Conference: 2011 PH Professional Network Symposium
Release Date: 09.22.2011
Presentation Type: Abstracts
Shelley Shapiro, MD, PhD 1, Glenna Traiger, RN, MSN, CNS-BC 1, Wendy Hill, RN, NP, MSN 1, Lixia Zhang, MStat 2, Aimee K Doran, MS, RN, CPNP 2
1. Greater Los Angeles VA Healthcare System and David Geffen School of Medicine at UCLA, Los Angeles CA
2. United Therapeutics Corporation, Research Triangle Park, NC
PURPOSE: The purpose of this retrospective study was to evaluate the safety and tolerability of transitioning pulmonary arterial hypertension (PAH) patients stable on sildenafil to tadalafil. This was assessed by adverse events (AEs), exercise capacity (6MWD), and the number of patients who were successfully transitioned.
BACKGROUND: PDE-5 inhibitors have been used to treat PAH since the approval of sildenafil in 2005. The approved dose of sildenafil is 20 mg TID, however, many patients require doses of 80-100 mg TID. This can result in patients taking 12-15 pills per day at substantial cost and inconvenience. Following approval of tadalafil in 2009, patients receiving sildenafil were switched to tadalafil at the time of insurance reauthorization or clinic visit to mitigate access, cost, and adherence issues.
METHODS: Retrospective chart reviews were conducted on all patients who were stable on sildenafil for at least three months before transition to tadalafil. Only patients with documented clinic visits and 6 minute walk tests on both drugs were selected. The study period was January 2009 to March 2011. Data collected included: demographics, etiology of PAH, diagnostic hemodynamics, 6 minute walk distance (6MWD) with Borg scale, PAH symptoms, PDE-5 inhibitor side effects, and concomitant medications. BNP levels were collected on patients also receiving endothelin receptor antagonists (ERAs) as part of their required monthly labs. Tadalafil dose reductions or discontinuations were noted. All patients were transitioned by discontinuing sildenafil after the evening dose and initiating tadalafil the next day.
RESULTS: One hundred-six patients (mean age 52 years, range 21-90) were evaluated; 98 patients were WHO Group 1 (45 idiopathic or heritable) and 8 patients were non-WHO Group 1. The mean pulmonary artery pressure at the time of diagnosis was 52 ± 17 mmHg. Seventy-six percent were receiving sildenafil 80-100mg TID. Concomitant PAH medications included parenteral or inhaled prostanoids, and ERAs. Thirty-four percent of patients were receiving monotherapy with sildenafil, 31% in combination with an ERA, 16% in combination with an inhaled or parenteral prostanoid, and 19% on triple drug therapy. Sixty percent of patients were on PPI-H2 blockers at the time of transition. Ninety-seven patients (92%) were able to transition to and maintain 40mg of tadalafil QD. There was no significant change in 6MWD with median time after transition 223 days. Seventy-six percent of patients had no change in 6MWD, 15% had increase of ≥15% and 9% had decrease of ≥15%. There was no significant change in BNP in the group of patients also receiving ERAs. Six patients discontinued tadalafil during the study period. One patient discontinued after undergoing pulmonary thromboembolectomy and two patients transitioned back to sildenafil (one for headache and myalgia and one for personal preference). Three deaths in the study group were unrelated to the transition; one patient awaiting lung transplant, one end stage PAH, and one after complications following gallbladder surgery. There was no difference in change in 6MWD between sildenafil doses (20 mg, 40-60mg or 80-100 mg TID). Headache was the most frequently observed AE occurring in 5 (4.7%) patients.
CONCLUSION: In this clinically treated group of PAH patients, transitioning from sildenafil to tadalafil 40 mg daily appears feasible without clinical deterioration or intolerable side effects.
CLINICAL IMPLICATIONS: This study provides guidance to physicians considering transition from sildenafil to tadalafil for select patients.
DISCLOSURES: SS is a consultant for United Therapeutics, Gilead, GT and WH are consultants for United Therapeutics, Gilead and Actelion. AD and LZ are employees of United Therapeutics.