2.1 Sample cohort assembly and drug exposure
We identified patients diagnosed with atrial fibrillation (AF) without any prior haemorrhagic and/or thromboembolic events for at least three months before the first OAC exposure in an inpatient or outpatient setting. These patients were followed for at least six months from the date of first OAC exposure. Patients were included in the final cohort if they had at least one OAC dispensing record per 90-day period in the six months following index exposure in an inpatient or outpatient setting i.e. a minimum of two drug dispensing records within a six-month period. For patients on warfarin, the presence of an International Normalised Ratio (INR; Concept ID: 3022217) measurement was used as an additional surrogate to ascertain continued warfarin exposure. These patients were followed up for the occurrence of haemorrhagic or thromboembolic events at any time after the first exposure to anticoagulants. Figure 3 outlines the protocol and definitions applied in this study.
The OACs included for analysis were warfarin (Concept ID: 1310149), rivaroxaban (40241331), apixaban (43013024), and dabigatran (45775372). The diagnosis codes for AF included ‘Atrial Flutter’ (Concept ID: 314665), ‘Atrial Fibrillation’ (313217), ‘Atrial Arrhythmia’ (4068155), and ‘Atrial Fibrillation and Flutter’ (4108832). The concept IDs for both thromboembolic and bleeding events are as shown in the Supplementary Table 1.