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Background: Ticagrelor has a Class I recommendation for use following percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS). However, ticagrelor needs to be taken twice a day, as compared to clopidogrel. Its adverse effects, such as dyspnea or bleeding, are known to be more common than with clopidogrel. Dyspnea may tend to be uncomfortable and limit activity. Major bleeding often leads to hospitalization or transfusions, and frequent minor bleeding, which might not result in patients seeking medical care, can make ACS patients feel unhealthy. Thus, these characteristics may affect the health-related quality of life (HQOL).Methods: In the PLEIO (comParison of ticagreLor and clopidogrEl on mIcrocirculation in patients with acute cOronary syndrome) trial, we randomized 120 participants to receive ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily for at least 12 months. We carried out an HQOL assessment with the Short Form 36 Health Survey (SF-36) questionnaire on the day of discharge following PCI, as well as six months later.Results: At discharge, the HQOL measures were similar in the ticagrelor and clopidogrel groups, both having a physical component summary (PCS) and a mental component summary (MCS) score. A six-month HQOL follow-up assessment showed that there were no differences between the two study groups in either the PCS or the MCS scores. In both groups, the PCS scores significantly increased over six months of treatment (both p < 0.01). However, the MCS score did not differ significantly. A baseline MCS score is an independent predictor of better physical and mental health status at six months.Conclusions: Ticagrelor, as compared to clopidogrel, did not significantly reduce the HQOL during the six months following PCI in patients with ACS. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT02618733. [ABSTRACT FROM AUTHOR]