Maya M Jeyaraman1, Rasheda Rabbani2, Leslie Copstein3, Wasan Sulaiman3, Farnaz Farshidfar3, Hessam H Kashani3, Sheikh M Z Qadar3, Qingdong Guan4, Becky Skidmore5, Elissavet Kardami6, John Ducas7, Samer Mansour8, Ryan Zarychanski9, Ahmed M Abou-Setta2. 1. The George and Fay Yee Center for Healthcare Innovation, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. Electronic address: maya.jeyaraman@umanitoba.com. 2. The George and Fay Yee Center for Healthcare Innovation, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. 3. The George and Fay Yee Center for Healthcare Innovation, University of Manitoba, Winnipeg, Manitoba, Canada. 4. Cellular Therapy Laboratory, CancerCare Manitoba, Winnipeg, Manitoba, Canada; Manitoba Center for Advanced Cell and Tissue Therapy, Winnipeg, Manitoba, Canada. 5. Information Specialist Consultant, Ottawa, Ontario, Canada. 6. Department of Human Anatomy and Cell Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. 7. Section of Cardiology, Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. 8. Centre Hospitalier de l'Université de Montreal, Montreal, Quebec, Canada; Faculty of Medicine, Department of Medicine, Université de Montréal, Montreal, Quebec, Canada; Centre de recherche du Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada. 9. The George and Fay Yee Center for Healthcare Innovation, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Haematology and Medical Oncology, Cancer Care Manitoba, Winnipeg, Manitoba, Canada.
Abstract
BACKGROUND: Randomized controlled trials (RCTs) on bone marrow stem cell (BMSC) therapy in ST-elevation myocardial infarction (STEMI) patients have reported conflicting results. Our main objective was to critically appraise and meta-analyze best-available evidence on efficacy and safety of intracoronary administration of autologous BMSC therapy in STEMI patients after primary percutaneous coronary intervention. METHODS: We conducted a search of MEDLINE, PubMed, EMBASE, CENTRAL, Global Health, CINAHL, and conference proceedings in February 2017. Our primary outcome was all-cause mortality. Secondary and safety outcomes included cardiac death, heart failure, arrhythmias, repeat myocardial infarction, or target vessel revascularizations; or improved health-related quality of life, left ventricular ejection fraction, or infarct size. Summary relative and absolute risks were obtained using random effects models. We also evaluated the strength of evidence. RESULTS: A comprehensive database search identified 42 RCTs (3365 STEMI patients). BMSC therapy did not significantly decrease mortality (risk ratio, 0.71; 95% confidence interval, 0.45-1.11; I2, 0%; absolute risk reduction, 0.1%; 95% confidence interval, -0.71 to 0.91; 40 trials; 3289 participants; I2, 0%; low strength of evidence). BMSC therapy had no effect on secondary or adverse outcomes. Trial sequential analysis for all-cause mortality showed no evidence of a clinically important difference, with a very low probability that future studies can change the current conclusion. CONCLUSIONS: On the basis of evidence from 42 RCTs published in the past 15 years, we provide conclusive evidence for a lack of beneficial effect for autologous BMSC therapy in patients with STEMI.
BACKGROUND: Randomized controlled trials (RCTs) on bone marrow stem cell (BMSC) therapy in ST-elevation myocardial infarction (STEMI) patients have reported conflicting results. Our main objective was to critically appraise and meta-analyze best-available evidence on efficacy and safety of intracoronary administration of autologous BMSC therapy in STEMI patients after primary percutaneous coronary intervention. METHODS: We conducted a search of MEDLINE, PubMed, EMBASE, CENTRAL, Global Health, CINAHL, and conference proceedings in February 2017. Our primary outcome was all-cause mortality. Secondary and safety outcomes included cardiac death, heart failure, arrhythmias, repeat myocardial infarction, or target vessel revascularizations; or improved health-related quality of life, left ventricular ejection fraction, or infarct size. Summary relative and absolute risks were obtained using random effects models. We also evaluated the strength of evidence. RESULTS: A comprehensive database search identified 42 RCTs (3365 STEMI patients). BMSC therapy did not significantly decrease mortality (risk ratio, 0.71; 95% confidence interval, 0.45-1.11; I2, 0%; absolute risk reduction, 0.1%; 95% confidence interval, -0.71 to 0.91; 40 trials; 3289 participants; I2, 0%; low strength of evidence). BMSC therapy had no effect on secondary or adverse outcomes. Trial sequential analysis for all-cause mortality showed no evidence of a clinically important difference, with a very low probability that future studies can change the current conclusion. CONCLUSIONS: On the basis of evidence from 42 RCTs published in the past 15 years, we provide conclusive evidence for a lack of beneficial effect for autologous BMSC therapy in patients with STEMI.