Association Between Genetic Variant Scores and DOACs (DARES2)

The primary endpoint is to determine the accuracy of the DSS in predicting clinical outcomes of major bleeding per International Society of Thrombosis and Haemostatis (ISTH) criteria in subjects on Direct Oral Anti-coagulants (DOACs). The DSS is calculated on a scale of 0 to 1, with scores below 0.3 correlated with a higher risk of ADRs and scores above 0.7 correlated with a lower risk of ADRs. We will determine the DSS of all subjects who experienced major bleeding and compare it to the DSS of control subjects who did not experience bleeding.

The secondary endpoint is to determine the accuracy of the DSS predicting clinical outcomes compared to clinical tools such as the HAS-BLED scoring system. A subject with a HAS-BLED score of > 4 points will be considered moderate-high risk of bleeding and a HAS-BLED score of 4 or less will be considered low risk. A DSS is calculated on a scale of 0 to 1, with scores below 0.3 correlated with a higher risk of ADRs and scores above 0.7 correlated with a lower risk of ADRs. Both DSS (low and high risk subjects) and HAS-BLED scores (low and high risk subjects) will be compared to actual clinical outcomes to assess the predictive accuracy of each scoring system.

The secondary endpoint is to determine the accuracy of the DSS in predicting treatment failures (e.g., recurrent MI, systemic embolism, or ischemic stroke) as compared to clinical outcomes while on DOACs. The DSS is calculated on a scale of 0 to 1, with preliminary studies demonstrating that scores below 0.3 correlated with a higher risk of ADRs and scores above 0.7 correlated with a lower risk of ADRs.

Novel variants will be assessed using whole genome sequencing to evaluate the genetic pathways in individuals with serious ADRs and treatment failures. Through our analyses we intend to identify novel genetic variants in subjects with serious ADRs or treatment failure while on P2Y12 inhibitors.