• 
• 

Three Part Question

In [haemodynamically unstable patients with atrial fibrillation undergoing DC shock] is [LMWH superior to unfractionated heparin] in [reducing the risk of thromboembolism]?

Clinical Scenario

A middle-aged man is brought into accident and emergency by ambulance, he told the paramedics that he is suffering from chest pain, breathlessness and palpitations which began 4 days ago but has suddenly got worse. On arrival his blood pressure is <90mmHg and on examination he has a raised JVP and a reduced level of consciousness. An ECG confirms atrial fibrillation. You decide that he should be cardioverted ASAP but do not know which method of anticoagulation would be best to reduce the risk of thromboembolsim associated with cardioversion.

Search Strategy

Embase 1980 to 2008 Week 24.
Medline 1950 to June Week 2 2008 using ovid interface
Cochrane Central Register of Controlled Trials

[exp electric countershock/ or electrical cardioversion.mp. or DC cardioversion.mp. or DC shock.mp. or cardioversion.mp.] AND [exp Heparin/ or Heparin.mp. or Low-Molecular-Weight/ or low molecular weight.mp. or low molecular weight heparin.mp. or unfractionated heparin.mp. or exp fragmin/ or fragmin.mp. or exp dalteparin/ or dalteparin.mp. or exp clexane/ or clexane.mp. or exp enoxaparin/ or enoxaparin.mp.] AND [exp Atrial Fibrillation/ or (atrial adj fibrillation).mp.] LIMIT to humans and english language

Search Outcome

310 papers found of which 308 irrelevant to the clinical question

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Stellbrink C et al. 2003 Germany	496 patients >18yrs, >45kg scheduled for cardioversion, AF confirmed by ECG with clinical symptoms of palpitations, dizziness, tacchycardia from 56 centres Enoxaparin subcutaneously (1mg/kg body wt. b.d. for 3-8d, then 40mg b.d. in pts <65kg and 60mg in those>60mg) for rest of study period Vs. Unfractionated heparin IV (80IU/kg followed by continuous infusion adjusted to APTT for at least 72h and followed by phenprocoumon PO	Controlled prospective randomized open-label multicentre trial (1b)	Cerebral ischaemic neurological events, systemic thromboembolism, death, major bleeding	Noninferiority of enoxaparin to unfractionated heparin plus phenprocoumon with regard to occurrence of adverse events, especially when TEE guidance is used	Did not recruit sufficient numbers to power the study (496 of 500 required to demonstrate noninferiority with a margin of 2%) Open-labelled as comparing oral medication with subcutaneous Outcomes were evaluated only during the planned therapy phase, this meant patients undergoing conventional cardioversion or with thrombi on TEE were evaluated for 49d whereas patients without thrombi on TEE were evaluated for just 28d Used phenprocoumon therefore caution when extrapolating data to warfarin
Klein AL et al. 2006 United States	155 patients with persistent or paroxysmal AF >2d duration with option of early electrical or chemical cardioversion from 17 sites Enoxaparin (LMWH) Vs. Unfractionated heparin	Prospective randomised controlled trial	Safety (cerebrovascular accident, TIA, peripheral embolism, major or minor bleeding, and death.)	Minor bleeding: LMWH= 3/76 (4%) UFH= 3/79 (4%) Thrombi:LMWH=5/76 UFH=4/79 No embolic events, major bleeds or deaths	[The authors declared a conflict of interest which was that the study was an investigator initiated trial that was supported by a grant-in-aid from Sanofi-aventis who manufacture enoxaparin (Lovenox)]
			Length of stay	Shorter in enoxaparin group 4d (3-5) vs. 5d (4-7) p=0.003 Median (interquartile range of 25 and 75%)
			Sinus rhythm at 5 weeks	LMWH= 55/72 (76%) UFH= 44/77 (57%) P=0.0129

Comment(s)

Enoxaparin is self-administered subcutaneously and its anticoagulant response is predictable(3) so prolonged in hospital therapy and monitoring of the activated partial thromboplastin time are unnecessary. Economic analyses by Zhao et al. in 2006 found that lower length of stay in the enoxaparin group translated to a costs saving of $2307 (95% CI, $1048 to $4309) compared with the unfractionated heparin group.

Clinical Bottom Line

Enoxaparin is noninferior to unfractionated heparin in the setting of cardioversion of haemodynamically stable atrial fibrillation with regards to safety.

References

1. Stellbrink C. Nixdorff U. Hofmann T. Lehmacher W. Daniel WG. Hanrath P. Geller C. Mugge A. Sehnert W. Schmidt-Lucke C. Schmidt-Lucke JA. Safety and efficacy of enoxaparin compared with unfractionated heparin and oral anticoagulants for prevention of thromboembolic complications in cardioversion of nonvalvular atrial fibrillation Circulation 2004; 109(8):997-1003
2. Klein AL. Jasper SE. Katz WE. Malouf JF. Pape LA. Stoddard MF. ACUTE II Steering and Publications Committe for the ACUTE II Investigators. The use of enoxaparin compared with unfractionated heparin for short-term antithrombotic therapy in atrial fibrillation patients undergoing transoesophageal echocardiography-guided cardioversion European Heart Journal 2006; 27(23):2858-65
3. Turpie AG, Mason JA. Review of enoxaparin and its clinical applications in venous and arterial thromboembolism Expert opinion pharmacotherapy. 2002; 3:575-598
4. Zhoa L, Lewis C, Jasper SE, Klein AL, Weintraub WS. Economic analysis of LMWH strategy compared with unfractionated heparin strategy for cardioversion of atrial fibrillation using transesophageal echocardiography: results from the ACUTE II study. Journal of American College Cardiology 2006; 47 (Supplement B): 1B:2901-2962