaneous oxygen measurements (mean difference 11.88; 95% CI 2.73-21.02), and pain score (mean difference -0.72; 95% CI -1.37 to -0.07) were significantly better in the treatment group than in the placebo group. CONCLUSIONS: This meta-analysis of placebo controlled trials showed no advantage of stem cell therapy on the primary outcome measures of amputation, survival, and amputation free survival in patients with CLI. The potential benefit of more sophisticated cell based strategies should be explored in future randomized placebo controlled trials.
Authors: Emerson C Perin; Michael P Murphy; Keith L March; Roberto Bolli; John Loughran; Phillip C Yang; Nicholas J Leeper; Ronald L Dalman; Jason Alexander; Timothy D Henry; Jay H Traverse; Carl J Pepine; R David Anderson; Scott Berceli; James T Willerson; Raja Muthupillai; Amir Gahremanpour; Ganesh Raveendran; Omaida Velasquez; Joshua M Hare; Ivonne Hernandez Schulman; Vijaykumar S Kasi; William R Hiatt; Bharath Ambale-Venkatesh; João A Lima; Doris A Taylor; Micheline Resende; Adrian P Gee; April G Durett; Jeanette Bloom; Sara Richman; Patricia G'Sell; Shari Williams; Fouzia Khan; Elsie Gyang Ross; Michelle R Santoso; JoAnne Goldman; Dana Leach; Eileen Handberg; Benjamin Cheong; Nichole Piece; Darcy DiFede; Barb Bruhn-Ding; Emily Caldwell; Judy Bettencourt; Dejian Lai; Linda Piller; Lara Simpson; Michelle Cohen; Shelly L Sayre; Rachel W Vojvodic; Lem Moyé; Ray F Ebert; Robert D Simari; Alan T Hirsch Journal: Circulation Date: 2017-02-16 Impact factor: 29.690