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  • Tricoci, PierluigiDuke Univ, Duke Clin Res Inst, Durham, NC USA (author)

Effects of genetic variation in protease activated receptor 4 after an acute coronary syndrome : Analysis from the TRACER trial

  • Article/chapterEnglish2018

Publisher, publication year, extent ...

  • Elsevier BV,2018
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-363094
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-363094URI
  • https://doi.org/10.1016/j.bcmd.2018.07.004DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Variation in platelet response to thrombin may affect the safety and efficacy of PAR antagonism. The Thr120 variant of the common single nucleotide polymorphism (SNP) rs773902 in the protease-activated receptor (PAR) 4 gene is associated with higher platelet aggregation compared to the Ala120 variant. We investigated the relationship between the rs773902 SNP with major bleeding and ischemic events, safety, and efficacy of PAR1 inhibition in 6177 NSTE ACS patients in the TRACER trial. There was a lower rate of GUSTO moderate/severe bleeding in patients with the Thr120 variant. The difference was driven by a lower rate in the smaller homozygous group (recessive model, HR 0.13 [0.02-0.92] P= 0.042). No significant differences were observed in the ischemic outcomes. The excess in bleeding observed with PAR1 inhibition was attenuated in patients with the Thr120 variant, but the interactions were not statistically significant. In summary, lower major bleeding rates were observed in the overall TRACER cohort with the hyperreactive PAR4 Thr120 variant. The increase in bleeding with vorapaxar was attenuated with the Thr120 variant, but we could not demonstrate an interaction with PAR1 inhibition. These findings warrant further exploration, including those of African ancestry where the A allele (Thr120) frequency is similar to 65%.

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  • Neely, MeganDuke Univ, Duke Clin Res Inst, Durham, NC USA (author)
  • Whitley, Michael J.Thomas Jefferson Univ, Dept Med, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA;Thomas Jefferson Univ, Cardeza Fdn Hematol Res, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA (author)
  • Edelstein, Leonard C.Thomas Jefferson Univ, Dept Med, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA;Thomas Jefferson Univ, Cardeza Fdn Hematol Res, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA (author)
  • Simon, Lukas M.Baylor Coll Med, Dept Human & Mol Genet, Houston, TX 77030 USA (author)
  • Shaw, ChadRice Univ, Dept Stat, Houston, TX 77251 USA;Baylor Coll Med, Dept Human & Mol Genet, Houston, TX 77030 USA (author)
  • Fortina, PaoloThomas Jefferson Univ, Canc Genom & Bioinformat Lab, Sidney Kimmel Canc Ctr, Philadelphia, PA 19107 USA (author)
  • Moliterno, David J.Univ Kentucky, Gill Heart Inst, Lexington, KY USA;Univ Kentucky, Div Cardiovasc Med, Lexington, KY USA (author)
  • Armstrong, Paul W.Univ Alberta, Div Cardiol, Edmonton, AB, Canada (author)
  • Aylward, PhilipFlinders Med Ctr, Div Med Cardiac & Crit Care Serv, Bedford Pk, SA, Australia (author)
  • White, HarveyAuckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand (author)
  • Van de Werf, FransUniv Leuven, Dept Cardiovasc Sci, Leuven, Belgium (author)
  • Jennings, Lisa K.Univ Tennessee, Hlth Sci Ctr, Memphis, TN USA;CirQuest Labs LLC, Memphis, TN USA (author)
  • Wallentin, Lars,1943-Uppsala universitet,Kardiologi,Uppsala kliniska forskningscentrum (UCR)(Swepub:uu)larswall (author)
  • Held, Claes,1956-Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Kardiologi(Swepub:uu)clahe947 (author)
  • Harrington, Robert A.Stanford Univ, Dept Med, Stanford, CA 94305 USA (author)
  • Mahaffey, Kenneth W.Stanford Univ, Dept Med, Stanford, CA 94305 USA (author)
  • Bray, Paul F.Univ Utah, Dept Internal Med, Div Hematol & Hematol Malignancies, Salt Lake City, UT 84112 USA;Univ Utah, Mol Med Program, Salt Lake City, UT USA (author)
  • Duke Univ, Duke Clin Res Inst, Durham, NC USAThomas Jefferson Univ, Dept Med, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA;Thomas Jefferson Univ, Cardeza Fdn Hematol Res, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA (creator_code:org_t)

Related titles

  • In:Blood Cells, Molecules & Diseases: Elsevier BV72, s. 37-431079-97961096-0961

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