LAUSR

The evaluation of novel antithrombotics requires a careful assessment of both efficacy and safety. Assessment of efficacy typically relies on a composite of cardiovascular death, myocardial infarction, and stroke (major adverse cardiac events) that are supposedly hard clinical outcomes with objective definitions that can be adjudicated in blinded fashion. There are well-known problems related to using composite outcome measures1 such as the effect of a new treatment on components of the composite being different in magnitude or in direction, or the fact that these components have markedly different severity, leading some to propose the weighting of different events based on their associated rates of disability or subsequent attributable mortality. In recent years, for instance, there has been increasing concern that some myocardial infarctions are actually rather clinically minor events in which minute amounts of myocardial injury can be detected by ultrasensitive high-sensitivity troponin. Assessment of safety generally relies on measuring rates of bleeding, categorized according to one or several of the many existing bleeding event classifications, although some antithrombotic agents can have off-target effects (such as dyspnea in the case of ticagrelor). The desire to assess the balance of risk and benefit in a single quantitative measure, and the wish to create a composite outcome encompassing both efficacy and safety, as well, have led to the computation of new composite variables: net clinical benefit (ie, the difference between the number of major adverse cardiac events avoided and the price to pay in terms of excess bleeding events) or net adverse clinical …