Milestones in therapeutic and antithrombotic strategies for chronic thromboembolic pulmonary hypertension.

Abstract

Chronic thromboembolic pulmonary hypertension (CTEPH) is a condition caused by persistent thrombus obstructing the pulmonary arteries, resulting in pulmonary hypertension. Pulmonary endarterectomy remains the gold standard treatment and can provide dramatic improvement in eligible patients. However, approximately 40 % of patients are inoperable. Over the past years, several randomized controlled trials have explored pulmonary vasodilators and balloon pulmonary angioplasty. Based on these trials, a multimodal treatment approach has been established. Balloon pulmonary angioplasty has shown hemodynamic improvement rather than pulmonary vasodilators in randomized controlled trials. Similarly, lifelong anticoagulation therapy is the cornerstone of CTEPH management. While vitamin K antagonists such as warfarin have been the standard recommended by CTEPH guidelines, recent studies, including the CTEPH AC Registry and the KABUKI trial, suggest that direct oral anticoagulants may be safe and effective alternatives. Several ongoing randomized controlled trials aim to refine treatment strategies. The IMPACT-CTEPH trial is investigating whether the initial combination therapy (riociguat + macitentan) is superior to monotherapy before balloon pulmonary angioplasty. The GO-CTEPH trial compares the efficacy of pulmonary endarterectomy and balloon pulmonary angioplasty in eligible patients. The THERAPY-HYBRID-BPA trial is evaluating the need for continued riociguat after balloon pulmonary angioplasty. The FIND-DCR study is evaluating a new imaging modality for the early detection of CTEPH. As research advances, multimodal approaches combining surgical, interventional, and pharmacological treatments are expected to improve patient outcomes and shape the future of CTEPH management.