Unstable angina non ST elevation myocardial infarction low molecular weight heparin therapy

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Unstable angina non ST elevation myocardial infarction low molecular weight heparin therapy On the Web

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editors-in-Chief: Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S.; Smita Kohli, M.D.

Overview

Low molecular weight heparin is a class of anticoagulant that is obtained by fractionation or depolymerisation of polymeric heparin. They are defined as heparin salts having an average molecular weight of less than 8000 Da. Examples include dalteparin, enoxaparin, nadroparin, ardeparin, certoparin, parnaparin, tinzaparin and reviparin.

Low Molecular Weight Heparin (LMWH)

Mechanism of Benefit

  • LMWH combine factor IIa and factor Xa inhibition and thus inhibit both the action and generation of thrombin.
  • It has a number of advantages over UFH such as its greater anti-factor Xa activity inhibits thrombin generation more effectively, lower rate of thrombocytopenia, high bioavailabiltiy, more consistent anticoagulant effect and no requirement of intensive lab monitoring.

Clinical Trial Data

  • Results from TIMI 11B study[1] showed superiority of LMWH over UFH for reducing a composite of death and serious cardiac ischemic events during the acute management of Unstable angina/NQMI patients without causing a significant increase in the rate of major hemorrhage.
  • Results from SYNERGY trial[2] revealed noninferiority of LMWH over UFH for the treatment of high-risk patients with non-ST-segment elevation ACS. However, both trials did show increased risk of major bleeding with LMWH.
  • A prospective analysis of the A to Z trial[3] showed that enoxaparin provided significant benefit over UFH in patients managed conservatively (who are typically on heparin/LMWH for at least 48 hours) but not in those with early invasive approach (who are taken to the catheterization laboratory within 48 hours and have their heparin discontinued thereafter).

Disadvantages of LMWH

  • LMWH are more affected by renal dysfunction than UFH, and the dose should be reduced in patients with a creatinine clearance <30 mL/min.
  • Also, in the event of bleeding, the anticoagulant effect of UFH can be reversed more effectively with protamine.

References

  1. Antman EM, McCabe CH, Gurfinkel EP, Turpie AG, Bernink PJ, Salein D, Bayes De Luna A, Fox K, Lablanche JM, Radley D, Premmereur J, Braunwald E (1999). "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. 100 (15): 1593–601. PMID 10517729. Retrieved 2011-04-11. Unknown parameter |month= ignored (help)
  2. Ferguson JJ, Califf RM, Antman EM, Cohen M, Grines CL, Goodman S, Kereiakes DJ, Langer A, Mahaffey KW, Nessel CC, Armstrong PW, Avezum A, Aylward P, Becker RC, Biasucci L, Borzak S, Col J, Frey MJ, Fry E, Gulba DC, Guneri S, Gurfinkel E, Harrington R, Hochman JS, Kleiman NS, Leon MB, Lopez-Sendon JL, Pepine CJ, Ruzyllo W, Steinhubl SR, Teirstein PS, Toro-Figueroa L, White H (2004). "Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial". JAMA : the Journal of the American Medical Association. 292 (1): 45–54. doi:10.1001/jama.292.1.45. PMID 15238590. Retrieved 2011-04-11. Unknown parameter |month= ignored (help)
  3. de Lemos JA, Blazing MA, Wiviott SD, Brady WE, White HD, Fox KA, Palmisano J, Ramsey KE, Bilheimer DW, Lewis EF, Pfeffer M, Califf RM, Braunwald E (2004). "Enoxaparin versus unfractionated heparin in patients treated with tirofiban, aspirin and an early conservative initial management strategy: results from the A phase of the A-to-Z trial". European Heart Journal. 25 (19): 1688–94. doi:10.1016/j.ehj.2004.06.028. PMID 15451146. Retrieved 2011-04-11. Unknown parameter |month= ignored (help)

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