Low Molecular Weight Heparin vs Unfractionated Heparin at Cardiac Surgery

NCT ID: NCT00420667

Last Updated: 2022-11-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-11-30
• Study Completion Date: 2005-05-31

Brief Summary

Because the impairment of platelet function may cause excess peri-operative bleeding, pre-operative aspirin discontinuation and heparin bridging are common at cardiac surgery. We aimed to evaluate the impact of a low-molecular-weight-heparin (LMWH), enoxaparin, and unfractionated heparin (UFH) on coagulation parameters and peri-operative bleeding in patients undergoing elective coronary artery bypass grafting (CABG) surgery after aspirin discontinuation.

The specific hypothesis of this study was that a 12 h interval is sufficient not to cause excess peri-operative bleeding, and is therefore an optimal compromise between antithrombotic efficacy and haemorrhagic safety.

Detailed Description

Since LMWH provide many pharmacokinetic advantages compared with UFH, and since they are a valid substitution for UFH in a number of settings, such as non-ST elevation acute coronary syndromes and prevention of venous thromboembolism, LMWH may provide a useful bridge to revascularization after aspirin discontinuation in patients undergoing CABG surgery. Obstacles to the spreading of this practice are mainly the absence of solid evidence of equivalence (or superiority) as to efficacy in this setting, and the proof of equal safety, namely the absence of excess bleeding because some studies have suggested an increased number of haemorrhagic complications after LMWH, particularly with the use of higher doses. This might here be a problem, as patients are here generally at high risk of thrombotic events and for this reason need higher doses than for prevention of venous thromboembolism.

Conditions

Coronary Disease; Coronary Artery Bypass Grafting

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Enoxaparin

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients aged 35-75 years with 3-vessel coronary artery disease (CAD)
• Candidates to elective CABG

Exclusion Criteria

• Other additional (valve, carotid, etc.) simultaneous surgery required,
• Off-pump surgery,
• Any altered liver and kidney laboratory parameters,
• A history of any haemorrhagic disorders,
• Platelet count <100,000 and >450.000/μL,
• Treatment with ticlopidine or clopidogrel in the last month.

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

G. d'Annunzio University

OTHER

Sponsor Role: lead

Responsible Party

Raffaele De Caterina

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Raffaele De Caterina, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Institute of Cardiology - G. d'Annunzio University, Chieti

Locations

Institute of Cardiology - S. Camillo Hospital

Chieti, CH, Italy

Countries

Italy

References

Eagle KA, Guyton RA, Davidoff R, Edwards FH, Ewy GA, Gardner TJ, Hart JC, Herrmann HC, Hillis LD, Hutter AM Jr, Lytle BW, Marlow RA, Nugent WC, Orszulak TA; American College of Cardiology; American Heart Association. ACC/AHA 2004 guideline update for coronary artery bypass graft surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for Coronary Artery Bypass Graft Surgery). Circulation. 2004 Oct 5;110(14):e340-437. No abstract available.

Reference Type: BACKGROUND

PMID: 15466654 (View on PubMed)

Goldman S, Zadina K, Moritz T, Ovitt T, Sethi G, Copeland JG, Thottapurathu L, Krasnicka B, Ellis N, Anderson RJ, Henderson W; VA Cooperative Study Group #207/297/364. Long-term patency of saphenous vein and left internal mammary artery grafts after coronary artery bypass surgery: results from a Department of Veterans Affairs Cooperative Study. J Am Coll Cardiol. 2004 Dec 7;44(11):2149-56. doi: 10.1016/j.jacc.2004.08.064.

Reference Type: BACKGROUND

PMID: 15582312 (View on PubMed)

Mangano DT; Multicenter Study of Perioperative Ischemia Research Group. Aspirin and mortality from coronary bypass surgery. N Engl J Med. 2002 Oct 24;347(17):1309-17. doi: 10.1056/NEJMoa020798.

Reference Type: BACKGROUND

PMID: 12397188 (View on PubMed)

Dacey LJ, Munoz JJ, Johnson ER, Leavitt BJ, Maloney CT, Morton JR, Olmstead EM, Birkmeyer JD, O'Connor GT; Northern New England Cardiovascular Disease Study Group. Effect of preoperative aspirin use on mortality in coronary artery bypass grafting patients. Ann Thorac Surg. 2000 Dec;70(6):1986-90. doi: 10.1016/s0003-4975(00)02133-0.

Reference Type: BACKGROUND

PMID: 11156107 (View on PubMed)

Ferraris VA, Ferraris SP. 1988: Preoperative aspirin ingestion increases operative blood loss after coronary artery bypass grafting. Updated in 1995. Ann Thorac Surg. 1995 Apr;59(4):1036-7. doi: 10.1016/0003-4975(95)00023-e. No abstract available.

