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

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 P ₂ Y ₁₂ 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.
Competing Interests: J.G.H. has received speaker honoraria from Dalcor and District 3 Innovation Centre. R.C.B. has received grants from AstraZeneca during the conduct of the study and has received personal fees from Ionis, Akcea, and Novartis outside the submitted work. M.Y.C. has received research support and consultation honoraria from AstraZeneca. E.M.J. is supported by research grants from Les Fonds la Recherche du Québec en Santé (FRQS) and the Canadian Institutes for Health Research (CIHR). R.D.L. has received grants from AstraZeneca during the conduct of the study; has consulted for Bayer, Boehringer Ingleheim, Daiichi Sankyo, Merck, and Portola; and has received grants and consulted for Sanofi, Bristol-Myers Squibb, Glaxo Smith Kline, Medtronic, and Pfizer outside the submitted work. T.Y.W. has received grants and personal fees from AstraZeneca, Bristol Myers Squibb, and Cryolife and has received grants from Chiesi, Merck, Portola, Regeneron, Boston Scientific, and Abbott outside the submitted work. L.K.N. has received grants from AstraZeneca during the conduct of the study and grants from Boehringer Ingelheim, Amylin, and GlaxoSmithKline and has received personal fees from GlaxoSmithKline outside the submitted work. M.L. has received speaker honoraria from Bayer, has participated in industry-funded trials from Idorsia, and has received in-kind and financial support for investigator-initiated grants from Leo Pharma, Roche Diagnostics, and Aggredyne. The remaining authors disclose no competing interests.
(© 2021 The Authors.)