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Medical Therapies for Chronic Thromboembolic Pulmonary Hypertension

An Evolving Treatment Paradigm

Department of Pulmonology, Academic Medical Center, University of Amsterdam, The Netherlands; Pulmonary Vascular Disease Unit, Papworth Hospital, Cambridge, United Kingdom; Hôpital Antoine Béclère, Clamart, France; and Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany

Correspondence and requests for reprints should be addressed to Paul Bresser, M.D., Department of Pulmonology, Academic Medical Center (AMC), P.O. Box 22660, Amsterdam 1100 DD, The Netherlands. E-mail: p.bresser{at}amc.uva.nl

ABSTRACT

Pulmonary endarterectomy (PEA) is recommended as the treatment of choice for eligible patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, only a proportion of patients fulfill the criteria for surgical intervention. In addition, operated patients with CTEPH may experience a gradual hemodynamic and symptomatic decline related to a secondary hypertensive arteriopathy in the small precapillary pulmonary vessels. It has also been questioned what can be done to reduce risks from PEA surgery to improve outcome in "high risk" patients with CTEPH with substantial impairment of pulmonary hemodynamics before surgery. Such patients may benefit from preoperative reduction of pulmonary vascular resistance by means of medical therapy. Conventional medical treatments, such as anticoagulation, diuretics, digitalis, and chronic oxygen therapy, show low efficacy in the treatment of CTEPH as they do not affect underlying disease processes. Over the last decade, several novel therapies have been developed for pulmonary arterial hypertension (PAH), including prostacyclin analogs (epoprostenol, beraprost, iloprost), endothelin receptor antagonists (bosentan, sitaxsentan, ambrisentan), and phosphodiesterase-5 inhibitors (sildenafil). Evidence of efficacy in PAH, coupled with studies showing histopathologic similarities between CTEPH and PAH, provides a rationale to extend the use of some of these medications to the treatment of CTEPH. However, direct evidence from clinical trials in CTEPH is limited to date. This article reviews evidence supporting, and issues surrounding, the possible use of novel PAH medications in CTEPH.

Key Words: bosentan • pharmacotherapy • prostanoid • pulmonary arterial hypertension • thromboembolic

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