No free lunches: balancing bleeding and efficacy with ticagrelor

Abstract

This editorial refers to ‘Bleeding complications with the P2Y12 receptor antagonists clopidogrel and ticagrelor in the PLATelet inhibition and patient Outcomes (PLATO) trial’[†][1], by R.C. Becker et al. , on page 2933 The development of new oral antagonists of the platelet P2Y12 receptor has generated both anticipation and anxiety among practising physicians. In a field in which clopidogrel was the only choice available for the better part of a decade, prasugrel and ticagrelor represent new treatment options in many parts of the world. Weighing efficacy, safety, and cost to determine appropriate use of these three agents will represent a great challenge over the next few years for physicians, as well as individuals and organizations involved in formulary decisions. To make appropriate decisions, both for the individual patient and for the larger healthcare system, in-depth understanding of safety data is absolutely critical. Thus, the comprehensive report from Becker et al . 1 describing bleeding complications in the PLATO trial is particularly timely and important. The primary bleeding definition in PLATO combined non-coronary artery bypass graft (CABG) and CABG-related events, which differs notably from other contemporary antiplatelet trials that have used non-CABG bleeding as the primary safety endpoint.2,3 While we do not dispute the importance of CABG bleeding, we believe a focus on total bleeding in the PLATO trial may provide a misleading assessment of the safety of ticagrelor relative to clopidogrel. A strong argument can be made that the CABG bleeding definition in PLATO was too soft: any transfusion of ≥ 4 units of red blood cells was defined as a major bleed, regardless of clinical consequences.4 In essence, usual operating room procedures related to transfusion of blood products met the definition of a major bleed. The result was that a huge proportion of … [1]: #fn-2