Journal Article

Granulocyte colony-stimulating factor for stem cell mobilisation in acute myocardial infarction: a randomised controlled trial

Marenzi, G, Gentile, Francesco, Madotto, Fabiana, Di Pasquale, G, Tonelli, C, Viecca, M, Pes, RM, Gaita, F, Castelli, C, Limido, A, Colombo, Gualtiero I, Casu, G, Maggiolini, Stefano, Landolina, ME, Piovaccari, G, Nassiacos, D, Pagnotta, A, Pantaleoni, M, Bassetti, Beatrice, Perna, GP, Lombardi, F, Severi, S, Sinagra, G, Rigo, F, Politi, A, Iliceto, S, Marzilli, M, Pompilio, Giulio, Malafronte, C, Mauro, C, Sommariva, L, Savonitto, S, Mafrici, A, Macchi, A, Bovenzi, FM, Trimarco, B, Mascelli, G, Villani, GQ, Campana, C, Maggioni, Aldo Pietro, Caico, SI, Tespili, M, Verzoni, A, Parati, G, Pirelli, S, Klugmann, S, Achilli, Felice, Sante Bongo, A, Olivari, Z, Planca, E, De Servi, S

2024

Overview

BackgroundTo determine whether granulocyte colony-stimulating factor (G-CSF) improves clinical outcomes after large ST-elevation myocardial infarction (STEMI) when administered early in patients with left ventricular (LV) dysfunction after successful percutaneous coronary intervention (PCI).MethodsSTEM-AMI OUTCOME was designed as a prospective, multicentre, nationwide, randomised, open-label, phase III trial (ClinicalTrials.gov ID: NCT01969890) to demonstrate the efficacy and safety of early G-CSF administration in reducing 2-year cardiac mortality and morbidity in patients with STEMI with LV ejection fraction ≤45% after PCI. The primary outcome was a composite of all-cause death, recurrence of myocardial infarction and hospitalisation for heart failure. Due to low recruitment and event rates, the study was discontinued and did not achieve adequate statistical power to verify the hypothesis.ResultsPatients were randomly allocated to G-CSF (n=260) or standard of care (SOC; n=261). No difference was found in the composite primary outcome between study groups (HR 1.20; 95% CI 0.63 to 2.28). The 2-year mortality was 2.31% in the G-CSF and 2.68% in the control group (HR 0.88; 95% CI 0.29 to 2.60). Adverse events did not differ between the G-CSF (n=65) and SOC groups (n=58; OR 1.17; 95% CI 0.78 to 1.75). In post hoc analyses on the intervention group, we observed a trend towards fewer composite primary outcomes in patients with low bone marrow (BM) cell mobilisation (n=108) versus those with high mobilisation (n=152, with peak leucocyte count >50×109/L; HR 2.86; 95% CI 0.96 to 8.56). Primary outcomes were lower in patients with severe LV systolic dysfunction at discharge treated with G-CSF than in controls (interaction β±SE, −0.08±0.04; p=0.034).ConclusionsAlthough inconclusive, this is the largest trial in the field of cell-based cardiac repair after STEMI providing evidence of the tolerability and long-term safety of G-CSF treatment. The results prompt further studies to understand which patient can benefit most from BM cell mobilisation.Trial registration number NCT01969890.

• Publisher: BMJ Publishing Group Ltd and British Cardiovascular Society,BMJ Publishing Group LTD
• Subject: Acute Coronary Syndrome / Aged / Angioplasty / Bone marrow / Clinical trials / Coronary artery disease / Ejection fraction / Female / Granulocyte Colony-Stimulating Factor - administration & dosage / Granulocyte Colony-Stimulating Factor - therapeutic use / Granulocytes / Heart attacks / Heart Failure - mortality / Heart Failure - physiopathology / Heart Failure - therapy / Hematopoietic Stem Cell Mobilization - methods / Hospitalization / Humans / Hypotheses / Hypothesis testing / Male / Middle Aged / Mortality / Myocardial Infarction / Outcome Assessment, Health Care / Patients / Percutaneous Coronary Intervention / Percutaneous Coronary Intervention - methods / Prospective Studies / Recurrence / ST Elevation Myocardial Infarction - mortality / ST Elevation Myocardial Infarction - physiopathology / ST Elevation Myocardial Infarction - therapy / Stem cells / Stroke Volume - physiology / Time Factors / Treatment Outcome / Ventricular Dysfunction, Left - physiopathology / Ventricular Dysfunction, Left - therapy / Ventricular Function, Left - physiology