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Antiplatelet Versus Anticoagulation Therapy After Extracardiac Conduit Fontan: A Systematic Review and Meta-Analysis

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Abstract

The benefits of prophylactic anticoagulation or antiplatelet therapy for patients undergoing extracardiac conduit (ECC) Fontan procedure still are a matter of debate. Through a systematic review and meta-analysis, this study aimed to determine the incidence of thromboembolism among patients undergoing ECC Fontan who received anticoagulation or antiplatelet therapy. Until February 2010, MEDLINE studies describing the incidence of thromboembolic events after ECC Fontan were reviewed. Information on type of drugs and clinical outcome was extracted. The 20 studies analyzed involved 1,075 patients: 220 (20.4%) in the antiplatelet group and 855 (79.5%) in the anticoagulation group. The mean follow-up period ranged from 2 to 144 months. The overall thromboembolism rate was 5.2% (95% confidence interval [CI], 3.8–7%; I2 = 0%; phet = 0.32). The effect of different therapeutic strategies on the occurrence of thromboembolic and bleeding events was analyzed. Interestingly, the anticoagulation therapy compared with the antiplatelet therapy was not associated with a significant reduction in the incidence of overall thromboembolic complications (5% vs 4.5%, respectively; I2 = 0%; phet = 0.80). Only two cases of bleeding were observed among patients receiving anticoagulant therapy at the time of the event. For patients undergoing ECC Fontan, the rate of thromboembolic and bleeding events associated with antiplatelet therapy is similar to that associated with anticoagulation therapy.

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References

  1. Alexi-Meskishvili V, Ovroutski S, Ewert P, Dähnert I, Berger F, Lange PE, Hetzer R (2000) Optimal conduit size for extracardiac Fontan operation. Eur J Cardiothorac Surg 18:690–695

    Article  CAS  PubMed  Google Scholar 

  2. Cheung YF, Chay GW, Chiu CS, Cheng LC (2005) Long-term anticoagulation therapy and thromboembolic complications after the Fontan procedure. Int J Cardiol 102:509–513

    Article  CAS  PubMed  Google Scholar 

  3. Chowdhury UK, Airan B, Kothari SS, Talwar S, Saxena A, Singh R, Subramaniam GK, Pradeep KK, Patel CD, Venugopal P (2005) Specific issues after extracardiac fontan operation: ventricular function, growth potential, arrhythmia, and thromboembolism. Ann Thorac Surg 80:665–672

    Article  PubMed  Google Scholar 

  4. d’Udekem Y, Iyengar AJ, Cochrane AD, Grigg LE, Ramsay JM, Wheaton GR, Penny DJ, Brizard CP (2007) The Fontan procedure: contemporary techniques have improved long-term outcomes. Circulation 116(11 Suppl):I157–I164

    PubMed  Google Scholar 

  5. Fiore AC, Turrentine M, Rodefeld M, Vijay P, Schwartz TL, Virgo KS, Fischer LK, Brown JW (2007) Fontan operation: a comparison of lateral tunnel with extracardiac conduit. Ann Thorac Surg 83:622–629 discussion 629–630

    Article  PubMed  Google Scholar 

  6. Giannico S, Hammad F, Amodeo A, Michielon G, Drago F, Turchetta A, Di Donato R, Sanders SP (2006) Clinical outcome of 193 extracardiac Fontan patients: the first 15 years. J Am Coll Cardiol 47:2065–2073. Epub 27 April 2006

    Google Scholar 

  7. Haas GS, Hess H, Black M, Onnasch J, Mohr FW, van Son JA (2000) Extracardiac conduit fontan procedure: early and intermediate results. Eur J Cardiothorac Surg 17:648–654

    Article  CAS  PubMed  Google Scholar 

  8. Ikai A, Fujimoto Y, Hirose K, Ota N, Tosaka Y, Nakata T, Ide Y, Sakamoto K (2008) Feasibility of the extracardiac conduit Fontan procedure in patients weighing less than 10 kilograms. J Thorac Cardiovasc Surg 135:1145–1152

