K K Ray1, S Francis, D C Crossman. 1. Cardiovascular Research Unit, Clinical Sciences Centre North, Northern General Hospital, Sheffield, UK. kkray@partners.org
Abstract
OBJECTIVES: Our aim was to determine a pharmacogenomic approach to heparin use in non-ST elevation acute coronary syndromes, specifically the impact of interleukin (IL)-1 receptor antagonist polymorphisms upon von Willebrand factor (vWF) responses to unfractionated heparin (UFH) and low molecular weight heparin (LMWH). BACKGROUND: In acute coronary syndromes (ACS), identification of specific biological or genetic targets to direct pharmacological treatment remains a challenge. vWF has been shown to predict future cardiovascular risk and the response to anticoagulant treatments during non-ST elevation ACS. IL-1 receptor antagonist (IL-1RN) polymorphisms predict the change in vWF between 24 and 48 h (Delta vWF) during non-ST elevation ACS. METHODS: We genotyped at the IL-1 locus, 67 patients with non-ST elevation ACS who received either LMWH or UFH, and measured vWF levels at 24 and 48 h. RESULTS: LMWH was superior to UFH in reducing the rise in vWF between 24 and 48 h in the cohort as a whole. However, when patients were stratified by IL-1RN genotype, LMWH was superior to UFH in reducing Delta vWF only in allele *2 carriers (0.51 iU mL(-1) vs. 1.37, P < 0.01), but not in non-carriers (- 0.03 iU mL(-1) vs. 0.15, P = NS). CONCLUSION: IL-1RN genotype may be a useful marker to identify patients that benefit from LMWH in non-ST elevation ACS.
OBJECTIVES: Our aim was to determine a pharmacogenomic approach to heparin use in non-ST elevation acute coronary syndromes, specifically the impact of interleukin (IL)-1 receptor antagonist polymorphisms upon von Willebrand factor (vWF) responses to unfractionated heparin (UFH) and low molecular weight heparin (LMWH). BACKGROUND: In acute coronary syndromes (ACS), identification of specific biological or genetic targets to direct pharmacological treatment remains a challenge. vWF has been shown to predict future cardiovascular risk and the response to anticoagulant treatments during non-ST elevation ACS. IL-1 receptor antagonist (IL-1RN) polymorphisms predict the change in vWF between 24 and 48 h (Delta vWF) during non-ST elevation ACS. METHODS: We genotyped at the IL-1 locus, 67 patients with non-ST elevation ACS who received either LMWH or UFH, and measured vWF levels at 24 and 48 h. RESULTS:LMWH was superior to UFH in reducing the rise in vWF between 24 and 48 h in the cohort as a whole. However, when patients were stratified by IL-1RN genotype, LMWH was superior to UFH in reducing Delta vWF only in allele *2 carriers (0.51 iU mL(-1) vs. 1.37, P < 0.01), but not in non-carriers (- 0.03 iU mL(-1) vs. 0.15, P = NS). CONCLUSION:IL-1RN genotype may be a useful marker to identify patients that benefit from LMWH in non-ST elevation ACS.