Genetic-Guided Pharmacotherapy for Atrial Fibrillation: A Systematic and Critical Review of Economic Evaluations

Objectives: This study aimed to examine the extent and quality of evidence from economic evaluations (EEs) of genetic-guided pharmacotherapy (PGx) for atrial fibrillation (AF) and to identify variables influential in changing base-case conclusions. Methods: From systematic searches, we included EEs of existing PGx testing to guide pharmacotherapy for AF, without restrictions on population characteristics or language. Articles excluded were genetic tests used to guide device-based therapy or focused on animals. Results: We found 18 EEs (46 comparisons), all model-based cost-utility analysis with or without cost-effectiveness analysis mostly from health system's perspectives, of PGx testing to determine coumadin/direct-acting anticoagulant (DOAC) dosing (14 of 18), to stratify patients into coumadin/DOACs (3 of 18), or to increase patients’ adherence to coumadin (1 of 18) versus non-PGx. Most PGx to determine coumadin dosing found PGx more costly and more effective than standard or clinical coumadin dosing (19 of 24 comparisons) but less costly and less effective than standard DOAC dosing (14 of 14 comparisons). The remaining comparisons were too few to observe any trend. Of 61 variables influential in changing base-case conclusions, effectiveness of PGx testing was the most common (37%), accounted for in the models using time-based or medication-based approaches or relative risk. The cost of PGx testing has decreased and plateaued over time. Conclusions: EEs to date only partially inform decisions on selecting optimal PGx testing for AF, because most evidence focuses on PGx testing to determine coumadin dosing, but less on other purposes. Future EE may refer to the list of influential variables and the approaches used to account for the effect of PGx testing to inform data collection and study design.