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Effect of dual pulmonary vasodilator therapy in pulmonary arterial hypertension associated with congenital heart disease: a retrospective analysis.

Monfredi O, Heward E, Griffiths L, Condliffe R, Mahadevan VS - Open Heart (2016)

Bottom Line: Pooled patient and treatment data showed initial improvement followed by stabilisation in mean 6 min walk distance (6MWD).For Down and non-Down patients, mean 6MWD increased and then stabilised on bosentan monotherapy.Mean 6MWD of patients on dual therapy at the time of analysis was 246.3 m before PAH-specific therapy initiation, 211.9 m immediately prior to addition of a second therapy and 214.4 m at last visit while on dual therapy. 1, 2 and 3-year survival rates for all patients from time of treatment initiation were 96%, 87% and 80%, respectively.

View Article: PubMed Central - PubMed

Affiliation: University of Manchester, Institute of Cardiovascular Sciences, Manchester, UK; Manchester Heart Centre, Manchester Royal Infirmary, UK; Laboratory of Cardiovascular Science, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA.

ABSTRACT

Background: Patients with pulmonary arterial hypertension (PAH) are managed according to evidence-based treatment guidelines.

Methods and results: In this single-centre retrospective analysis, we examined outcomes of patients with PAH caused by congenital heart disease (PAH-CHD) with respect to exercise capacity and survival of adults treated with either bosentan or sildenafil monotherapy or bosentan-sildenafil dual therapy between January 2007 and January 2014. Of the 82 patients analysed, 29 had Down syndrome; 54 (65.8%) received bosentan monotherapy, 16 (19.5%) sildenafil monotherapy and 12 (14.6%) dual therapy. Mean treatment duration was 2.5 years for all patients and 4.1 years for 38 patients treated for ≥2 years. Pooled patient and treatment data showed initial improvement followed by stabilisation in mean 6 min walk distance (6MWD). For Down and non-Down patients, mean 6MWD increased and then stabilised on bosentan monotherapy. Mean 6MWD of patients on dual therapy at the time of analysis was 246.3 m before PAH-specific therapy initiation, 211.9 m immediately prior to addition of a second therapy and 214.4 m at last visit while on dual therapy. 1, 2 and 3-year survival rates for all patients from time of treatment initiation were 96%, 87% and 80%, respectively.

Conclusions: For the majority of patients, monotherapy with a PAH-specific medication provided improved and sustained exercise benefits. For the small percentage of patients who required it, add-on therapy appeared to prevent further deterioration in exercise capacity but did not improve 6MWD.

No MeSH data available.


Related in: MedlinePlus

(A) Absolute and B) change from baseline in 6 min walk distance over time for patients on bosentan monotherapy by Down syndrome status. For the patients who had data post 24 months the mean±SD treatment duration from commencement of bosentan monotherapy to the latest time point was 4.1±1.1 (median 3.8 years, range 2.5–6.1 years) for patients without Down syndrome (n=21) and 4.5±1.5 years (median 4.4 years, range 2.6–6.9 years) for patients with Down syndrome (n=6). p Values tested whether change in 6MWD from baseline at each time point was significantly different from no change; **p<0.001, ***p<0.0001. 6MWD, 6 min walk distance; DS, Down syndrome.
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OPENHRT2016000399F2: (A) Absolute and B) change from baseline in 6 min walk distance over time for patients on bosentan monotherapy by Down syndrome status. For the patients who had data post 24 months the mean±SD treatment duration from commencement of bosentan monotherapy to the latest time point was 4.1±1.1 (median 3.8 years, range 2.5–6.1 years) for patients without Down syndrome (n=21) and 4.5±1.5 years (median 4.4 years, range 2.6–6.9 years) for patients with Down syndrome (n=6). p Values tested whether change in 6MWD from baseline at each time point was significantly different from no change; **p<0.001, ***p<0.0001. 6MWD, 6 min walk distance; DS, Down syndrome.

Mentions: There were no significant differences between 6MWD at baseline between treatment groups for patients without Down syndrome. For patients without and with Down syndrome, 6MWD initially increased and then stabilised over time with bosentan monotherapy (figure 2A). For patients without Down syndrome who were treated with bosentan monotherapy, the changes in 6MWD from baseline were significant at each time point up to month 24 (figure 2B). For patients with Down syndrome the change in 6MWD from baseline was not significant at any time point. 6MWD data for patients on sildenafil monotherapy are not described due to small patient numbers (n=2). It is important to note that assessment of response in patients with Down syndrome can be difficult to determine, as it is usually dependent on clinical symptoms and the views of those caring for the patient. Evidence that patients with Down syndrome respond less well to PAH-specific therapy may have more to do with the difficulty in assessing response than to any intrinsic difference in response to therapy compared with non-Down syndrome patients.


