Clinical and haemodynamic effects of sildenafil in pulmonary hypertension: acute and mid-term effects

Mikhail, Ghada; Prasad, Sanjay; Li, Wei; Rogers, Paula; Chester, Adrian H.; Bayne, Stephanie; Stephens, David A.; Khan, Mohammed Juned; Gibbs, J. Simon R.; Evans, Timothy W.; Mitchell, Andrew Robert John; Yacoub, Magdi H.; Gatzoulis, Michael Α.

doi:10.1016/j.ehj.2004.01.013

Cited by 90 publications

(67 citation statements)

References 25 publications

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“…Erectile dysfunction (ED) is a common medical condition linked both to endothelial dysfunction [1][2][3][4][5][6][7][8][9][10][11][12][13] as well as multiple other comorbid conditions. [14][15][16][17] Historically, the treatment for ED has been limited to a selected group of specialists, namely urologists and sexual therapists.…”

Section: Introductionmentioning

confidence: 99%

The effects of chronic phosphodiesterase-5 inhibitor use on different organ systems

et al. 2006

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Phosphodiesterase-5 (PDE-5) inhibitors selectively inhibit PDE-5 enzymes that are present in various tissues like penile tissue, platelets, vascular, and smooth muscle tissue. The drug's actions on these tissues have lead to the successful therapeutic use in patients suffering from conditions such as erectile dysfunction (ED) and pulmonary hypertension. PDE-5 inhibitors (PDE-5i) act on the erectile tissue causing penile smooth muscle relaxation and vasodilatation leading to penile erection. In addition, in particular when used in conjunction with prostaglandin inhibitors, PDE-5i cause vasodilatation in pulmonary vasculature hence decreasing both the pulmonary arterial pressure and resistance. PDE-5i have also shown to mildly decrease blood pressure, increase cardiac index, and increase coronary blood flow in experimental animals as well as in human studies. The Food and Drug Administration (FDA) has approved three PDE-5i for the treatment of ED: sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis) and one for pulmonary hypertension: sildenafil (Revatio). These agents are highly selective for PDE-5 enzymes as compared to other subclasses of PDE enzymes and have the almost identical pharmacological action but slightly different pharmacokinetics. Only little data exist about long-term use of PDE-5i and their effects on different organ system. This paper reviews the current information available on chronic PDE-5 inhibitor use.

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Section: Introductionmentioning

confidence: 99%

The effects of chronic phosphodiesterase-5 inhibitor use on different organ systems

et al. 2006

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“…11,12 In adults with PH, sildenafil has improved survival rates, exhibited low toxicity, and is available as an enteral preparation that is more practical for long-term, outpatient therapy. [13][14][15][16][17][18][19][20] Early clinical experience indicates that sildenafil treatment may be efficacious for infants with BPD-PH, with evidence suggesting that sildenafil normalizes lung development and may improve outcomes. [21][22][23][24][25] However, practice patterns for sildenafil treatment in infants with BPD-PH have not been fully reported; these patterns include variables associated with exposure, timing of initiation, length of treatment, and interhospital variation in use.…”

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confidence: 99%

Sildenafil Treatment of Infants With Bronchopulmonary Dysplasia–Associated Pulmonary Hypertension

Backes

Reagan

Smith

et al. 2016

Hospital Pediatrics

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OBJECTIVE: This study had 2 goals: (1) to identify clinical and demographic characteristics associated with sildenafil exposure for infants with bronchopulmonary dysplasia (BPD)-associated pulmonary hypertension (PH); and (2) to characterize hospital-specific treatment frequency, age at first administration, and length of sildenafil treatment. METHODS: This retrospective cohort study used data from the Pediatric Health Information System to determine variables associated with sildenafil exposure and between-hospital variations in sildenafil utilization patterns. The study included infants with BPD-PH who were discharged between January 1, 2006, and December 31, 2013. RESULTS: Within 36 US pediatric hospitals, 3720 infants were diagnosed with BPD, of whom 598 (16%) also had a diagnosis of PH (BPD-PH). Among infants with BPD-PH, 104 infants (17%) received sildenafil. The odds for sildenafil treatment among infants born between 25 and 26 weeks’ gestational age (GA) and <24 weeks’ GA, respectively, were 2.26 (95% confidence interval [CI]: 1.20–4.24) and 3.21 (95% CI: 1.66–6.21) times those of infants born at 27 to 28 weeks’ GA. Severity of BPD correlated with sildenafil exposure, with adjusted odds ratios (ORs) for moderate BPD (OR: 3.03 [95% CI: 1.03–8.93]) and severe BPD (OR: 7.56 [95% CI: 2.50–22.88]), compared with mild BPD. Greater rates of sildenafil exposure were observed among small for GA neonates (OR: 2.32 [95% CI: 1.21–4.46]). The proportion of infants with BPD-PH exposed to sildenafil varied according to hospital (median: 15%; 25th–75th percentile: 0%–25%), as did the median duration of therapy (52 days; 25th–75th percentile: 28–109 days). CONCLUSIONS: The odds of sildenafil treatment were greatest among the most premature infants with severe forms of BPD. The frequency and duration of sildenafil exposure varied markedly according to institution. Patient-centered trials for infants with BPD-PH are needed to develop evidence-based practices.

