Sex differences among elderly ACS patients undergoing percutaneous coronary intervention receiving Ticagrelor 60 mg vs. 90 mg

No sex-based data are available on the pharmacodynamic and pharmacokinetic profile of ticagrelor 60 mg twice daily as alternative to its standard dose during the early phase after acute coronary syndrome (ACS). This post-hoc study is a sex-based secondary analysis of the PLINY THE ELDER randomized, crossover trial (NCT04739384), which compared ticagrelor 60 vs. 90 mg in elderly patients with ACS undergoing percutaneous coronary intervention (PCI). The primary endpoint was the pre-dose P2Y₁₂ reaction units (PRU) using the VerifyNow-P2Y₁₂ (Accumetrics, San Diego, CA, USA) at 14 days after treatment with ticagrelor 60 or 90 mg twice daily. A total of 50 elderly patients with ACS was included in the study. Of these patients, 28 (56%) were males and 22 (44%) females. The two doses of ticagrelor had a comparable PRU in both males (pre-dose: LSM difference_{60 vs. 90} -7.00, 95%CI -25.3 to 11.3, p = 0.44; post-dose: LSM difference_{60 vs. 90} 3.90, 95%CI -10.6 to 18.5, p = 0.59) and females (pre-dose: LSM difference_{60 vs. 90} -0.89, 95%CI -20.3 to 18.5, p = 0.93; post-dose: LSM difference_{60 vs. 90} -1.10, 95%CI -16.6 to 14.3, p = 0.88), with no evidence of sex-based interaction (pre-dose: p for interaction = 0.88; post-dose: p for interaction = 0.65). Consistently, transmittance aggregometry and multiple electrode aggregometry showed a similar pharmacodynamic profile between the two doses of ticagrelor in both male and female patients. Plasma levels of ticagrelor were significantly lower using the reduced dose of ticagrelor as compared with the standard dose in both males (pre-dose: LSM difference_{60 vs. 90} -212, 95%CI -391 to -33.0, p < 0.002; post-dose: LSM difference_{60 vs. 90} -308, 95%CI -510 to -105, p = 0.004) and females (pre-dose: LSM difference_{60 vs. 90} -131, 95%CI -332 to 69.1, p = 0.19; post-dose: LSM difference_{60 vs. 90} -670, 95%CI -898 to -442, p < 0.001). Ticagrelor 60 mg and ticagrelor 90 twice daily yielded the same magnitude of platelet inhibition among elderly patients with ACS irrespective of sex.