Clinical trial perspective: Optimizing crossover from ticagrelor to clopidogrel in patients with acute coronary syndrome (CAPITAL OPTICROSS)

Abstract

Guideline-recommended treatment in patients with acute coronary syndrome is dual anti-platelet therapy (DAPT) with aspirin and a P2Y12 inhibitor, with clopidogrel or ticagrelor the preferred options for initial therapy. Ticagrelor has been demonstrated to have improved efficacy, and is preferred over clopidogrel in the absence of contraindications or the need for oral anticoagulation. However, it is not uncommon that patients are switched to clopidogrel after starting on ticagrelor. Reasons for this may be related to recognition of the increased risk of bleeding, the higher costs of ticagrelor, or adverse effects such as adenosine-mediated dyspnea. It is therefore important to understand the optimal dosing strategy in patients undergoing a switch from ticagrelor to clopidogrel. A loading dose of clopidogrel is standard when initiating therapy for acute coronary syndrome or before coronary stenting. However, whether this is required in patients who have already achieved adequate platelet inhibition with ticagrelor is unknown. Owing to the short half-life of the unbound active metabolite of clopidogrel at standard doses, there are concerns of high on-treatment platelet activity for a period of time following switching. However, this must be balanced against concerns of an increased risk of bleeding if a loading dose is used. To investigate this, the Optimizing Crossover From Ticagrelor To Clopidogrel In Patients With Acute Coronary Syndrome (CAPITAL OPTICROSS) clinical trial was conducted to compare a clopidogrel bolus dose with no bolus among patients currently treated with ticagrelor and whose treating physician had decided to switch therapy to clopidogrel. This review summarizes the CAPITAL OPTICROSS trial and its findings, and discusses the implications for clinical practice.