Riociguat Emerges as Key Alternative for Nonresponders to Traditional Treatments in Pulmonary Arterial Hypertension

Recent advancements in the treatment of pulmonary arterial hypertension (PAH) have shifted clinical practices toward combination therapies, particularly highlighting the role of riociguat, according to an article published in Respiratory Medicine.

“In this review, we cover the clinical evidence for riociguat combination regimens for patients with PAH and discuss their evolving role in upfront combination therapy and switching from a PDE5i as an alternative to escalating therapy,” wrote Franck Rahaghi, Advanced Lung Disease Clinic, Cleveland Clinic in Florida, Weston, FL, and coauthors.

PAH is a progressive disease that can lead to severe complications, including right heart failure. Traditionally, treatment options focused on monotherapy; however, recent studies have shown that combining medications targeting different pathways can yield better outcomes. The pivotal AMBITION study established that initial combination therapy with ambrisentan and tadalafil significantly reduced clinical failure risks compared with monotherapy. As a result, updated guidelines now recommend upfront combination therapy as the standard care for patients with PAH.

The REPLACE study has further underscored the potential of riociguat, a soluble guanylate cyclase stimulator, as a viable option for patients who do not adequately respond to phosphodiesterase-5 inhibitors (PDE5is). In this study, patients who switched from PDE5i therapy to riociguat exhibited notable clinical improvements, achieving a higher rate of clinical response and fewer instances of clinical worsening compared to those who continued with PDE5is. Specifically, 41% of riociguat-treated patients showed clinical improvement at 24 weeks, compared to only 20% in the PDE5i group.

Moreover, switching to riociguat has been associated with enhanced exercise capacity and improved functional class in patients previously treated with PDE5is. The RESPITE study corroborated these findings, indicating significant gains in exercise performance and overall health status after transitioning to riociguat.

Despite these promising results, clinicians are advised to consider individual patient characteristics when deciding on treatment regimens. Factors such as previous treatment responses and comorbidities play critical roles in determining the most effective therapeutic strategy. Guidelines now suggest that switching from PDE5i to riociguat may be particularly beneficial for patients at intermediate risk of mortality who have not met treatment goals with existing therapies.

“Based on the current evidence, the combination of riociguat plus an [endothelin receptor antagonist] is an attractive option to improve patients’ risk status,” concluded the study authors.

Reference

Rahaghi FF, Trivieri MG, Sahay S. The role of riociguat in combination therapies for pulmonary arterial hypertension. Respir Med. 2023;211:107196. doi:10.1016/j.rmed.2023.107196