Effect of dual pulmonary vasodilator therapy in pulmonary arterial hypertension associated with congenital heart disease: a retrospective analysis.

Monfredi O, Heward E, Griffiths L, Condliffe R, Mahadevan VS - Open Heart (2016)

(A) Absolute and B) change from baseline in 6 min walk distance over time for patients on bosentan monotherapy by Down syndrome status. For the patients who had data post 24 months the mean±SD treatment duration from commencement of bosentan monotherapy to the latest time point was 4.1±1.1 (median 3.8 years, range 2.5–6.1 years) for patients without Down syndrome (n=21) and 4.5±1.5 years (median 4.4 years, range 2.6–6.9 years) for patients with Down syndrome (n=6). p Values tested whether change in 6MWD from baseline at each time point was significantly different from no change; **p<0.001, ***p<0.0001. 6MWD, 6 min walk distance; DS, Down syndrome.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4836289&req=5

OPENHRT2016000399F2: (A) Absolute and B) change from baseline in 6 min walk distance over time for patients on bosentan monotherapy by Down syndrome status. For the patients who had data post 24 months the mean±SD treatment duration from commencement of bosentan monotherapy to the latest time point was 4.1±1.1 (median 3.8 years, range 2.5–6.1 years) for patients without Down syndrome (n=21) and 4.5±1.5 years (median 4.4 years, range 2.6–6.9 years) for patients with Down syndrome (n=6). p Values tested whether change in 6MWD from baseline at each time point was significantly different from no change; **p<0.001, ***p<0.0001. 6MWD, 6 min walk distance; DS, Down syndrome.
Mentions: There were no significant differences between 6MWD at baseline between treatment groups for patients without Down syndrome. For patients without and with Down syndrome, 6MWD initially increased and then stabilised over time with bosentan monotherapy (figure 2A). For patients without Down syndrome who were treated with bosentan monotherapy, the changes in 6MWD from baseline were significant at each time point up to month 24 (figure 2B). For patients with Down syndrome the change in 6MWD from baseline was not significant at any time point. 6MWD data for patients on sildenafil monotherapy are not described due to small patient numbers (n=2). It is important to note that assessment of response in patients with Down syndrome can be difficult to determine, as it is usually dependent on clinical symptoms and the views of those caring for the patient. Evidence that patients with Down syndrome respond less well to PAH-specific therapy may have more to do with the difficulty in assessing response than to any intrinsic difference in response to therapy compared with non-Down syndrome patients.

Bottom Line: Pooled patient and treatment data showed initial improvement followed by stabilisation in mean 6 min walk distance (6MWD).For Down and non-Down patients, mean 6MWD increased and then stabilised on bosentan monotherapy.Mean 6MWD of patients on dual therapy at the time of analysis was 246.3 m before PAH-specific therapy initiation, 211.9 m immediately prior to addition of a second therapy and 214.4 m at last visit while on dual therapy. 1, 2 and 3-year survival rates for all patients from time of treatment initiation were 96%, 87% and 80%, respectively.

View Article: PubMed Central - PubMed

Affiliation: University of Manchester, Institute of Cardiovascular Sciences, Manchester, UK; Manchester Heart Centre, Manchester Royal Infirmary, UK; Laboratory of Cardiovascular Science, National Institute on Aging-Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA.

ABSTRACT

Background: Patients with pulmonary arterial hypertension (PAH) are managed according to evidence-based treatment guidelines.

Methods and results: In this single-centre retrospective analysis, we examined outcomes of patients with PAH caused by congenital heart disease (PAH-CHD) with respect to exercise capacity and survival of adults treated with either bosentan or sildenafil monotherapy or bosentan-sildenafil dual therapy between January 2007 and January 2014. Of the 82 patients analysed, 29 had Down syndrome; 54 (65.8%) received bosentan monotherapy, 16 (19.5%) sildenafil monotherapy and 12 (14.6%) dual therapy. Mean treatment duration was 2.5 years for all patients and 4.1 years for 38 patients treated for ≥2 years. Pooled patient and treatment data showed initial improvement followed by stabilisation in mean 6 min walk distance (6MWD). For Down and non-Down patients, mean 6MWD increased and then stabilised on bosentan monotherapy. Mean 6MWD of patients on dual therapy at the time of analysis was 246.3 m before PAH-specific therapy initiation, 211.9 m immediately prior to addition of a second therapy and 214.4 m at last visit while on dual therapy. 1, 2 and 3-year survival rates for all patients from time of treatment initiation were 96%, 87% and 80%, respectively.

Conclusions: For the majority of patients, monotherapy with a PAH-specific medication provided improved and sustained exercise benefits. For the small percentage of patients who required it, add-on therapy appeared to prevent further deterioration in exercise capacity but did not improve 6MWD.

No MeSH data available.


Related in: MedlinePlus