Enoxaparin Outcomes in Patients With Moderate Renal Impairment | Clinical Pharmacy and Pharmacology | JAMA Internal Medicine | JAMA Network
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1.
Hirsh J, Bauer KA, Donati MB, Gould M, Samama MM, Weitz JI.American College of Chest Physicians.  Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition).  Chest. 2008;133(6):(suppl)  141S-159S18574264PubMedGoogle ScholarCrossref
2.
 Lovenox [prescribing information]. http://products.sanofi.us/lovenox/lovenox.html. Accessed September 29, 2011
3.
Hulot JS, Vantelon C, Urien S,  et al.  Effect of renal function on the pharmacokinetics of enoxaparin and consequences on dose adjustment.  Ther Drug Monit. 2004;26(3):305-31015167633PubMedGoogle ScholarCrossref
4.
Chow SL, Zammit K, West K, Dannenhoffer M, Lopez-Candales A. Correlation of antifactor Xa concentrations with renal function in patients on enoxaparin.  J Clin Pharmacol. 2003;43(6):586-59012817521PubMedGoogle Scholar
5.
Becker RC, Spencer FA, Gibson M,  et al; TIMI 11A Investigators.  Influence of patient characteristics and renal function on factor Xa inhibition pharmacokinetics and pharmacodynamics after enoxaparin administration in non–ST-segment elevation acute coronary syndromes.  Am Heart J. 2002;143(5):753-75912040334PubMedGoogle ScholarCrossref
6.
Bazinet A, Almanric K, Brunet C,  et al.  Dosage of enoxaparin among obese and renal impairment patients.  Thromb Res. 2005;116(1):41-5015850607PubMedGoogle ScholarCrossref
7.
Green B, Greenwood M, Saltissi D,  et al.  Dosing strategy for enoxaparin in patients with renal impairment presenting with acute coronary syndromes.  Br J Clin Pharmacol. 2005;59(3):281-29015752373PubMedGoogle ScholarCrossref
8.
Sanderink GJ, Guimart CG, Ozoux ML, Jariwala NU, Shukla UA, Boutouyrie BX. Pharmacokinetics and pharmacodynamics of the prophylactic dose of enoxaparin once daily over 4 days in patients with renal impairment.  Thromb Res. 2002;105(3):225-23111927128PubMedGoogle ScholarCrossref
9.
Bruno R, Baille P, Retout S,  et al.  Population pharmacokinetics and pharmacodynamics of enoxaparin in unstable angina and non–ST-segment elevation myocardial infarction.  Br J Clin Pharmacol. 2003;56(4):407-41412968985PubMedGoogle ScholarCrossref
10.
Thorevska N, Amoateng-Adjepong Y, Sabahi R,  et al.  Anticoagulation in hospitalized patients with renal insufficiency: a comparison of bleeding rates with unfractionated heparin vs enoxaparin.  Chest. 2004;125(3):856-86315006942PubMedGoogle ScholarCrossref
11.
Gerlach AT, Pickworth KK, Seth SK, Tanna SB, Barnes JF. Enoxaparin and bleeding complications: a review in patients with and without renal insufficiency.  Pharmacotherapy. 2000;20(7):771-77510907967PubMedGoogle ScholarCrossref
12.
Barras MA, Duffull SB, Atherton JJ, Green B. Individualized compared with conventional dosing of enoxaparin.  Clin Pharmacol Ther. 2008;83(6):882-88817928819PubMedGoogle ScholarCrossref
13.
Cestac P, Bagheri H, Lapeyre-Mestre M,  et al.  Utilisation and safety of low molecular weight heparins: prospective observational study in medical inpatients.  Drug Saf. 2003;26(3):197-20712580648PubMedGoogle ScholarCrossref
14.
Fox KA, Antman EM, Montalescot G,  et al.  The impact of renal dysfunction on outcomes in the ExTRACT-TIMI 25 trial.  J Am Coll Cardiol. 2007;49(23):2249-225517560289PubMedGoogle ScholarCrossref
15.
Hulot JS, Montalescot G, Lechat P, Collet JP, Ankri A, Urien S. Dosing strategy in patients with renal failure receiving enoxaparin for the treatment of non–ST-segment elevation acute coronary syndrome.  Clin Pharmacol Ther. 2005;77(6):542-55215961985PubMedGoogle ScholarCrossref
16.
Barras MA, Duffull SB, Atherton JJ, Green B. Individualized dosing of enoxaparin for subjects with renal impairment is superior to conventional dosing at achieving therapeutic concentrations.  Ther Drug Monit. 2010;32(4):482-48820592650PubMedGoogle ScholarCrossref
17.
Kruse MW, Lee JJ. Retrospective evaluation of a pharmacokinetic program for adjusting enoxaparin in renal impairment.  Am Heart J. 2004;148(4):582-58915459586PubMedGoogle ScholarCrossref
18.
Hammerstingl C. Monitoring therapeutic anticoagulation with LMWHs: is it useful or misleading?  Cardiovasc Hematol Agents Med Chem. 2008;6:282-28618855641PubMedGoogle ScholarCrossref
19.
Barrowcliffe TW. Laboratory monitoring of low-molecular-weight heparin therapy—part II.  J Thromb Haemost. 2005;3(3):575-57615748251PubMedGoogle ScholarCrossref
20.
Janmahasatian S, Duffull SB, Chagnac A, Kirkpatrick CMJ, Green B. Lean body mass normalizes the effect of obesity on renal function.  Br J Clin Pharmacol. 2008;65(6):964-96518279477PubMedGoogle ScholarCrossref
21.
Pesola GR, Akhavan I, Madu A, Shah NK, Carlon GC. Prediction equation estimates of creatinine clearance in the intensive care unit.  Intensive Care Med. 1993;19(1):39-438440797PubMedGoogle ScholarCrossref
22.
Schulman S, Beyth RJ, Kearon C, Levine MN.American College of Chest Physicians.  Hemorrhagic complications of anticoagulant and thrombolytic treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition).  Chest. 2008;133(6):(suppl)  257S-298S18574268PubMedGoogle ScholarCrossref
