Rationale and design of MANJUSRI trial: A randomized, open-label, active-controlled multicenter study to evaluate the safety of combined therapy with ticagrelor and warfarin in AF subjects after PCI-eS

BackgroundLong-term oral anticoagulant treatment is obligatory in patients with atrial fibrillation (AF, score of CHA2DS2VASc ≥ 2). When these patients undergo percutaneous coronary intervention with a drug-eluting stent (PCI-eS), there is also an indication for aspirin and clopidogrel treatment, according to the ESC Guidelines. However, triple therapy has been known to increase the risk of bleeding complications. Unfortunately, there is little prospective data available to resolve this issue. Therefore, it is imperative that an optimal therapy for AF patients with indications of both anticoagulation and antiplatelet intervention to prevent thrombotic complications without increasing the risk of bleeding is found.ObjectivesThis prospective, randomized, multicenter study is going to assess the hypothesis that in persistent or permanent AF patients (score of CHA2DS2VASc ≥ 2) after PCI-eS, the combination therapy of oral anticoagulation (warfarin) and ticagrelor (90 mg/bid) could reduce the risk of bleeding events.DesignA multicenter, active-controlled, open-label, randomized trial is to be performed to evaluate dual antithrombotic therapy (ticagrelor + warfarin) in persistent or permanent AF patients (score of CHA2DS2VASc ≥ 2) after PCI-eS versus the combination of triple antithrombosis (clopidogrel + aspirin + warfarin). The primary endpoint is the overall bleeding up to 6 months, according to TIMI criteria and classifications. The secondary endpoints are the major bleeding events up to 6 months, according to TIMI criteria. The sample size is estimated at 296.ConclusionThis study is intended to provide information about the safety characteristics of warfarin and ticagrelor in persistent or permanent AF patients after PCI-eS. No prospective randomized study has been conducted on the issue of antithrombotic therapy using warfarin and ticagrelor in these patients. Therefore, the MANJUSRI trial will help to explore and determine a new potential therapeutic regimen for AF patients after PCI-eS.Trial registrationClinical Trials.gov # NCT02206815, registered July 30, 2014.