From the Guidelines
Adempas (riociguat) significantly improves pulmonary arterial hypertension (PAH) by stimulating soluble guanylate cyclase, leading to vasodilation in the pulmonary arteries and reducing pulmonary vascular resistance and pressure, as evidenced by a 12-week study showing a mean increase of 30m in 6MWD and a decrease in PVR by 223 dyn/s/cm5 1.
Mechanism of Action
Adempas (riociguat) works by stimulating soluble guanylate cyclase (sGC), an enzyme in the cardiopulmonary system, which increases the production of cyclic guanosine monophosphate (cGMP), leading to vasodilation in the pulmonary arteries.
Clinical Benefits
The clinical benefits of Adempas include:
- Improved 6-minute walk distance (6MWD) by a mean of 30m compared to placebo 1
- Decreased pulmonary vascular resistance (PVR) by 223 dyn/s/cm5 compared to placebo 1
- Improved hemodynamic variables, including mean pulmonary artery pressure (mPAP) and cardiac output (CO) 1
- Reduced incidence of clinical worsening events, such as death, hospitalization, and disease progression 1
Dosage and Administration
The standard dosing of Adempas begins at 1 mg three times daily and may be titrated up to a maximum of 2.5 mg three times daily based on blood pressure response, with dose adjustments typically occurring every 2 weeks 1.
Safety Considerations
Patients should be monitored for hypotension, as Adempas can lower blood pressure significantly, and it is contraindicated during pregnancy due to potential harm to the fetus, with women of reproductive potential requiring participation in the REMS program with monthly pregnancy testing 1.
Common Side Effects
Common side effects of Adempas include headache, dizziness, dyspepsia, and peripheral edema 1.
From the Research
Mechanism of Action
- Adempas (Riociguat) stimulates soluble guanylate cyclase via the nitric oxide pathway, leading to improved exercise capacity and hemodynamic parameters in PAH patients 2, 3.
- Riociguat enhances the synthesis of cyclic guanosine monophosphate (cGMP), a mediator of vasodilation, which is similar to the mechanism of action of sildenafil 4.
Clinical Benefits
- Riociguat has been shown to improve symptomatic and hemodynamic parameters, increase 6-min walk distance, and improve or stabilize World Health Organization functional class in PAH patients 2, 3.
- Clinical trial data demonstrate that riociguat significantly improves exercise capacity and hemodynamic parameters in PAH/CTEPH patients 2.
- Riociguat has been associated with an improvement in respiratory and hemodynamic parameters and a favorable tolerability profile in patients with PAH-CTD who were switched from a PDE-5i to riociguat 5.
Patient Selection
- Riociguat is an option for patients with chronic thromboembolic pulmonary hypertension that markedly restricts their activities of daily living 4.
- Selected patients with PAH may benefit from switching from PDE-5i to riociguat, but this strategy needs to be further studied 6.
- Riociguat can be considered for patients with PAH-CTD who have not achieved a satisfactory clinical response to a PDE-5i 5.
Safety and Tolerability
- The main adverse effects of riociguat are related to its vasodilatory properties, and include headache, arterial hypotension, dizziness, and peripheral oedema 4, 3.
- Riociguat can also cause bleeding, including potentially severe pulmonary haemorrhage, and has a potential for serious bleeding and fetal harm 4, 3.
- Riociguat is contraindicated in pregnant patients, and its use is subject to pharmacodynamic interactions with many other drugs 4, 3.