23.
Nieuwenhuis HK, Albada J, Banga JD, Sixma JJ. Identification of risk factors for bleeding during treatment of acute venous thromboembolism with heparin or low molecular weight heparin.  Blood. 1991;78(9):2337-23431657248PubMedGoogle Scholar
24.
Cohen M, Demers C, Gurfinkel E,  et al; Efficacy and Safety of Subcutaneous Enoxaparin in Non–Q-Wave Coronary Events Study Group.  A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease.  N Engl J Med. 1997;337:447-452Google ScholarCrossref
25.
Levine M, Gent M, Hirsh J,  et al.  A comparison of low-molecular weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis.  N Engl J Med. 1996;334:677-681Google ScholarCrossref
26.
Merli G, Spiro T, Olsson C,  et al.  Subcutaneous enoxaparin once or twice daily compared with intravenous unfractionated heparin for treatment of venous thromboembolic disease.  Ann Intern Med. 2001;134:191-202Google Scholar
27.
Decousus H, Leizorovicz A, Parent F,  et al.  A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis.  N Engl J Med. 1998;338(7):409-415Google ScholarCrossref
28.
Antman EM, McCabe CH, Gurfinkel EP,  et al.  Enoxaparin prevents death and cardiac ischemic events in unstable angina/non–Q-wave myocardial infarction: results of the Thrombolysis In Myocardial Infarction (TIMI) 11B trial.  Circulation. 1999;100:1593-1601Google ScholarCrossref
29.
Blazing MA, de Lemos JA, White HD,  et al.  Safety and efficacy of enoxaparin vs unfractionated heparin in patients with non–ST-segment elevation acute coronary syndromes who receive tirofiban and aspirin: a randomized controlled trial.  JAMA. 2004;292:55-64Google ScholarCrossref
30.
Cohen M, Théroux P, Borzak S,  et al.  Randomized double-blind safety study of enoxaparin versus unfractionated heparin in patients with non–ST-segment elevation acute coronary syndromes treated with tirofiban and aspirin: the ACUTE II study.  Am Heart J. 2002;144:470-477Google ScholarCrossref
31.
Antman EM, Morrow DA, McCabe CH,  et al; ExTRACT-TIMI 25 Investigators.  Enoxaparin versus unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction.  N Engl J Med. 2006;354:1477-1488Google ScholarCrossref
32.
Fox KA, Bassand JP, Mehta SR,  et al; OASIS 5 Investigators.  Influence of renal function on the efficacy and safety of fondaparinux relative to enoxaparin in non–ST-segment elevation acute coronary syndromes.  Ann Intern Med. 2007;147(5):304-31017785485PubMedGoogle Scholar
33.
Collet JP, Montalescot G, Fine E,  et al.  Enoxaparin in unstable angina patients who would have been excluded from randomized pivotal trials.  J Am Coll Cardiol. 2003;41(1):8-1412570937PubMedGoogle ScholarCrossref
34.
Bounameaux H, de Moerloose P. Is laboratory monitoring of low-molecular-weight heparin therapy necessary? no.  J Thromb Haemost. 2004;2(4):551-55415102007PubMedGoogle ScholarCrossref
35.
Harenberg J. Is laboratory monitoring of low-molecular-weight heparin therapy necessary? yes.  J Thromb Haemost. 2004;2(4):547-55015102006PubMedGoogle ScholarCrossref
36.
Boneu B. Laboratory monitoring of low-molecular-weight heparin therapy—part II.  J Thromb Haemost. 2005;3(3):573-57415748249PubMedGoogle ScholarCrossref
37.
Hemker HC, Al Dieri R, Béguin S. Laboratory monitoring of low-molecular-weight heparin therapy—part II: monitoring LMWH therapy? for the moment a non-question.  J Thromb Haemost. 2005;3:571-57315748248PubMedGoogle ScholarCrossref
38.
Barras MA, Duffull SB, Atherton JJ, Green B. Modelling the occurrence and severity of enoxaparin-induced bleeding and bruising events.  Br J Clin Pharmacol. 2009;68(5):700-71119916994PubMedGoogle ScholarCrossref
39.
European Heart Rhythm Association (EHRA); European Cardiac Arrhythmia Society (ECAS); American College of Cardiology (ACC); American Heart Association (AHA); Society of Thoracic Surgeons (STS). Calkins H, Brugada J, Packer DL,  et al.  HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for personnel, policy, procedures and follow-up: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation [published correction appears in Heart Rhythm. 2009;6(1):148].  Heart Rhythm. 2007;4(6):816-86117556213PubMedGoogle ScholarCrossref
40.
Ahmed I, Gertner E, Nelson WB,  et al.  Continuing warfarin therapy is superior to interrupting warfarin with or without bridging anticoagulation therapy in patients undergoing pacemaker and defibrillator implantation.  Heart Rhythm. 2010;7(6):745-74920176137PubMedGoogle ScholarCrossref
41.
Di Biase L, Burkhardt JD, Mohanty P,  et al.  Periprocedural stroke and management of major bleeding complications in patients undergoing catheter ablation of atrial fibrillation: the impact of periprocedural therapeutic international normalized ratio.  Circulation. 2010;121(23):2550-255620516376PubMedGoogle ScholarCrossref
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    2 Comments for this article
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    Which kind of major bleeding?
    Andrea Salvi | Internal Medicine, Ospedale Civile di Brescia, Italy

