Safety and Efficacy of Transition From Subcutaneous Treprostinil to Oral Sildenafil in Patients With Pulmonary Arterial Hypertension

• Published in: The Journal of heart and lung transplantation Vol. 26; no. 11; pp. 1079 - 1083
• Main Authors: Keogh, Anne M., MBBS, MD, Jabbour, Andrew, MBBS(Hons), Weintraub, Robert, MBBS(Hons), Brown, Karen, Hayward, Chris S., MBBS, MD, Macdonald, Peter S., MBBS, PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.11.2007; Elsevier Science
• Subjects: Administration, Oral; Adult; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - adverse effects; Antihypertensive Agents - therapeutic use; Biological and medical sciences; Drug-Related Side Effects and Adverse Reactions; Epoprostenol - administration & dosage; Epoprostenol - adverse effects; Epoprostenol - analogs & derivatives; Epoprostenol - therapeutic use; Exercise Tolerance; Female; Humans; Hypertension, Pulmonary - drug therapy; Hypertension, Pulmonary - etiology; Hypertension, Pulmonary - physiopathology; Injections, Subcutaneous; Male; Medical sciences; Middle Aged; Piperazines - administration & dosage; Piperazines - adverse effects; Piperazines - therapeutic use; Pneumology; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; Purines - administration & dosage; Purines - adverse effects; Purines - therapeutic use; Quality of Life; Sildenafil Citrate; Sulfones - administration & dosage; Sulfones - adverse effects; Sulfones - therapeutic use; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart; Vasodilator Agents - administration & dosage; Vasodilator Agents - adverse effects; Vasodilator Agents - therapeutic use; Heart; Vasodilator agent; Prostaglandin I2; 3',5'-Cyclic-GMP phosphodiesterase; Toxicity; Cardiovascular disease; Esterases; Phosphoric diester hydrolases; Efficiency; Surgery; Treprostinil; Complication; Safety; Human; Enzyme; Respiratory disease; Subcutaneous; Oral administration; Enzyme inhibitor; Patient; Artery; Pulmonary hypertension; Phosphodiesterase inhibitor; Phosphodiesterase 5 inhibitor; Oral cavity; Treatment; Transition; Hydrolases; Sildenafil
• ISSN: 1053-2498; 1557-3117
• DOI: 10.1016/j.healun.2007.07.040

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.