P2Y12 inhibition in high bleeding risk patients: making the right decision in a complex setting

We read with great interest the SWEDEHEART report by Tjerkaski et al.1 regarding the comparison of ticagrelor vs. clopidogrel in patients with myocardial infarction (MI) and high bleeding risk. Although the results are adding much needed evidence in this conflicting field, there are several limitations that raise important clinical questions about the proper selection of P2Y12 inhibitors post-MI in high bleeding risk (HBR) individuals. Firstly, the cohort analysed in this study included patients who managed both interventionally and medically. In total, approximately 69% of patients included were treated by percutaneous coronary intervention (PCI) (55.6% in clopidogrel group vs. 84.2% in ticagrelor group) and these participants were at higher risk for thrombosis/ischemia and thus could be more benefited by a more potent P2Y12 inhibitor. Therefore, a difference in major adverse cardiovascular events (MACE) or net adverse clinical events (NACE) between the two tested P2Y12 inhibitors could have been better estimated, in a comparison between patients undergoing PCI compared to those conservatively managed. Given the different DAPT recommendations for HBR patients along the study's time frame, it is possible that different DAPT strategies were followed in this patient cohort.1 As recognized by the authors, DAPT duration, despite not being analysed in this study, has a major role in determining ischemic and bleeding risk.2 However, not only DAPT duration, but also DAPT de-escalation to a less potent P2Y12 inhibitor strategies were not accounted for in this analysis. DAPT de-escalation has shown to reduce bleeding events without increasing ischemic events,3 which could particularly benefit HBR patients. Nevertheless, DAPT de-escalation could offer an alternative to short DAPT duration, without trading off ischemic protection. Finally, in patients undergoing PCI, procedural characteristics such as stent length, number of stents implanted, multivessel disease, and procedural complexity largely increase post-procedural ischemic risk.4,5 Therefore, not only bleeding, but ischemic risk as well has a key role in selecting the appropriate P2Y12 inhibitors. Stratification by ischemic risk scores, such as the ESC/EACTS high ischemic risk score proposed at the 2018 ESC/EACTS guidelines for myocardial revascularization, have not been applied to this study.6 Thus, the absence of difference in MACE and NACE in HBR patients shown in this trial suggests that, potentially, HBR patients with increased ischemic risk could tolerate a more potent DAPT strategy without increasing adverse outcomes rates, at the expense of higher bleeding rates. Therefore, personalized recommendations on DAPT, based on ischemic and bleeding scores, could provide the key for better management of high risk and complex coronary artery disease patients. None. Conflict of interest: none declared. Not applicable.