De-escalation from Prasugrel or Ticagrelor to Clopidogrel in Patients with Acute Coronary Syndrome Managed with Percutaneous Coronary Intervention: An Updated Meta-analysis of Randomized Clinical Trials

Introduction We aimed to evaluate the clinical benefits of a de-escalation strategy from prasugrel or ticagrelor to clopidogrel versus continuation of prasugrel or ticagrelor along with aspirin in both strategies for patients presenting with acute coronary syndrome (ACS) and treated with percutaneous coronary intervention (PCI), and to analyze the effect of the recently published randomized clinical trial (RCT) by Park et al., which included the largest sample size ever and the largest switched number of patients, on current guidelines and practices. Data Sources The PubMed, EMBASE, Scopus, Web of Science, Cochrane Central, and Google Scholar databases were searched systematically from inception to May 2021 by using the search terms ('de-escalation' OR 'switching') AND ('antiplatelet' OR 'clopidogrel' OR 'ticagrelor' OR 'prasugrel') AND ('percutaneous coronary intervention' OR 'PCI'' OR 'Acute coronary syndrome' OR 'ACS'). Study Selection and Data Extraction We included RCTs that reported the primary outcomes, i.e. net clinical benefits and Bleeding Academic Research Consortium (BARC) type 2 or higher bleeding. A combination of both ischemic and bleeding events was defined as a net clinical benefit. Data Synthesis A total of four RCTs were included, with 5952 patients. A random-effects meta-analysis revealed that a de-escalation strategy was associated with lower ischemic and bleeding events (net clinical benefits; risk ratio [RR] 0.63, 95% confidence interval [CI] 0.47-0.85; p = 0.003), and lower BARC type 2 or higher bleeding (RR 0.51, 95% CI 0.29-0.91; p = 0.02) when compared with a continuation strategy. Relevance to Patient Care and Clinical Practice The current guidelines recommend potent P2Y12 prasugrel or ticagrelor for 12 months despite their association with a high risk of bleeding. Our meta-analysis updates cardiologists, providing them with the best available evidence in managing patients with ACS who underwent PCI. Conclusion Among patients with ACS treated with PCI, a de-escalation strategy (prasugrel or ticagrelor to clopidogrel) is associated with lower ischemic and bleeding events (net clinical benefits) and lower BARC type 2 or higher bleeding; however, due to the limited number of included studies, further high-quality studies are needed to establish the clinical efficacy of the de-escalation strategy.