Combination Therapy With Oral Sildenafil and Beraprost for Pulmonary Arterial Hypertension Associated With CREST Syndrome

Abstract

SUMMARYPulmonary arterial hypertension (PAH) is commonly associated with CREST (Calcinosis, Raynaud phenomenon, Esophageal motility disorders, Sclerodactyly, and Telangiectasia) syndrome. Sildenafil, an oral phosphodiesterase type-5 inhibitor, may offer benefits in the pharmacological management of PAH. However, little is known about the long-term hemodynamic effects of sildenafil, and the potential role of sildenafil in longterm combination with beraprost, an oral prostacyclin analogue, remains unclear. We therefore examined the hemodynamic effect of oral sildenafil alone and when coadministered with beraprost in a patient with PAH associated with CREST syndrome.Traces of the acute hemodynamic effects of beraprost (20 µg) disappeared after 2 hours. In contrast, the acute hemodynamic effects of sildenafil (50 mg) produced a greater reduction in PAP (31%) and PVR (40%), and these effects also disappeared after 5 hours.After 1 month of combination therapy of sildenafil (25 mg) twice daily and beraprost (20 µg) 3 times daily, the fall in pulmonary artery pressure and pulmonary vascular resistance was sustained (31% in both). Furthermore, the patient had significantly improved her 3-minute walk test and NYHA function class without significant adverse effects at the reported doses. The findings indicate that oral sildenafil is a potent pulmonary vasodilator that appears to act synergistically with oral beraprost to cause sustained pulmonary vasodilatation in a patient with PAH associated with CREST syndrome. (Int Heart J 2007; 48: 417-422) Key words: Pulmonary artery hypertension, CREST syndrome, Sildenafil, Beraprost PULMONARY artery hypertension (PAH) is a life-threatening disease characterized by progressive pulmonary hypertension that leads to right ventricular failure and death. 1) PAH comprises idiopathic PAH and PAH in the setting of collagen disease (eg, in localized cutaneous systemic sclerosis, also known as the From the

Dual therapy in IPAH and SSc-PAH. A qualitative systematic review

“…30 Six studies reported haemodynamics (PAP and/or PVR) as outcomes, all of which demonstrated a beneficial effect with dual therapy. 20,28,29,31,33,36 None of the studies reported quality of life as an outcome. Both randomized trials demonstrated improvement in 6MWD, 37,38 and one trial demonstrated improvement in quality of life and time-to-clinical worsening.…”

Efficacy of Oral Sildenafil in a Beraprost-Treated Patient With Severe Pulmonary Hypertension Secondary to Type I Glycogen Storage Disease

“…Because combined therapy of BPS and sildenafil has recently been reported as effective in ameliorating PAH in rats 21 and patients, 22 these drugs may inhibit the development of pulmonary hypertension additively and synergistically. Furthermore, in a patient with PAH secondary to collagen disease combination therapy with BPS and sildenafil was efficacious, 23 and may be also effective in such patients with secondary PAH.…”

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“…PAH associated with CVD is most commonly observed in systemic sclerosis, mixed connective tissue disease (Figure 3). This patient group is related to interstitial fibrosis, which is most commonly manifested histologically as nonspecific interstitial pneumonia [11], pulmonary vascular disease, or both. A study of PH in 722 patients with systemic sclerosis in the United Kingdom showed a prevalence of approximately 12%, and more than 10% of patients with severe PAH have an associated connective tissue disease, such as mixed connective tissue disease, polymyositis, dermatomyositis, and systemic lupus erythematosus [12].…”