    Article  PubMed  Google Scholar 

  9. Jacobs ML, Pelletier GJ, Pourmoghadam KK, Mesia CI, Madan N, Stern H, Schwartz R, Murphy JD (2008) Protocols associated with no mortality in 100 consecutive Fontan procedures. Eur J Cardiothorac Surg 33:626–632

    Article  PubMed  Google Scholar 

  10. Jacobs ML, Pourmoghadam KK, Geary EM, Reyes AT, Madan N, McGrath LB, Moore JW (2002) Fontan’s operation: is aspirin enough? Is coumadin too much? Ann Thorac Surg 73:64–68

    Article  PubMed  Google Scholar 

  11. Juni P, Witschi A, Bloch R, Egger M (1999) The hazards of scoring the quality of clinical trials for meta-analysis. JAMA 282:1054–1060

    Article  CAS  PubMed  Google Scholar 

  12. Kajimoto H, Nakazawa M, Murasaki K, Hagiwara N, Nakanishi T (2009) Increased P-selectin expression on platelets and decreased plasma thrombomodulin in Fontan patients. Circ J 73:1705–1710

    Article  CAS  PubMed  Google Scholar 

  13. Khairy P, Fernandes SM, Mayer JE Jr, Triedman JK, Walsh EP, Lock JE, Landzberg MJ (2008) Long-term survival, modes of death, and predictors of mortality in patients with Fontan surgery. Circulation 117:85–92

    Article  PubMed  Google Scholar 

  14. Laschinger JC, Redmond JM, Cameron DE, Kan JS, Ringel RE (1996) Intermediate results of the extracardiac Fontan procedure. Ann Thorac Surg 62:1261–1267 discussion 1266–1267

    Article  CAS  PubMed  Google Scholar 

  15. Lemler MS, Ramaciotti C, Stromberg D, Scott WA, Leonard SR (2006) The extracardiac lateral tunnel Fontan, constructed with bovine pericardium: comparison with the extracardiac conduit Fontan. Am Heart J 151:928–933

    Article  PubMed  Google Scholar 

  16. Mahnke CB, Boyle GJ, Janosky JE, Siewers RD, Pigula FA (2005) Anticoagulation and incidence of late cerebrovascular accidents following the Fontan procedure. Pediatr Cardiol 26:56–61

    Article  CAS  PubMed  Google Scholar 

  17. Merten M, Chow T, Hellums JD, Thiagarajan P (2000) A new role for P-selectin in shear-induced platelet aggregation. Circulation 102:2045–2050

    CAS  PubMed  Google Scholar 

  18. Monagle P, Chalmers E, Chan A, DeVeber G, Kirkham F, Massicotte P, Michelson AD; American College of Chest Physicians (2008) Antithrombotic therapy in neonates and children: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. 8th ed. Chest 133:887S–968S

  19. Monagle P, Cochrane A, McCrindle B, Benson L, Williams W, Andrew M (1998) Thromboembolic complications after Fontan procedures: the role of prophylactic anticoagulation. J Thorac Cardiovasc Surg 115:493–498

    Article  CAS  PubMed  Google Scholar 

  20. Nakano T, Kado H, Ishikawa S, Shiokawa Y, Ushinohama H, Sagawa K, Fusazaki N, Nishimura Y, Tanoue Y, Nakamura T, Ueda Y (2004) Midterm surgical results of total cavopulmonary connection: clinical advantages of the extracardiac conduit method. J Thorac Cardiovasc Surg 127:730–737

    Article  PubMed  Google Scholar 

  21. Nakata T, Fujimoto Y, Hirose K, Osaki M, Tosaka Y, Ide Y, Tachi M, Sakamoto K (2009) Functional single ventricle with extracardiac total anomalous pulmonary venous connection. Eur J Cardiothorac Surg 36:49–56 discussion 56

    Article  PubMed  Google Scholar 

  22. Ochiai Y, Imoto Y, Sakamoto M, Sese A, Tsukuda M, Watanabe M, Ohno T, Joo K (2010) Longitudinal growth of the autologous vessels above and below the Gore-Tex graft after the extracardiac conduit Fontan procedure. Eur J Cardiothorac Surg 37:996–1001

