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

Arthritis Care Res (Hoboken). 2014 Feb;66(2):285-92. doi: 10.1002/acr.22169.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00731302.

Publication types

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

MeSH terms

  • Adult
  • Aspirin / therapeutic use*
  • Biomarkers / blood
  • Blood Platelets / drug effects*
  • Blood Platelets / enzymology
  • C-Reactive Protein / metabolism
  • Chi-Square Distribution
  • Cyclooxygenase 1 / blood*
  • Cyclooxygenase Inhibitors / therapeutic use*
  • Female
  • Humans
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / complications
  • Lupus Erythematosus, Systemic / diagnosis
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / enzymology
  • Male
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / complications*
  • Middle Aged
  • Obesity / complications
  • Prospective Studies
  • Thromboxane B2 / blood
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers
  • Cyclooxygenase Inhibitors
  • Thromboxane B2
  • C-Reactive Protein
  • Cyclooxygenase 1
  • PTGS1 protein, human
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT00731302