    It would be very interesting to know the kind of major bleeding observed in patients submitted to bridging therapy. Is the observed bleeding related to the invasive procedure? And if so, was the last dose of enoxaparine stopped at least 24 hours before the procedure? And how many hours after the procedure has the enoxaparine been reassumed?  

    CONFLICT OF INTEREST: None Reported
    Which kind of major bleeding?
    Douglas DeCarolis | Minneapolis VA Health Care System


    Dr. Salvi,  

    Thank you for your interest and questions. Major bleeding was defined as a bleed causing hospital admission, prolonged hospital stay, or need for emergency room visit/medical attention. Almost all of bleeds in the bridge cohort were related to the the procedure. The majority were related to cardiac procedures (i.e., atrial arrhythmia ablation, coronary angiography, coronary intervention). The types of bleeding relating to these procedures scaled from hematoma at puncture sites to retroperitineal, intraabdominal, and pelvic bleeding (with rectal sheath hematoma). We also observed 3 gastrointestinal/rectal bleeds requiring medical attention after colonoscopy and from surgical
    sites post surgery. 

    Regarding the time period between the last pre-intervention and first post-intervention enoxaparin dose, the Minneapolis VAHCS has an active anticoagulation clinic that protocolizes this transition. Patients are instructed to take the last dose of enoxaparin on the morning 1 day prior to scheduled procedure and to restart on the day (morning) after the procedure. 

    Douglas DeCarolis










    CONFLICT OF INTEREST: None Reported
    READ MORE
    Original Investigation
    Dec 10/24, 2012

    Enoxaparin Outcomes in Patients With Moderate Renal Impairment

    Author Affiliations

    Author Affiliations: Pharmacy Service (Drs DeCarolis, Thorson, Clairmont, and Leuthner), Center for Chronic Disease Outcomes Research (Dr Rector), and Hematology/Oncology Section (Dr Johnson), Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota.

    Arch Intern Med. 2012;172(22):1713-1718. doi:10.1001/2013.jamainternmed.369
    Abstract

    Background Enoxaparin sodium has predictable pharmacokinetics that allow for simplified dosing without laboratory monitoring. Reliance on renal function for excretion may lead to accumulation of enoxaparin in patients with moderate renal impairment. However, there is no dose adjustment recommended for these patients. We conducted a review to compare bleeding events in patients with moderate renal impairment compared with those with normal renal function.

    Methods Patients received enoxaparin sodium, 1 mg/kg, every 12 hours or 1.5 mg/kg once daily between June 1 and November 30, 2009. Moderate renal impairment was defined as creatinine clearance (CrCl) of 30 to 50 mL/min. Normal renal function was defined as CrCl greater than 80 mL/min. The primary outcome was major bleeding, defined as any bleeding resulting in death, hospital admission, lengthened hospital stay, or an emergency department visit. The secondary outcome was thromboembolism.

    Results A total of 164 patients met the inclusion criteria: 105 with normal renal function and 59 with moderate renal impairment. The primary outcome occurred in 6 of 105 patients (5.7%) with normal renal function vs 13 of 59 patients (22.0%) with moderate renal impairment, representing an unadjusted odds ratio of 4.7 (95% CI, 1.7-13.0; P = .002). The odds ratio using multivariable logistic regression adjusting for differences in risk was 3.9 (95% CI, 0.97-15.6; P = .055). There was no recurrent thromboembolism in either group.

    Conclusions Our results suggest an increased risk of major bleeding in patients with moderate renal impairment who receive enoxaparin. Because enoxaparin is frequently used and outcomes can be life saving or life threatening, we encourage further study of the appropriate dose in patients with moderate renal impairment.

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