Content area
Full Text
Published online: 29 October 2014
© Springer International Publishing Switzerland 2014
Abstract Riociguat (Adempas®), a soluble guanylate cyclase stimulator, is a new, first-in-class drug approved for the treatment of patients with chronic thromboembolic pulmonary hypertension (CTEPH) [inoperable or persistent/ recurrent following surgery] or pulmonary arterial hypertension (PAH). It has been designated an orphan medicine by the European Medicines Agency and the US FDA. This article reviews the available pharmacological properties of oral riociguat and its clinical efficacy and tolerability in adults with CTEPH or PAH. Riociguat is effective and well tolerated in patients with inoperable CTEPH or persistent/recurrent CTEPH following pulmonary endarterectomy, and in patients with PAH. It has a positive result on exercise capacity and pulmonary haemodynamics, and improves WHO functional class. Most adverse events can be attributed to the vasodilatory mechanism of riociguat; however, there is a potential for serious bleeding and fetal harm, and riociguat use is contraindicated in pregnant patients. Pulmonary endarterectomy remains the first treatment of choice for CTEPH, as it is potentially curative. Head-to-head trials comparing riociguat with the approved phosphodiesterase type 5 inhibitors in patients with PAH would be of value for the placement of riociguat in the management of this disease. Riociguat is a promising addition to the treatment options for patients with CTEPH or PAH.
1 Introduction
Pulmonary hypertension, defined as a mean pulmonary arterial pressure (mPAP) of C25 mmHg at rest [1-3], has been further classified by the World Health Organisation (WHO) into five different groups: pulmonary arterial hypertension (PAH), pulmonary hypertension with left heart disease, pulmonary hypertension associated with lung diseases and/or hypoxaemia, chronic thromboembolic pulmonary hypertension (CTEPH), and pulmonary hyper- tension with unclear and/or multifactorial mechanisms [1, 2].
The cumulative incidence of CTEPH was estimated to be 1.0 % 6 months after an acute pulmonary embolism, 3.1 % after 1 year and 3.8 % after 2 years [1]; however, most experts have settled on an incidence of 0.5-2 % after acute pulmonary embolism [2]. The lowest estimated prevalence of PAH is 5.9-15 cases per million adult pop- ulation [1, 2] (PAH prevalence in Europe has been esti- mated at 15-50 cases per million population [2]), and the lowest estimated incidence is 2.4 cases per million adult population per year [2]. PAH has...