A nticoagulation A nticoagulation for for C ardioversion C ardioversion using using E noxaparin E noxaparin Stellbrink C, Nixdorff U, Hofmann T, Kühle K, Grewe R, Hanrath P, Lehmacher W, Schmidt-Lucke JA - on behalf of the ACE Investigators -
Potential Advantages of LMWH in Potential Advantages of LMWH in AF Cardioversion Cardioversion AF Conventional Anticoagulation: • ...is frequently underused due to fear of bleeding complications 1 . • ...requires frequent anticoagulation monitoring. Low Molecular Weight Heparins: • ...allow ambulatory therapy initiation (s.c. administration). ...do not require routine anticoagulation checks 2 . • • ...are safe and effective in non-randomized studies of cardioversion 5,6 . 1 Lip et al., Br Heart J 1994; 2 Hirsh et al. Chest 2001; 3 Cohen et al. NEJM 1997; 4 ASSENT-3 Lancet 2001; 5 Harenberg Semin Thromb Hemost 1997; 6 Roijer et al. Eur Heart J 2000
Aim of the Study of the Study Aim Evaluate in a prospective randomized, open- label multicenter trial the efficacy and safety of – s.c. enoxaparin vs. – i.v. UFH and phenprocoumon (PPC) in cardioversion of non-valvular AF
Study Design Design Study Stratum B: Stratum A: TEE guidance no TEE guidance UFH/PPC ENOXAPARIN TEE: TEE: Thrombus? Thrombus? NO YES NO YES UFH/PPC ENOXAPARIN PPC ENOXAPARIN 21 21 21 21 days days days days 28 TEE: 28 TEE: days Thrombus? days Thrombus? NO YES NO YES ENOXAPARIN PPC END END 28 28 28 days days 28 days days PPC ENOXAPARIN ENOXAPARIN PPC = CARDIOVERSION; AF=ATRIAL FIBRILLATION; TEE=TRANSESOPHAGEAL ECHOCARDIOGRAPHY; UFH=UNFRACTIONATED HEPARIN; PCC=PHENPROCOUMON
Study Endpoints* * Study Endpoints 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 *All serious adverse events adjudicated by independent CEC Blinded review of all primary endpoint events by independent ERC
Results: Primary Endpoint Results: Primary Endpoint 8 7,7 UFH/PPC 6 5.7 Enoxaparin 6 non-inferiority ∆ = 2% Combined event rate ( %) p = 0,016 n = 12/212 test on 4 non-inferiority 4 3.2 n = 7/216 2 2 0 statistical assumption results of per-protocol analysis (n = 428)
Primary Endpoint Events Endpoint Events Primary (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 Enoxaparin • ...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 ...may be the preferred drug for this purpose. ...may be the preferred drug for this purpose.
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