Advertisement

Long-Term Pulmonary Hemodynamic Effects of Ambrisentan in Pulmonary Arterial Hypertension

      The long-term effects of endothelin receptor antagonists on pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) in patients with pulmonary arterial hypertension (PAH) are not well studied. This post hoc analysis examined changes in pulmonary hemodynamics in a cohort of patients with PAH who underwent follow-up right heart catheterization (RHC) in a long-term ambrisentan study (ARIES-E). A retrospective review was conducted of patients who underwent RHC after >3 months of ambrisentan therapy. Changes from baseline in mean PAP, mean right atrial pressure, cardiac index, and PVR were assessed and correlations between these hemodynamic changes and exercise capacity were examined. Sixty-eight patients who received ambrisentan in the ARIES studies had ≥1 follow-up RHC while receiving ambrisentan. Fifty-eight patients were on ambrisentan alone at the time of the first RHC. Median time from initiation of ambrisentan therapy to follow-up RHC was 60 weeks (range 14 to 158). Significant improvements compared to baseline were observed for mean PAP (−7.6 mm Hg, 95% confidence interval [CI] −10.0 to −5.1), PVR (−266 dyne × s/cm5, 95% CI −350 to −180), and cardiac index (0.4 L/min/m2, 95% CI 0.2 to 0.6 L/min/m2); for patients on ambrisentan alone, changes in mean PAP and PVR were inversely correlated with change from baseline 6-minute walking distance (r = −0.41 and −0.43, respectively, p <0.001 for the 2 comparisons) at time of follow-up RHC. In conclusion, ambrisentan may provide sustained improvements in pulmonary hemodynamics in patients with PAH who receive long-term treatment and these changes correlate with improvements in exercise capacity.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Galiè N.
        • Olschewski H.
        • Oudiz R.J.
        • Torres F.
        • Frost A.
        • Ghofrani H.A.
        • Badesch D.B.
        • McGoon M.D.
        • McLaughlin V.V.
        • Roecker E.B.
        • Gerber M.J.
        • Dufton C.
        • Wiens B.L.
        • Rubin L.J.
        • Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy Studies (ARIES) Group
        Ambrisentan for the treatment of pulmonary arterial hypertension: results of the Ambrisentan in Pulmonary Arterial Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy (ARIES) study 1 and 2.
        Circulation. 2008; 117: 3010-3019
        • Galié N.
        • Badesch D.
        • Oudiz R.
        • Simonneau G.
        • McGoon M.D.
        • Keogh A.M.
        • Frost A.E.
        • Zwicke D.
        • Naeije R.
        • Shapiro S.
        • Olschewski H.
        • Rubin L.J.
        Ambrisentan therapy for pulmonary arterial hypertension.
        J Am Coll Cardiol. 2005; 46: 529-535
        • Oudiz R.J.
        • Galiè N.
        • Olschewski H.
        • Torres F.
        • Frost A.
        • Ghofrani H.A.
        • Badesch D.B.
        • McGoon M.D.
        • McLaughlin V.V.
        • Roecker E.B.
        • Harrison B.C.
        • Despain D.
        • Dufton C.
        • Rubin L.J.
        • ARIES Study Group
        Long-term ambrisentan therapy for the treatment of pulmonary arterial hypertension.
        J Am Coll Cardiol. 2009; 54: 1971-1981
        • Barst R.J.
        • Rubin L.J.
        • Long W.A.
        • McGoon M.D.
        • Rich S.
        • Badesch D.B.
        • Groves B.M.
        • Tapson V.F.
        • Bourge R.C.
        • Brundage B.H.
        • Koerner S.K.
        • Langleben D.
        • Keller C.A.
        • Murali S.
        • Uretsky B.F.
        • Clayton L.M.
        • Jöbsis M.M.
        • Blackburn Jr, S.D.
        • Shortino D.
        • Crow J.W.
        • The Primary Pulmonary Hypertension Study Group
        A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension.
        N Engl J Med. 1996; 334: 296-302
        • Channick R.N.
        • Simonneau G.
        • Sitbon O.
        • Robbins I.M.
        • Frost A.
        • Tapson V.F.
        • Badesch D.B.
        • Roux S.
        • Rainisio M.
        • Bodin F.
        • Rubin L.J.
        Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study.
        Lancet. 2001; 358: 1119-1123
        • Galiè N.
        • Ghofrani H.A.
        • Torbicki A.
        • Barst R.J.
        • Rubin L.J.
        • Badesch D.
        • Fleming T.
        • Parpia T.
        • Burgess G.
        • Branzi A.
        • Grimminger F.
        • Kurzyna M.
        • Simonneau G.
        • Sildenafil Use in Pulmonary Arterial Hypertension (SUPER) Study Group
        Sildenafil citrate therapy for pulmonary arterial hypertension.
        N Engl J Med. 2005; 353: 2148-2157
        • Badesch D.B.
        • Champion H.C.
        • Sanchez M.A.
        • Hoeper M.M.
        • Loyd J.E.
        • Manes A.
        • McGoon M.
        • Naeije R.
        • Olschewski H.
        • Oudiz R.J.
        • Torbicki A.
        Diagnosis and assessment of pulmonary arterial hypertension.
        J Am Coll Cardiol. 2009; 54: S55-S66
        • Fisher M.R.
        • Forfia P.R.
        • Chamera E.
        • Housten-Harris T.
        • Champion H.C.
        • Girgis R.E.
        • Corretti M.C.
        • Hassoun P.M.
        Accuracy of Doppler echocardiography in the hemodynamic assessment of pulmonary hypertension.
        Am J Respir Crit Care Med. 2009; 179: 615-621
        • Sitbon O.
        • Badesch D.B.
        • Channick R.N.
        • Frost A.
        • Robbins I.M.
        • Simonneau G.
        • Tapson V.F.
        • Rubin L.J.
        Effects of the dual endothelin receptor antagonist bosentan in patients with pulmonary arterial hypertension: a 1-year follow-up study.
        Chest. 2003; 124: 247-254
        • Langleben D.
        • Hirsch A.M.
        • Shalit E.
        • Lesenko L.
        • Barst R.J.
        Sustained symptomatic, functional, and hemodynamic benefit with the selective endothelin-A receptor antagonist, sitaxsentan, in patients with pulmonary arterial hypertension: a 1-year follow-up study.
        Chest. 2004; 126: 1377-1381
        • Provencher S.
        • Sitbon O.
        • Humbert M.
        • Cabrol S.
        • Jaïs X.
        • Simonneau G.
        Long-term outcome with first-line bosentan therapy in idiopathic pulmonary arterial hypertension.
        Eur Heart J. 2006; 27: 589-595
        • Galiè N.
        • Brundage B.H.
        • Ghofrani H.A.
        • Oudiz R.J.
        • Simonneau G.
        • Safdar Z.
        • Shapiro S.
        • White R.J.
        • Chan M.
        • Beardsworth A.
        • Frumkin L.
        • Barst R.J.
        • Pulmonary Arterial hypertension and Response to Tadalafil (PHIRST) Study Group
        Tadalafil therapy for pulmonary arterial hypertension.
        Circulation. 2009; 119: 2894-2903