PMID- 31096477 OWN - NLM STAT- MEDLINE DCOM- 20190610 LR - 20210112 IS - 1536-5964 (Electronic) IS - 0025-7974 (Print) IS - 0025-7974 (Linking) VI - 98 IP - 20 DP - 2019 May TI - What is the position of pulmonary arterial hypertension-specific drug therapy in patients with Eisenmenger syndrome: A systematic review and meta-analysis. PG - e15632 LID - 10.1097/MD.0000000000015632 [doi] LID - e15632 AB - 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. FAU - Li, Qiang AU - Li Q AD - Department of Cardiology. AD - Ministry of Education Key Laboratory of Child Development and Disorders. AD - China International Science and Technology Cooperation Base of Child Development and Critical Disorders. AD - Chongqing Key Laboratory of Pediatrics. FAU - Kuang, Hong-Yu AU - Kuang HY AD - Department of Cardiology. AD - Ministry of Education Key Laboratory of Child Development and Disorders. AD - China International Science and Technology Cooperation Base of Child Development and Critical Disorders. AD - Chongqing Key Laboratory of Pediatrics. FAU - Wu, Yu-Hao AU - Wu YH AD - Department of Cardiothoracic Surgery, Children's Hospital of Chongqing Medical University, Chongqing, China. FAU - Lu, Tie-Wei AU - Lu TW AD - Department of Cardiology. AD - Ministry of Education Key Laboratory of Child Development and Disorders. AD - China International Science and Technology Cooperation Base of Child Development and Critical Disorders. AD - Chongqing Key Laboratory of Pediatrics. FAU - Yi, Qi-Jian AU - Yi QJ AD - Department of Cardiology. AD - Ministry of Education Key Laboratory of Child Development and Disorders. AD - China International Science and Technology Cooperation Base of Child Development and Critical Disorders. AD - Chongqing Key Laboratory of Pediatrics. LA - eng PT - Journal Article PT - Meta-Analysis PT - Systematic Review PL - United States TA - Medicine (Baltimore) JT - Medicine JID - 2985248R RN - 0 (Antihypertensive Agents) RN - 0 (Endothelin Receptor Antagonists) RN - 0 (Phenylpropionates) RN - 0 (Phosphodiesterase 5 Inhibitors) RN - 0 (Prostaglandins) RN - 0 (Pyridazines) RN - 0 (Pyrimidines) RN - 0 (Sulfonamides) RN - HW6NV07QEC (ambrisentan) RN - Q326023R30 (Bosentan) RN - S88TT14065 (Oxygen) RN - Z9K9Y9WMVL (macitentan) SB - IM MH - Antihypertensive Agents/administration & dosage/adverse effects/*therapeutic use MH - Bosentan/therapeutic use MH - Eisenmenger Complex/*drug therapy MH - Endothelin Receptor Antagonists/administration & dosage/adverse effects/*therapeutic use MH - Exercise Tolerance/drug effects MH - Hemodynamics MH - Humans MH - Hypertension, Pulmonary/drug therapy MH - Oxygen/blood MH - Phenylpropionates/therapeutic use MH - Phosphodiesterase 5 Inhibitors/administration & dosage/adverse effects/*therapeutic use MH - Prostaglandins/administration & dosage/adverse effects/*therapeutic use MH - Pyridazines/therapeutic use MH - Pyrimidines/therapeutic use MH - Sulfonamides/therapeutic use PMC - PMC6531184 COIS- The authors have stated that there exist no conflicts of interest in this study. EDAT- 2019/05/18 06:00 MHDA- 2019/06/14 06:00 PMCR- 2019/05/17 CRDT- 2019/05/18 06:00 PHST- 2019/05/18 06:00 [entrez] PHST- 2019/05/18 06:00 [pubmed] PHST- 2019/06/14 06:00 [medline] PHST- 2019/05/17 00:00 [pmc-release] AID - 00005792-201905170-00048 [pii] AID - MD-D-18-07751 [pii] AID - 10.1097/MD.0000000000015632 [doi] PST - ppublish SO - Medicine (Baltimore). 2019 May;98(20):e15632. doi: 10.1097/MD.0000000000015632.