P2Y12-ADP Receptor Blockade in Chronic Kidney Disease Patients With Acute Coronary Syndromes

Abstract

Because of its high prevalence, chronic kidney disease (CKD) remains a major health hazard throughout the world. Patients with CKD have a high prevalence and incidence of acute coronary syndromes (ACS). Despite decades of improved care, their higher risk profile persists and cardiovascular diseases remain their leading cause of death. Along with the reduction of glomerular filtration rate, several physiological processes are impacted and participate in the pathophysiology of ischemic and bleeding events. CKD is associated with an accelerated and severe course of atherothrombotic disease, and this relates to a modified vascular milieu with alterations on the level of the coagulation cascade and platelet aggregation. In addition, pharmacokinetics of several drugs, in particular antithrombotics, are altered and differ from that of non-CKD patients. Patients with CKD therefore represent a challenging population for both physicians and researchers. In addition to these perturbations of physiological processes, CKD patients face 2 major issues. First, there is a clear gap in scientific research as they are commonly underrepresented or excluded from major clinical trials. This is particularly true regarding antithrombotic treatment during ACS. Second, there is a gap in offering evidence-based treatment for these patients including state-of-the art options for revascularization and modern antiplatelet treatment, both of which are commonly underused. During the last decade, new potent oral P2Y₁₂-ADP receptor antagonists, prasugrel and ticagrelor, which are more potent antiplatelet agents compared with clopidogrel, were introduced for ACS treatment. However, despite the fact that CKD patients represent a large proportion of those experiencing an ACS and are considered at high risk, there is a lack of dedicated trials and we are left with subgroup analysis of large randomized clinical trials were stage 4 and dialysis patients were rare. In the present review we summarize the mechanisms involved in the high ischemic and bleeding risk of CKD patients and the risk-benefit ratio of potent antiplatelet drugs during ACS.

Keywords: P2Y12 receptor; acute coronary syndrome; antiplatelet agents; chronic kidney disease.