Evaluation of adverse drug reactions associated with direct oral anticoagulants recorded in the Italian Pharmacovigilance Network database using a specifically developed risk index

Abstract

The introduction into clinical practice of direct oral anticoagulants (DOAC) has widened the scenario in the prevention and treatment of thromboembolism. However, the evaluation of the balance between the thrombotic and hemorrhagic risks is a critical issue in the choice of an oral anticoagulant agent. The availability of safety and efficacy data for each drug represents the basis to operate treatment choices. As there are no head-to-head studies comparing the different DOACs in terms of safety and efficacy, and considering the differences in registrative trial designs and characteristics of enrolled populations, several meta-analyses and real-life studies have tried to trace the safety and efficacy profiles on DOACs, but at present no definitive conclusions can be drawn due to numerous existing biases. One possible aid to help clinicians in their treatment choice is the evaluation of self-reported adverse drug reactions (ADRs) available in drug regulatory agency databases such as the Italian Medicines Agency (AIFA) pharmacovigilance database. We conducted a search in the National Pharmacovigilance Network database, available on AIFA website, in order to retrieve all the ADRs related to oral anticoagulants occurred in the period 2016-2017. We then calculated an ADR risk index (RI) for each drug, where an RI =1 indicates a balance between the percentage of ADR share and the percentage of market share for each DOAC; and an RI <1 indicates a rate of ADR lower than the rate of market share (more safe DOAC). The results showed that rivaroxaban is the DOAC with the lowest RI among the four molecules available today in Italy. Despite the limitations of this study, we believe that ADR RI can be a valuable adjunctive tool to help clinicians in their everyday clinical practice.