This is phase III trial to evaluate whether edoxaban, a direct factor Xa inhibitor, is noninferior to warfarin in preventing worsening of chronic thromboembolic pulmonary hypertension (CTEPH).

Inclusion Criteria:

1. Patient who once* diagnosed with CTEPH based on at least 2 imaging study (VQ scan, CT pulmonary angiogram, or catheter-based pulmonary angiogram) and hemodynamic criteria (MPAP >=25 mmHg and PAWP =< 15 mmHg). *Patients treated with PEA, BPA, or vasodilators, who do not meet hemodynamic criteria at the registration, are eligible.
2. Patients who are not planned to require increased / changed / discontinuation of PEA, BPA, or pulmonary vasodilators within 12months
3. Stable administration of vitamin K antagonists
4. WHO functional class I-III
5. Patients who meet A) B)and C) by 90 days prior to baseline. A)No addition, reduction, or change of endothelin antagonists, soluble guanylate cyclase stimulants, phosphodiesterase-5 inhibitors, prostacyclin, and its derivatives, or calcium antagonists. B)Appropriate anticoagulants have been continued. C)No BPA has been done.
6. Patients who have not undergone PEA from 180 days prior to baseline right heart catheterization to the start date of study drug administration
7. Patients with a 6-minute walking distance >=150m

Exclusion Criteria:

1. Patients with severe lung disease (FEV1.0/FVC < 60% or %TLC < 60%)
2. Patients with acute or chronic disabilities that interfere with clinical trial requirements
3. Patients with acute symptomatic PE within 180 days prior to the start of study drug administration
4. Patients with congenital heart disease who have not undergone radical surgery
5. Patients who cannot provide informed consent due to mental disorders, dementia, or other illnesses
6. Patients with advanced cancer
7. Patients with a life expectancy of less than 1 year
8. Patients with active hemorrhagic lesions
9. Patients with comorbidities requiring vitamin K antagonist
10. Patients receiving other study drug within 30 days prior to randomization
11. Patients with renal dysfunction (Ccr 15 mL/min)
12. Patients with liver dysfunction (Child-Pugh B or C)
13. Females of reproductive age not using an acceptable form of contraception/Pregnant/Breastfeeding
14. Patients contraindicated for edoxaban or warfarin
15. Patients with hypersensitivity to any of the drug

Data are available upon reasonable request. The deidentified participant data collected in this study will be shared with manufacturers of investigational drugs, Ministry of Health, Labor and Welfare, and regulatory authorities related to pharmaceutical affairs.

Data are attributed to Kyushu University and Daiichi Sankyo Co., Ltd. Protocols, informed consent form, and statistical analysis plans will be shared upon reasonable request.

Contact: abe.kotaro.232@m.kyushu-u.ac.jp