Adempas therapy significantly improves lung and heart function in patients with chronic thromboembolic pulmonary hypertension (CTEPH) previously treated off-label with sildenafil, according to a Polish study.
The study reporting the findings, “Sequential treatment with sildenafil and riociguat in patients with persistent or inoperable chronic thromboembolic pulmonary hypertension improves functional class and pulmonary hemodynamics,” was published in the International Journal of Cardiology.
CTEPH is a rare type of pulmonary hypertension (PH) caused by the accumulation of blood clots (emboli) in the blood vessels of the lungs. These clots obstruct blood flow, resulting in an abnormal increase in blood pressure.
Riociguat, marketed by Bayer as Adempas, is approved for the treatment of patients with inoperable or persistent CTEPH and pulmonary arterial hypertension (PAH). Also approved for use in PAH, sildenafil is marketed as Revatio by Pfizer in both the U.S. and European Union. Both drugs relax and widen the blood vessels, but they do so in different ways.
Sildenafil use is not approved for the treatment of CTEPH, although it often is given to patients as an off-label therapy — off-label meaning the use of a drug to treat a disease or medical condition for which it is not approved.
In the study, researchers assessed CTEPH patients who received off-label treatment with sildenafil and then switched treatments to Adempas once it was approved for use in the European Union (in 2014).
A total of 28 patients with inoperable or persistent CTEPH (18 women, age 50-80 years) participated in the study. All patients received 25 mg of sildenafil, three times a day (TID) for at least three months. One day after the last sildenafil dose, patients were started on Adempas. They received increasing Adempas doses starting at 1 mg, TID, which then was gradually increased to a maximum dose of 2.5 mg, TID.
Patients were assessed before the start of sildenafil treatment (baseline), before the start of Adempas treatment, and then at the median follow-up of 5.6 months. Right heart catheterization was used to check the lung and heart function during each assessment.
Furthermore, the cardiac output — a measure of heart function — was 11% higher than the baseline level after both treatments.
After switching treatments from sildenafil to Adempas, the PVR assessed at the median follow-up decreased by 14%, while the mPAP was reduced by 6%. There also was a significant increase in the cardiac output by 11% after the treatment switch.
The World Health Organization (WHO) Functional classification system (FC) classifies PH into four classes (I-IV) based on the severity of the disease. The higher the FC, the more severe the disease.
Researchers found that before Adempas treatment, 71.4% of the patients were classified as FC III or IV (severe disease), but the change in treatment from sildenafil to Adempas reduced the number of patients in that category to 57.1%.
The most common side effects seen with Adempas treatment were low blood pressure, headache, and difficulty swallowing. However, none of the patients stopped treatment or switched to sildenafil due to these side effects.
“Replacing sildenafil with riociguat [Adempas] in patients with inoperable or persistent CTEPH may improve the hemodynamic parameters of the pulmonary circulation and physical functioning as assessed using the WHO classification,” researchers wrote.
“The use of riociguat [Adempas] may reduce the need for other antihypertensive medications used to treat systemic hypertension in CTEPH patients, but further research is needed,” the team concluded.