edoxaban and Hypertension--Pulmonary

Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of prior pulmonary thromboembolism (PE), caused by incomplete clot dissolution after PE. In patients with CTEPH, lifelong anticoagulation is mandatory to prevent recurrence of PE and secondary in situ thrombus formation. Warfarin, a vitamin K antagonist, is commonly used for anticoagulation in CTEPH based on historical experience and evidence. The anticoagulant activity of warfarin is affected by food and drug interactions, requiring regular monitoring of prothrombin time. The lability of anticoagulant effect often results in haemorrhagic and thromboembolic complications. Thus, lifelong warfarin is a handicap in terms of safety and convenience. Currently, the use of direct oral anticoagulants (DOACs) in CTEPH has increased with the advent of four DOACs. The safety of DOACs is superior to warfarin, with less intracranial bleeding in patients with non-valvular atrial fibrillation and venous thromboembolism. Edoxaban, the latest DOAC, also has proven efficacy and safety for those diseases in two large clinical trials; the ENGAGE-AF trial and HOKUSAI-VTE trial. The present trial seeks to evaluate whether edoxaban is non-inferior to warfarin in preventing worsening of CTEPH.. The KABUKI trial (is an investigator-initiated, multicentre, phase 3, randomised, single-blind, parallel-group, warfarin-controlled, non-inferiority trial to evaluate the efficacy and safety of edoxaban versus warfarin (vitamin K Antagonist) in subjects with chronic thromBoembolic pUlmonary hypertension taking warfarin (vitamin K antagonIst) at baseline) is designed to prove the non-inferiority of edoxaban to warfarin in terms of efficacy and safety in patients with CTEPH.. This study is approved by the Institutional Review Board of each participating institution. The findings will be published in a peer-reviewed journal, including positive, negative and inconclusive results.. NCT04730037.. This paper was written per the study protocol V.4.0, dated 29 January 2021.

Topics: Anticoagulants; Atrial Fibrillation; Humans; Hypertension, Pulmonary; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Single-Blind Method; Stroke; Venous Thromboembolism; Vitamin K; Warfarin

Antiphospholipid syndrome (APS) is a cause of chronic thromboembolic pulmonary hypertension (CTEPH) and it is associated with an increased risk of postoperative neurological complications. We experienced a case of reversible parkinsonism after pulmonary endarterectomy (PEA) and subsequent multiple cerebral infarctions under standard anticoagulation therapy in a patient with CTEPH associated with APS. Strict management using a combination of antiplatelet and anticoagulation therapy should be considered in patients with a high titer of triple antiphospholipid antibodies in the perioperative period. We should be aware of the high risk of postoperative neurologic manifestations in patients with APS.

Topics: Adult; Anticoagulants; Antiphospholipid Syndrome; Cerebral Infarction; Chronic Disease; Endarterectomy; Heparin; Humans; Hypertension, Pulmonary; Male; Parkinsonian Disorders; Postoperative Complications; Pyridines; Thiazoles; Treatment Outcome; Warfarin