Abstract
The decision to prescribe anticoagulant therapy must consider the balance between reducing the risk of thromboembolic events and increasing the risk of bleeding. Although assessments of net clinical outcomes with oral anticoagulants are not new, this article presents an evaluation of benefit-risk by considering only events of substantial and comparable clinical relevance (i.e., events with serious long-term sequelae likely to have irreversible consequences, including death). This is based on the concept of the number of patients who need to be treated to elicit one beneficial [number needed to treat (NNT)] or harmful [number needed to harm (NNH)] event. The approach is illustrated using data from phase III trials of rivaroxaban, selected because it has the broadest range of approved indications of the novel oral anticoagulants. For example, in the ATLAS ACS 2 TIMI 51 trial of rivaroxaban plus standard antiplatelet therapy following an acute coronary syndrome event, the current analysis demonstrates that 63 patients need to be treated (over 24 months) to prevent one all-cause mortality event compared with placebo (NNT = 63). Conversely, 500 patients need to be treated to cause one additional intracranial hemorrhage (NNH = 500). The most relevant and clinically meaningful assessment of benefit-risk may therefore be achieved by focusing only on events of greatest concern to patients and physicians, namely those with (potentially) long-lasting, severe consequences. Although there are clear limitations to this type of analysis, rivaroxaban appears to demonstrate a broadly favorable benefit-risk profile across multiple clinical indications.