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THE ADDITION OF SILDENAFIL TO BOSENTAN THERAPY IN THE TREATMENT OF PULMONARY ARTERIAL HYPERTENSION FREE TO VIEW

Stephen C. Mathai, MD*; Micah R. Fisher, MD; Traci Housten-Harris, RN; Reda E. Girgis, MB, BCh; Paul M. Hassoun, MD
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Johns Hopkins University, Baltimore, MD


Chest


Chest. 2005;128(4_MeetingAbstracts):161S-b-162S. doi:10.1378/chest.128.4_MeetingAbstracts.161S-b
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Abstract

PURPOSE:  Pulmonary arterial hypertension (PAH) is a progressive disease that often results in right heart failure and death. Combination therapy targeting several pathways involved in the pathogenesis of pulmonary hypertension has been recommended. In this study, we review our experience with the addition of sildenafil to bosentan therapy in patients with PAH.

METHODS:  Eighteen patients with pulmonary hypertension (12 with PAH related to connective tissue disease, 4 with IPAH, 2 with PAH related to anorexigen use) who received combination therapy with bosentan and sildenafil between January 2002 and April 2005 were included. Bosentan was used as first-line therapy. Sildenafil was added for clinical deterioration based upon symptoms, New York Heart Association (NYHA) assessment, and/or deterioration in six minute walk distance (6MWD). Demographics, clinical data, and hemodynamic data were collected at baseline; clinical data were again collected just prior to adding sildenafil and 1-3 months after starting sildenafil.

RESULTS:  Of 18 patients in whom sildenafil was added to bosentan therapy, 4 (22.2%) discontinued therapy due to side effects. One patient died from complications related to progressive right heart failure. Five patients required additional therapy due to disease progression. Prior to starting bosentan therapy, the mean 6MWD was 281.5±115.2m. The mean 6MWD after initiation of sildenafil improved significantly compared to 6MWD prior to initiation (223.6±106.5m vs. 307.6±122.5m, p=0.04). The proportion of patients who were considered NYHA class I or II after the addition of sildenafil therapy versus prior to initiation also increased significantly (0% vs. 27.7%, p = 0.02).

CONCLUSION:  Overall, the addition of sildenafil to bosentan therapy improved NYHA class and functional capacity assessed by 6MWD in this group of patients with pulmonary arterial hypertension. However, a significant proportion of patients had to discontinue sildenafil due to adverse effects or required escalation in therapy due to clinical deterioration.

CLINICAL IMPLICATIONS:  Addition of sildenafil to bosentan therapy may be of benefit in patients with pulmonary arterial hypertension. Long-term follow-up is needed to ascertain the clinical efficacy and tolerability of this combination of therapies.

DISCLOSURE:  Stephen Mathai, None.

Monday, October 31, 2005

2:30 PM - 4:00 PM


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