Optimal Antithrombotic Therapy for ACS Patients Concomitant With AF and Implanted With New-generation DES (OPTIMA-3, 4)
Optimal Antithrombotic Therapy for ACS Patients Concomitant With AF and Implanted With New-generation DES (OPTIMA-3, 4)
It is a multi-center randomized clinical trial (RCT) which will enroll 3746 patients with
 acute coronary syndrome (ACS) concomitant non-valvular atrial fibrillation (NVAF) and
 undergoing new generation drug eluting stent (DES) implantation at 70 centers nationwide in
 China and contains two sub-studies.

 In the OPTIMA-3 sub-study, 2274 subjects who choose warfarin as anticoagulant will randomly
 receive triple antithrombotic therapy (warfarin with targeted INR 2.0-3.0, clopidogrel 75 mg
 od and aspirin 100 mg od) for 1 month or 6 months in a 1:1 ratio then quit aspirin till 12
 months after percutaneous coronary intervention (PCI). The primary endpoint of the OPTIMAL-3
 is a composite of cardiovascular death, myocardial infarction, ischemic stroke, systemic
 thromboembolism and unplanned revascularization up to 12 months; the major secondary endpoint
 is the International Society of Thrombosis and Hemostasis (ISTH) major bleeding or clinically
 relevant non-major bleeding (CRNMB).

 In the OPTIMA-4 sub-study, 1472 subjects who prefer dabigatran will be randomly assigned in a
 1:1 ratio to a dual antithrombotic therapy of dabigatran 110 mg twice daily with ticagrelor
 90 mg twice daily or with clopidogrel 75 mg od for 12 months after PCI. The primary safety
 endpoint of the OPTIMAL-4 is ISTH major bleeding or CRNMB at 12 months; the primary efficacy
 endpoint is a composite of cardiovascular death, myocardial infarction, ischemic stroke,
 systemic thromboembolism and unplanned revascularization.

 Other secondary endpoints comprise death (cardiovascular, non- cardiovascular), MI (fatal or
 non-fatal, Q-wave or non-Q-wave), unplanned revascularization (target or non-target vessel,
 target or non-target lesion), stent thrombosis (possible, probable, definite), stroke
 (hemorrhage or ischemic), all bleeding (ISTH and BARC criteria) and net adverse events.

 All endpoints will be collected and compared between subgroups and sub-studies during
 hospitalization and in 1 month (± 7 days), 6 months (± 7 days) and 12 months (± 7 days) for
 office visits and in 2 weeks (± 7 days), 2 months (± 7 days) and 3 months (± 7 days) for
 phone call visits.
Inclusion Criteria:

 -  ≥ 18 years;

 -  ACS patients concomitant non-valvular AF (paroxysmal, persistent and permanent)
 underwent PCI and new-generation DES implantation;

 -  CHA2DS2-VASc score ≥ 2;

 -  Acceptable risk of bleeding at the discretion of the researchers (e.g. HAS-BLED score
 ≤ 2)

 -  Consent to participate in the trial

 Exclusion Criteria:

 -  DES implanted in the left main coronary artery

 -  Cardiogenic shock or Killip III-IV

 -  STEMI patients with malignant arrhythmias or underwent electrodefibrillation or CPR or
 with cardiac mechanical complications (heart rupture, ventricular septal perforation,
 nipple muscle fracture, etc.)

 -  History of gastrointestinal or intracranial hemorrhage; active bleeding, trauma or
 major surgery within one month; suspected or diagnosed aortic dissection

 -  Ischemic stroke with limb dysfunction or dysphasia

 -  Known allergy or intolerance to the study medications: warfarin, clopidogrel, aspirin,
 dabigatran, ticagrelor and heparin

 -  Participating in other ongoing trials

 -  Planned surgery in 12 months requiring to withdraw the antiplatelet agents

 -  Planned RFCA or left atrial appendage occlusion in the next 12m

 -  Abnormal liver or kidney function (ALT ≥ 3 ULN; estimated CrCl < 30 ml/min calculated
 by Cockcroft-Gault equation); diagnosed liver cirrhosis

 -  Hematological disease with bleeding tendency; hemoglobin < 100 g/L, platelet count <
 100 × 10^9 /L

 -  Malignancies or life expectancy less than 1 year

 -  Pregnant (present, suspected, or planned) or lactating woman

 -  Patients who are taking drugs which may interact with study agents, such as
 miconazole, ketoconazole, fluconazole, voriconazole, itraconazole, posaconazole,
 efinaconazole, and rifampicin, etc.

 -  Patients with any other conditions that may not be suitable to participate in the
 trial at the discretion of the researchers.