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Simvastatin reduces vaso-occlusive pain in sickle cell anaemia: a pilot efficacy trial.
Br J Haematol. 2017 05; 177(4):620-629.BJ

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.

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Authors+Show Affiliations

Hoppe C
Department of Hematology-Oncology, UCSF Benioff Children's Hospital Oakland, CA, USA.
Jacob E
School of Nursing, University of California Los Angeles, Los Angeles, CA, USA.
Styles L
Pharmacyclics, Inc, Sunnyvale, USA.
Kuypers F
Children's Hospital Oakland Research Institute, Oakland, USA.
Larkin S
Children's Hospital Oakland Research Institute, Oakland, USA.
Vichinsky E
Department of Hematology-Oncology, UCSF Benioff Children's Hospital Oakland, CA, USA.

MeSH

AdolescentAdultAnalgesicsAnemia, Sickle CellArterial Occlusive DiseasesBiomarkersC-Reactive ProteinChildE-SelectinFemaleHumansHydroxymethylglutaryl-CoA Reductase InhibitorsIntercellular Adhesion Molecule-1MaleNitric OxidePainSimvastatinVascular Cell Adhesion Molecule-1Vascular Endothelial Growth Factor AYoung Adult

Pub Type(s)

Clinical Trial
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28369718

Citation

Hoppe, Carolyn, et al. "Simvastatin Reduces Vaso-occlusive Pain in Sickle Cell Anaemia: a Pilot Efficacy Trial." British Journal of Haematology, vol. 177, no. 4, 2017, pp. 620-629.
Hoppe C, Jacob E, Styles L, et al. Simvastatin reduces vaso-occlusive pain in sickle cell anaemia: a pilot efficacy trial. Br J Haematol. 2017;177(4):620-629.
Hoppe, C., Jacob, E., Styles, L., Kuypers, F., Larkin, S., & Vichinsky, E. (2017). Simvastatin reduces vaso-occlusive pain in sickle cell anaemia: a pilot efficacy trial. British Journal of Haematology, 177(4), 620-629. https://doi.org/10.1111/bjh.14580
Hoppe C, et al. Simvastatin Reduces Vaso-occlusive Pain in Sickle Cell Anaemia: a Pilot Efficacy Trial. Br J Haematol. 2017;177(4):620-629. PubMed PMID: 28369718.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Simvastatin reduces vaso-occlusive pain in sickle cell anaemia: a pilot efficacy trial. AU - Hoppe,Carolyn, AU - Jacob,Eufemia, AU - Styles,Lori, AU - Kuypers,Frans, AU - Larkin,Sandra, AU - Vichinsky,Elliott, Y1 - 2017/03/28/ PY - 2016/10/05/received PY - 2016/12/06/accepted PY - 2017/4/4/pubmed PY - 2017/8/2/medline PY - 2017/4/4/entrez KW - clinical effect KW - inflammation KW - sickle cell anaemia KW - simvastatin KW - vaso-occlusive pain SP - 620 EP - 629 JF - British journal of haematology JO - Br J Haematol VL - 177 IS - 4 N2 - 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. SN - 1365-2141 UR - https://www.unboundmedicine.com/medline/citation/28369718/Simvastatin_reduces_vaso_occlusive_pain_in_sickle_cell_anaemia:_a_pilot_efficacy_trial_ L2 - https://doi.org/10.1111/bjh.14580 DB - PRIME DP - Unbound Medicine ER -