Pharmacological therapy for patients with chronic thromboembolic pulmonary hypertension

Abstract

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.

FIGURE 1

Mean change from baseline in 6-min walking distance (6MWD) in the Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial (CHEST)-1 and CHEST-2 studies. Data are observed values; error bars represent sem. Reproduced from [44] with permission from the publisher.

FIGURE 2

Kaplan–Meier plots for a) clinical worsening and b) survival in the overall population during the Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial (CHEST)-2 study. At 1 year, the estimated rate of clinical worsening-free survival was 88% and the estimated rate of survival was 97%. Reproduced from [44] with permission from the publisher.