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Cardiology in Review 2017Treatment options for patients with the Eisenmenger syndrome have until recently been scarce, but new knowledge in the field of pulmonary arterial hypertension has... (Review)
Review
Treatment options for patients with the Eisenmenger syndrome have until recently been scarce, but new knowledge in the field of pulmonary arterial hypertension has expanded the therapeutic possibilities for these patients. Advanced therapy with pulmonary vasodilators has become part of the standard treatment, offering long-term benefits on exercise capacity, clinical symptoms, and possibly survival. However, there are currently only few studies to guide the use of advanced therapies in this population, and important questions such as indications for initiation or escalation of advanced therapy and valid effect parameters and treatment goals remain unanswered. This review covers the pharmacology, therapeutic options, risk stratification, and treatment strategy of pulmonary arterial hypertension-specific drugs in patients with Eisenmenger syndrome.
Topics: Antihypertensive Agents; Disease Management; Eisenmenger Complex; Humans; Practice Guidelines as Topic; Vasodilator Agents
PubMed: 27054605
DOI: 10.1097/CRD.0000000000000107 -
Heart (British Cardiac Society) Sep 2014To investigate survival in patients with Eisenmenger syndrome based on a systematic review of the literature and reanalysis of data. We specifically tested the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To investigate survival in patients with Eisenmenger syndrome based on a systematic review of the literature and reanalysis of data. We specifically tested the hypothesis that previous publications have been subject to immortal time bias, confounding survival analyses.
METHODS
A systematic review of the literature was performed to evaluate survival in treatment naïve patients with Eisenmenger syndrome and standardised mortality ratios were calculated. Furthermore, we used a contemporary cohort of 219 treatment naïve patients with Eisenmenger syndrome from the own institution as a comparison group.
RESULTS
Overall, 12 studies (published 1971-2013) were identified, including a total of 1131 patients. Only one study seemed to deal appropriately with immortal time bias in this setting. All other studies did not account for this effect, thus overestimating survival prospects of patients with Eisenmenger syndrome by up to 20 years. After accounting for this effect we found high standardised mortality ratios, a 10-year mortality rate approaching 30-40% and no evidence of superior survival prospects of current era patients compared with those seen in the 1970s, 1980s and 1990s. Only, a historical Eisenmenger-cohort from the 1950s/1960s had worse survival.
CONCLUSIONS
The current analysis challenges the traditional view of benign survival prospects of patients with Eisenmenger syndrome. In addition, survival prospects do not seem to have considerably improved over the last decades in untreated patients. These results support a proactive treatment strategy including a more aggressive approach trying to avoid the development of the condition.
Topics: Bias; Eisenmenger Complex; Humans; Prognosis; Risk Factors; Survival Analysis; Survival Rate; Time Factors
PubMed: 25099652
DOI: 10.1136/heartjnl-2014-305690 -
Medicine May 2019It is commonly reported a limitation of therapeutic strategy in Eisenmenger syndrome (ES) historically. This qualitative systematic review is conducted to evaluate the... (Meta-Analysis)
Meta-Analysis
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 = 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 = 47.5%; WMD: 88.68 m, 95% CI [54.05, 123.3], P < .001; FC: I = 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 a long-term treatment, bosentan has been supported for a lasting effect on exercise tolerance. A further multicenter research with a large sample about pharmacotherapy of ES is necessary.
Topics: Antihypertensive Agents; Bosentan; Eisenmenger Complex; Endothelin Receptor Antagonists; Exercise Tolerance; Hemodynamics; Humans; Hypertension, Pulmonary; Oxygen; Phenylpropionates; Phosphodiesterase 5 Inhibitors; Prostaglandins; Pyridazines; Pyrimidines; Sulfonamides
PubMed: 31096477
DOI: 10.1097/MD.0000000000015632 -
American Journal of Cardiovascular... Apr 2018The efficacy of endothelin receptor antagonists (ERAs) in the management of Eisenmenger syndrome (ES) remains controversial. The aim of this study is to systemically... (Review)
Review
INTRODUCTION
The efficacy of endothelin receptor antagonists (ERAs) in the management of Eisenmenger syndrome (ES) remains controversial. The aim of this study is to systemically review the safety and effects of ERAs in improving the quality of life and basic cardiac functions of these patients.
METHODS
Twelve databases were searched, including PubMed, Web of Science, Scopus, Virtual Health Library, World Health Organization (WHO) Global Health Library, Google Scholar, POPLINE, Systems for Information of Grey Literature in Europe, New York Academy of Medicine, ClinicalTrials.gov, metaRegister of Controlled Trials and the WHO International Clinical Trials Registry Platform, through August 2016. We included randomized clinical trials addressing the effect of ERAs on cardiac functions in patients with ES. The quality of studies was assessed using the Cochrane Collaboration tool.
RESULTS
We included two trials represented by four papers, of which three papers reported the efficacy of bosentan against placebo and one paper reported the results of a combination of bosentan and sildenafil versus placebo and bosentan. One trial showed a significant effect of bosentan treatment over placebo on indexed pulmonary vascular resistance and mean pulmonary artery pressure, but a non-significant increase in 6-min walk distance and a non-significant effect on systemic pulse oximetry. The other trial reported the safe but non-significant effect of combination therapy of bosentan and sildenafil compared with bosentan and placebo.
CONCLUSIONS
This study demonstrated safety and improved hemodynamic effects of bosentan in ES, with a controversial effect on exercise capacity. Further randomized controlled trials with longer follow-up duration are needed to confirm these results.
Topics: Antihypertensive Agents; Blood Pressure; Bosentan; Clinical Trials as Topic; Eisenmenger Complex; Endothelin Receptor Antagonists; Humans; Quality of Life; Sildenafil Citrate; Sulfonamides; Vasodilator Agents
PubMed: 28660556
DOI: 10.1007/s40256-017-0240-5