February 17, 2004

Safety and Efficacy of Enoxaparin Compared With Unfractionated Heparin and Oral Anticoagulants for Prevention of Thromboembolic Complications in Cardioversion of Nonvalvular Atrial Fibrillation

Q: What is the clinical evidence from this study?

Study design: RCT. Population: Nonvalvular Atrial Fibrillation (n=496). Intervention: Enoxaparin vs. intravenous UFH followed by the oral anticoagulant phenprocoumon. Primary outcome: embolic events, all-cause death, and major bleeding complications (p=0.013).

Key Result

Enoxaparin was noninferior to UFH plus phenprocoumon for the composite of embolic events, death, and major bleeding in cardioversion of atrial fibrillation (2.8% vs 4.8%; P=0.013 for noninferiority).

Study Design

Type

RCT (n=496)

Randomization

randomized

Multicenter

Yes

Structured PICO

Does subcutaneous enoxaparin prevent embolic events, death, and major bleeding noninferiorly to intravenous UFH followed by phenprocoumon in patients scheduled for cardioversion of nonvalvular atrial fibrillation?

Population

496 patients scheduled for cardioversion of nonvalvular atrial fibrillation of >48 hours' and ≤1 year's duration, stratified to cardioversion with (n=431) and without (n=65) guidance by transesophageal echocardiography (TEE).

Intervention

Enoxaparin administered subcutaneously

Comparator

Intravenous unfractionated heparin (UFH) followed by the oral anticoagulant phenprocoumon

Outcome

Composite of embolic events, all-cause death, and major bleeding complicationscomposite

Subcutaneous enoxaparin is noninferior to intravenous UFH followed by phenprocoumon for preventing thromboembolic complications, death, and major bleeding in patients undergoing cardioversion for nonvalvular atrial fibrillation.

Main Result

Absolute Event Rate: 2.8% vs 4.8%

p-value: p=0.013

Abstract

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 < or =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.