Comparison of low-dose and full-dose apixaban in combination with ticagrelor as dual antithrombotic therapy following percutaneous coronary intervention in patients with atrial fibrillation: the LoDAT study
Percutaneous coronary intervention with stenting in patients with atrial fibrillation
The trial is a pharmacodynamic study to determine the effect of reduced-dose apixaban 2.5 mg BD with ticagrelor 90 mg BD on haemostasis, fibrin clot dynamics and platelet function compared to the standard treatment of apixaban 5 mg BD with ticagrelor 90 mg BD. In a randomised open-label parallel-group design, patient participants receiving, or prescribed to start receiving, apixaban 5 mg BD and ticagrelor 90 mg BD without aspirin for prevention of stent thrombosis and stroke will be randomised 1:1 to receive either apixaban 2.5 mg BD with ticagrelor 90 mg BD or apixaban 5 mg BD with ticagrelor 90 mg BD. Randomisation will be handled by an online interactive web-based randomisation service, sealedenvelope.com. At visit 3, following 28(-2) days on the study medication schedule, participants will attend a study visit at which a skin bleeding time measurement will be performed and blood samples will be obtained 2 to 4 hours after the last dose of IMP of the treatment period. The blood samples will be tested for fibrin clot dynamics and platelet function. Plasma and serum samples will be stored for later analysis of unspecified markers relevant to drug effect and cardiovascular disease. Participants will be transitioned back to standard-of-care treatment with apixaban 5 mg BD and ticagrelor 90 mg BD at the end of the treatment period and followed up by telephone call 14(±2) days later (visit 4).
1. Provision of informed consent prior to any study-specific procedures. 2. Male or female aged greater than 18 years. 3. PCI within the last 7 days for treatment of an acute or chronic coronary syndrome. 4. Current or previous atrial fibrillation for which long-term oral anticoagulation is indicated. 5. Receiving, or prescribed by the clinical care team to start receiving, apixaban 5 mg BD and ticagrelor 90 mg BD as DAT without aspirin.
1. At least two out of the three following criteria for approved use of the apixaban 2.5 mg BD dose for prevention of stroke and systemic embolism in non-valvular atrial fibrillation: (i) age ≥80 years; (ii) body weight ≤60 kg; (iii) serum creatinine ≥133 umol/L. 2. Active clinically significant bleeding 3. Any history of haemorrhagic stroke or other intracranial haemorrhage 4. Estimated glomerular filtration rate <30 ml/min 5. Any planned surgery or other procedure expected to occur within 1 month of randomisation that may require suspension or discontinuation of apixaban or ticagrelor therapy 6. Prior intention by patient or physician to discontinue apixaban or ticagrelor within the study period 7. Planned treatment following randomization with antiplatelet medication apart from ticagrelor (e.g. aspirin, clopidogrel, prasugrel, dipyridamole, ticlopidine) 8. Planned treatment following randomization with an oral anticoagulant apart from apixaban (e.g. warfarin, dabigatran, rivaroxaban, edoxaban) or parenteral anticoagulant (e.g. unfractionated heparin, low-molecular-weight heparin, bivalirudin) except for short-term parenteral anticoagulation required to cover a staged or urgent vascular procedure 9. Current or planned use of a GPIIb/IIIa inhibitor (e.g. tirofiban) 10. Current or planned use of a fibrinolytic agent (e.g. tissue plasminogen activator) 11. Requiring or likely to require treatment with an oral non-steroidal anti-inflammatory drug (NSAID), including regular or intermittent/as required use except for intermittent use of topical preparations that are not expected to have measurable systemic effect 12. Current or planned use of a strong CYP3A4 inhibitor (eg, ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin [but not erythromycin or azithromycin], nefazadone, ritonavir, saquinavir, nelfinavir, indinavir, atanazavir, cobicistat or over 1 litre daily of grapefruit juice) or strong CYP3A4 inducer (e.g. rifampin/rifampicin, rifabutin, ph