Platelet P2Y12 inhibitors are functionally overdosed during infection

Time of primary review: 68 days Antiplatelet therapy is an integral part of cardiovascular pharmacotherapy. Dysregulated platelet activation is prevented through blockade of various surface receptors such as COX1 (i.e. by acetylsalicylic acid—the most prevalent antiplatelet agent) or P2Y12 (by thienopyridines1 that differ in potency, CYP2C19-dependent metabolism or administration route).2 P2Y12 inhibitor therapy requires a balanced risk–benefit assessment, as intensified platelet inhibition reduces thrombotic complications at the expense of an increased bleeding risk. Bleeding events remain common, are associated with increased mortality and are frequently observed in patients with infection receiving P2Y12 therapy.3–5 We demonstrated that infection renders platelets hyporeactive towards activation by agonists, such as adenosine diphosphate (ADP) or collagen6 and hypothesized that this acquired platelet dysfunction impacts the efficacy of P2Y12 inhibitors in infection. From June 2022 to December 2024, n = 38 ‘sepsis’ patients fulfilling the Sepsis-3-criteria (‘sep’ = ΔSOFA-Score ≥2) and n = 33 patients with ‘infection without sepsis’ (‘inf’ = ΔSOFA-Score