title: Simvastatin reduces vaso-occlusive pain in sickle cell anaemia: a pilot efficacy trial.
abstract: Sickle cell anaemia (SCA) is a progressive vascular disease characterized by episodic vaso-occlusive pain. Despite the broad impact of inflammation on acute and chronic clinical manifestations of SCA, no directed anti-inflammatory therapies currently exist. Statins are cholesterol-lowering agents shown to confer protection from vascular injury by suppressing inflammation. We previously documented a reduction in soluble biomarkers of inflammation in patients with sickle cell disease treated with simvastatin. To determine the potential clinical efficacy of simvastatin, we treated 19 SCA patients with single daily dose simvastatin for 3 months and assessed changes from baseline in the frequency and intensity of diary-reported pain and levels of circulating nitric oxide metabolites (NOx), high sensitivity C-reactive protein (hs-CRP), vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), ICAM-3, E-selectin, and vascular endothelial growth factor (VEGF). Treatment with simvastatin resulted in a significant reduction in the frequency of pain (P = 0·0003), oral analgesic use (P = 0·003) and circulating hs-CRP (P = 0·003), soluble (s)E-selectin (P = 0·01), sICAM-1 (P = 0·02), sICAM-3 (P = 0·02) and sVEGF (P = 0·01). Simvastatin had no effect on pain intensity or levels of NOx, sP-selectin and sVCAM-1. The observed reductions in pain rate and markers of inflammation were greatest in subjects receiving hydroxycarbamide (HC), suggesting a synergistic effect of simvastatin. These results provide preliminary clinical data to support a larger trial of simvastatin in SCA.
authors.affiliation: Department of Hematology-Oncology, UCSF Benioff Children's Hospital Oakland, CA, USA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Hoppe
authors.affiliation: School of Nursing, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Eufemia
authors.initials: E
authors.lastname: Jacob
authors.affiliation: Pharmacyclics, Inc, Sunnyvale, USA.
authors.forename: Lori
authors.initials: L
authors.lastname: Styles
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, USA.
authors.forename: Frans
authors.initials: F
authors.lastname: Kuypers
authors.affiliation: Children's Hospital Oakland Research Institute, Oakland, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Larkin
authors.affiliation: Department of Hematology-Oncology, UCSF Benioff Children's Hospital Oakland, CA, USA.
authors.forename: Elliott
authors.initials: E
authors.lastname: Vichinsky
mesh_terms: D000293:Adolescent; D000328:Adult; D000700:Analgesics / Q000627:therapeutic use*; D000755:Anemia, Sickle Cell / Q000150:complications*; D001157:Arterial Occlusive Diseases / Q000150:complications; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D019040:E-Selectin / Q000378:metabolism; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D010146:Pain / Q000517:prevention & control*; D019821:Simvastatin / Q000627:therapeutic use*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
chemical_list: D000700:Analgesics; D015415:Biomarkers; D019040:E-Selectin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D002097:C-Reactive Protein; D019821:Simvastatin
keywords: clinical effect; inflammation; sickle cell anaemia; simvastatin; vaso-occlusive pain