    Article  PubMed  Google Scholar 

  23. Ochiai Y, Imoto Y, Sakamoto M, Kajiwara T, Sese A, Watanabe M, Ohno T, Joo K (2009) Midterm follow-up of the status of Gore-Tex graft after extracardiac conduit Fontan procedure. Eur J Cardiothorac Surg 36:63–67 discussion 67–68

    Article  PubMed  Google Scholar 

  24. Petrossian E, Reddy VM, Collins KK, Culbertson CB, MacDonald MJ, Lamberti JJ, Reinhartz O, Mainwaring RD, Francis PD, Malhotra SP, Gremmels DB, Suleman S, Hanley FL (2006) The extracardiac conduit Fontan operation using minimal approach extracorporeal circulation: early and midterm outcomes. J Thorac Cardiovasc Surg 132:1054–1063

    Article  PubMed  Google Scholar 

  25. Ravn HB, Hjortdal VE, Stenbog EV, Emmertsen K, Kromann O, Pedersen J, Sorensen KE (2001) Increased platelet reactivity and significant changes in coagulation markers after cavopulmonary connection. Heart 85:61–65

    Article  CAS  PubMed  Google Scholar 

  26. Rosenthal DN, Friedman AH, Kleinman CS, Kopf GS, LE Rosenfeld, Hellenbrand WE (1995) Thromboembolic complications after Fontan operations. Circulation 92:II287–II293

    CAS  PubMed  Google Scholar 

  27. Seipelt RG, Franke A, Vazquez-Jimenez JF, Hanrath P, von Bernuth G, Messmer BJ, Mühler EG (2002) Thromboembolic complications after Fontan procedures: comparison of different therapeutic approaches. Ann Thorac Surg 74:556–562

    Article  PubMed  Google Scholar 

  28. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of Observational Studies in Epidemiology (MOOSE) group. JAMA 283:2008–2012

    Article  CAS  PubMed  Google Scholar 

  29. Takawira F, Ayer JG, Onikul E, Hawker RE, Kemp A, Nicholson IA, Sholler GF (2008) Evaluation of the extracardiac conduit modification of the Fontan operation for thrombus formation using magnetic resonance imaging. Heart Lung Circ 17:407–410

    Article  PubMed  Google Scholar 

  30. Terrin N, Schmid CH, Lau J (2005) In an empirical evaluation of the funnel plot, researchers could not visually identify publication bias. J Clin Epidemiol 58:894–901

    Article  PubMed  Google Scholar 

  31. Tomita H, Yamada O, Ohuchi H, Ono Y, Arakaki Y, Yagihara T, Echigo S (2001) Coagulation profile, hepatic function, and hemodynamics following Fontan-type operations. Cardiol Young 11:62–66

    CAS  PubMed  Google Scholar 

  32. Varma C, Warr MR, Hendler AL, Paul NS, Webb GD, Therrien J (2003) Prevalence of “silent” pulmonary emboli in adults after the Fontan operation. J Am Coll Cardiol 41:2252–2258

    Article  PubMed  Google Scholar 

  33. Walker HA, Gatzoulis MA (2005) Prophylactic anticoagulation following the Fontan operation. Heart 91:854–856

    Article  CAS  PubMed  Google Scholar 

  34. Woods RK, Dyamenahalli U, Duncan BW, Rosenthal GL, Lupinetti FM (2003) Comparison of extracardiac Fontan techniques: pedicled pericardial tunnel versus conduit reconstruction. J Thorac Cardiovasc Surg 125:465–471

    Article  PubMed  Google Scholar 

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Correspondence to Chiara Marrone.

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Marrone, C., Galasso, G., Piccolo, R. et al. Antiplatelet Versus Anticoagulation Therapy After Extracardiac Conduit Fontan: A Systematic Review and Meta-Analysis. Pediatr Cardiol 32, 32–39 (2011). https://doi.org/10.1007/s00246-010-9808-4

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  • DOI: https://doi.org/10.1007/s00246-010-9808-4

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