Clinical Research in Cardiology

, Volume 97, Issue 6, pp 389–396 | Cite as

AFFECT: a prospective, open-label, multicenter trial to evaluate the feasibility and safety of a short-term treatment with subcutaneous certoparin in patients with persistent non-valvular atrial fibrillation

  • Ulrich Tebbe
  • Ralph Oeckinghaus
  • Karl-Friedrich Appel
  • Hubertus Heuer
  • Hendrik Haake
  • Egbert Eggers
  • Karlheinz Seidel
  • Jan Adams
  • Job Harenberg
ORIGINAL PAPER

Abstract

Background

Patients with persistent atrial fibrillation (AF) scheduled for electrical cardioversion need immediate anticoagulation. Unfractionated heparin (UFH) is often used for early anticoagulation in these patients before oral anticoagulation becomes effective. However, dose adjustment is required to achieve a two- to three-fold prolongation of the activated partial thromboplastin. Low molecular weight heparins, given in body weight-adjusted or independent fixed dosage, require less laboratory monitoring and are also effective within hours of first dosing. They seem to be an attractive alternative to UFH. Previous evidence has shown that these drugs are safe and effective in this indication.

Patients and methods

In this prospective, open-label, multicenter pilot study, 203 patients were enrolled with persistent non-valvular AF scheduled for electrical cardioversion. Patients received a fixed dose of 8000 U anti-Xa certoparin twice daily starting immediately after enrolment and before cardioversion was performed. Patients with AF > 48 h underwent transoesophageal echocardiography (TEE) before cardioversion to exclude intra-atrial thrombi. After cardioversion, overlapping oral anticoagulation was started. Treatment with certoparin was stopped only after two consecutive days with INR values >2.

Objectives

The objective was to document the feasibility and safety of a short-term treatment with a fixed, body weight-independent certoparin regimen (2 × 8000 U anti-Xa).

Results

Out of 203 patients enrolled, 200 received at least one dose of certoparin and were included in the analysis (safety population). Median treatment duration with certoparin was 7 days. Bleedings were observed in 8 patients (4.0%) and were classified as major (1.5%) or minor (2.5%). Cerebral ischemia was reported for 1 patient (0.5%). One patient showed mild thrombocytopenia (0.5%). There were no reports of venous thromboembolism or death during the treatment period.

Conclusion

Certoparin administered at 8000 U anti-Xa twice daily independent of body weight was safe and appeared to be effective in patients with non-valvular AF undergoing electrical cardioversion. Its ease of use and the possibility of treatment on an outpatient basis make it an attractive option for early anticoagulation in AF.

Keywords

cardioversion transoesophageal echocardiography atrial fibrillation anticoagulation low molecular weight heparin certoparin 

