Safety and efficacy of transition from subcutaneous treprostinil to oral sildenafil in patients with pulmonary arterial hypertension.
BACKGROUND
Sildenafil is a selective inhibitor of phosphodiesterase type 5 (PDE5), and has been shown to improve 6-minute walk distance (SMWD) and World Health Organization (WHO) functional class in patients with idiopathic pulmonary arterial hypertension (iPAH) and PAH associated with connective tissue disease or with repaired congenital systemic-to-pulmonary shunts. Despite the efficacy of sildenafil in patients on conventional therapy with diuretics and anti-coagulants, little is known of the safety and efficacy of transitioning patients already established on parenteral prostanoid therapy to sildenafil.


METHODS
We studied 14 patients on long-term subcutaneous treprostinil for PAH (from a cohort of 51 patients [27%]), who wished to discontinue treatment because of injection-site pain. The etiology of their PAH included iPAH (7 of 14), PAH secondary to scleroderma (2 of 14), thromboembolic disease (3 of 14) and PAH post-surgical correction of ventricular septal defect (2 of 14). Treprostinil was gradually weaned and all patients were started open-label with 50 mg sildenafil four times per day for 3 months. New York Heart Association (NYHA) functional class, SMWD, echocardiogram and quality-of-life (QOL) measures were determined at baseline and after 3 months of therapy with sildenafil.


RESULTS
Of 14 patients, 4 discontinued the transition because of deterioration during treprostinil withdrawal, despite the introduction of sildenafil. Replacement of chronic subcutaneous treprostinil with sildenafil was possible in 10 of 14 patients (71%), who demonstrated stable NYHA class (mean +/- SD: 3.1 +/- 0.3 at baseline to 2.6 +/- 0.8 at 3 months, p = 0.138), stable SMWD (434 +/- 83 m at baseline, 451 +/- 72 at 3 months, p = 0.23) and significantly improved QOL measures at 3 months.


CONCLUSIONS
The transition from subcutaneous treprostinil to sildenafil was safely achieved in most (71%), but not all, patients with pulmonary arterial hypertension of varied etiology. These patients had an improvement in both NYHA functional class and QOL, and maintained stable walk distances over a 3-month period on sildenafil therapy.
Keogh
Anne M
AM
Heart Lung Transplant Unit, St Vincent's Hospital, Sydney, Australia.
Jabbour
Andrew
A
Weintraub
Robert
R
Brown
Karen
K
Hayward
Chris S
CS
Macdonald
Peter S
PS
D000284:Administration, Oral; D000328:Adult; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D064420:Drug-Related Side Effects and Adverse Reactions; D011464:Epoprostenol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017079:Exercise Tolerance; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011687:Purines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011788:Quality of Life; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D011464:Epoprostenol; C427248:treprostinil