PURPOSE: B-type natriuretic peptide (BNP) has been proposed as a prognostic indicator of mortality in patients with pulmonary arterial hypertension (PAH) and reductions in BNP have been shown to parallel improvements in hemodynamics and 6-minute walk distance (6MWD) in patients with PAH. Ambrisentan is an ETA-selective endothelin receptor antagonist that has been shown to improve 6MWD in the two Phase 3 placebo-controlled studies (ARIES-1 and ARIES-2).
METHODS: In these studies, 393 patients with idiopathic PAH or PAH associated with connective tissue disease, anorexigen use or HIV infection received placebo, 2.5, 5, or 10 mg ambrisentan for 12 weeks. Post-hoc analyses are presented for 330 patients with BNP data prior to first dose and at the end of the study: placebo (n=105); ambrisentan (n=225).
RESULTS: At baseline, mean plasma BNP was similar for the placebo and ambrisentan treatment groups (range: 254.4 to 259.2 pg/mL). At week 12, plasma BNP decreased from baseline in the ambrisentan group (-34.2%; 95% CI: -42.3% to -25.0%; p<0.001), but increased in the placebo group (+17.8%; 95% CI: -0.5% to 39.3%; p=0.056). This change was greater for the ambrisentan group compared to placebo (p<0.001). A substantial decrease in BNP was observed at week 12 for patients with a ≥10% increase from baseline 6MWD (-37.2%; 95% CI: -46.8% to -25.9%; p<0.001); whereas little change was observed for patients with a <10% increase from baseline 6MWD (-5.6%; 95% CI: -17.6% to 8.1%; p=0.410). A substantial decrease in BNP was observed at week 12 for patients with WHO functional class improvement (-42.2%; 95% CI: -53.8% to -27.7%; p<0.001); whereas only a slight decrease was observed for patients with no WHO functional class improvement (-13.1%; 95% CI: -22.9% to -1.8%; p=0.023).
CONCLUSION: Ambrisentan therapy resulted in a decrease in plasma BNP concentrations compared to placebo. Decreases in plasma BNP were associated with improvements in 6MWD and WHO class.
CLINICAL IMPLICATIONS: Change in plasma BNP concentration may provide additional information to assess response to therapy in patients with PAH.
DISCLOSURE: Nazzareno Galie, Other Dr. Galie’ has served on the advisory boards of Pfizer, Actelion, Schering, Encysive, Myogen and Mondobiotech and has been paid lecture fees by Actelion and Schering. He has received grant support from Pfizer, Actelion, Schering, Encysive and Myogen; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. ambrisentan