75Safety and efficacy of rivaroxaban in combination with anti-arrhythmic drugs in patients with non-permanent atrial fibrillation

Abstract

Abstract Background Rivaroxaban is useful for stroke prevention in atrial fibrillation (AF) patients. Most patients with non-permanent AF also treated with anti-arrhythmic drugs (AADs) to prevent the recurrence of arrhythmia. But there are limited data regarding drug-drug interactions between rivaroxaban and AADs despite its high clinical relevance. Purpose To compare the bleeding risks and ischemic events between the use of rivaroxaban alone and the concomitant use of AADs. Methods This is a multicenter retrospective study, which identified patients with a diagnosis of non-permanent AF who received rivaroxaban more than 1 month between December 1, 2011 and November 30, 2016. The study divided patients into 4 groups : rivaroxaban alone, combined with amiodarone, dronedarone and propafenone. We compared the clinical events and cumulative incidences to compare the endpoints including efficacy endpoint (new ischemic stroke, intracranial hemorrhage, or new embolism), safety endpoints (Hb fall more than 2g/dL or transfusion more than 2U PRBC, critical site bleeding, or fatal bleeding.) and major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, new ischemic stroke, new embolism, or intracranial hemorrhage. Results Of 1777 enrolled patients, the rivaroxaban alone was 1205 cases, 177 in amiodarone group, 231 in dronedarone group and 164 in propafenone group. There was no statistically significant difference on efficacy endpoints, safety endpoints and MACE between the 4 groups. The average dosage of rivaroxaban was insignificantly the lowest in the group combined with dronedarone (12.3mg, p = 0.146). The rate of new embolism (0%, p = 0.029), recurrent heart failure admission rate (3.9%, p < 0.001), and all-cause mortality (3.0%, p = 0.013) in dronedarone group showed a significant lower occurrence rate. The occurrence rate of new ischemic stroke (0.9%, p = 0.549), new hemorrhagic stroke (0.4%, p = 0.546), efficacy endpoints (1.7%, p = 0.369) and MACE (3.9%, p = 0.72) in dronedarone droup were the lowest but insignificant. The cumulative incidences of efficacy endpoints, safety endpoints and MACE during follow-up period were also similar in these four groups.(Picture 1) Conclusions In patients with non-permanent atrial fibrillation, this real-world study showed that there were no significant differences between using rivaroxaban alone or concomitant with an AAD (dronedarone/amiodarone/propafenone) on events such as new ischemic stroke, intracranial hemorrhage, GI bleeding and MACEs. The happening of new embolism was lower especially in the group combined with dronedarone. The safety and efficacy between rivaroxaban alone and combined with rhythm control using AADs proved to be the same. Relative low dose rivaroxaban combined with dronedarone did not increase the bleeding risk, and may decrease the probability of thromboembolism. Abstract Figure. Picture 1