Sex Differences in the Effectiveness and Safety of Aspirin

To the Editor We have read with great interest the study by Benziger et al, who reported exploratory analysis of the ADAPTABLE trial that evaluated potential sex differences in efficacy and safety outcomes in patients with established atherosclerotic cardiovascular disease receiving 2 aspirin doses, 81 mg and 325 mg, respectively. Although no significant differences between sexes were present regarding primary effectiveness and safety outcomes, there were notable differences regarding particular outcomes (incident stroke occurring more frequently in female participants, incident revascularization procedures occurring more frequently in male participants, and higher aspirin dose associated with higher mortality but lower incident major bleeding risk among female participants, without similar differences among male participants). Although random error and hidden biases may be driving these somewhat paradoxical findings, some of them may also represent true biological phenomena, as we elaborate further.