Unstable angina non ST elevation myocardial infarction anticoagulant therapy
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Overview of Anticoagulant Therapy in UA / NSTEMI
Anticoagulation, traditionally with unfractionated heparin(UFH), is a cornerstone of therpay for patients with UA/NSTEMI. Some of the agents available in this category include unfractionated heparin, low molecular weight heparin, fondaparinux, bivalirudin and warfarin. These agents are also sometimes referred to as antithrombins, although, it should be noted that they often inhibit one or more proteins in the coagulation cascade before thrombin.
Unfractionated Heparin(UFH)
Unfractionated heparin exerts its anticoagulant effect by potentiating the action of circulating antithrombin, a proteolytic enzyme that inactivates factor IIa (thrombin), factor IXa, and factor Xa. It prevents thrombus propagation but does not lyse existing thrombi. A meta-analysis showed that in aspirin-treated patients with acute coronary syndrome without ST elevation, short-term unfractionated heparin or LMWH halves the risk of myocardial infarction or death[1]. This is a short acting drug with an anticoagulation half life of 1.5hrs. Hence, frequent monitoring of the anticoagulant response using activated partial thromboplastin time (APTT) is recommended with titrations made according to a standardized nomogram aiming for an APTT range between 1.5 to 2 times control or 50 to 70 seconds . Side effects include bleeding(specially with elevated APTT) and heparin induced thrombocytopenia
Low Molecular Weight Heparin(LMWH)
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. Results from TIMI 11B study[2] showed superiority of LMWH over UFH for reducing a composite of death and serious cardiac ischemic events during the acute management of UA/NQMI patients without causing a significant increase in the rate of major hemorrhage. Results from SYNERGY trial[3] 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[4] 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 are that they 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.
Direct Thrombin Inhibitors
ACC / AHA Guidelines (DO NOT EDIT) [5]
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Class IIa
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See Also
Sources
- The ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction [5]
References
- ↑ Eikelboom JW, Anand SS, Malmberg K, Weitz JI, Ginsberg JS, Yusuf S (2000). "Unfractionated heparin and low-molecular-weight heparin in acute coronary syndrome without ST elevation: a meta-analysis". Lancet. 355 (9219): 1936–42. doi:10.1016/S0140-6736(00)02324-2. PMID 10859038. Unknown parameter
|month=ignored (help) - ↑ Antman EM, McCabe CH, Gurfinkel EP; et al. (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. Unknown parameter
|month=ignored (help) - ↑ Ferguson JJ, Califf RM, Antman EM; et al. (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. 292 (1): 45–54. doi:10.1001/jama.292.1.45. PMID 15238590. Unknown parameter
|month=ignored (help) - ↑ de Lemos JA, Blazing MA, Wiviott SD; et al. (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". Eur. Heart J. 25 (19): 1688–94. doi:10.1016/j.ehj.2004.06.028. PMID 15451146. Unknown parameter
|month=ignored (help) - ↑ 5.0 5.1 Anderson JL, Adams CD, Antman EM; et al. (2007). "ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine". JACC. 50 (7): e1–e157. PMID 17692738. Text "doi:10.1016/j.jacc.2007.02.013 " ignored (help); Unknown parameter
|month=ignored (help)