Abstract
Background
New oral anticoagulants (NOACs) (vs warfarin) in the general population are associated with 34% less major bleeding events. We compared the risk of bleeding and cardiovascular disease (CVD) events between NOACs and warfarin in people with type 2 diabetes (T2DM).
Methods
Incident NOAC users (cases) and matched controls (incident warfarin users) with T2DM were identified from within 40 UK general practice records (1/4/2017-31/3/2018). Coarsened Exact Matching restricted the comparison to areas of sufficient overlap in characteristics (i-iv) and missingness. Entropy Balancing sequentially balanced NOAC and warfarin users on their distribution of (i) age, sex, general practice, first anticoagulant prescription year, diabetes duration, (ii) body mass index, systolic blood pressure, total cholesterol, HbA1c, (iii) bleeding/CVD history, (iv) treatment (Antiplatelet, Corticosteroids, statins, anti-hypertensives, anti-diabetes treatment number). Continuous covariates were balanced for mean, variance, and skewness. Pre-processing/balancing occurred without reference to outcomes. Multivariable logistic regression modelling estimated bleeding and CVD relative risks (RRs: incident non-elective hospitalisation within 12 months since first anticoagulant prescription), identified from linked hospitalisation data (Secondary Uses Service dataset), using entropy balancing weights from steps i-iv.
Results
The twelve month RRs of bleeding with NOAC (n = 967) vs matched/balanced warfarin (n = 911) were 0.94(0.62-1.45), 0.95(0.62-1.46), 0.98(0.65-1.48) and 0.98(0.67-1.43) through steps i-iv. CVD RR was increased with NOAC treatment through steps i-iv: 1.15(1.00-1.31), 1.22(1.06-1.39), 1.34(1.13-1.60) and 1.43(1.20-1.70).
Conclusion
Among T2DM patients, risk of bleeding among NOAC and warfarin incident users was similar. However, NOAC use significantly increased the risk of CVD events. Further external replication studies are warranted.