Navigating Safety of Anticoagulant Use From Precision Medicine to Direct Oral Anticoagulants

Background: This dissertation focuses on assessing avenues for safe delivery of oral anticoagulants. In that, three studies have been undertaken to address gaps in practice pertaining to Vitamin K Antagonist (VKA) and direct-acting anticoagulant (DOAC) delivery using a mixed-methods approach. More specifically, we identified factors influencing pharmacogenetic (PGx) testing implementation into routine clinical care and assessed utilization patterns (adherence, persistence and transitions) among DOAC initiators Methods: Individual, face-to-face, semi-structured interviews were conducted with healthcare providers at an urban academic medical center to identify factors influencing PGx testing. Transcripts were analyzed thematically using constant comparison. Additionally, to assess utilization patterns in DOAC initiators, Truven Health MarketScan® Commercial and Medicare Supplemental databases were used (2009-2013). Atrial fibrillation (AF) patients newly initiating a DOAC with a minimum of 6 months of continuous health plan enrollment pre and post-index date were included in the cohort. DOAC adherence was measured as proportion of days covered (PDC). Results: Among 38 interviewees, 21 (55.3%) physicians and 17 (44.7%) pharmacists participated. Factors found to influence provider selection of PGx testing were perceptions related to the clinical utility of the PGx test, lack of comfort in interpretation of the test and lack of knowledge related to PGx. Among 66,090 DOAC users, adherence and persistence declined over time, but both declined in a greater magnitude for anticoagulant (AC) naïve compared to AC experienced. The mean PDC in AC naïve and non-AC naïve patients at 6 and 12 months was 72.3% vs. 83.3% (p<0.001) and 63.7% vs. 79.9% (p<0.001), respectively. Additionally, AC naïve user status was a predictor of lower adherence. Lastly, in a cohort of 34,022 AC naïve users, 6,613 (19.4) switched from their index DOAC. Of those that switched, 2912 (44.0%) switched to an alternate DOAC and 2,945 (44.5%) to warfarin. Interestingly, 48.3% patients switch within 6 months of therapy initiation. Conclusion: This dissertation presents timely studies focusing on contemporary practice in antithrombotic therapy. Addressing barriers to implementation of practice modalities such as PGx testing by increasing provider comfort, confidence and knowledge as well as providing enhanced, structured educational support to patients using DOACs are solutions to navigating safety in this evolving landscape.