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CYP2C19*17 May Increase the Risk of Death Among Patients with an Acute Coronary Syndrome and Non-Valvular Atrial

D A Sychev1, O A Baturina2, K B Mirzaev1

  • 1Russian Medical Academy of Continuous Professional Education, Ministry of Health of the Russian Federation, Moscow, Russian Federation.

Pharmacogenomics and Personalized Medicine
|March 12, 2020
PubMed

Insights

Genetic polymorphisms in CYP2C19, CYP3A4, CYP3A5, and ABCB1 did not significantly impact clopidogrel activity or rivaroxaban levels in acute coronary syndrome patients. However, CYP2C19*17 may influence bleeding risk in combined therapy.

Area of Science:

  • Pharmacogenomics
  • Cardiovascular Medicine
  • Internal Medicine

Background:

  • Investigating genetic influences on antithrombotic therapy efficacy and safety.
  • Focus on patients with acute coronary syndrome (ACS) and non-valvular atrial fibrillation (AF).

Purpose of the Study:

  • Assess the impact of CYP2C19, CYP3A4, CYP3A5, and ABCB1 gene polymorphisms.
  • Evaluate effects on clopidogrel antiplatelet activity, rivaroxaban concentration, and clinical outcomes.
  • Determine relevance in ACS and AF patients receiving combined antithrombotic therapy.

Main Methods:

  • Multicenter prospective registry study.
  • 103 patients with non-valvular AF, with or without percutaneous coronary intervention.
  • Assessed primary outcomes (bleeding, death, stroke) and secondary outcomes (platelet reactivity, rivaroxaban concentration).

Main Results:

  • No significant association found between studied polymorphisms (CYP3A5*3, CYP2C19*2, *17, ABCB1 3435 C>T, ABCB1 rs4148738) and clinical outcomes.
  • No studied genetic markers affected rivaroxaban equilibrium concentration in plasma.
  • No significant impact of polymorphisms on clopidogrel antiplatelet activity.

Conclusions:

  • Genetic factors, particularly CYP2C19*17, may be clinically relevant for bleeding risk.
  • Highlights potential clinical significance in patients on dual or triple antithrombotic therapy with rivaroxaban and clopidogrel.
  • Suggests further investigation into specific genetic variants and their role in antithrombotic therapy complications.
Abstract

Keywords:
acute coronary syndromeatrial fibrillationclopidogrelpolymorphismrivaroxaban

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