Differential modulation of polyunsaturated fatty acids in patients with myocardial infarction treated with ticagrelor or clopidogrel

Cell Rep Med. 2021 Jun 4;2(6):100299. doi: 10.1016/j.xcrm.2021.100299. eCollection 2021 Jun 15.

Abstract

Untargeted metabolomics is used to refine the development of biomarkers for the diagnosis of cardiovascular disease. Myocardial infarction (MI) has major individual and societal consequences for patients, who remain at high risk of secondary events, despite advances in pharmacological therapy. To monitor their differential response to treatment, we performed untargeted plasma metabolomics on 175 patients from the platelet inhibition and patient outcomes (PLATO) trial treated with ticagrelor and clopidogrel, two common P2Y12 inhibitors. We identified a signature that discriminates patients, which involves polyunsaturated fatty acids (PUFAs) and particularly the omega-3 fatty acids docosahexaenoate and eicosapentaenoate. The known cardiovascular benefits of PUFAs could contribute to the efficacy of ticagrelor. Our work, beyond pointing out the high relevance of untargeted metabolomics in evaluating response to treatment, establishes PUFA metabolism as a pathway of clinical interest in the recovery path from MI.

Trial registration: ClinicalTrials.gov NCT00391872.

Keywords: bioinformatics; clopidogrel; data science; metabolomics; myocardial infarction; polyunsaturated fatty acids; t-SNE; ticagrelor.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / drug therapy*
  • Acute Coronary Syndrome / metabolism
  • Acute Coronary Syndrome / pathology
  • Aged
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism
  • Clopidogrel / therapeutic use*
  • Fatty Acids, Unsaturated / agonists
  • Fatty Acids, Unsaturated / metabolism*
  • Female
  • Humans
  • Lipid Metabolism / drug effects
  • Male
  • Metabolomics / methods
  • Middle Aged
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Purinergic P2Y Receptor Antagonists / therapeutic use*
  • Ticagrelor / therapeutic use*
  • Treatment Outcome

Substances

  • Fatty Acids, Unsaturated
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Clopidogrel
  • Ticagrelor

Associated data

  • ClinicalTrials.gov/NCT00391872