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Accepted Articles of Congress

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  • Omega-3 Fatty Acid Supplementation and CYP2C19 Genotype Effects on Clopidogrel Efficacy: A Systematic Review

  • Alireza Pourrahim,1,* Mohammad Mahdi Pourrahim,2 Omid Raiesi,3 Alireza Vasiee,4
    1. Student Research Committee, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
    2. Student Research Committee, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
    3. Omid Raiesi
    4. Department of Nursing, Faculty of Nursing and Midwifery, Ilam University of Medical Sciences, Ilam, Iran


  • Introduction: Clopidogrel’s antiplatelet effect is highly dependent on CYP2C19‐mediated bioactivation, with loss-of-function alleles (e.g., *2, *3) linked to higher on-treatment platelet reactivity and adverse cardiovascular events. Omega-3 polyunsaturated fatty acids (PUFAs) modulate platelet function and may enhance clopidogrel responsiveness, particularly in genetically predisposed poor metabolizers. We conducted a systematic review to quantify the combined impact of omega-3 supplementation and CYP2C19 genotype on platelet inhibition and clinical outcomes.
  • Methods: We searched PubMed, EMBASE, Web of Science, and Scopus from inception to June 2025 using (“omega-3”) AND (“clopidogrel”) AND (“CYP2C19”) AND (“platelet reactivity”) and their related MeSH terms. Randomized controlled trials and prospective cohorts reporting platelet reactivity units (PRU), high on-treatment platelet reactivity (HPR) rates, or major adverse cardiovascular events (MACE) stratified by CYP2C19 genotype were included. Two reviewers independently screened studies, extracted data, and assessed RCT bias with the Cochrane Risk of Bias tool and cohort quality with the Newcastle–Ottawa Scale. Pooled estimates were calculated using random-effects models.
  • Results: Seven studies (n = 1,802 patients; 22% poor metabolizers, 38% intermediate, 40% extensive; omega-3 dose 1–4 g/day; follow-up 3–12 months) met inclusion criteria. Across all genotypes, omega-3 supplementation yielded an additional 45 PRU reduction (95% CI 32–58; p < 0.02) versus control. In CYP2C19 poor metabolizers (n = 396), the pooled mean PRU decrease was 52 (95% CI 38–66; p < 0.01), reducing HPR prevalence from 58% to 31% (OR 0.35; 95% CI 0.24–0.50; p < 0.01). Intermediate metabolizers (n = 684) experienced a 48 PRU drop (95% CI 35–61; p < 0.001) and HPR reduction from 42% to 20% (OR 0.33; 95% CI 0.22–0.49; p < 0.01). Over a median 9-month follow-up, omega-3 users demonstrated a 25% lower MACE risk (HR 0.75; 95% CI 0.60–0.93; p = 0.009). No significant bleeding increase was observed (risk difference 0.8%; 95% CI ‑0.5–2.1; p = 0.22).
  • Conclusion: Omega-3 fatty acid supplementation significantly augments clopidogrel-induced platelet inhibition across CYP2C19 genotypes, with the greatest benefit in poor and intermediate metabolizers. This dual strategy reduces HPR rates by over 50% and lowers short-term MACE without increasing bleeding risk. Prospective genotype-guided RCTs are warranted to confirm these findings and optimize personalized antiplatelet regimens.
  • Keywords: clopidogrel; omega-3 fatty acids; CYP2C19 genotype; platelet reactivity units

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