Edoxaban versus warfarin in chronic thromboembolic pulmonary hypertension

In patients with chronic thromboembolic pulmonary hypertension (CTEPH) who had received re-perfusion treatment, edoxaban showed non-inferiority to warfarin for preventing the worsening of pulmonary haemodynamics.

“Direct oral anticoagulants (DOACs) are first-line anticoagulants for the treatment of acute pulmonary embolism and the prevention of recurrent pulmonary embolism,” said Dr Kazuya Hosokawa (Kyushu University, Japan) [1,2]. “It has, however, not been established whether DOACs are safe and effective in patients with CTEPH.”

The multicentre, single-blind, non-inferiority, warfarin-controlled, phase 3 KABUKI trial (NCT04730037) compared edoxaban with warfarin in patients with CTEPH [2]. Participants (n=74) were randomised 1:1 and the primary endpoint was the ratio of pulmonary vascular resistance (PVR) at 48 weeks to the PVR at baseline.

The PVR ratio was non-inferior with edoxaban (treatment effect 0.92; 95% CI 0.82–1.03), reaching the non-inferiority threshold, which was an upper limit of the confidence interval of 1.19 (P_{non-inferiority}<0.001). Clinically relevant bleeding occurred in 2.7% of the edoxaban-treated participants and in 5.4% of the warfarin-treated participants (P=1.00).

One serious adverse event was observed in the edoxaban arm, a case of worsening pulmonary hypertension, and 3 serious adverse events were reported in the warfarin arm, being 1 tooth extraction, a haemorrhagic duodenal ulcer, and a case of urothelial transitional cell carcinoma.

“The trial was not designed to assess the effects of edoxaban on clinical outcomes,” Dr Hosokawa mentioned as a study limitation. “Also, the small sample size and single-country design limit the generalisability of the findings.” According to Dr Teresa Carman (University Hospitals, OH, USA), a discussant of the trial, some questions remain: “Will DOACs do as well in patients prior to reperfusion or in patients with underlying chronic vascular changes?” she wondered. “And can we extrapolate these findings to patients with more severe WHO class III disease?” Further studies are needed to address these issues.

1. 
   
   1. Stevens SM, et al. Chest. 2021;160(6):e545–e608.
   2. Hosokawa K, et al. A multicenter, randomised, warfarin-controlled trial of edoxaban in patients with chronic thromboembolic pulmonary hypertension: KABUKI trial. FS07, AHA Scientific Sessions 2023, 11–13 November, Philadelphia, USA.

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Posted on 29 January 202413 June 2024