References

  1. 1.
    Bechtold H, Janssen D (2004) Anticoagulation with low-molecular-weight heparin in patients with heart diseases. Eur J Med Res 9:186–198PubMedGoogle Scholar
  2. 2.
    Becker T, Kleemann T, Strauss M, Doenges K, Schneider S, Senges J, Seidl K (2007) Long-term prognosis after cardioversion of the first episode of symptomatic atrial fibrillation: a condition believed to be benign revised. Clin Res CardiolGoogle Scholar
  3. 3.
    Collet JP, Montalescot G, Lison L, Choussat R, Ankri A, Drobinski G, Sotirov I, Thomas D (2001) Percutaneous coronary intervention after subcutaneous enoxaparin pretreatment in patients with unstable angina pectoris. Circulation 103:658–663PubMedGoogle Scholar
  4. 4.
    de Luca I, Sorino M, De Luca L, Colonna P, Del Salvatore B, Corliano L (2005) Pre- and post-cardioversion transesophageal echocardiography for brief anticoagulation therapy with enoxaparin in atrial fibrillation patients: a prospective study with a 1-year follow-up. Int J Cardiol 102:447–454PubMedCrossRefGoogle Scholar
  5. 5.
    Frydman AM, Bara L, Le Roux Y, Woler M, Chauliac F, Samama MM (1988) The antithrombotic activity and pharmacokinetics of enoxaparine, a low molecular weight heparin, in humans given single subcutaneous doses of 20 to 80 mg. J Clin Pharmacol 28:609–618PubMedGoogle Scholar
  6. 6.
    Fuster V, Ryden LE, Cannom DS, Crijns HJ, Curtis AB, Ellenbogen KA, Halperin JL, Le Heuzey JY et al (2006) ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 114:e257–e354PubMedCrossRefGoogle Scholar
  7. 7.
    Harenberg J, Riess H, Buller HR, Brom J, Weidinger G, Huisman MV (2003) Comparison of six-month outcome of patients initially treated for acute deep vein thrombosis with a low molecular weight heparin Certoparin at a fixed, body-weight-independent dosage or unfractionated heparin. Haematologica 88:1157–1162PubMedGoogle Scholar
  8. 8.
    Hylek EM, Singer DE (1994) Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med 120:897–902PubMedGoogle Scholar
  9. 9.
    Hylek EM, Skates SJ, Sheehan MA, Singer DE (1996) An analysis of the lowest effective intensity of prophylactic anticoagulation for patients with nonrheumatic atrial fibrillation. N Engl J Med 335:540–546PubMedCrossRefGoogle Scholar
  10. 10.
    Kirchmaier CM, Wolf H, Schafer H, Ehlers B, Breddin HK (1998) Efficacy of a low molecular weight heparin administered intravenously or subcutaneously in comparison with intravenous unfractionated heparin in the treatment of deep venous thrombosis. Certoparin-study group. Int Angiol 17:135–145PubMedGoogle Scholar
  11. 11.
    Kleemann T, Becker T, Donges K, Vater M, Gut B, Schneider S, Senges J, Seidl K (2007) The prognostic impact of successful cardioversion of atrial fibrillation in patients with organic heart disease. Clin Res Cardiol 96:103–108PubMedCrossRefGoogle Scholar
  12. 12.
    Klein AL, Grimm RA, Murray RD, Apperson-Hansen C, Asinger RW, Black IW, Davidoff R, Erbel R et al (2001) Use of transesophageal echocardiography to guide cardioversion in patients with atrial fibrillation. N Engl J Med 344:1411–1420PubMedCrossRefGoogle Scholar
  13. 13.
    Klein AL, Jasper SE, Katz WE, Malouf JF, Pape LA, Stoddard MF, Apperson-Hansen C, Lieber EA (2006) The use of enoxaparin compared with unfractionated heparin for short-term antithrombotic therapy in atrial fibrillation patients undergoing transoesophageal echocardiography-guided cardioversion: assessment of Cardioversion Using Transoesophageal Echocardiography (ACUTE) II randomized multicentre study. Eur Heart J 27:2858–2865PubMedCrossRefGoogle Scholar
  14. 14.
    Lethen H, Oberst P, Bermes A, Zuercher F, Kersting S, Lambertz H (2006) Longterm results after TEE-guided electrical cardioversion of atrial fibrillation using a short term anticoagulation strategy with enoxaparin. Relevance of LAA flow for an event free outcome. Circulation 114:361Google Scholar
  15. 15.
    Murray RD, Deitcher SR, Shah A, Jasper SE, Bashir M, Grimm RA, Klein AL (2001) Potential clinical efficacy and cost benefit of a transesophageal echocardiography-guided low-molecular-weight heparin (enoxaparin) approach to antithrombotic therapy in patients undergoing immediate cardioversion from atrial fibrillation. J Am Soc Echocardiogr 14:200–208PubMedCrossRefGoogle Scholar
  16. 16.
    Rosenkranz S, Maier LS, Maack C, Bohm M (2007) Hotline update of clinical trials and registries presented at the German Cardiac Society Meeting 2007: 2L-Registry, Kardio-Pro, EVER, AFFECT, VTACH, ARTS II, OPTAMI, PEPCAD I, PEPCAD II, GERSHWIN, SPICE, FIX-CHF and CREDIT. Clin Res Cardiol 96:457–468PubMedCrossRefGoogle Scholar
  17. 17.
    Schmidt-Lucke C, Paar WD, Stellbrink C, Nixdorff U, Hofmann T, Meurer J, Grewe R, Daniel WG et al (2007) Quality of anticoagulation with unfractionated heparin plus phenprocoumon for the prevention of thromboembolic complications in cardioversion for non-valvular atrial fibrillation. Sub-analysis from the anticoagulation in cardioversion using enoxaparin (ACE) trial. Thromb Res 119:27–34PubMedCrossRefGoogle Scholar
  18. 18.
    Stellbrink C, Nixdorff U, Hofmann T, Lehmacher W, Daniel WG, Hanrath P, Geller C, Mugge A et al (2004) Safety and efficacy of enoxaparin compared with unfractionated heparin and oral anticoagulants for prevention of thromboembolic complications in cardioversion of nonvalvular atrial fibrillation: the anticoagulation in cardioversion using enoxaparin (ACE) trial. Circulation 109:997–1003PubMedCrossRefGoogle Scholar
  19. 19.
    Wyse DG, Waldo AL, DiMarco JP, Domanski MJ, Rosenberg Y, Schron EB, Kellen JC, Greene HL et al (2002) A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 347:1825–1833PubMedCrossRefGoogle Scholar
  20. 20.
    Young E, Wells P, Holloway S, Weitz J, Hirsh J (1994) Ex-vivo and in-vitro evidence that low molecular weight heparins exhibit less binding to plasma proteins than unfractionated heparin. Thromb Haemost 71:300–304PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Ulrich Tebbe
    • 1
  • Ralph Oeckinghaus
    • 1
  • Karl-Friedrich Appel
    • 2
  • Hubertus Heuer
    • 3
  • Hendrik Haake
    • 4
  • Egbert Eggers
    • 5
  • Karlheinz Seidel
    • 6
  • Jan Adams
    • 7
  • Job Harenberg
    • 8
  1. 1.Klinikum Lippe GmbH, Fachbereich Herz-KreislaufDetmoldGermany
  2. 2.Ambulantes Herzzentrum KasselKasselGermany
  3. 3.St.-Johannes Hospital DortmundDortmundGermany
  4. 4.Krankenhaus St. Franziskus, MönchengladbachMönchengladbachGermany
  5. 5.Kreiskrankenhaus TorgauTorgauGermany
  6. 6.Herzzentrum LudwigshafenLudwigshafenGermany
  7. 7.Novartis Pharma GmbHNurembergGermany
  8. 8.Medizinische Klinik, Universitätsklinikum MannheimMannheimGermany

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