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“…6,7) Pulmonary vasodilator therapy improves outcomes in patients with idiopathic PAH, and has also been reported to be effective in patients with other types of PAH. [8][9][10][11][12][13] This therapy may reduce pulmonary vascular resistance (Rp) in patients who were previously thought to have irreversible pulmonary vascular disease.…”

Section: R Ecent Advances In Pediatric Cardiac Surgery Techniquesmentioning

confidence: 99%

“…6,42) These vasodilators have been shown to improve functional status and survival in patients with idiopathic PAH. [6][7][8][9][10][11][12][13] Pulmonary vasodilator therapy is now being used to treat PAH in patients with CHD, including those with Eisenmenger syndrome. Many reports have indicated that the endothelin receptor antagonist bosentan is effective for improving clinical outcomes and exercise capacity in patients with Eisenmenger syndrome.…”

Section: How Does Pulmonary Vasodilator Therapy Affect Outcomes In Pamentioning

confidence: 99%

“…44) Although there are no double-blind, placebo-controlled studies of the effects of phosphodiesterase-5 inhibitors in patients with CHD and PAH, a prospective open-label study found that sildenafil therapy was effective for improving pulmonary hemodynamics, functional class, and exercise tolerance with few significant side effects. 11,12) Unfortunately, evidence of the effectiveness of prostacyclin therapy for Eisenmenger syndrome is limited to small studies and case reports. 45,46) Fernandes, et al 47) reported that continuous intravenous epoprostenol therapy improved pulmonary hemodynamics, functional class, and exercise tolerance in patients with Eisenmenger syndrome.…”

Section: How Does Pulmonary Vasodilator Therapy Affect Outcomes In Pamentioning

confidence: 99%

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Can Pulmonary Vasodilator Therapy Expand the Operative Indications for Congenital Heart Disease?

Inai

2015

Int. Heart J.

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SummaryThe operability of congenital heart disease with left to right shunt depends on the severity of the pulmonary vascular disease induced by the increased pulmonary blood flow. Although some recommendations exist regarding operative indications according to pathological, hemodynamic, and epidemiological factors, the evidence underlying these recommendations is not conclusive. Recently, oral pulmonary vasodilator therapy has been reported to improve outcomes in patients with idiopathic pulmonary arterial hypertension, and this therapy also appears to be effective in patients with congenital heart disease and pulmonary arterial hypertension, including those with postoperative pulmonary hypertension and Eisenmenger syndrome. It is expected that the availability of novel pulmonary vasodilator therapy will expand the operative indications in patients with congenital heart disease with left to right shunt, but there is currently insufficient evidence to definitively determine this. A multicenter double-blind study should be conducted to further examine this issue. (Int Heart J 2015; 56: S12-S16)

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Clinical and haemodynamic effects of sildenafil in pulmonary hypertension: acute and mid-term effects

Abstract: Sildenafil is well tolerated in its intravenous and oral forms and appears to improve both pulmonary haemodynamics and the clinical status of patients with pulmonary hypertension after 3 months of oral therapy.

Cited by 90 publications

References 25 publications

The effects of chronic phosphodiesterase-5 inhibitor use on different organ systems

The effects of chronic phosphodiesterase-5 inhibitor use on different organ systems

Sildenafil Treatment of Infants With Bronchopulmonary Dysplasia–Associated Pulmonary Hypertension

Can Pulmonary Vasodilator Therapy Expand the Operative Indications for Congenital Heart Disease?

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