Non-vitamin K Oral Anticoagulants Versus Warfarin for Patients with Atrial Fibrillation: Absolute Benefit and Harm Assessments Yield Novel Insights

SummaryBackground and Objectives Benefits and/or harms (including costs) of non-vitamin K oral anticoagulants (NOACs) versus warfarin therapy need appreciation in relative and absolute terms. Methods Accordingly, we derived clinically relevant relative and absolute benefit/harm parameters for NOACs (apixaban, dabigatran, rivaroxaban, edoxaban) compared to warfarin from four clinical trials involving atrial fibrillation (AF) patients. For each trial, we tabulated patient numbers enduring four important outcomes and calculated unadjusted relative risk reduction (RRR) and number needed to treat (NNT)/year values (and 95% confidence intervals) for the NAOC compared to warfarin. These outcomes were as follows: stroke/systemic embolism (primary endpoint), hemorrhagic stroke, major bleeds, and death. We also addressed drug acquisition costs. Results Each NOAC was noninferior to warfarin for primary-outcome prevention; RRRs were 12–33% and NNT/year values were 182–481, and all but one indicated statistically significant superiority. All the NOACs yielded statistically significant reductions in hemorrhagic stroke risk; RRRs were 42–74% and NNT/year values were 364–528. Major bleeding risk was comparable in both groups. Apixaban yielded a lower NNT/year for preventing death than for primary-outcome prevention. Compared to warfarin, NOAC acquisition costs were 70- to 140-fold greater. Conclusions For the primary outcome, the absolute benefits of NOACs were modest (NNT/year values being large). Reduced hemorrhagic stroke rates with NOACs could be due to superior embolic infarct prevention and fewer consequential hemorrhagic transformations. Among apixaban recipients, the absolute mortality benefit exceeded that for the primary outcome, indicating prevention of additional unrelated deaths. The substantially greater NOAC acquisition costs need viewing against probable greater safety and the avoidance of monitoring bleeding risks.