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Aim: Activated blood platelet products facilitate myocardial intracellular Ca2+ overload, thereby provoking afterdepolarizations and increasing susceptibility of ischemic myocardium to ventricular fibrillation (VF). These effects are counteracted in vitro by acetylsalicylic acid (ASA), but no prior study investigated whether ASA is associated with decreased out-of-hospital cardiac arrest (OHCA) risk on a population level. Therefore, we studied whether ASA and other antiplatelet drugs (carbasalate calcium, clopidogrel) are associated with decreased risk of OHCA. Methods: We conducted a population-based case-control study among individuals (772 OHCA-cases with documented VT/VF, 2444 non-OHCA-controls) who had used antiplatelet drugs in the year before index-date (OHCA-date), and studied the association between current antiplatelet drug use and OHCA-risk with multivariable logistic regression analysis. Results: ASA use was associated with reduced OHCA-risk (adjusted odds ratio (ORadj) 0.6 [0.5–0.8]), and more so in women (ORadj 0.3 [0.2–0.6]) than in men (ORadj 0.7 [0.5–0.95], Pinteraction 0.021). Carbasalate calcium was associated with decreased OHCA-risk in women (ORadj 0.5 [0.3–0.9]), but not in men (ORadj 1.3 [0.96–1.7], Pinteraction 0.005). Clopidogrel was not associated with reduction in OHCA-risk. Risk reduction associated with ASA in patients with OHCA was similar in the presence of acute myocardial infarction (AMI) (ORadj 0.6 [0.4–0.9]) and in the absence of AMI (ORadj 0.7 [0.4–1.2]). Conclusion: ASA use was associated with reduced OHCA-risk in both sexes, and more so in women, while carbasalate calcium only protected women. Clopidogrel was not associated with reduced OHCA-risk. [ABSTRACT FROM AUTHOR]