• Thromboembolic Disease
• Pulmonary Clinical Trials

• Pulmonary & Critical Care
• Thromboembolic Disease
• Pulmonary Clinical Trials

Combination treatment of beraprost and sildenafil results in improved 6-minute walk test (6MWT) distance and decreases N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and time to worsening in patients with pulmonary arterial hypertension (PAH). Zhi-Cheng Jing, MD, Fu Wai Hospital & National Center for Cardiovascular Disease, Beijing, China, presented data from the Beraprost Combined Therapy With Sildenafil for Pulmonary Arterial Hypertension study [BEST; ChiCTR-TCC-12002776].

Patients with PAH have poor long-term survival rates, highlighting a need for a first-line combination therapy. This is particularly important in China, where many novel targeted agents for the treatment of PAH are not available in typical daily practice. The hypothesis of the BEST study was that the addition of beraprost to sildenafil would improve efficacy in the treatment of PAH.

In the open-label BEST study, 60 patients with PAH receiving sildenafil monotherapy were randomized to receive beraprost in addition to sildenafil, or continue with sildenafil monotherapy. Patients aged 18 to 65 years who had World Health Organization functional class (WHO-FC) II to IV symptomatic PAH and a 6MWT of 150 to 450 meters at baseline who were receiving sildenafil monotherapy for 3 to 6 months were included in the study.

Follow-up at 12 weeks and 24 weeks included a 6MWT, WHO-FC assessment, and NT-proBNP analysis. The primary endpoint was improvement in the distance of the 6MWT. WHO-FC, NT-proBNP levels, hemodynamic parameters, and time to clinical worsening were the secondary endpoints.

At 12 weeks, patients treated with combination therapy demonstrated a mean 6MWT distance increase of 43.6 meters, as compared with 7.4 meters in the sildenafil monotherapy group (p=0.072). At 24 weeks, patients that received combination therapy had a mean 6MWT distance increase of 50.8 meters, as compared with 5.6 meters in the monotherapy arm (p=0.04).

A significant decrease in NT-proBNP levels was observed in the combination-therapy arm of 437 pg/mL at Week 12 and 399 pg/mL at Week 24, as compared with a 300-pg/mL increase at Week 12 (p<0.001) and a 46-pg/mL increase at Week 24 in the monotherapy arm (p<0.001). In addition, significantly more patients in the combination arm improved WHO-FC by at least one class, as compared with patients in the monotherapy arm (p=0.01). Event-free survival was significantly greater in the beraprost plus sildenafil group, as compared with the sildenafil monotherapy group (p=0.027).

Adverse events such as headache, diarrhea, nausea, dizziness, and jaw pain occurred significantly more frequently in the combination arm, as compared with the monotherapy arm. Flushing and extremity pain occurred with similar frequency among both study groups.

Prof. Jing said that, in his opinion, the BEST Study suggests that adding beraprost to sildenafil therapy in the treatment of PAH is effective and well tolerated, but should be further evaluated in additional studies.

• © 2013 MD Conference Express®