A nticoagulation for for C ardioversion C ardioversion using - - PowerPoint PPT Presentation

A Anticoagulation

nticoagulation for for

C Cardioversion

ardioversion using using

E Enoxaparin

noxaparin

Stellbrink C, Nixdorff U, Hofmann T, Kühle K, Grewe R, Hanrath P, Lehmacher W, Schmidt-Lucke JA

• on behalf of the ACE Investigators -

• ...is frequently underused due to fear of bleeding

complications1.

• ...requires frequent anticoagulation monitoring.

Potential Advantages of LMWH in Potential Advantages of LMWH in AF AF Cardioversion Cardioversion

• ...allow ambulatory therapy initiation (s.c. administration).
• ...do not require routine anticoagulation checks2.
• ...are safe and effective in non-randomized studies of

cardioversion5,6.

1Lip et al., Br Heart J 1994; 2Hirsh et al. Chest 2001; 3Cohen et al. NEJM 1997; 4ASSENT-3 Lancet 2001; 5Harenberg Semin Thromb Hemost 1997; 6Roijer et al. Eur Heart J 2000

Conventional Anticoagulation: Low Molecular Weight Heparins:

Aim Aim

• f the Study
• f the Study

Evaluate in a prospective randomized, open- label multicenter trial the efficacy and safety

• f

– s.c. enoxaparin

vs. – i.v. UFH and phenprocoumon (PPC) in cardioversion of non-valvular AF

Study Study Design Design

=CARDIOVERSION; AF=ATRIAL FIBRILLATION; TEE=TRANSESOPHAGEAL ECHOCARDIOGRAPHY; UFH=UNFRACTIONATED HEPARIN; PCC=PHENPROCOUMON

ENOXAPARIN Stratum A: no TEE guidance PPC

21 days 21 days 28 days 28 days NO YES TEE: Thrombus? 28 days

PPC END PPC

TEE: Thrombus? 21 days

PPC

28 days NO YES 28 days 21 days

END

TEE: Thrombus? NO YES TEE: Thrombus?

ENOXAPARIN

28 days

ENOXAPARIN ENOXAPARIN

NO YES

ENOXAPARIN UFH/PPC Stratum B: TEE guidance UFH/PPC ENOXAPARIN

Composite primary endpoint:

• Cerebral-ischemic neurological events,
• Systemic thromboembolism,
• Major bleeding complications and
• Death from any cause

Secondary endpoints: Successful cardioversions, patients in sinus rhythm at study end, other bleeding complications (except major bleedings), injection hematoma ∅ ≥ 5 cm

Study Endpoints Study Endpoints* *

*All serious adverse events adjudicated by independent CEC Blinded review of all primary endpoint events by independent ERC

Results: Primary Endpoint Results: Primary Endpoint

6 2 2 4 6

statistical assumption

UFH/PPC Enoxaparin

Combined event rate (%) non-inferiority ∆ = 2%

8

results of per-protocol analysis

p = 0,016 test on non-inferiority

n = 7/216

(n = 428)

n = 12/212 3.2 5.7 7,7 4

Primary Primary Endpoint Events Endpoint Events (ITT, n=496) (ITT, n=496)

Events Enoxaparin UFH/PPC (n=248) (n=248) Composite Endpoint n (%) 7 (2.8%) 12 (4.8%)

• Embolic events

n (%) 2 (0.8%) 4 (1.6%)

• Major hemorrhage n (%)

2 (0.8%) 6 (2.4%)

• Deaths

n (%) 3 (1.2%) 5 (2.0%)

Conclusions Conclusions

• ...is non-inferior to UFH/phenprocoumon for the

prevention of bleeding and embolism in cardioversion of non-valvular AF.

• ...offers
• ease of s.c. administration
• reduced need for anticoagulation monitoring

Enoxaparin

...may be the preferred drug for this purpose. ...may be the preferred drug for this purpose.