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A Multicenter, Retrospective Study of Patients with Pulmonary Arterial Hypertension Transitioned from Parenteral Prostacyclin Therapy to Inhaled Iloprost

Richard Channick


Robert Frantz


Steven Kawut


Harold Palevsky

R. Tumuluri

Roxana Sulica


Paula Lauto

W. Benton

B. deBoisblanc

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Conference: 2011 PH Professional Network Symposium

Release Date: 09.22.2011

Presentation Type: Abstracts

R. Channick, MD1; R. Frantz, MD2; S. Kawut, MD, MS3; H. Palevsky, MD3; R. Tumuluri, MD4; R. Sulica, MD5; P. Lauto, RN, BSN, CCRN7; W. Benton, PharmD6; B. deBoisblanc, MD7
1. Massachusetts General Hospital, Boston, MA
2. College of Medicine, Mayo Clinic, Rochester, MN
3. University of Pennsylvania School of Medicine, Philadelphia, PA
4. St. Luke's Medical Center, Milwaukee, WI
5. Beth Israel Medical Center, New York, NY
6. Actelion Pharmaceuticals US, Inc., South San Francisco, CA
7. Louisiana State University Health Science Center/Ochsner Clinic Foundation, New Orleans, LA.

PURPOSE: The profile of patients who are transitioned from parenteral prostacyclin analog therapy to inhaled iloprost is unknown. We aimed to study the characteristics of patients who attempted to transition to inhaled therapy.

METHODS: We performed a retrospective cohort study of adults with pulmonary arterial hypertension (PAH) who were treated with intravenous (IV) or subcutaneous (SC) prostacyclin analogs from 11 centers. Transition Day 1 was defined as the first day of inhaled iloprost therapy. Post-Transition Day 1 was defined as the first day of inhaled iloprost free of parenteral prostacyclin therapy. Outcomes evaluated included patient- and drug-related parameters, reason for transition, and duration of persistence. Persistence was defined as remaining parenteral prostacyclin therapy-free and maintaining inhaled iloprost therapy for at least ninety days post-transition. Patients without events were censored at one year.

RESULTS: Thirty-seven eligible subjects were identified; 70.3% were female, mean±SD age was 46.5±13.4 years, duration of PAH was 4.6±4.4 years, and 6-minute walk test distance was 400.5±117.8 m. All patients transitioned were judged clinically stable prior to initiating transition to inhaled iloprost. Last mean±SD stable dose of parenteral prostacyclin pre-transition was IV epoprostenol 17.2±7.7 ng/kg/min, SC treprostinil 30.1±17.7 ng/kg/min, and IV treprostinil 38.0±37.8 ng/kg/min. In total, 29/37 (78.4%) patients remained persistent at 1 year and 97.3% survived to 1 year. PAH-related oral medication usage during transition (from Transition Day 1 to Post-Transition Day 0) included sildenafil, 51.4%; bosentan, 43.2%; calcium channel blockers, 8.1%; and ambrisentan, 2.7%. The mean±SD length of the transition period was 10.5±13.9 days. A transition dosing algorithm was used in 10 (27.0%) patients. Seven patients achieved clinical improvement prior to transition, and all patients were transitioned successfully. Post-transition, seven patients (18.9%) experienced clinical worsening. The majority of persistent patients (26/29) received oral endothelin receptor antagonist (ERA) or phosphodiesterase-5 (PDE-5) inhibitor therapy during transition, the most common being bosentan, sildenafil, or a combination of the two. Cox proportional hazards analysis showed that patients receiving PAH-related oral therapies (ERA, PDE-5 inhibitor or any oral) demonstrated a reduced risk of non-persistence versus no oral therapy.

CONCLUSIONS: In selected patients, transitioning from parenteral prostacyclin to inhaled iloprost appears safe and feasible, with a high rate of long-term success. Concomitant use of oral drugs appears to play an important role in persistence. Further study is needed to define selection criteria and, potentially, develop a transition algorithm.