ABSTRACT
Acute coronary syndromes (ACS) refer to a spectrum of myocardial ischemic disorders characterized by atherothrombotic plaque disruption. The management of ACS presents a challenge to the cardiologist because treatment strategies continue to evolve. Thrombin plays a pivotal role in thrombus formation, converting fibrinogen to fibrin, activating platelets, and recruiting additional platelets into the platelet-rich thrombus. In addition to unfractionated heparin (UFH), newer antithrombotic agents are now available and have significantly changed contemporary clinical practice. Low-molecular-weight heparins (LMWHs) has been shown to be superior to UFH in several trials. Direct thrombin inhibitors (DTIs) have been shown to be effective in patients undergoing elective coronary interventions and are being evaluated in patients with ACS. We review two classes of antithrombotic drugs, the LMWHs and the DTIs and discuss their current roles in the management of patients with ACS.
KEYWORDS
Acute coronary syndromes - low-molecular-weight heparins - direct thrombin inhibitors - bivalirudin - enoxaparin
REFERENCES
-
1
Furie B, Furie B C.
Molecular and cellular biology of blood coagulation.
N Engl J Med.
1992;
326
800-806
-
2
Eikelboom J, White H, Yusuf S.
The evolving role of direct thrombin inhibitors in acute coronary syndromes.
J Am Coll Cardiol.
2003;
41
70S-78S
-
3
Eikelboom J W, Anand S S, Malmberg K et al..
Unfractionated heparin and low-molecular-weight heparin in acute coronary syndrome without ST elevation: a meta-analysis.
Lancet.
2000;
355
1936-1942
-
4
Weitz J I, Leslie B, Hudoba M.
Thrombin binds to soluble fibrin degradation products where it is protected from inhibition by heparin-antithrombin but susceptible to inactivation by antithrombin-independent inhibitors.
Circulation.
1998;
97
544-552
-
5
Weitz J I, Hudoba M, Massel D, Maraganore J, Hirsh J.
Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III-independent inhibitors.
J Clin Invest.
1990;
86
385-391
-
6
Cohen M, Demers C, Gurfinkel E P 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;
337
447-452
-
7
Antman E M, Cohen M, Radley D et al..
Assessment of the treatment effect of enoxaparin for unstable angina/non-Q-wave myocardial infarction. TIMI 11B-ESSENCE meta-analysis.
Circulation.
1999;
100
1602-1608
-
8
Blazing M A, de Lemos J A, White H D 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
55-64
-
9
Ferguson J J, Califf R M, Antman E M et al..
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.
2004;
292
45-54
-
10
Petersen J L, Mahaffey K W, Hasselblad V et al..
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;
292
89-96
-
11
Mukherjee D, Topol E J.
The role of low-molecular-weight heparin in cardiovascular diseases.
Prog Cardiovasc Dis.
2002;
45
139-156
-
12
Wong G C, Giugliano R P, Antman E M.
Use of low-molecular-weight heparins in the management of acute coronary artery syndromes and percutaneous coronary intervention.
JAMA.
2003;
289
331-342
-
13
Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 Investigators .
Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial infarction.
Lancet.
2001;
358
605-613
-
14 Wallentin L. ASSENT 3 PLUS, 75th Scientific Sessions. Chicago, IL; American Heart Association 2002
-
15
Weitz J I, Bates E R.
Direct thrombin inhibitors in cardiac disease.
Cardiovasc Toxicol.
2003;
3
13-25
-
16
Organization to Assess Strategies for Ischemic Syndromes (OASIS-2) Investigators .
Effects of recombinant hirudin (lepirudin) compared with heparin on death, myocardial infarction, refractory angina, and revascularisation procedures in patients with acute myocardial ischemia without ST elevation: a randomised trial.
Lancet.
1999;
353
429-438
-
17
White H D, Aylward P E, Frey M J et al..
Randomized, double-blind comparison of hirulog versus heparin in patients receiving streptokinase and aspirin for acute myocardial infarction (HERO).
Circulation.
1997;
96
2155-2161
-
18
White H.
Thrombin-specific anticoagulation with bivalirudin versus heparin in patients receiving fibrinolytic therapy for acute myocardial infarction: the HERO-2 randomised trial.
Lancet.
2001;
358
1855-1863
-
19
Kong D F, Topol E J, Bittl J A et al..
Clinical outcomes of bivalirudin for ischemic heart disease.
Circulation.
1999;
100
2049-2053
-
20
Antman E M, McCabe C H, Braunwald E.
Bivalirudin as a replacement for unfractionated heparin in unstable angina/non-ST-elevation myocardial infarction: observations from the TIMI 8 trial.
Am Heart J.
2002;
143
229-234
-
21
Lincoff A M, Kleiman N S, Kottke-Marchant K et al..
Bivalirudin with planned or provisional abciximab versus low-dose heparin and abciximab during percutaneous coronary revascularization: results of the Comparison of Abciximab Complications with Hirulog for Ischemic Events Trial (CACHET).
Am Heart J.
2002;
143
847-853
-
22
Lincoff A M, Bittl J A, Harrington R A et al..
Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE-2 randomized trial.
JAMA.
2003;
289
853-863
-
23
Weitz J I.
Low-molecular-weight heparins.
N Engl J Med.
1997;
337
688-698
Debabrata MukherjeeM.D.
Division of Cardivascular Medicine, Gill Heart Institute
900 S. Lime Stone, 326 B Wellington Bldg
Lexing ton, KY 40536-0200
Email: Mukherjee@uky.edu