Clinical efficacy of sildenafil in primary pulmonary hypertension

Sastry, B.K.S.; Narasimhan, Chitra; Reddy, N. Krishna; Raju, Bindu

doi:10.1016/j.jacc.2003.10.056

Cited by 453 publications

(102 citation statements)

References 23 publications

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“…9,10 The cost of treatment with sildenafil 50 mg orally every 8 hours is CAN $6000 per year, which is 6 to 7 times cheaper than bosentan and 15 times cheaper than epoprostenol. The efficacy, simplicity, and potential cost savings of the oral PD-5 regimen support the need for larger trials and perhaps a head-to-head comparison of sildenafil and bosentan in PAH.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Treatment With Oral Sildenafil Is Safe and Improves Functional Capacity and Hemodynamics in Patients With Pulmonary Arterial Hypertension

et al. 2003

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Background-The prognosis and functional capacity of patients with pulmonary arterial hypertension (PAH) is poor, and there is a need for safe, effective, inexpensive oral treatments. A single dose of sildenafil, an oral phosphodiesterase type-5 (PD-5) inhibitor, is an effective and selective pulmonary vasodilator in PAH. However, the long-term effects of PD-5 inhibition and its mechanism of action in human pulmonary arteries (PAs) are unknown. Methods and Results-We hypothesized that 3 months of sildenafil (50 mg orally every 8 hours) added to standard treatment would be safe and improve functional capacity and hemodynamics in PAH patients. We studied 5 consecutive patients (4 with primary pulmonary hypertension, 1 with Eisenmenger's syndrome; New York Heart Association class II to III). Functional class improved by Ն1 class in all patients. Pretreatment versus posttreatment values (meanϮSEM) were as follows: 6-minute walk, 376Ϯ30 versus 504Ϯ27 m, PϽ0.0001; mean PA pressure, 70Ϯ3 versus 52Ϯ3 mm Hg, PϽ0.007; pulmonary vascular resistance index 1702Ϯ151 versus 996Ϯ92 dyne · s · cm Ϫ5 · m Ϫ2, PϽ0.006. The systemic arterial pressure was unchanged, and no adverse effects occurred. Sildenafil also reduced right ventricular mass measured by MRI. In 7 human PAs (6 cardiac transplant donors and 1 patient with PAH on autopsy), we showed that PD-5 is present in PA smooth muscle cells and that sildenafil causes relaxation by activating large-conductance, calcium-activated potassium channels. Figure 1. Short-term inhaled nitric oxide (iNO) reduces pulmonary vascular resistance in PAH, 4,5 but ambulatory delivery in humans is cumbersome. Another strategy is to prolong the survival of cGMP in PASMCs by inhibiting type-5 phosphodiesterase (PD-5), an isoform that is primarily located in the penis and lungs, which rapidly degrades cGMP. Because of PD-5's tissue distribution (pulmonaryϾsystemic vasculature), PD-5 inhibitors are attractive candidate pulmonary vasodilators that minimally decrease systemic blood pressure. (75 mg) is an effective and relatively selective pulmonary vasodilator. 4,5 We hypothesized that PD-5 inhibition acutely causes human PA dilatation, in part by opening of BK Ca channels, and that it chronically improves hemodynamics and functional capacity in moderately severe PAH. Conclusion-This MethodsWe studied 5 consecutive patients with PAH (nϭ4 New York Heart Association [NYHA] class III; patient 3 class II). All subjects provided informed consent. Patients with class IV PAH were excluded because they often require epoprostenol, which could confound the assessment of sildenafil's effects. All the patients had been stable for Ͼ3 months, and their standard therapy was not altered before initiation of sildenafil. All were on diuretics and coumadin, and patients 2 and 4 were on Ca 2ϩ channel blockers because they had been shown to respond to iNO with Ͼ20% decrease in pulmonary vascular resistance (Figure 2). No patient was taking nitrates. All patients had primary pulmonary hypertension (PPH) except patient 2, w...

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Section: Discussionmentioning

confidence: 99%

Long-Term Treatment With Oral Sildenafil Is Safe and Improves Functional Capacity and Hemodynamics in Patients With Pulmonary Arterial Hypertension

et al. 2003

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“…The pediatric studies have included patients with PHTN of various etiologies. Eight prospective studies, including a series of 87 children (ages ranging from infancy to 19 years) taking oral sildenafil, describe sildenafil's efficacy for improving hemodynamics and exercise tolerance [6,36,45,58,59,62,63,69]. Three of the prospective studies were randomized controlled trials involving pediatric patients with either persistent PHTN of the newborn or PHTN related to congenital heart disease [6,58,62].…”

Section: Sildenafil Efficacymentioning

confidence: 99%

“…Abdominal discomfort [69] Not otherwise described NR For this review, the incidence of each reported adverse event was calculated using the sum of all the patients receiving sildenafil in the studies and case reports. All the studies and case reports made reference to adverse events, often noting that no event was experienced, although few investigations specifically stated how or which adverse events were monitored.…”

Section: Sildenafil Safetymentioning

confidence: 99%

Sildenafil for the Treatment of Pulmonary Hypertension in Pediatric Patients

et al. 2009

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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.…”

mentioning

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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Clinical efficacy of sildenafil in primary pulmonary hypertension

Abstract: Sildenafil significantly improves exercise tolerance, cardiac index, and QOL in patients with PPH.

Cited by 453 publications

References 23 publications

Long-Term Treatment With Oral Sildenafil Is Safe and Improves Functional Capacity and Hemodynamics in Patients With Pulmonary Arterial Hypertension

Long-Term Treatment With Oral Sildenafil Is Safe and Improves Functional Capacity and Hemodynamics in Patients With Pulmonary Arterial Hypertension

Sildenafil for the Treatment of Pulmonary Hypertension in Pediatric Patients

Sildenafil Treatment of Infants With Bronchopulmonary Dysplasia–Associated Pulmonary Hypertension

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