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The Efficacy and Safety of Aerosolized Iloprost in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis

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Abstract

Background

This systematic review and meta-analysis was conducted to investigate the efficacy and safety of the chronic administration of aerosolized iloprost for pulmonary arterial hypertension (PAH).

Methods

All the relevant studies were obtained from three databases, namely, PubMed, Web of Science and the Cochrane Library, from the inception of each database to June 1, 2018. In our study, chronic treatment was defined as a period lasting at least 3 months. The rate of each event was analyzed by SPSS as a percentage with 95% confidence intervals (CIs). For the meta-analysis, a randomized effect model or a fixed effect model was applied according to the results of the heterogeneity test.

Results

Ten studies were included in this study, with a total of 370 patients treated with inhaled iloprost, including 214 in five randomized controlled trials and 156 in five prospective clinical trials. Among the patients who received inhaled iloprost, there was a significant improvement in the 6-min walk distance (6MWD) in the short-medium and prolonged treatment groups. Notably, the functionality improved by at least 1 class in 48.7% of the treated patients. In all the pooled studies, the estimated 3-month, 6-month, 1-year and 2-year event-free survival rates were 96.6%, 92.3%, 62.6% and 39.6%, respectively. In addition, there were eight adverse drug responses.

Conclusion

In this systematic review and meta-analysis, inhaled iloprost has been shown to be a safe and well-tolerated agent for PAH in the first 3 months after diagnosis. If used for a prolonged period, aerosol iloprost monotherapy could contribute to an unsatisfactory improvement in vascular remodeling and even a decreased event-free survival rate.

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References

  1. Kang BJ, Lee SD, Oh YM, et al. Improved survival of Korean patients with idiopathic pulmonary arterial hypertension after the introduction of targeted therapies. Heart Lung. 2014;43(6):561–8.

    Article  PubMed  Google Scholar 

  2. Galie N, Hoeper MM, Humbert M, et al. Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J. 2009;34(6):1219–63.

    Article  CAS  PubMed  Google Scholar 

  3. Galie N, Rubin L. Pulmonary arterial hypertension: epidemiology, pathobiology, assessment and therapy. J Am Coll Cardiol. 2004;43:S1–90.

    Article  Google Scholar 

  4. Benza RL, Miller DP, Barst RJ, et al. An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from the REVEAL Registry. Chest. 2012;142(2):448–56.

    Article  PubMed  Google Scholar 

  5. Galie N, Palazzini M, Manes A. Pulmonary arterial hypertension: from the kingdom of the near-dead to multiple clinical trial meta-analyses. Eur Heart J. 2010;31(17):2080–6.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Alehan D, Yıldırım I, Sahin M, et al. Long-term inhaled iloprost use in children with pulmonary arterial hypertension. Cardiol Young. 2012;22(4):396–403.

    Article  PubMed  Google Scholar 

  7. Galia N, Manes A, Negro L, et al. A meta-analysis of randomized controlled trials in pulmonary arterial hypertension. Eur Heart J. 2009;30(4):394–403.

    Article  Google Scholar 

  8. Baker SE. Inhaled iloprost in pulmonary arterial hypertension. Ann Pharmacother. 2005;39(7):1265–74.

    Article  CAS  PubMed  Google Scholar 

  9. Machherndl S, Kneussl M, Baumgartner H, et al. Long-term treatment of pulmonary hypertension with aerosolized iloprost. Eur Respir J. 2001;17(1):8–13.

    Article  CAS  PubMed  Google Scholar 

  10. Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. Epidemiol Biostat Pub Health. 2009;6(4):e1–34 [J Clin Epidemiol. 2009,62(10): e1–34].

    Google Scholar 

  11. Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions, vol. 5. New York: Wiley-Blackwell; 2008. p. S38.

    Book  Google Scholar 

  12. Higgins JP, Altman DG, Gotzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomized trials. BMJ. 2011;343:d5928.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Wells G, Shea B, O’Connell D, et al. The Newcastle–Ottawa Scale (NOS) for assessing the quality of non-randomized studies in meta-analyses. http://www.ohri.ca/programs/clinical_epidemiology/ oxford.asp. Accessed Jan 2014.

  14. Hoeper MM, Leuchte H, Halank M, et al. Combining inhaled iloprost with bosentan in patients with idiopathic pulmonary arterial hypertension. Eur Respir J. 2006;28(4):691–4.

    Article  CAS  PubMed  Google Scholar 

  15. Olschewski H, Simonneau G, Galiè N, et al. Inhaled iloprost for severe pulmonary hypertension. New Engl J Med. 2002;11(6):19–23.

    Google Scholar 

  16. Mclaughlin VV, Oudiz RJ, Frost A, et al. Randomized study of adding inhaled iloprost to existing bosentan in pulmonary arterial hypertension. Am J Respir Crit Care. 2006;174(11):1257–63.

    Article  CAS  Google Scholar 

  17. Frost A, Mclaughlin VV, Oudiz RJ, et al. STEP-OPEN LABEL EXTENSION: long-term benefits of inhaled iloprost addition to bosentan for treatment of pulmonary arterial hypertension. https://www.researchgate.net/publication/237111142. Accessed 14 Apr 2015

  18. Olschewski H, Hoeper MM, Behr J, et al. Long-term therapy with inhaled iloprost in patients with pulmonary hypertension. Respir Med. 2010;104(5):731–40.

