Withdrawal of long‐term epoprostenol therapy in pulmonary arterial hypertension (PAH)

Abstract

Once initiated for pulmonary arterial hypertension (PAH), epoprostenol treatment usually needs to be delivered for an indefinite duration. It is possible that some participants could be transitioned from epoprostenol to oral therapies. We retrospectively evaluated eight PAH participants transitioned from epoprostenol to PAH oral drugs. The criteria for epoprostenol withdrawal were: (1) persistent improvement of clinic and hemodynamic status; (2) stable dose of epoprostenol for the last three months; and (3) the participant’s preference for oral therapy after evaluation of risk-benefit. We evaluated the clinical, functional, and hemodynamic status at baseline, at withdrawal, and after the transition to oral PAH therapy. The transition was completed in all eight participants. Four participants had a complete successful transition (CT) with a stable clinical and hemodynamic course and four participants had a partial successful transition (PT) remaining stable clinically, with a mild hemodynamic worsening, but without need to re-initiate epoprostenol therapy. The four CT participants were treated with epoprostenol for a shorter period of time (CT group: 35 ± 30 versus PT group: 79 ± 49 months, P = 0.08). Mean epoprostenol dosage was lower in the CT group (CT group: 15 ± 1.5 ng/kg/min versus PT group: 24 ± 11 ng/kg/min, P = 0.09). Safe withdrawal of epoprostenol treatment and transition to oral PAH therapy was possible in a small and highly selected group of participants. The majority of these participants had a porto-pulmonary PAH or PAH associated to HIV infection.

Pause at Your Own Peril: A Case Series on Rebound Pulmonary Hypertension

“…These include the PGI2 analogs and PGI2 IP receptor agonist, selexipag [5]. The rapid discontinuation of this medication has catastrophic consequences, including rapid right heart failure and cardiogenic shock [2][3][4]. The potency of prostacyclin medications is the reason for the aggressive withdrawal symptoms.…”

“…Despite being such a detrimental disease, pharmaceuticals have improved patient symptoms, quality of life, and survival. The abrupt disruption of these medications can result in rebound pulmonary hypertension, right heart failure, and cardiogenic shock [2][3][4]. Although PAH literature has increased over the years, there is little data about rebound PAH after the brief discontinuation of medications and how to restart them.…”

Transitioning Stable Patients with Pulmonary Arterial Hypertension from Parenteral Prostanoids to Oral Selexipag

“…First, hemodynamics obtained during the transition were not very useful in predicting later hemodynamic results. It therefore seems plausible that some benefits from parenteral prostacyclin may continue for weeks or months following dose decrease or discontinuation [ 28 , 29 ]. The reverse has previously been shown during epoprostenol initiation, where the acute hemodynamic changes have failed to predict long-term hemodynamic response [ 30 ].…”

Epoprostenol discontinuation in patients with pulmonary arterial hypertension: a complex medical and social problem

“…In a recent retrospective study, epoprostenol withdrawal was done in eight patients with PAH (mainly portopulmonary PAH and PAH associated with HIV) based on the patient’s request (and not because of major side effects). 7 These patients had persistent improvement of clinical and hemodynamic status (NYHA class I or II, CI > 2.5 L/min/m 2 , stable dose of epoprostenol over the last three months, and lower mPAP and PVR). All patients completed the transition; half of them experienced mild hemodynamic deterioration without the need to reinitiate epoprostenol.…”