Dyspnea remains a frequent adverse effect limiting ticagrelor use in acute coronary syndrome (ACS), and its predictors are not fully defined. A prospective cohort study published in Clinical Cardiology evaluated whether genetic variation in cytochrome P450 3A enzymes influences susceptibility to ticagrelor-associated dyspnea.

The study enrolled 385 patients with ACS treated with ticagrelor and followed them for one year. Participants were genotyped for cytochrome P450 3A4 (CYP3A4) rs2242480 and cytochrome P450 3A5 (CYP3A5) rs776746. Dyspnea was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, and bleeding events were classified using Bleeding Academic Research Consortium (BARC) criteria. Associations were analyzed using logistic regression and generalized multifactor dimensionality reduction models.

The CYP3A5 rs776746 CC genotype was associated with the highest incidence of dyspnea. Compared with CC carriers, patients with the CT genotype had a 55% lower risk, and those with the TT genotype had a 91% lower risk. When CT and TT genotypes were analyzed together, carriers had a 63% lower dyspnea risk. CC genotype carriers exhibited a 2.3-fold higher dyspnea incidence. No significant associations were identified for CYP3A4 rs2242480. Genetic variation was not associated with bleeding outcomes.

These findings identify CYP3A5 rs776746 genotype as a determinant of ticagrelor-associated dyspnea risk in ACS, without an observed effect on bleeding.