Lessons derived from post authorisation safety studies (ETNA-AF and XANTUS) on once daily direct oral anticoagulants for atrial fibrillation.

ABSTRACT

BACKGROUND: Phase III trials should be integrated by post authorisation safety studies (PASS) to confirm their conclusions in real life. In this setting, comorbidities are commonly more prevalent, decisions about drugs and regimens are left to the attending physicians and therapy monitoring is not usually as strict as in pivotal trials. AIMS AND METHODS: To evaluate real life safety and effectiveness of edoxaban and rivaroxaban, ETNA-AF Europe (ETNA-AF-Eu) and XANTUS studies were reviewed and compared. A further comparison between data collected in these studies and in the pivotal studies ENGAGE AF-TIMI 48 and ROCKET-AF was also performed. RESULTS: ETNA-AF-Eu and XANTUS showed lower bleeding, stroke, cardiovascular- and all-cause mortality rates as compared to those observed in Phase 3 trials, even when including subgroups with lower comorbidities. Patients in ETNA-AF-Eu were older, with a larger proportion of octogenarians (≥85 years in 10.5%) and patients with impaired renal function as compared to patients in XANTUS (CrCl <50 ml/min in 18.2% vs 12.2%) and in ENGAGE AF-TIMI 48 and ROCKET-AF, without paying any excess tribute in terms of safety. Therapy persistence was very high in the two real life studies (91.9% in ETNA-AF-Eu and 79.9% in XANTUS), thus showing that edoxaban and rivaroxaban are well tolerated in real life. CONCLUSION: The ETNA-AF-Eu and XANTUS confirmed the safety and effectiveness of edoxaban and rivaroxaban in real life.