Long‐Term Ticagrelor in Stable Patients With Prior Myocardial Infarction: Bleeding Avoidance First and Foremost

Abstract

Over 100 000 patients with different manifestations of cardiovascular disease have been studied in large-scale clinical trials evaluating the safety and efficacy of ticagrelor alone or in combination with aspirin. As a result of these studies, the Food and Drug Administration granted indication to ticagrelor for the secondary prevention of patients presenting with acute coronary syndrome,1 prior myocardial infarction (MI),2 and acute noncardioembolic ischemic stroke,3 as well as for the primary prevention of high-risk patients with stable coronary artery disease.4 However, given that any advantage in ischemic event prevention may be counterbalanced by an increase in bleeding harm, identifying those patients in whom the ischemia-bleeding trade-off of an intensified antithrombotic regimen provides a net clinical benefit remains a major challenge. International guidelines and academic collaborations have repeatedly emphasized the negative prognostic role of bleeding. Risk prediction models and expert consensus documents have been proposed to untangle the complex interplay between ischemic and bleeding risk and guide clinical decisions.5–7 Nonetheless, several questions remain to be answered. Although no one would argue on the detrimental consequences of bleeding, the correct characterization of various types of hemorrhagic events and their causative role with respect to subsequent mortality are still a matter of debate. Bleeding in itself can be heterogeneous in cause and magnitude, and can thus impact differently on patient prognosis. A specific bleeding site can be more associated with one antithrombotic agent compared with another (eg, gastrointestinal adverse effects of aspirin). Furthermore, the clinical relevance of bleeding may also depend on the patient comorbid conditions and functional status.