A Multicenter, Single-Blind, Randomized, Warfarin-Controlled Trial of Edoxaban in Patients With Chronic Thromboembolic Pulmonary Hypertension: KABUKI Trial.
Ontology highlight
ABSTRACT:
SUBMITTER: Hosokawa K
PROVIDER: S-EPMC10814998 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
Publications
A Multicenter, Single-Blind, Randomized, Warfarin-Controlled Trial of Edoxaban in Patients With Chronic Thromboembolic Pulmonary Hypertension: KABUKI Trial.
Hosokawa Kazuya K Watanabe Hiroko H Taniguchi Yu Y Ikeda Nobutaka N Inami Takumi T Yasuda Satoshi S Murohara Toyoaki T Hatano Masaru M Tamura Yuichi Y Yamashita Jun J Tatsumi Koichiro K Tsujino Ichizo I Kobayakawa Yuko Y Adachi Shiro S Yaoita Nobuhiro N Minatsuki Shun S Todaka Koji K Fukuda Keiichi K Tsutsui Hiroyuki H Abe Kohtaro K
Circulation 20231113 5
Similar Datasets
Project description:Introduction 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. Methods and analysis 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. Ethics and dissemination 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. Trial registration number NCT04730037. Protocol version This paper was written per the study protocol V.4.0, dated 29 January 2021.
| S-EPMC9301811 | biostudies-literature
Project description:Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of pulmonary embolism and a major cause of chronic PH leading to right heart failure and death. Lung ventilation/perfusion scintigraphy is the screening test of choice; a normal scan rules out CTEPH. In the case of an abnormal perfusion scan, a high-quality pulmonary angiogram is necessary to confirm and define the pulmonary vascular involvement and prior to making a treatment decision. PH is confirmed with right heart catheterisation, which is also necessary for treatment determination. In addition to chronic anticoagulation therapy, each patient with CTEPH should receive treatment assessment starting with evaluation for pulmonary endarterectomy, which is the guideline recommended treatment. For technically inoperable cases, PH-targeted medical therapy is recommended (currently riociguat based on the CHEST studies), and balloon pulmonary angioplasty should be considered at a centre experienced with this challenging but potentially effective and complementary intervention.
| S-EPMC6351341 | biostudies-literature
Project description:Chronic pulmonary thromboembolic disease is an important cause of severe pulmonary hypertension, and as such is associated with significant morbidity and mortality. The prognosis of this condition reflects the degree of associated right ventricular dysfunction, with predictable mortality related to the severity of the underlying pulmonary hypertension. Left untreated, the prognosis is poor. Pulmonary endarterectomy is the treatment of choice to relieve pulmonary artery obstruction in patients with chronic thromboembolic pulmonary hypertension and has been remarkably successful. Advances in surgical techniques along with the introduction of pulmonary hypertension-specific medication provide therapeutic options for the majority of patients afflicted with the disease. However, a substantial number of patients are not candidates for pulmonary endarterectomy due to either distal pulmonary vascular obstruction or significant comorbidities. Therefore, careful selection of surgical candidates in expert centres is paramount. The current review focuses on the diagnostic approach to chronic thromboembolic pulmonary hypertension and the available surgical and medical therapeutic options.
| S-EPMC4391185 | biostudies-literature
Project description:We sequenced RNA from pulmonary arteries from CTEPH, IPAH or healthy, failed donors
2019-02-18 | GSE84538 | GEO
Project description:We present the case of a 78-year-old female undergoing pulmonary endarterectomy (PEA) because of suspected chronic thromboembolic pulmonary hypertension (CTEPH). During surgery firm black masses were encountered in the aortopulmonary window and on the cranial part of the right pulmonary artery (PA). After PA arteriotomy we visualized intraluminal black firm stenosing plaques at the orifices of the three right and of the left lingular and lower lobar branches. Since no dissection plane could be obtained the procedure was discontinued. Subsequent bronchoscopy visualized a submucosal dark black-blue discoloration in both main bronchi. Pathological analysis revealed anthracofibrosis, which could be explained by biomass smoke exposure in the past. We are the first to provide intravascular pictures and pathologic images of this very rare entity. Moreover, we report stenoses at the orifices of the three right-sided lobar and of the left-sided lingular and lower lobe arteries, in contrast to three previous reports that report on single locations caused by extrinsic PA compression from lymphadenopathy. Our case, however, suggests extension of fibrosis with anthracotic pigment into the PA wall. We conclude that in the absence of a clear history of exposure to carbon smoke and with consequently no diagnostic bronchoscopy, anthracofibrosis of the lungs may mimic CTEPH not only by external compression but also by extension into pulmonary vascular structures. PEA-surgery should not be attempted in these cases.
