Published Online
on February 16, 2004

A more recent version of this article appeared on March 2, 2004

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Submitted on April 24, 2003
Revised on September 17, 2003
Accepted on November 14, 2003

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

Christoph Stellbrink MD^*, Uwe Nixdorff MD, Thomas Hofmann MD, Walter Lehmacher PhD, Werner Günther Daniel MD, Peter Hanrath MD, Christoph Geller MD, Andreas Mügge MD, Walter Sehnert MD, Caroline Schmidt-Lucke MD, Jan-André Schmidt-Lucke MD, and on Behalf of the ACE (Anticoagulation in Cardioversion using Enoxaparin) Study Group

From the Medizinische Klinik I, Rheinisch-Westfälische Technische Hochschule Aachen (C.S., P.H.); Medizinische Klinik II, Friedrich-Alexander-Universität Erlangen-Nürnberg (U.N., W.G.D.); Medizinische Klinik/Kardiologie, Universitäts-Krankenhaus Eppendorf (T.H.); Institut für Medizinische Statistik, Informatik, und Epidemiologie, Universität Köln (W.L.); Abteilung für Kardiologie und Pulmonologie, Otto-Guericke-Universität Magdeburg (C.G., C.S.-L.); Medizinische Klinik II, St Josef-Hospital Bochum (A.M.); Abteilung für Innere Medizin, Evangelisches Krankenhaus Herne (W.S.); and Klinik für Innere Medizin, Park-Krankenhaus Leipzig-Südost (J.-A.S.-L.), Germany.

^* To whom correspondence should be addressed. E-mail: cstellbrink{at}ukaachen.de.

Background--Anticoagulation in cardioversion of atrial fibrillation is currently performed with unfractionated heparin (UFH) and oral anticoagulants, with or without guidance by transesophageal echocardiography (TEE). Low-molecular-weight heparins may reduce the risk of bleeding, may obviate the need for intravenous access, and do not require frequent anticoagulation monitoring.

Methods and Results--In a randomized, prospective multicenter trial, we compared the safety and efficacy of enoxaparin administered subcutaneously with intravenous UFH followed by the oral anticoagulant phenprocoumon in 496 patients scheduled for cardioversion of atrial fibrillation of >48 hours’ and 1 year’s duration. Patients were stratified to cardioversion with (n=431) and without (n=65) guidance by TEE. The study aimed to demonstrate noninferiority of enoxaparin compared with UFH+phenprocoumon with regard to the incidence of embolic events, all-cause death, and major bleeding complications. Secondary end points included successful cardioversion, maintenance of sinus rhythm until study end, and minor bleeding complications. Of 496 randomized patients, 428 were analyzed per protocol. Enoxaparin was noninferior to UFH+phenprocoumon with regard to the incidence of the composite primary end point in a per-protocol analysis (7 of 216 patients versus 12 of 212 patients, respectively; P=0.016) and in an intention-to-treat analysis (7 of 248 patients versus 12 of 248 patients, respectively; P=0.013). There was no significant difference between the 2 groups in the number of patients reverted to sinus rhythm.

Conclusions--Enoxaparin is noninferior to UFH+phenprocoumon for prevention of ischemic and embolic events, bleeding complications, and death in TEE-guided cardioversion of atrial fibrillation. Its easier application and more stable anticoagulation may make it the preferred drug for initiation of anticoagulation in this setting.

Key words: heparin • fibrillation • cardioversion • anticoagulants • echocardiography

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