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Dabigatran etexilate and reduction in serum apolipoprotein B
  1. Philip Joseph1,
  2. Guillaume Pare1,
  3. Lars Wallentin2,
  4. Stuart Connolly1,
  5. Salim Yusuf1,
  6. Jia Wang1,
  7. Michael Ezekowitz3,
  8. John Eikelboom1,
  9. Agneta Siegbahn2,
  10. Paul Reilly4,
  11. Ellison Themeles1,
  12. Jonas Oldgren2
  13. on behalf of the RE-LY Investigators
  1. 1Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada
  2. 2Department of Medical Sciences, Uppsala Clinical Research Centre, Uppsala University, Uppsala, Sweden
  3. 3Jefferson Medical College, Wynnewood, Pennsylvania, USA
  4. 4Department of Clinical Development and Clinical Biostatistics, Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut, USA
  1. Correspondence to Dr Philip G Joseph, Population Health Research Institute, C2 6A DB-CVSRI, 237 Barton St East, Hamilton, Ontario, Canada L8L 2X2; philip.joseph{at}phri.ca

Abstract

Objective Carboxylesterases, which convert dabigatran etexilate to its active form, dabigatran, have also been shown to influence lipoprotein metabolism, although any pleotropic effects of the drug based on this possible mechanism has not been evaluated. We examined the effects of dabigatran etexilate on serum lipoprotein markers in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) study.

Methods 2513 participants from the RE-LY randomised control trial with baseline and 3-month apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1) measurements were included. We prospectively compared the effects of dabigatran 110 mg twice daily, dabigatran 150 mg twice daily and warfarin on changes in ApoB and ApoA1 concentrations using a mixed model analysis.

Results From baseline to 3 months, a significant reduction in ApoB concentration was observed with low-dose dabigatran (−0.057 (95% CI −0.069 to −0.044) g/L, p<0.001) and high-dose dabigatran (−0.065 (95% CI −0.078 to −0.053) g/L, p<0.001) but not warfarin (−0.006 g/L (95% CI −0.018 to 0.007) g/L, p=0.40). Compared with warfarin, ApoB reduction was significantly greater with both doses of dabigatran (p<0.001 for both groups). Reductions in ApoA1 concentrations did not statistically differ with either dose of dabigatran when compared with warfarin.

Conclusions Dabigatran is associated with a significant (∼7%) reduction in ApoB concentration, suggesting a novel effect of this drug on lipoprotein metabolism. Further studies are needed to determine the mechanism of this observed effect, and its impact on clinical outcomes.

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