Reversal of Platelet Inhibition in Patients Receiving Ticagrelor.

Antiplatelet treatment is one of the pillars of contemporary therapy in acute coronary syndromes. It is based on dual antiplatelet therapy (DAPT) consisting of aspirin and a P2Y12 receptor inhibitor. Antiaggregatory treatment reduces ischemic events, but at cost of increased bleeding rates. As a result of irreversible inhibition of platelet P2Y12 receptors, the antiplatelet action of clopidogrel and prasugrel is prolonged for the lifespan of thrombocytes and lasts up to 7 days. The antiaggregatory effect of ticagrelor may persist up to 5 days despite its reversible nature of P2Y12 receptor inhibition. These pharmacodynamic properties may prove problematic in patients requiring immediate reversal of antiplatelet effects due to severe or life-threatening bleeding, or in presence of indications for an urgent surgery. The current review summarizes available knowledge on different strategies of restoring platelet function in patients treated with ticagrelor. Non-specific methods are discussed, including platelet transfusion, human albumin supplementation and hemadsorption. Finally, bentracimab, the first specific antidote for ticagrelor, and in fact against any antiplatelet agent, is described.

A new approach to ticagrelor-based de-escalation of antiplatelet therapy after acute coronary syndrome. A rationale for a randomized, double-blind, placebo-controlled, investigator-initiated, multicenter clinical study.

The risk of ischemic events gradually decreases after acute coronary syndrome (ACS), reaching a stable level after 1 month, while the risk of bleeding remains steady during the whole period of dual antiplatelet treatment (DAPT). Several de-escalation strategies of antiplatelet treatment aiming to enhance safety of DAPT without depriving it of its efficacy have been evaluated so far. We hypothesized that reduction of the ticagrelor maintenance dose 1 month after ACS and its continuation until 12 months after ACS may improve adherence to antiplatelet treatment due to better tolerability compared with the standard dose of ticagrelor. Moreover, improved safety of treatment and preserved anti-ischemic benefit may also be expected with additional acetylsalicylic acid (ASA) withdrawal. To evaluate these hypotheses, we designed the Evaluating Safety and Efficacy of Two Ticagrelor-based De-escalation Antiplatelet Strategies in Acute Coronary Syndrome - a randomized clinical trial (ELECTRA-SIRIO 2), to assess the influence of ticagrelor dose reduction with or without continuation of ASA versus DAPT with standard dose ticagrelor in reducing clinically relevant bleeding and maintaining anti-ischemic efficacy in ACS patients. The study was designed as a phase III, randomized, multicenter, double-blind, investigator-initiated clinical study with a 12-month follow-up (ClinicalTrials.gov Identifier: NCT04718025; EudraCT number: 2020-005130-15).