PURPOSE:Purpose: Edema and fluid retention are often observed in patients with pulmonary arterial hypertension (PAH) due to disease progression/heart failure, dietary indiscretion and medication noncompliance and is also a side effect of endothelin receptor antagonists (ERAs). Ambrisentan (ABS) is an ETA-selective ERA approved for the treatment of PAH. We examined data from ARIES-1 and ARIES-2 to identify patients at risk for edema and to explore clinical outcomes for patients experiencing edema.
METHODS:Methods: A post-hoc analysis of 132 patients who received placebo and 261 patients who received ABS in the ARIES study was performed. Any adverse events related to edema/fluid retention (eAEs) were included.
RESULTS:Results: A total of 19 (14%) PLB and 61 (23%) ABS patients reported eAEs, of which 3 (2.3%) PLB and 2 (0.8%) ABS patients discontinued treatment early due to eAEs. PLB patients reporting eAEs were more likely to be WHO class III/IV at baseline compared to PLB patients not reporting eAE. ABS patients reporting eAEs were older, had higher BMI, and were more likely to be WHO class III/IV at baseline compared to ABS patients not reporting eAEs. Mean (±SEM) 6-minute walk distance (6MWD) decreased 8.9±7.5 meters from baseline at week 12 for all PLB patients; whereas 6MWD increased 19.7±6.4 meters for ABS patients reporting eAEs (+28.6 meters; 95% CI: 4.7 to 52.0). B-type natriuretic peptide (BNP) increased 11% (95% CI: -6% to 31%) from baseline at week 12 for all PLB patients; whereas BNP decreased 28% (95% CI: -42% to 10%) for ABS patients reporting eAEs.
CONCLUSION:Conclusions: Nearly all ABS patients who reported eAEs continued therapy. Improvements in 6MWD and BNP were observed in these patients compared to PLB patients.
CLINICAL IMPLICATIONS:Edema is associated with all ERAs and may be more likely to be reported in patients who are older, have a higher BMI, and more advanced WHO class. It is a manageable side-effect and patients with PAH who experience edema on ambrisentan may still derive significant clinical benefit.
DISCLOSURE:Shelley Shapiro, Employee Gilead Sciences; No Product/Research Disclosure Information