Effect of Bosentan on Exercise Capacity and Clinical Worsening in Patients with Dual down and Eisenmenger Syndrome

Serino, G.; Guazzi, Marco; Micheletti, Angelo; Lombardi, Carlo; Danesi, Rossella; Negura, Diana; Carminati, Mário; Chessa, Massimo

doi:10.4137/cmc.s10237

Cited by 15 publications

(7 citation statements)

References 26 publications

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“…Importantly in the current study, patients achieved a significant increase in 6MWD with long-term bosentan therapy. These findings are similar to those from a recently published series of patients which demonstrated that 6MWD increased in patients with Down’s syndrome during the first 12 months of bosentan therapy – achieving early significance – and this improvement from baseline was maintained during a further 24 months of therapy [18]. Although it has been shown that there is no discrepancy between improvement in 6MWD and haemodynamic parameters in patients with Down’s syndrome [20], it is clear from the contrasting results from published small studies that we still need to understand more about use of the 6MWT in this population.…”

Section: Discussionsupporting

confidence: 90%

Long-term results of treatment with bosentan in adult Eisenmenger’s syndrome patients with Down’s syndrome related to congenital heart disease

Crepaz

Romeo

Montanaro

et al. 2013

BMC Cardiovasc Disord

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BackgroundPatients with Down’s syndrome and shunt lesions are at high risk of developing pulmonary arterial hypertension (PAH) earlier than patients without Down’s syndrome. However, data on the efficacy of PAH-specific therapy in patients with Down’s syndrome are limited. The aim of this retrospective analysis was to determine the long-term efficacy of the dual endothelin receptor antagonist, bosentan, in Eisenmenger's syndrome (ES) patients with Down’s syndrome.MethodsIn this observational study adults with Down’s syndrome with a confirmed diagnosis of ES (World Health Organization functional class III) and receiving bosentan therapy and were followed up long term. Clinical evaluation at baseline and follow-up visits included resting transcutaneous arterial oxygen saturation and laboratory assessments. Exercise capacity was evaluated using a 6-minute walk test where transcutaneous arterial oxygen saturation at peak exercise (SpO2), 6-minute walk distance (6MWD) and Borg dyspnoea index were assessed. A full echocardiographic assessment was conducted at baseline and follow-up visits.ResultsOverall, seven adults (mean age 29.6 ± 11.2 years; 57% male) received bosentan at a starting dose of 62.5 mg twice daily. This was increased to the target dose of 125 mg twice daily 4 weeks later. All patients remained on bosentan until the end of the study. After a mean (± standard deviation) duration of 52.2 ± 3.9 months (range: 46.0–55.5 months), 6MWD had increased from 199.6 ± 69.1 metres to 303.7 ± 99.9 metres (P < 0.05) and SpO2 at the end of the 6-minute walk test had increased from 61.6 ± 7.6% to 74.7 ± 6.2% (P < 0.05). Echocardiography demonstrated a significant change in acceleration time from 62.9 ± 11.6 m/s to 83.0 ± 9.6 m/s (P = 0.0156), and acceleration time/ejection time ratio from the pulmonary flow from 0.24 ± 0.04 at baseline to 0.30 ± 0.02 (P = 0.0156) at final follow-up.ConclusionsLong-term treatment with bosentan significantly improved exercise capacity and oxygen saturation following exercise in adult ES patients with Down’s syndrome. These data confirm that the presence of Down’s syndrome does not affect the response to oral bosentan therapy.

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Section: Discussionsupporting

confidence: 90%

Long-term results of treatment with bosentan in adult Eisenmenger’s syndrome patients with Down’s syndrome related to congenital heart disease

Crepaz

Romeo

Montanaro

et al. 2013

BMC Cardiovasc Disord

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“…Crepaz et al [12] assessed the effect of bosentan monotherapy for an assessment and the mean 6MWD increased from 199.6 ± 69.1 m at baseline versus 303.7 ± 99.9 m ( P = .016), in addition to a significant change of mean SpO 2 at the end of 6MWD, while without an obvious decrease of BDI (from 3.6 ± 1.4 to 2.4 ± 1.1), approving a possible improvement of clinical exercise capacity. In the Serino et al study, [13] it more identified that trisomy 21 influenced the response little to a dual ERA bosentan therapy in ES patients.…”

Section: Resultsmentioning

confidence: 99%

What is the position of pulmonary arterial hypertension-specific drug therapy in patients with Eisenmenger syndrome