    Article  PubMed  Google Scholar 

  19. Hoeper MM, Schwarze M, Ehlerding S, et al. Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue. N Engl J Med. 2000;342(25):1866–70.

    Article  CAS  PubMed  Google Scholar 

  20. Opitz CF, Wensel R, Winkler J, et al. Clinical efficacy and survival with first-line inhaled iloprost therapy in patients with idiopathic pulmonary arterial hypertension. Eur Heart J. 2005;26(18):1895–902.

    Article  CAS  PubMed  Google Scholar 

  21. Chon MK, Cho KI, Cha KS, et al. Effects of long-term iloprost treatment on right ventricular function in patients with Eisenmenger syndrome. J Cardiol. 2017;69(5):741–6.

    Article  PubMed  Google Scholar 

  22. Saji T, Myoishi M, Sugimura K, et al. Efficacy and safety of inhaled iloprost in Japanese patients with pulmonary arterial hypertension-Insights from the IBUKI and AIR studies. Circ J. 2016;80(4):835–42.

    Article  CAS  PubMed  Google Scholar 

  23. Cha KS, Cho KI, Seo JS, et al. Effects of inhaled iloprost on exercise capacity, quality of life, and cardiac function in patients with pulmonary arterial hypertension secondary to congenital heart disease (the Eisenmenger syndrome) (from the EIGER Study). Am J Cardiol. 2013;112(11):1834–9.

    Article  CAS  PubMed  Google Scholar 

  24. Widmar B. When cure is care: diagnosis and management of pulmonary arterial hypertension. J Am Acad Nurse Pract. 2005;17(3):104–12.

    Article  PubMed  Google Scholar 

  25. Zhang H, Li X, Huang J, et al. Comparative efficacy and safety of prostacyclin analogs for pulmonary arterial hypertension: a network meta-analysis. Medicine. 2016;95(4):e2575.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Frumkin LR. The pharmacological treatment of pulmonary arterial hypertension. Pharmacol Rev. 2012;64(3):583–620.

    Article  CAS  PubMed  Google Scholar 

  27. Tissot C, Beghetti M. Review of inhaled iloprost for the control of pulmonary artery hypertension in children. Vasc Health Risk Manag. 2009;5(1):325–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Galie N, Humbert M, Vachiery JL, et al. Effects of beraprost sodium, an oral prostacyclin analogue, in patients with pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol. 2002;39(9):1496–502.

    Article  CAS  PubMed  Google Scholar 

  29. Ryerson CJ, Nayar S, Swiston JR, et al. Pharmacotherapy in pulmonary arterial hypertension: a systematic review and meta-analysis. Respir Res. 2010;11(1):1–10.

    Article  CAS  Google Scholar 

  30. Coeytaux RR, Schmit KM, Kraft BD, et al. Comparative effectiveness and safety of drug therapy for pulmonary arterial hypertension: a systematic review and meta-analysis. Chest. 2014;145(5):1055–63.

    Article  PubMed  Google Scholar 

  31. Liu HL, Chen XY, Li JR, et al. Efficacy and safety of PAH-specific therapy in pulmonary arterial hypertension: a meta-analysis of randomized clinical trials. Chest. 2016;150(2):353–66.

    Article  PubMed  Google Scholar 

  32. Zhang C, Huang Y, Huang T, et al. Effects of iloprost combined with low dose tadalafil in adult congenital heart disease patients with severe pulmonary arterial hypertension: a single-center, open-label controlled study. Zhonghua Xin Xue Guan Bing Za Zhi. 2014;42(6):474–80.

    CAS  PubMed  Google Scholar 

  33. Han X, Zhang Y, Dong L, et al. Treatment of pulmonary arterial hypertension using initial combination therapy of bosentan and iloprost. Respir Care. 2017;62(4):489–96.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Cardiology, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, China

    Hongyu Kuang, Qiang Li, Qijian Yi & Tiewei Lu

  2. Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 400014, China

    Hongyu Kuang, Qiang Li, Qijian Yi & Tiewei Lu

  3. China International Science and Technology Cooperation Base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, China

    Hongyu Kuang, Qiang Li, Qijian Yi & Tiewei Lu

Authors
  1. Hongyu Kuang
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  2. Qiang Li
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  3. Qijian Yi
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  4. Tiewei Lu
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Contributions

Author contributions were as follows: HK and QL: study design, literature search, systematic review and data collection, statistical analysis, interpretation of results, and preparation of the manuscript; QY: a contribution to critical review of the manuscript; TL: principal investigator, study design, statistical analysis and an assessment of all results. The typographical and grammatical errors were checked and corrected by the authors above. The corresponding author confirmed all contributing authors gave permission to be named. TL takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

Corresponding author

Correspondence to Tiewei Lu.

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No external funding was used in the preparation of this manuscript.

Conflict of interest

Hongyu Kuang, Qiang Li, Qijian Yi and Tiewei Lu declare they have no potential conflicts of interest that might be relevant to the contents of this manuscript.

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Cite this article

Kuang, H., Li, Q., Yi, Q. et al. The Efficacy and Safety of Aerosolized Iloprost in Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis. Am J Cardiovasc Drugs 19, 393–401 (2019). https://doi.org/10.1007/s40256-018-00324-2

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  • DOI: https://doi.org/10.1007/s40256-018-00324-2

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