| S-EPMC10323163 | biostudies-literature
Project description:Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the leading causes of severe pulmonary hypertension (PH). The disease is still underdiagnosed, and the true prevalence is unknown. CTEPH is characterized by intraluminal non-resolving thrombus organization and fibrous stenosis, or complete obliteration of pulmonary arteries, promoted by progressive remodeling of the pulmonary vasculature. One consequence of this is an increase in pulmonary vascular resistance and pressure, resulting in PH and progressive right heart failure, leading to death if left untreated. Endovascular disobliteration by pulmonary endarterectomy (PEA) is the preferred treatment for CTEPH patients. PEA surgery is the only technique that can potentially cure CTEPH disease, especially in patients with fresh or organized thrombi of the proximal branches of pulmonary arteries. However, not all patients are eligible for PEA surgery. Recent research has provided evidence suggesting balloon pulmonary angioplasty (BPA) and targeted medical therapy as additional promising available treatments options for inoperable CTEPH and recurrent/persistent PH after PEA surgery. Studies on BPA have shown it to improve pulmonary hemodynamics, symptoms, exercise capacity and RV function in inoperable CTEPH. Subsequently, BPA has developed into an essential component of the modern era of CTEPH treatment. Large randomized controlled trials have demonstrated varying significant improvements with targeted medical therapy in technically inoperable CTEPH patients. Thus, treatment of CTEPH requires a comprehensive multidisciplinary assessment, including an experienced PEA surgeon, PH specialist, BPA interventionist and CTEPH-trained radiologist at expert centers. In this comprehensive review, we address the latest developments in the fast-evolving field of CTEPH. These include advancements in imaging modalities and developments in operative and interventional techniques, which have widened the range of patients who may benefit from these procedures. The efficacy and safety of targeted medical therapies in CTEPH patients are also discussed. As the treatment options for CTEPH improve, hybrid management involving multiple treatments in the same patient may become a viable option in the near future.
| S-EPMC7590968 | biostudies-literature
Project description:Purpose of reviewChronic thromboembolic pulmonary hypertension (CTEPH), included in group 4 PH, is an uncommon complication of acute pulmonary embolism (PE), in which emboli in the pulmonary vasculature do not resolve but rather form into an organized scar-like obstruction which can result in right ventricular (RV) failure. Here we provide an overview of current diagnosis and management of CTEPH.Recent findingsCTEPH management is complex with treatments that range from surgery, percutaneous interventions, to medical therapies. Current CTEPH medical therapies have largely been repurposed from pulmonary arterial hypertension (PAH). The diagnosis of CTEPH can be challenging, requiring a multimodality approach to differentiate from disease mimics. While these treatments improve symptoms, they may not reverse the underlying pathology of CTEPH.
| S-EPMC8375459 | biostudies-literature
Project description:BackgroundUnresolved thromboemboli in the pulmonary arteries (PA) is known to cause chronic thromboembolic pulmonary hypertension (CTEPH). However, it remains unknown if vascular dysfunction in pulmonary arteries exists in patients with CTEPH.Methods and resultsWe enrolled 7 female patients with CTEPH in this study, who have stable pulmonary hemodynamics after balloon pulmonary angioplasty (age; 73.6 ± 3.0 years old, mean right atrial pressure; 4.1 ± 0.4 mm Hg, mean pulmonary arterial pressure; 29.4 ± 2.7, mean pulmonary artery wedge pressure; 8.1 ± 1.2, pulmonary vascular resistance; 397.3 ± 51.7 dynes, cardiac index; 3.1 ± 0.2 L/min/m2). Pulmonary artery vascular function was evaluated by measuring pulmonary artery vasomotion in response to acetylcholine (Ach) at 10-month follow-up after balloon pulmonary angioplasty. All pulmonary vasoactive drugs were discontinued on the day of the procedures. The endothelium-dependent vasomotor response was evaluated by intra-pulmonary artery infusion of Ach at the dose of 10- 8 mol/l, and the vaso-spastic response was at 10- 6 mol/l. We evaluated vasomotor responses at the same segment in each patient, by measuring % changes of luminal area detected by quantitative pulmonary arterial optical frequency-domain imaging (OFDI), where OFDI catheter was fixed during the procedure. Endothelial dysfunction was observed at the dose of Ach at 10- 8 mol/l and vasoconstriction was also confirmed at the dose of Ach at 10- 6 mol/l in the diseased pulmonary arteries in CTEPH.ConclusionsThese results indicated that the pulmonary artery dysfunction exists in patients with CTEPH, which may be involved in the pathogenesis and progression of CTEPH.
| S-EPMC5683704 | biostudies-literature
Project description:Chronic thromboembolic pulmonary hypertension (CTEPH) is thought to result from incomplete resolution of pulmonary thromboemboli that undergo organisation into fibrous tissue within pulmonary arterial branches, filling pulmonary arterial lumina with collagenous obstructions. The treatment of choice is pulmonary endarterectomy (PEA) in CTEPH centres, which has low post-operative mortality and good long-term survival. For patients ineligible for PEA or who have recurrent or persistent pulmonary hypertension after surgery, medical treatment with riociguat is beneficial. In addition, percutaneous balloon pulmonary angioplasty (BPA) is an emerging option, and promises haemodynamic and functional benefits for inoperable patients. In contrast to conventional angioplasty, BPA with undersized balloons over guide wires exclusively breaks intraluminal webs and bands, without dissecting medial vessel layers, and repeat sessions are generally required. Observational studies report that BPA improves haemodynamics, symptoms and functional capacity in patients with CTEPH, but controlled trials with long-term follow-up are needed. Complications include haemoptysis, wire injury, vessel dissection, vessel rupture, reperfusion pulmonary oedema, pulmonary parenchymal bleeding and haemorrhagic pleural effusions. This review summarises the available evidence for BPA, patient selection, recent technical refinements and periprocedural imaging, and discusses the potential future role of BPA in the management of CTEPH.
| S-EPMC9489135 | biostudies-literature
Project description:The hallmark of chronic thromboembolic pulmonary hypertension (CTEPH) is fibrotic transformation of pulmonary arterial thrombus, leading to mechanical obstruction of pulmonary arteries. We report the transcriptome profile of fibroblasts isolated from pairs of CTEPH thrombus and pulmonary artery adventitia of the same patient. Fibroblasts isolated from CTEPH thrombus demonstrated upregulation of genes associated with the TGF-β pathway indicating that TGF-β upregulation is associated with the intravascular remodeling process.
2020-12-31 | GSE149413 | GEO