Physicians' Academy for Cardiovascular Education

Reduced doses NOAC show similar efficacy and bleeding risk but possibly higher mortality risk

Effectiveness and safety of reduced dose non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study.

Literature - Nielsen PB, Skjøth F, Søgaard M et al., - BMJ. 2017; 10;356:j510. doi: 10.1136/bmj.j510

Main results

Inverse probability of treatment weight was applied to account for baseline differences, which resulted in comparable distribution of variables between treatment groups in this cohort, thus allowing for comparisons.

The subgroup of patients with an indication for dose reduction (n=21949), showed worse outcomes than the main analysis.


These propensity-weighted real world data on the effectiveness and safety of low dose NOAC regimens as compared with warfarin in patients with AF showed a non-significant trend towards higher thromboembolic events and similar rates of bleeding for apixaban (2.5 mg). Low-dose rivaroxaban (15 mg) and dabigatran (110 mg) showed a non-significant trend towards lower one year rates of ischaemic stroke or SE, and similar (rivaroxaban) and lower (dabigatran) rates of bleeding.

While standard dosing regimes have consistently favoured a NOAC over warfarin with regard to mortality, some of the current analyses on reduced doses indicated an increased mortality risk. Although inverse probability treatment weighting allows for causal inference on average treatment effects, it is possible that some unmeasured residual confounding and selective prescribing behaviour remain.


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