Reference Type: BACKGROUND

PMID: 7695387 (View on PubMed)

Karthik S, Grayson AD, McCarron EE, Pullan DM, Desmond MJ. Reexploration for bleeding after coronary artery bypass surgery: risk factors, outcomes, and the effect of time delay. Ann Thorac Surg. 2004 Aug;78(2):527-34; discussion 534. doi: 10.1016/j.athoracsur.2004.02.088.

Reference Type: BACKGROUND

PMID: 15276512 (View on PubMed)

Sethi GK, Copeland JG, Goldman S, Moritz T, Zadina K, Henderson WG. Implications of preoperative administration of aspirin in patients undergoing coronary artery bypass grafting. Department of Veterans Affairs Cooperative Study on Antiplatelet Therapy. J Am Coll Cardiol. 1990 Jan;15(1):15-20. doi: 10.1016/0735-1097(90)90168-o.

Reference Type: BACKGROUND

PMID: 2404046 (View on PubMed)

Sirvinskas E, Veikutiene A, Grybauskas P, Cimbolaityte J, Mongirdiene A, Veikutis V, Raliene L. Influence of aspirin or heparin on platelet function and postoperative blood loss after coronary artery bypass surgery. Perfusion. 2006 Jan;21(1):61-6. doi: 10.1191/0267659106pf845oa.

Reference Type: BACKGROUND

PMID: 16485701 (View on PubMed)

Hirsh J, Raschke R. Heparin and low-molecular-weight heparin: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep;126(3 Suppl):188S-203S. doi: 10.1378/chest.126.3_suppl.188S.

Reference Type: BACKGROUND

PMID: 15383472 (View on PubMed)

Petersen JL, Mahaffey KW, Hasselblad V, Antman EM, Cohen M, Goodman SG, Langer A, Blazing MA, Le-Moigne-Amrani A, de Lemos JA, Nessel CC, Harrington RA, Ferguson JJ, Braunwald E, Califf RM. Efficacy and bleeding complications among patients randomized to enoxaparin or unfractionated heparin for antithrombin therapy in non-ST-Segment elevation acute coronary syndromes: a systematic overview. JAMA. 2004 Jul 7;292(1):89-96. doi: 10.1001/jama.292.1.89.

Reference Type: BACKGROUND

PMID: 15238596 (View on PubMed)

Clark SC, Vitale N, Zacharias J, Forty J. Effect of low molecular weight heparin (fragmin) on bleeding after cardiac surgery. Ann Thorac Surg. 2000 Mar;69(3):762-4; discussion 764-5. doi: 10.1016/s0003-4975(99)01366-1.

Reference Type: BACKGROUND

PMID: 10750757 (View on PubMed)

Prandoni P. Heparins and venous thromboembolism: current practice and future directions. Thromb Haemost. 2001 Jul;86(1):488-98.

Reference Type: BACKGROUND

PMID: 11487039 (View on PubMed)

Mismetti P, Laporte S, Darmon JY, Buchmuller A, Decousus H. Meta-analysis of low molecular weight heparin in the prevention of venous thromboembolism in general surgery. Br J Surg. 2001 Jul;88(7):913-30. doi: 10.1046/j.0007-1323.2001.01800.x.

Reference Type: BACKGROUND

PMID: 11442521 (View on PubMed)

Jones HU, Muhlestein JB, Jones KW, Bair TL, Lavasani F, Sohrevardi M, Horne BD, Doty D, Lappe DL. Preoperative use of enoxaparin compared with unfractionated heparin increases the incidence of re-exploration for postoperative bleeding after open-heart surgery in patients who present with an acute coronary syndrome: clinical investigation and reports. Circulation. 2002 Sep 24;106(12 Suppl 1):I19-22.

Reference Type: BACKGROUND

PMID: 12354703 (View on PubMed)

Burger W, Chemnitius JM, Kneissl GD, Rucker G. Low-dose aspirin for secondary cardiovascular prevention - cardiovascular risks after its perioperative withdrawal versus bleeding risks with its continuation - review and meta-analysis. J Intern Med. 2005 May;257(5):399-414. doi: 10.1111/j.1365-2796.2005.01477.x.

Reference Type: BACKGROUND

PMID: 15836656 (View on PubMed)

Sun JC, Crowther MA, Warkentin TE, Lamy A, Teoh KH. Should aspirin be discontinued before coronary artery bypass surgery? Circulation. 2005 Aug 16;112(7):e85-90. doi: 10.1161/CIRCULATIONAHA.105.546697. No abstract available.

Reference Type: BACKGROUND

PMID: 16103244 (View on PubMed)

Other Identifiers

001

Identifier Type: -

Identifier Source: org_study_id