Outcome of patients with primary pulmonary hypertension after listing for transplantation: benefits of therapy with iloprost and bosentan

Advances in medical treatment for primary pulmonary hypertension (PPH) have improved both short- and long-term outcome of patients. However, for end-stage PPH there is controversy about long-term efficiency of this treatment and its reliability for patient withdrawal from the list for lung or heart-lung transplantation (Tx). We evaluated the benefits and safety of iloprost (prostacyclin analog) and bosentan (endothelin-receptor antagonist) in patients with end-stage PPH before and after Tx-listing.

Methods: We evaluated all end-stage PPH patients (NYHA class: late III-IV) referred between 1/1996 and 6/2004 for Tx-listing. Attention was focused on hemodynamic testing, medical treatment, and survival without Tx.

Results: Of 54 PPH patients referred for Tx-listing, 23 (42,6%) died before Tx (during 4,2±3,9 months), whereas the 5-year post-Tx survival reached 50±9%. Mortality on the Tx-list was lower in responders to hemodynamic testing treated with iloprost and/or bosentan (p<0,01). In the conventionally treated group (n=15) pre-transplant mortality reached 60,0%; in those treated with iloprost and/or bosentan (n=39) it was 35,9%. After Tx-listing, none of those treated without iloprost or bosentan survived >12,7 months without Tx (median survival without Tx 3,1 months). Among 19 patients treated with iloprost or bosentan who were not/not yet transplanted, 14 (73,7%) died on Tx-list (4,5±3,4 months after listing), one could be withdrawn from Tx-listing and four are still alive 10–30 months after listing.

Conclusions: Iloprost and bosentan are effective bridge-to-transplant therapy options. However, in end-stage PPH, neither bosentan nor iloprost allow reliable patient withdrawal from the Tx-list and thus Tx remains the best therapeutic option.