Kuang

et al. 2019

Medicine

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Background: It is commonly reported a limitation of therapeutic strategy in Eisenmenger syndrome (ES) historically. This qualitative systematic review is conducted to evaluate the safety and efficacy of pulmonary arterial hypertension-specific drug therapy (PAH-SDT) for ES patients for a clinical therapeutic strategy based on evidence. Methods: PubMed, EMBASE, and the Cochrane Library databases have been systematically reviewed up to January 2019. Two reviewers independently conducted a literature search, quality evaluation, and data extraction. The occurrence of death, deterioration, and adverse events (AEs) has respectively been described as a count or percentage. Meta-analysis was conducted by Stata 15.1, and weighted mean differences (WMD) with 95% confidence intervals (CI) were recorded for continuous data. Randomized-effect model or fixed-effect model was applied according to the heterogeneity test. Results: Fifteen citations recruiting 456 patients associated with ES were eventually pooled, which involved 4 RCTs, 6 prospective studies, and 5 retrospective studies. Within the first year, it indicated PAH-SDT significantly ameliorated exercise capacity in 6-minute walk distance (6MWD) ( I 2 = 60.5%; WMD: 53.86 m, 95% CI [36.59, 71.13], P < .001), functional class (FC) (WMD = –0.71, 95% CI [–0.98, –0.44], P < .001) and Borg dyspnea index (WMD = –1.28, 95% CI [–1.86, –0.70], P < .001), in addition to hemodynamics, especially mean pulmonary arterial pressure by 5.70 mmHg (WMD = –5.70 mmHg, 95% CI [–8.19, –3.22], P < .001) and pulmonary vascular resistance by 4.20 wood U (WMD: –4.20, 95% CI [–7.32, –1.09], P = .008), but unsatisfactory effects in oxygen saturation at exercise ( P = .747). In a prolonged medication, bosentan, a dual ERA, has been proved acting an important role in improving exercise tolerance of patients with ES (6MWD: I 2 = 47.5%; WMD: 88.68 m, 95% CI [54.05, 123.3], P < .001; FC: I 2 = 0.0%; WMD = –0.65, 95% CI [–1.10, –0.19], P = .006). While a nonsignificant change of 6MWD was noted in a long-term therapy of ambrisentan ( P = .385). There existed rare evidence about the efficacy and safety of macitentan, phosphodiesterase-5 inhibitors (PDE5i), and prostanoids in a prolonged medication. Most AEs were recorded as mild to moderate with PAH-SDT, but about 4.3% individuals treated with endothelin receptor antagonists (ERAs) suffered from serious ones, and 3.9% suffered from death. Conclusions: This systematic review and meta-analysis proved PAH-SDT as a safe and effective role in ES in an early stage. However, in...

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“…Fifth, Down syndrome was enrolled in MAESTRO but was not included in the BREATHE-5 study. Previous studies showed that the efficacy of pulmonary vasodilators is particularly limited in ES patients with Down syndrome [27][28][29][30][31] .…”

Section: Disccussionmentioning

confidence: 99%

Efficacy and safety of pulmonary vasodilators in the patients with Eisenmenger syndrome: a meta‐analysis of randomized controlled trials

Hou

Shu

et al. 2021

Pulm. circ.

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Background: Few meta-analyses evaluated the efficacy and safety of pulmonary vasodilators in patients with Eisenmenger syndrome (ES). Recently, some studies have reported conflicting results regarding improvements in exercise capacity. This study evaluated the efficacy and safety of pulmonary vasodilators in patients with ES. Methods and Results: Relevant studies were identified by searching major databases. Pooled outcomes were used to assess the efficacy and safety of pulmonary vasodilators. In total, 5 studies with 508 patients were included. Meta-analysis indicated that the pulmonary vasodilators reduced the mortality (odd risk (OR) = 0.35; 95% CI, 0.13 to 0.95; P = 0.04), slashed the mean pulmonary artery pressure (mean difference (MD) = -4.35 mmHg; 95% CI, -7.19 to -1.50; P = 0.003), decreased pulmonary vascular resistance index (MD = -480.08 dynÂ·sÂ·cm-5Â·m2; 95% CI, -753.51 to -206.64; P = 0.0006), increased the 6-minute walk distance (MD = 28.38 m; 95% CI, 2.99 to 53.77; P = 0.03), and elevated the systemic oxygen saturation at rest (MD = 1.00%; 95% CI, 0.12 to 1.88; P = 0.03). Pulmonary vasodilators were generally well tolerated. Conclusions: Pulmonary vasodilators decrease mortality and improve hemodynamics and exercise capacity in patients with ES. Overall, pulmonary vasodilators are well tolerated

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Effect of Bosentan on Exercise Capacity and Clinical Worsening in Patients with Dual down and Eisenmenger Syndrome

Cited by 15 publications

References 26 publications

Long-term results of treatment with bosentan in adult Eisenmenger’s syndrome patients with Down’s syndrome related to congenital heart disease

Long-term results of treatment with bosentan in adult Eisenmenger’s syndrome patients with Down’s syndrome related to congenital heart disease

What is the position of pulmonary arterial hypertension-specific drug therapy in patients with Eisenmenger syndrome

Efficacy and safety of pulmonary vasodilators in the patients with Eisenmenger syndrome: a meta‐analysis of randomized controlled trials

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