Bleeding Related to Oral Anticoagulant Drugs as Cause of Emergency Department Admission: Analysis of Data from the Tuscan MEREAFaPS Network

Introduction: The introduction of novel oral anticoagulants (NOAs: dabigatran, rivaroxaban, apixaban) into clinical practice was expected to reduce the incidence of bleeding associated with traditional oral anticoagulants [1]. Aim: To assess the trend of the contribution of admissions to Emergency Department (ED) for adverse drug reactions (ADRs) attributable to bleeding in patients receiving oral anticoagulants after marketing authorization of NOAs. Methods: The analysis was performed using data in Tuscany collected from January 2012 to December 2014, during MEREAFaPS, an observational study investigating drug-related admissions to EDs in Italy. Dabigatran, rivaroxaban and apixaban were introduced in Italy in 2008, 2009 and 2012, respectively, for prevention of venous thromboembolism; they were then approved for prevention of stroke and systemic embolism in non-valvular atrial fibrillation in 2013. In 2012 there were no reports of bleedings associated with NOAs. Cases were patients with a report of bleeding (MedDRA) associated with oral anticoagulants. The rate of overall and serious bleeding was weighed by the number of ADR reports and by the total number of admissions recorded in the Tuscan MEREAFaPS Network. Results: The analysis included 1,017,034 ED admissions, of which 6254 were related to ADRs (0.61 %) and 443 (231 males and 212 females) were bleedings associated with oral anticoagulants (0.044 %). Among these, 186 cases were serious ADRs. The most frequently recorded serious bleeding ADRs included: melena (16.7 %); epistaxis (12.9 %); rectal bleeding (11.8 %); hematemesis (8.6 %); cerebral hemorrhage (8.6 %); hematuria (8.1 %). The prevalences of anticoagulants associated with bleeding-related admissions were: warfarin (92.1 %); acenocoumarol (1.8 %); dabigatran (4.1 %); rivaroxaban (2.0 %) and apixaban (0 %). The annual incidences rates of bleeding associated with anticoagulants were 27, 17 and 34 cases per 100 admissions due to any ADR per 1,000,000 admissions/year in 2012, 2013 and 2014, respectively. When only serious bleedings were considered, the incidence rates were 9, 7 and 16 cases of bleeding per 100 admissions due to any ADR per 1,000,000 admissions/ year in 2012, 2013 and 2014, respectively. Conclusion: Our preliminary analysis suggests that the introduction of NOA into the clinical practice has not reduced the proportion of ADRs attributable to anticoagulant-related bleeding among the overall ADRs that cause drug-related admission to ED. In this setting, the use of NOAs is likely too limited to account for a reduction of this trend.