Managing chronic thromboembolic pulmonary hypertension: pharmacological treatment options

Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition in which organised thrombi obstruct the pulmonary vessels, causing increased pulmonary vascular resistance, progressive pulmonary hypertension (PH) and right heart failure. The treatment of choice is pulmonary endarterectomy, which restores pulmonary haemodynamics with acceptable periprocedural mortality rates in the majority of suitable patients. However, CTEPH may be inoperable owing to surgically inaccessible thrombi or comorbid diseases that confer an unacceptably high risk. Pharmacotherapies, although not yet approved, may be useful in this situation or for treating residual or recurrent PH following surgery. Vasodilator drugs for PH are attracting growing interest as potential treatments for CTEPH because this disease has recently been labelled as a "dual'' pulmonary vascular disorder: major vessel obstruction and remodelling is combined with a small vessel arteriopathy that is histologically indistinguishable from the classical pulmonary arteriopathy observed in pulmonary arterial hypertension. Of three completed randomised controlled trials in patients with CTEPH, only one was powered to detect a treatment effect. The BENEFIT trial employed the dual endothelin-receptor antagonist bosentan. Although haemodynamics improved significantly, the second component of the primary end-point, exercise capacity, was not met. More evidence is required to resolve whether vasodilator treatments are beneficial for inoperable chronic thromboembolic pulmonary hypertension.