Which DOAC is safest to use in AF patients on dronedarone therapy?

Among patients on concomitant treatment with direct oral anticoagulants (DOACs) and dronedarone, no difference is seen in survival free from the composite endpoint (ie, clinically relevant bleeding, thromboembolic event, and all-cause death) and from clinically relevant bleeding between groups of coadministration, according to a study.

However, survival free from major bleeding was significantly lower among users of dabigatran.

Moreover, “DOACs contraindicated by 2015 EHRA guide (and not by the latest 2018/2021 EHRA guides) are associated with lower survival from either clinically relevant bleeding or clinically relevant major bleeding,” said lead author Dr Riccardo Vio from Hospital dell’Angelo, Mestre-Venice, Italy, who presented the results at the European Heart Rhythm Association Congress 2022 (EHRA 2022).

Vio and his colleagues performed a retrospective study to compare survival free from the composite endpoint of clinically relevant bleeding, thromboembolic event, and all-cause death between atrial fibrillation (AF) patients on treatment with dronedarone and different DOACs, and to compare survival free from 1) clinically relevant bleeding and 2) clinically relevant major bleeding.

The study was conducted at a local health unit from 1 January 2016 to 31 December 2020. The investigators included AF patients with concomitant prescriptions of DOACs and dronedarone and classified them into four groups: rivaroxaban, apixaban, edoxaban, and dabigatran.

Clinically relevant major bleeding was defined as fatal bleeding or that leading to transfusion of ≥2 units of blood, while nonmajor bleeding was defined as any sign of haemorrhage that did not fit the criteria of major bleeding but did not result in hospitalization or emergency room admission. Thromboembolic events were defined as ischaemic stroke, transient ischaemic attack (TIA), and systemic embolism.

Of the 165 patients included, 46 (28 percent) were on rivaroxaban, 66 (40 percent) on apixaban, 45 (27 percent) on edoxaban, and eight (5 percent) on dabigatran. [Vio R, et al, EHRA 2022]

Over a median follow-up of 339 days, 14 patients (8 percent) encountered the primary composite endpoint and eight (5 percent) had clinically relevant bleedings, of whom one was a clinically relevant major bleeding (ie, fatal spontaneous intracerebral haemorrhage), two had TIA, and five died.

There was no difference observed in survival free from the primary composite endpoint (p=0.19) and from clinically relevant bleeding (p=0.69) between coadministration groups, but dabigatran users had markedly lower survival free from clinically relevant major bleeding (p=0.003).

Of note, a secondary analysis revealed that DOACs contraindicated by the 2015 EHRA guide (dabigatran, edoxaba 60 mg), and not by the 2018/2021 EHRA guides (rivaroxaban, dabigatran, edoxaban 60 mg), led to lower survival from either clinically relevant bleeding (p=0.03) or clinically relevant major bleeding (p<0.001).

“The use of DOACs in patients with AF is associated with bleedings,” the investigators said. “Interactions with dronedarone may increase this risk, but data on concomitant treatment of DOACs with dronedarone are limited.”