Discontinuation Versus Continuation of Riociguat Monotherapy in Chronic Thromboembolic Pulmonary Hypertension Successfully Treated With Balloon Pulmonary Angioplasty

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but severe complication of acute pulmonary embolism, characterized by persistent obstruction of the pulmonary arteries by organized thrombi and secondary microvasculopathy. International guidelines recommend a multimodal approach combining pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA), and medical treatment with riociguat, to address the full spectrum of CTEPH lesions. BPA and riociguat are recommended for symptomatic patients with inoperable CTEPH or persistent pulmonary hypertension after PEA. Riociguat is administered before BPA to reduce periprocedural complications by improving pulmonary hemodynamics. While this pre-BPA strategy is well established, post-BPA management is poorly studied, especially in patients achieving therapeutic goals, defined as WHO functional class I or II and near-normal resting pulmonary hemodynamics (70 to 80% of cases). In such cases, riociguat monotherapy is often continued long-term, despite its cost, burden, and potential side effects, which may negatively impact patients' quality of life. Retrospective single-center studies suggest that discontinuation of medical treatment does not lead to significant clinical deterioration. Therefore, we propose conducting a multicenter trial using a PROBE (prospective, randomized, open-label, blinded endpoint) design and a Bayesian approach to test if stopping riociguat monotherapy after successful BPA is associated with an acceptably low risk of clinical worsening over a follow-up period of at least one year compared to continuation. The trial will also assess the cost-effectiveness of riociguat discontinuation.