Differential response to intravenous prostacyclin analog therapy in patients with pulmonary arterial hypertension.
BACKGROUND
Treprostinil is an intravenous prostacyclin analog approved for the treatment of pulmonary arterial hypertension (PAH). Few studies have compared the pharmacodynamics and effectiveness of treprostinil and epoprostenol in patients with high-risk PAH.


METHODS
Case series of patients with PAH admitted to a Medical Intensive Care Unit for transition from epoprostenol to intravenous treprostinil for refractory class III-IV functional symptoms or right heart failure. Mixed linear models were used for comparisons between repeated hemodynamic measurements.


RESULTS
Five of fourteen patients treated with intravenous treprostinil during the study period underwent transition to epoprostenol. Two had PAH associated with systemic sclerosis, three had idiopathic PAH. Pulmonary arterial pressures (PAP) and pulmonary vascular resistance significantly increased within 1 h after discontinuation of treprostinil in all subjects. Mean PAPs immediately prior to discontinuation of treprostinil (53.4 ± 7.5 mmHg) were significantly lower than the values 1 h after discontinuation (63.6 ± 9.6 mmHg, p = 0.026), but were significantly higher than the values following transition to epoprostenol (45.4 ± 5.5, p = 0.0493); 4/5 subjects had short-term clinical follow-up data available; all improved in functional class. No subject experienced adverse events during the transition.


CONCLUSIONS
High-risk PAH patients with an inadequate response to treprostinil may have significant clinical and hemodynamic response to epoprostenol. Following discontinuation of treprostinil in these patients, the hemodynamic effects of discontinuation were seen in substantially shorter time than what is known to be the pharmacokinetic terminal half-life.
The Pulmonary Center, Boston University School of Medicine, 715 Albany Street, R-304, Boston, MA 02118-2394, USA. allan.walkey@bmc.org
Allan J
AJ
Walkey
Daniel
D
Fein
Kevin J
KJ
Horbowicz
Harrison W
HW
Farber
D000328:Adult; D000368:Aged; D011464:Epoprostenol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged
D011464:Epoprostenol; C427248:treprostinil