Addition of Oral Sildenafil to Beraprost Is a Safe and Effective Therapeutic Option for Patients with Pulmonary Hypertension

Ikeda, Daisuke; Tsujino, Ichizo; Ohira, Hiroshi; Itoh, Naofumi; Kamigaki, Mitsunori; Ishimaru, Shin’ichi; Sakaue, Shinji; Nishimura, Masaharu

doi:10.1097/01.fjc.0000155386.49103.ce

Cited by 40 publications

(19 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, Ikeda, et al 14) reported that the addition of oral sildenafil to bera-prost for patients with pulmonary hypertension represents a safe and effective treatment in the acute phase. However, the effects of long-term use in chronic cases remain unclear.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2007

View full text Add to dashboard Cite

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

show abstract

Section: Discussionmentioning

confidence: 99%

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

et al. 2007

View full text Add to dashboard Cite

show abstract

“…BPS increases cyclic adenosine monophosphate, whereas sildenafil inhibits the degradation of cGMP. 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.…”

Section: Discussionmentioning

confidence: 99%

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

Ueno

Murakami

Takeda

et al. 2009

Circ J

View full text Add to dashboard Cite

ype Ia glycogen storage disease (GSD) is an autosomal recessive disorder caused by glucose-6-phosphatase deficiency and it is the best-known form of glycogenosis. In type Ia GSD, the liver, kidney, and intestinal mucosa are damaged by storage of excessive amounts of glycogen, 1 and pulmonary arterial hypertension (PAH) is a rare and severe complication. Several cases complicated by PAH have been reported, and the outcomes were poor. [2][3][4][5] Histological examination of the lung demonstrated pulmonary hypertensive arteriopathy indistinguishable from classical primary pulmonary hypertension. 2,3 PAH is a disease with a poor prognosis and is characterized by progressive elevation of pulmonary vascular resistance, ultimately leading to right ventricular failure and death. 6 Since the 1990 s continuous intravenous infusion of prostacyclin (PGI2) has been administered to improve PAH. 7,8 The oral PGI2 analog, beraprost sodium (BPS), has been reported as effective against PAH in animal models 9 and human patients. 10 Another new treatment for PAH is oral sildenafil, a phosphodiesterase-5 (PDE-5) inhibitor approved for erectile dysfunction. Cyclic guanosine monophosphate (cGMP) has a vasodilating action, but a short life because of rapid degradation by PDE-5, which is abundantly expressed in lung tissue. Sildenafil inhibits PDE-5 and causes nitric oxide-mediated pulmonary vasodilation by promoting an increased and sustained level of cGMP. 11 Recent studies suggest that sildenafil is effective against PAH. 12 We report a patient with PAH secondary to type Ia GSD who was treated with BPS and sildenafil in whom the combination therapy was effective in ameliorating pulmonary hypertension. Case ReportA 17-year-old Japanese boy diagnosed with type Ia GSD was admitted to our institution because of shortness of breath and easy fatigability. His sister had also been diagnosed with type Ia GSD. The patient was found to have hepatomegaly at 1 year of age and was diagnosed based on the results of glucagon challenge tests. Because of poor compliance with cornstarch therapy, the manifestations of GSD (ie, short stature, hypercholesterolemia, liver dysfunction) did not improve much. Although electrocardiography (ECG) and echocardiography at 15 years of age showed normal findings, the patient complained of chest pain when he was admitted. ECG showed right ventricular hypertrophy, his cardiac condition was New York Heart Association (NYHA) IV and the B-type natriuretic peptide (BNP) concentration was 391.0 pg/ml. Echocardiographic examination showed significant elevation of the right ventricular pressure (RVp) and decreased cardiac output. The pressure gradient between the right ventricle (RV) and right atrium (RA) calculated from the tricuspid regurgitation velocity using the simplified Bernoulli equation was 92 mmHg, and the cardiac index (CI) calculated as the area of the left ventricular outflow × Doppler time-velocity integral 13 was 2.2 L · min -1 · m -2 . Based on these findings, he was diagnosed with PAH secondary to GSD. Be...

show abstract

“…However, smaller studies provide evidence for a substantial improvement in exercise ability and symptomatic benefit, which has been sustained at 3 and 6 months [33]. As the combined use of drugs with various mechanisms of action is an attractive option for the treatment of PAH, adjunctive treatment with sildenafil and bosentan [27] or beraprost [32] has produced favorable outcomes. Especially for the long-term treatment of diseases such as pulmonary hypertension, development of long-acting forms of PDE5 inhibitors is desired.…”

Section: Abbildungmentioning

confidence: 99%

Current Therapy of Pulmonary Hypertension

Baumhäkel¹,

Cremers²,

Böhm

2005

Herz

View full text Add to dashboard Cite

Pulmonary arterial hypertension (PAH) affects vascular proliferation and remodeling in small pulmonary arteries and results in right ventricular failure and death due to a progressive increase in pulmonary vascular resistance. Recent advances in understanding of the molecular mechanisms involved in PAH suggest that endothelial dysfunction plays a major role. Impaired production of vasoactive mediators, such as prostacyclin and nitric oxide, accompanied with prolonged overexpression of vasoconstrictors such as endothelin-1, affects vascular tone and reinforces vascular remodeling. As the latter substances represent logical pharmacological targets, new drugs affecting these mechanisms have evolved during the past 2 decades and led to umpteen placebo-controlled trials in bygone years. Prognosis and quality of life of patients suffering from PAH seem to improve due to these new treatment strategies resulting in a reduction of mortality and morbidity, but there is still a substantial need for further long-term and head-to-head trials.

show abstract

Addition of Oral Sildenafil to Beraprost Is a Safe and Effective Therapeutic Option for Patients with Pulmonary Hypertension

Cited by 40 publications

References 9 publications

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

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

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

Current Therapy of Pulmonary Hypertension

Contact Info

Product

Resources

About