Abstract

Four direct oral anticoagulants (DOACs) have been approved for clinical use by many medicines regulatory agencies around the world. Due to increasing use of these drugs in routine practice, we planned an original study to investigate their worldwide diffusion using a popular Web-search engine. Two electronic searches were performed using Google Trends, the former using the keywords "warfarin" AND "heparin" AND "fondaparinux", and the latter using the keywords "warfarin" AND "dabigatran" AND "rivaroxaban" AND "apixaban" AND "edoxaban", both using the search criterion "prescription drug". No language restriction was applied, and the searches were carried out from the first date available in Google Trends (January 1st, 2004) to present time (June 1st, 2017). The median Google Trends score of warfarin (i.e., 86) was consistently higher than that of heparin (54; P<0.001), fondaparinux (6; P<0.001), dabigatran (11; P<0.001), rivaroxaban (5; P<0.001), apixaban (1; P<0.001) and edoxaban (1; P<0.001). Specific analysis of the trends shows that the score of warfarin exhibits a highly significant decrease over time (r=-0.40; P<0.001), whilst that of heparin has remained virtually unchanged (r=0.12; P=0.127), and that of fondaparinux has marginally increased (r=0.16; P=0.038). As regards DOACs, the scores of these drugs significantly increased during the search period (dabigatran, r=0.79; rivaroxaban, r=0.99; apixaban, r=0.98; edoxaban, r=0.78; all P<0.001). When the analysis was limited to the past five years, the dabigatran score significantly decreased (r=-0.57; P<0.001), whereas that of the other DOACs exhibited an even sharper increase. Most Google searches for DOACs were performed in North America, central-eastern Europe and Australia. The results of our analysis suggest that the popularity of DOACs is constantly increasing around the world, whereas that of warfarin has exhibited a constant and inexorable decline.

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