Riociguat for pulmonary hypertension

Abstract

Pulmonary hypertension, an elevation of the mean pulmonary artery pressure ≥25 mmHg, ultimately leads to premature death due to right ventricular dysfunction. Ten treatments from three classes of drugs are licensed for the management of pulmonary arterial hypertension. These treatments have improved exercise capacity but median survival is still poor. Additionally there are no licensed therapies for the other groups of pulmonary hypertension. Riociguat is a novel drug that stimulates soluble guanylate cyclase independently of nitric oxide and in synergy with nitric oxide. This review summarises the available evidence for riociguat in the treatment across all groups of pulmonary hypertension with a focus on pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

Keywords::

• BAY 63-2521
• chronic thromboembolic pulmonary hypertension
• nitric oxide
• pulmonary arterial hypertension
• pulmonary hypertension heart disease
• pulmonary hypertension lung disease
• riociguat
• soluble guanylate cyclase stimulator

Financial & competing interests disclosure

JE Cannon has received reimbursements of travel expenses to congresses and speakers fees from Actelion, GSK and Pfizer. J Pepke-Zaba has received reimbursements of travel expenses to congresses and speakers’ fees from Actelion, Pfizer, GSK, Bayer, LungRX and United Therapeutics, has participated to advisory boards for Actelion, United Therapeutics, Bayer, Pfizer, Lilly, Novartis, has received funds for research and education from Actelion, Pfizer, GSK, has received consultancy fee from Actelion. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Pulmonary hypertension (PH) is defined as a mean pulmonary artery pressure ≥25 mmHg and is a common complication of a wide range of diseases.

• The causes of pulmonary hypertension are divided into five groups: group 1 pulmonary arterial hypertension (PAH), group 2 PH due to left heart disease, group 3 PH due to lung disease or hypoxia, group 4 chronic thromboembolic PH (CTEPH) and group 5 PH with unclear and/or multifactorial mechanisms.

• The current pharmacological treatments for PAH target the imbalance between vasodilators like nitric oxide and prostacyclin and the vasoconstrictors, for example, endothelin.

• Animal models suggest that targeting the nitric oxide signaling pathway using a soluble guanylate cyclase stimulator like riociguat is more effective than a phosphodiesterase type 5 inhibitor like sildenafil.

• Riociguat was well tolerated by healthy volunteers and patients with PAH and CTEPH. The commonest adverse events included headache, dyspepsia and peripheral edema.

• Riociguat has been shown to improve exercise capacity in PAH patients, both treatment naive and in patients already on baseline therapy with an endothelin receptor antagonist or prostenoid.

• Riociguat is the first pharmacological therapy that has been shown to improve exercise capacity in CTEPH patients in a Phase III randomized, placebo-controlled clinical trial.

• The response to riociguat in other groups of PH in early phase clinical trials is promising but has not been as effective compared with the trials with PAH and CTEPH patients.

• The open-label, long-term pulmonary arterial hypertension-soluble guanylate cyclase stimulaTor 2 and chronic thromboembolic pulmonary hypertension-soluble guanylate cyclase stimulator trial 2 studies showed that riociguat treatment is well tolerated with a good safety profile in patients with PAH and CTEPH.

Notes