-
The Canadian Journal of Cardiology Mar 2009Congenital heart disease (CHD) with systemic-topulmonary shunting is associated with pulmonary arterial hypertension (PAH). There are similar clinical and... (Review)
Review
BACKGROUND
Congenital heart disease (CHD) with systemic-topulmonary shunting is associated with pulmonary arterial hypertension (PAH). There are similar clinical and pathophysiological features between CHD with shunt-associated PAH and idiopathic PAH. Endothelin-receptor antagonists (ERAs) are oral medications that improve pulmonary hemodynamics, symptoms and functional capacity in many PAH patients. However, the role of ERAs in CHD with shunt-associated PAH is unclear.
METHODS
MEDLINE, EMBASE and the Cumulative Index of Nursing and Allied Health Literature (CINAHL) databases were searched for articles published from 1966 through September 2006, as well as bibliographies of all retrieved papers. All published English-language studies of adult CHD patients with shunt-associated PAH treated with ERAs were reviewed for clinical, functional and hemodynamic outcomes.
RESULTS
Ten studies of 174 adult CHD subjects with shunt-associated PAH were identified. Other than one placebo-controlled, randomized clinical trial, all studies were open-label, uncontrolled observational trials. Subjects were treated with the ERA bosentan for a mean (+/- SD) of 9+/-7 months. Nine studies reported improved World Health Organization (WHO) modification of the New York Heart Association functional class, with 95 of 164 subjects (58%) improving by at least one functional class. The 6 min walk distance improved in all eight studies in which it was assessed. Bosentan was generally well tolerated; 2.3% of subjects withdrew because of elevated liver enzymes. Two patients with WHO functional class IV PAH died during bosentan therapy.
CONCLUSION
Treatment of CHD patients with shunt-associated PAH with the ERA bosentan is associated with an improvement in functional class and objectively measured exercise capacity. The consistency of the uncontrolled data and the positive results of a single randomized clinical trial suggest a role for ERA therapy in CHD patients with shunt-associated PAH. Caution is suggested when considering bosentan therapy for CHD patients with WHO functional class IV PAH.
Topics: Antihypertensive Agents; Bosentan; Eisenmenger Complex; Endothelin Receptor Antagonists; Exercise Test; Heart Defects, Congenital; Hemodynamics; Humans; Hypertension, Pulmonary; Pulmonary Circulation; Sulfonamides
PubMed: 19279988
DOI: 10.1016/s0828-282x(09)70041-8 -
Frontiers in Cardiovascular Medicine 2022Pulmonary arterial hypertension (PAH) is a fatal disease characterized by pulmonary vascular remodeling and increased pulmonary artery pressure, leading to impaired lung...
Efficacy and safety of endothelin receptor antagonists, phosphodiesterase type 5 Inhibitors, and prostaglandins in pediatric pulmonary arterial hypertension: A network meta-analysis.
BACKGROUND
Pulmonary arterial hypertension (PAH) is a fatal disease characterized by pulmonary vascular remodeling and increased pulmonary artery pressure, leading to impaired lung oxygenation, right heart failure, and even death. Although great advances have been made in PAH-targeted medications for pediatric patients, the efficacy and safety of these treatments are controversial.
METHODS
We retrieved relevant articles from electronic databases including PubMed, EMBASE, Web of Science, and Cochrane Library until 12 April 2022. To compare the effectiveness and safety of endothelin receptor antagonists (ERAs), phosphodiesterase type 5 Inhibitors (PDE-5i), and prostaglandins (ProA) in the treatment of pediatric PAH, we investigated six hemodynamic parameters, four respiratory parameters, intensive care unit (ICU) stay duration, length of hospital stay, and two safety outcomes.
RESULTS
A total of 27 randomized controlled trials (RCTs) were included in the meta-analysis with 1,574 pediatric participants. The duration of mechanical ventilation was shorter for patients using bosentan, sildenafil, and ProsA, compared with that for patients using the placebo. Bosentan helped to shorten more time for mechanical ventilation than ProsA did, while ProsA was more effective than sildenafil in this respect. As for the length of stay in the ICU, patients administered by ProsA or sildenafil needed shorter ICU stay, compared to those using the placebo, while ProsA was more effective for shortening ICU stay time. In light of safety outcomes, there was a statistically significant difference between the sildenafil and the placebo group. Sildenafil surpassed ProsA in reducing the incidence of pulmonary hypertension (PH) crisis.
CONCLUSIONS
ERAs were more effective than ProsA in shortening the duration of mechanical ventilation, while ProsA were better for shortening the duration of mechanical ventilation and ICU stay than PDE-5i. PDE-5i were found to generate more benefits in decreasing the occurrence of PH crisis, though further investigation is warranted.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=351505.
PubMed: 36712266
DOI: 10.3389/fcvm.2022.1055897 -
Pulmonary Circulation 2017Pulmonary arterial hypertension (PAH) is a progressive potentially fatal disease. Multiple pharmacologic options are now available, which facilitated transitions between...
