Unfractionated heparin in Acute Coronary syndromes

Unfractionated heparin is a mixture of different weights of heparin (5 to 30k) that have varying effects on factors IIa, IXa, and Xa. Low-molecular-weight heparin (LMWH) is a subset of heparin (weight ~5k) that has activity on factor Xa, but not on IIa. LMWH has the advantage of less binding to protein and dose-independent clearance.

Mrs. ACS is a 74-year-old female who is admitted to the intensive care unit (ICU) for an acute coronary syndrome. She presents to the emergency department with substernal chest pain with radiation to the neck, diaphoresis, and dizziness.

Her electrocardiogram (ECG) shows T-wave flattening in the inferior leads (II, III, and aVF). No ST-segment elevations are noted. The patient is started on aspirin, nitroglycerin, and metoprolol.

As you write for a heparin drip, the nurse asks, Why don’t we do Lovenox [enoxaparin], that way I don’t have to start a drip.

Discussion

Acute coronary syndrome is a relatively new classification term for a set of acute coronary diseases. Causes of acute coronary syndrome include ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), and unstable angina.

STEMI is defined as myocardial infarction involving ST-segment elevation of 0.1 mV in two or more consecutive leads or a new left bundle branch block. NSTEMI refers to acute myocardial damage from atherosclerotic disease that results in release of cardiac biomarkers without causing ST-segment elevation.

Unstable angina refers to myocardial damage that does not result in release of cardiac biomarkers or ST-segment elevation. These definitions are important because they relate to the pathogenesis, severity of disease, and management strategy of the affected patients.

In the treatment of acute coronary syndrome, anticoagulant therapy is indicated to minimize further thrombus formation. Heparin is the recommended parenteral anticoagulant in treatment of acute coronary syndrome.

Heparin accelerates the action of antithrombin. This leads to inactivation of factors IIa (thrombin), IXa, and Xa. This leads to decrease thrombus formation.

This leads to more predictable dosing and a longer half-life (3 to 6 hours). Because of the longer half-life, LMWH can be administered subcutaneously twice a day as opposed to a continuous infusion for unfractionated heparin (half-life 1 to 2 hours).

In patients with unstable angina or NSTEMI, enoxaparin (Lovenox) is preferable to unfractionated heparin in patients not scheduled for a coronary artery bypass graft within 24 hours.

Four trials have evaluated the benefits of low-molecular-weight heparin over unfractionated heparin in the treatment of unstable angina or NSTEMI.

The two trials that used enoxaparin each showed a reduction in the composite end point of death, myocardial infarction, and recurrent ischemia when compared with unfractionated heparin.

The TIMI 11B trial showed a 12% relative risk reduction (19.6% unfractionated heparin vs. 17.3% LMWH). The ESSENCE trial showed a 19% relative risk reduction (23.3% unfractionated heparin vs. 19.8% LMWH).

The two trials that used another form of LMWH (dalteparin and nadroparin) demonstrated a trend toward increased risk of the composite end point, although this was not statistically significant.

The advantages of LMWH are the ease of administration, absence of need for monitoring, and lower association with heparin-induced thrombocytopenia. In all trials, there was an increased risk of minor bleeding, but no difference in risk of major bleeding.

Unfractionated heparin is preferred in patients who have a planned percutaneous coronary intervention and coronary artery bypass graft because LMWH is less effectively reversed with protamine and does not allow monitoring to adjust the level of anticoagulation.

Suggested Readings

Antman EM, McCabe CH, Gurfinkle EP, et al. Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction; results of the thrombolysis inmyocardial infarction (TIMI) 11B trial. Circulation 1999;100:1593–1601.

Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: 2002. Summary article from the Committee on the Management of Patients with Unstable Angina. Circulation 2002;106.

Cohen M, Demers C, Gurfinkle EP, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med 1997.

Comparison of two treatment durations (6 days and 14 days) of a low molecular weight heparin with a 6-day treatment of unfractionated heparin in the initial management of unstable angina or non-Q wave myocardial infarction: FRAX. I.S. Eur Heart J 1999.

Klein W, Buchwald A, Hillis SE, et al. Comparison of low-molecular-weight heparin with unfractionated heparin acutely and with placebo for 6weeks in the management of unstable coronary artery disease. Fragmin in Unstable Coronary Artery Disease Study (FRIC). Circulation 1997.

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