Switching from sildenafil to riociguat for the treatment of PAH and inoperable CTEPH: Real-life experiences

Abstract

Riociguat is a novel soluble guanylate cyclase stimulator that is approved for the treatment of patients with pulmonary arterial hypertension (PAH) and patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent/recurrent CTEPH after pulmonary endarterectomy (PEA). As riociguat is a relatively new drug, experience of its use in clinical practice is limited, especially in patients who would not have met the inclusion criteria for the pivotal Phase III clinical trials, PATENT-1 and CHEST-1.This article shares our initial practical and clinical experience in switching patients with PAH and CTEPH from the phosphodiesterase type-5 inhibitor sildenafil to riociguat, based on three selected case reports of patients who discontinued sildenafil therapy owing to side effects or disease progression (one patient with idiopathic PAH and two patients with persistent/recurrent CTEPH after PEA). Two cases illustrate our experience with direct switch from sildenafil to riociguat (6–8 h between the last sildenafil dose and the first riociguat dose), and one case illustrates switch to riociguat in a patient who underwent treatment with other PAH-specific therapies between stopping sildenafil and starting riociguat. Symptoms improved with riociguat therapy in two cases; in the third case the patient experienced worsening symptoms 1 month after initiating riociguat and was switched back to sildenafil. These case experiences contribute practical information to assist clinicians in the switch from sildenafil to riociguat therapy in patients with PAH or CTEPH.

Real-World Switching to Riociguat: Management and Practicalities in Patients with PAH and CTEPH

“…AEs were rarely reported during the treatment-free period, and during the dose-adjustment period, only one patient discontinued riociguat, and 11 patients experienced AEs that resulted in dose reduction or interruption. Although it is important to interpret these observations with caution based on the inherent selection bias of a retrospective chart review (discussed below), they are in line with the results of published case studies and retrospective analyses of both PAH and CTEPH patients switching from other PH-targeted therapies (mainly PDE5i) to riociguat in real-world clinical practice [ 18 , 20 , 42 – 45 ]. The results from CAPTURE also support preliminary data from the RESPITE clinical trial, which indicated that switching from sildenafil or tadalafil to riociguat in patients with PAH not reaching treatment goals was safe and well tolerated [ 25 ].…”

“…This strategy of switching patients from one PH-targeted therapy to another is largely unexplored in clinical practice. Small studies and case reports have demonstrated positive outcomes after switching, but these have largely involved switching within a drug class, and were mainly due to lack of efficacy [ 18 – 20 ] or safety and tolerability [ 21 , 22 ] of the former drug.…”

Pulmonary thromboendarterectomy is a curative resolution for chronic thromboembolic pulmonary hypertension associated with antiphospholipid syndrome: a retrospective cohort study

“…In 2010, a systematic review and meta-analysis by Becattini, consisting of 543 papers, analysed the efficacy of bosentan for CTEPH, 22 and found that it may improve haemodynamic response and probably exercise capacity in patients with CTEPH. Some studies also showed that a PDE5i, such as sildenafil, 23–35 could be useful in improving symptoms and long-term function in CTEPH patients. Different studies of CTEPH patients yield different results regarding the effect on cardiac function.…”

Treatment Selection in Pulmonary Arterial Hypertension: Phosphodiesterase Type 5 Inhibitors versus Soluble Guanylate Cyclase Stimulator

“…Endothelial NO synthase expression, NO production and NO availability are substantially reduced in patients with PAH, 5,10 so the sGC stimulator may be effective in patients who have not sufficiently responded to a PDE5 inhibitor. [34][35][36] The recent open-label, uncontrolled, phase…”