Contemporary pharmacotherapeutic options for chronic thromboembolic pulmonary hypertension

INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) is driven by both proximal thromboembolic obstruction and microvasculopathy. While pulmonary endarterectomy (PEA) and balloon pulmonary angioplasty (BPA) are effective for selected patients, pharmacotherapy is indispensable in the contemporary era. This review provides an updated overview of medical therapy within a multimodal treatment paradigm. AREAS COVERED: This review examines lifelong anticoagulation, including comparative evidence for vitamin K antagonists and direct oral anticoagulants, and the efficacy and safety of approved and off-label PH-targeted therapies for inoperable CTEPH or persistent/recurrent PH after PEA. Riociguat, phosphodiesterase type 5 inhibitors, endothelin receptor antagonists, treprostinil, and selexipag are reviewed, together with combination therapy, pharmacotherapy before and after PEA or BPA, and assessment of treatment response. EXPERT OPINION: Riociguat has the strongest evidence for symptomatic inoperable CTEPH or persistent/recurrent PH after PEA; subcutaneous treprostinil may benefit selected patients with severe disease. PH-targeted therapy should not delay PEA referral. Anatomical inoperability, procedural risk, limited specialist access, and informed refusal require different responses. After intervention, decisions to continue medication should consider residual disease, symptoms, right ventricular function, and exercise limitation, not resting hemodynamics alone. Comparative studies should determine who benefits from medication before BPA and when it can safely be withdrawn.