Addition of sildenafil to bosentan monotherapy in pulmonary arterial hypertension

¹ Johns Hopkins University, Dept of Medicine, Division of Pulmonary and Critical Care Medicine
² Emory University, Dept of Medicine, Division of Pulmonary and Critical Care Medicine
³ Johns Hopkins University, Dept of Medicine, Division of Cardiology

^* To whom correspondence should be addressed. E-mail: phassoun{at}jhmi.edu.

	Abstract

Combination therapy has been recommended for the treatment of pulmonary arterial hypertension (PAH). However, there is scant information on combination therapy after failure of monotherapy, particularly in patients with scleroderma-associated PAH (PAH-SSD).

Among 82 consecutive patients with PAH who received initial bosentan monotherapy, 13 idiopathic PAH (IPAH) and 12 PAH-SSD patients requiring additional therapy with sildenafil were studied. Sildenafil was added for clinical deterioration based upon symptoms, New York Heart Association (NYHA) classification, or six minute walk distance (6MWD). Clinical data and hemodynamics were collected at baseline. Assessments were made at 1-3 month intervals.

At baseline, there were no differences in demographics, NYHA, hemodynamics, or 6MWD between the two groups. After initiation of bosentan, both groups experienced clinical improvement, but ultimately deteriorated (median time to monotherapy failure, 792 vs. 458 days, IPAH and PAH-SSD respectively, log-rank P=0.06). After addition of sildenafil, more IPAH patients tended to improve in NYHA class (5/13 vs. 2/12) and walked farther (mean difference in 6MWD, 47±77m vs. -7±40m, P=0.04) compared to PAH-SSD patients.

Addition of sildenafil after bosentan monotherapy failure improved NYHA and 6MWD in IPAH patients, but failed to improve either parameter in PAH-SSD patients. Additional studies are needed to assess the tolerability and efficacy of this combination in patients with PAH-SSD.

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