Cardiovascular risks and bleeding with non-vitamin K antagonist oral anticoagulant versus warfarin in patients with type 2 diabetes: a tapered matching cohort study

BACKGROUND: We compared the risk of bleeding and cardiovascular disease (CVD) events between non-vitamin K antagonist oral anticoagulant (NOAC) and warfarin in people with type 2 diabetes (T2DM). METHODS: 862 Incident NOAC users and 626 incident warfarin users with T2DM were identified from within 40 UK general practice (1/4/2017–30/9/2018). Outcomes included incident hospitalisation for bleeding, CVD and re-hospitalisation for CVD within 12 months since first anticoagulant prescription, identified from linked hospitalisation data. A tapered matching method was applied to form comparison cohorts: coarsened exact matching restricted the comparison to areas of sufficient overlap in missingness and characteristics: (i) demographic characteristics; (ii) clinical measurements; (iii) prior bleeding and CVD history; (iv) prescriptions with bleeding; (v) anti-hypertensive treatment(s); (vi) anti-diabetes treatment(s). Entropy balancing sequentially balanced NOAC and warfarin users on their distribution of (i–vi). Weighted logistic regression modelling estimated outcome odds ratios (ORs), using entropy balancing weights from steps i–vi. RESULTS: The 12-month ORs of bleeding with NOAC (n = 582) vs matched/balanced warfarin (n = 486) were 1.93 (95% confidence interval 0.97–3.84), 2.14 (1.03–4.44), 2.31 (1.10–4.85), 2.42 (1.14–5.14), 2.41 (1.12–5.18), and 2.51 (1.17–5.38) through steps i–vi. ORs for CVD re-hospitalisation was increased with NOAC treatment through steps i–vi: 2.21 (1.04–4.68), 2.13 (1.01–4.52), 2.47 (1.08–5.62), 2.46 (1.02–5.94), 2.51 (1.01–6.20), and 2.66 (1.02–6.94). CONCLUSIONS: Incident NOAC use among T2DM is associated with increased risk of bleeding hospitalisation and CVD re-hospitalisation compared with incident warfarin use. For T2DM, caution is required in prescribing NOACs as first anticoagulant treatment. Further large-scale replication studies in external datasets are warranted.