Pulmonary arterial hypertension (PAH) is a rare yet progressive disease that affects the blood vessels in the lungs. This disease could result in difficulty breathing, fatigue, chest pain, and eventually, heart failure.

A drug class called phosphodiesterase type 5 inhibitors (PDE-5 inhibitors) is a commonly used therapy in PAH. However, some patients have an insufficient response to these drugs, leaving them with limited treatment options. Fortunately, a new medication known as riociguat offers hope for these patients.

What Is Pulmonary Arterial Hypertension?

PAH is a type of pulmonary hypertension where the blood pressure in the arteries of the lungs is significantly higher than the standard rate. This occurs when the arteries narrow or become blocked, leading to increased resistance to blood flow.

As a result, the right side of the heart must work overtime, pumping blood to the lungs, creating additional strain on the organ. If left untreated, this extra strain may result in heart failure.

PDE-5 Inhibitors as a Treatment for PAH

PDE-5 inhibitors help PAH patients by dilating blood vessels and reducing the narrowing of the arteries, making it easier for the heart to pump blood to the lungs. The most common PDE-5 inhibitors used to treat PAH are sildenafil and tadalafil.

However, some patients may not respond well to these medications. This could be due to various factors such as genetic predisposition or an underlying medical condition. When PDE-5 inhibitors fail, physicians have limited options for continuing therapy.

How Riosiguate Works

Riosiguate (Adempas) is a type of soluble guanylate cyclase stimulator that acts similarly to PDE-5 inhibitors by relaxing the arteries, but also has a distinct mechanism of action.

Riosiguate works by promoting the production of cyclic guanosine monophosphate (cGMP), which relaxes the blood vessels and improves blood flow.

Additionally, riosiguate can improve cardiac function by helping the heart pump more efficiently, reducing the risk of heart failure.

Results of Clinical Trials

Riosiguate has undergone several clinical trials to determine its safety and efficacy in treating patients with PAH.

One of these studies is the PATENT-1 study, which included 443 PAH patients who had an inadequate response or could not tolerate PDE-5 inhibitors.

Results showed that patients who received riosiguate had significant improvement in their six-minute walking distance (6MWD), a test that measures exercise tolerance and response to therapy.

After 12 weeks of treatment, patients who received riosiguate had an increase of 30 meters in their 6MWD compared to placebo. Additionally, patients who received riosiguate had a lower risk of hospitalizations or death compared to the placebo group.

The PATENT-2 study showed similar results, with patients who received riosiguate demonstrating improved exercise capacity and a reduced risk of clinical worsening compared to those who received placebo.

Side Effects and Safety

All medications have potential side effects, and riosiguate is no exception. The most common side effects of riosiguate include:.

headache
dizziness
nausea
vomiting
diarrhea
low blood pressure
fluid retention

Furthermore, riosiguate is contraindicated in patients who take nitrate-containing medications. Riosiguate could cause significantly low blood pressure when taken with nitrates, leading to a severe drop in blood pressure that could be life-threatening.

Therefore, a physician should review a patient’s medical history fully before prescribing riosiguate.

Conclusion

Riosiguate represents a novel and promising therapy for PAH patients with an insufficient response to PDE-5 inhibitors.

Clinical studies have shown that this medication improves exercise capacity, reduces the risk of clinical worsening, and improves cardiac function. However, as with all medications, potential side effects must be considered, and physicians must be cautious when prescribing riosiguate.