Suboptimal inhibition of platelet cyclooxygenase 1 by aspirin in systemic lupus erythematosus: association with metabolic syndrome.

Kawai VK, Avalos I, Oeser A, Oates JA, Milne GL, Solus JF, Chung CP, Stein CM
Arthritis Care Res (Hoboken). 2014 66 (2): 285-92

PMID: 24022862 · PMCID: PMC3946810 · DOI:10.1002/acr.22169

OBJECTIVE - Low-dose aspirin prevents platelet aggregation by suppressing thromboxane A2 (TXA2 ) synthesis. However, in some individuals TXA2 suppression by aspirin is impaired, indicating suboptimal inhibition of platelet cyclooxygenase 1 (COX-1) by aspirin. Because patients with systemic lupus erythematosus (SLE) have increased risk of thrombotic events, many receive aspirin; however, the efficacy of aspirin in SLE has not been determined. We examined the hypothesis that aspirin response is impaired in SLE.

METHODS - We assessed the effect of aspirin by measuring concentrations of the stable metabolite of TXA2 , serum thromboxane B2 (sTXB2 ), before and after treatment with daily aspirin (81 mg) for 7 days in 34 patients with SLE and 36 control subjects. The inability to suppress sTXB2 synthesis to <10 ng/ml represents suboptimal inhibition of platelet COX-1 by aspirin.

RESULTS - Aspirin almost completely suppressed sTXB2 in control subjects to median 1.5 ng/ml (interquartile range [IQR] 0.8-2.7) but had less effect in patients with SLE (median 3.1 ng/ml [IQR 2.2-5.3]) (P = 0.002). A suboptimal effect of aspirin was present in 15% (5 of 34) of the patients with SLE but not in control subjects (0 of 36) (P = 0.023). Incomplete responders were more likely to have metabolic syndrome (P = 0.048), obesity (P = 0.048), and higher concentrations of C-reactive protein (CRP) (P = 0.018).

CONCLUSION - The pharmacologic effect of aspirin is suboptimal in 15% of patients with SLE but in none of the control subjects, and the suboptimal response was associated with metabolic syndrome, obesity, and higher CRP concentrations.

Copyright © 2014 by the American College of Rheumatology.

MeSH Terms (19)

Adult Aspirin Biomarkers Blood Platelets C-Reactive Protein Chi-Square Distribution Cyclooxygenase 1 Cyclooxygenase Inhibitors Female Humans Lupus Erythematosus, Systemic Male Metabolic Syndrome Middle Aged Obesity Prospective Studies Thromboxane B2 Time Factors Treatment Outcome

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