Pharmacological therapy for patients with chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but life-threatening disease resulting from unresolved thromboembolic obstructions. Pulmonary endarterectomy (PEA) surgery is the gold-standard treatment as it is potentially curative; however, not all patients are deemed operable and up to one-third have persistent or recurrent CTEPH after the procedure. Pulmonary arterial hypertension (PAH) and CTEPH have similar clinical presentations and histopathological features, so agents shown to be effective in PAH have often been prescribed to patients with CTEPH in the absence of proven therapies. However, clinical evidence for this strategy is not compelling. A number of small uncontrolled trials have investigated endothelin receptor antagonists, prostacyclin analogues and phosphodiesterase type 5 inhibitors in CTEPH with mixed results, and a phase III study of the endothelin receptor antagonist bosentan met only one of its two co-primary end-points. Recently, however, the soluble guanylate cyclase stimulator, riociguat, was approved in the USA and Europe for the treatment of inoperable or persistent/recurrent CTEPH following positive results from the phase III CHEST study (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase-Stimulator Trial). This article reviews the current evidence for the use of pharmacological therapies in CTEPH.