Pulmonary arterial hypertension (PAH) is a progressive potentially fatal disease. Multiple pharmacologic options are now available, which facilitated transitions between different therapeutic options, although the evidence for such transitions has not been well described. We sought to review the evidence supporting the safety and/or efficacy of transitioning between PAH-specific medications. We performed a systematic review of all published studies in the Medline database between 1 January 2000 and 30 June 2016 reporting on any transition between the currently Food and Drug Administration (FDA)-approved PAH-specific medications. Studies reporting on three or more adult patients published in the English language reporting on transitions between FDA-approved PAH medications were extracted and tabulated. Forty-one studies met the selection criteria, nine of which included less than eight patients (and thus were reported separately in the supplement), for a total of 32 studies. Transitioning from parenteral epoprostenol to parenteral treprostinil appears to be safe and efficacious in patients who have less severe disease and more favorable hemodynamics. Transitioning from a prostacyclin analogue to an oral medication may be successful in patients who have favorable hemodynamics and stable disease. There is conflicting evidence supporting the transition from a parenteral to an inhaled prostacyclin analogue, even in patients who are on background oral therapy. Currently, the only evidence in support of transitioning between oral PDE5 inhibitors is from sildenafil to tadalafil. Patients on higher doses of sildenafil are more likely to fail. In patients with liver abnormalities due to bosentan or sitaxentan, the transition to ambrisentan appears to be safe and can result in clinical improvement. Studies regarding PAH medication transitions are limited. Patients who have less severe disease, better functional status, and are on lower medications doses may be more successful at transitioning.
PubMed: 28597769
DOI: 10.1177/2045893217706357 -
Journal of Thoracic Disease Mar 2015Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD) without effective drugs to treat. We conducted a systematic review...
Pulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD) without effective drugs to treat. We conducted a systematic review and meta-analysis in order to evaluate whether PH specific therapies were effective for stable COPD patients. Data were extracted from PubMed, Cochrane Central Register of Controlled Trials and China Knowledge Resource Integrated Database. Randomized controlled trials (RCTs) with PH specific therapy treated more than 4 weeks in COPD were selected. The main outcome was exercise capacity; meanwhile pulmonary arterial pressure (PAP), hypoxemia and health related life quality were also measured. We included nine trials involving 365 subjects, among which two were treated with bosentan and seven with sildenafil. The study time varied from 4 weeks to 18 months and mostly it was 12 weeks. In a pooled analysis of nine trials, exercise capacity of COPD patients was improved by PH-specific therapy [mean difference (MD) 66.39 m, 95% confidence intervals (CI): 59.44-73.34]. COPD with severe PH (mean PAP >35 mmHg by right heart catheterization or systolic PAP >50 mmHg by echocardiography) improved the exercise capacity (MD 67.24 m, 95% CI: 60.26-74.23), but COPD without PH at rest did not (MD -9.24 m, 95% CI: -75.08 to 56.31). Meanwhile PAP was decreased (MD -9.02 mmHg, 95% CI: -10.71 to -7.34 mmHg). Although hypoxemia and life quality were not improved, the dyspnea was alleviated or at least not aggravated (Borg dyspnea index, MD -0.86, 95% CI: -1.86 to 0.14). In conclusion, PH specific drugs (especially sildenafil) could improve exercise capacity and decrease PAP in COPD patients with severe PH.
PubMed: 25922708
DOI: 10.3978/j.issn.2072-1439.2015.02.08 -
Open Heart 2018Pulmonary arterial hypertension (PAH) secondary to congenital heart disease (CHD) is the third most common cause of PAH, and it is becoming increasingly common as...
Pulmonary arterial hypertension (PAH) secondary to congenital heart disease (CHD) is the third most common cause of PAH, and it is becoming increasingly common as improvements in the management of CHD have led to increased life expectancy for these patients. The medical management of PAH due to CHD (PAH-CHD) is largely the same as what has been used for the treatment of idiopathic PAH, though the body of literature supporting this management decision is very small. There are currently few studies available which specifically focus on the treatment of PAH-CHD. The purpose of this literature review is to compare the results of those studies that assessed the response to medical therapy among adults with PAH-CHD; studies were excluded if they focused on paediatric patients, did not include an assessment of 6 min walking distance or specifically assessed combination therapies. This review found that riociguat, bosentan, epoprostenol and sildenafil were all capable of improving functional capacity and haemodynamic parameters in patients with PAH-CHD, but whether this corresponds to an increase in mortality remains to be seen. Limitations of this review include the small sample size and variable duration of the included studies, which makes drawing direct comparisons between studies and the study drugs difficult. The lack of large, randomised double-blind clinical trials comparing different drugs head to head highlights an area that is ripe for ongoing medical research, the results of which may help shape future treatment algorithms tailored specifically for adults with PAH-CHD.
PubMed: 29344382
DOI: 10.1136/openhrt-2017-000744