Mortality and oral anticoagulants in the Food and Drug Administration Adverse Event Reporting System

OBJECTIVE: The comparative crude death rates (CDR) among non-vitamin K antagonist oral anticoagulants (NOACs) are unknown. Further, whether NOACs improve survival when compared with warfarin is also unclear. We compared CDR co-reported for four NOACs combined or separately versus warfarin within the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. METHODS: We selected CDR from the FAERS database linked to four NOACs and warfarin. The primary endpoints were differences in proportional reporting ratios (PRRs), and Chi-Square (χ(2))for dabigatran, rivaroxaban, apixaban and edoxaban when compared with warfarin. RESULTS: The FAERS database contains significantly less death reports associated with all NOACs combined (14 917 out of 128 267 reports (11.63%); PRR=1.089; χ(2)=70.0; p=6.05e(−17)) than for warfarin (19 493 out of 153 911 reports (12.67%)). The numbers for rivaroxaban (6318 out of 64 512 reports or (9.79%); PRR=1.293; χ(2)=359.4; p=3.72e(−80)), apixaban (1693 out of 17 789 reports (9.52%); PRR=1.331; χ(2)=145.8; p=1.43e(−33)) and edoxaban (53 out of 755 reports (7.02%); PRR=1.804; χ(2)=21.18; p=4.18e(−06)) were favourable as compared with warfarin, while the numbers of fatalities co-reported with dabigatran (6989 out of 46 250 reports (15.11%); PRR=0.838; χ(2)=185.2; p=3.61e(−42)) were higher than for warfarin. CONCLUSION: Overall, based on these CDR, NOACs appear to be associated with a mortality benefit over warfarin. Among NOACs, we observed remarkably similar for factor Xa inhibitors (rivaroxiban, apixaban and edoxaban) but unfavourable signal for the direct thrombin inhibitor (dabigatran). However, these data are clearly not sufficient to change the prescription patterns.