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Use of direct thrombin inhibitors in acute coronary syndrome
1Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, New York, USA.
Insights
Direct thrombin inhibitors show promise in managing acute coronary syndrome (ACS), with some agents reducing mortality compared to unfractionated heparin (UH). However, long-term benefits are unproven, limiting their use to patients with UH-induced thrombocytopenia.
Area of Science:
- Cardiology
- Pharmacology
- Thrombosis Research
Background:
- Acute coronary syndrome (ACS) management traditionally uses aspirin and unfractionated heparin (UH).
- Refractory angina and myocardial infarction (MI) persist despite current therapies.
- Direct thrombin inhibitors (DTIs) like lepirudin, desirudin, and bivalirudin are explored for improved antithrombotic effects.
Purpose of the Study:
- To evaluate the rationale and clinical evidence for using direct thrombin inhibitors in ACS management.
- To compare the efficacy and safety of DTIs against standard anticoagulation with UH.
Main Methods:
- Systematic review of published clinical trials from 1966 to April 2000.
- Exclusion of pilot studies with fewer than 500 patients.
Main Results:
- Lepirudin (medium dose) reduced death, MI, and refractory angina versus UH, but increased minor bleeding.
- Bivalirudin showed comparable efficacy to UH in periprocedural settings with less bleeding, but its ACS role is unstudied.
- Desirudin was comparable to UH in acute MI but had a narrow therapeutic index with increased moderate bleeding.
Conclusions:
- Current trials support short-term DTI use (3-5 days) in ACS.
- Long-term benefits of DTIs on morbidity and mortality remain unproven.
- DTIs are recommended as an alternative for patients with UH-induced thrombocytopenia requiring anticoagulation.
Objective:
This paper examines the rationale for using direct thrombin inhibitors in the management of acute coronary syndrome (ACS).
Background:
With traditional management of ACS using aspirin and unfractionated heparin (UH), refractory angina and new myocardial infarction (MI) continue to develop. Growing understanding of the pathophysiology of ACS has led to the search for more effective therapies directed toward preventing formation of fibrin- and platelet-rich thrombi in the coronary arteries. Current pharmacologic approaches include use of direct thrombin inhibitors (lepirudin, desirudin, and bivalirudin).
Methods:
We reviewed all published clinical trials abstracted in MEDLINE from 1966 to April 2000, excluding pilot studies enrolling <500 patients.
Results:
Use of lepirudin at medium doses (0.4-mg/kg bolus + 0.15 mg/kg/h) resulted in lower rates of death, new MI, and refractory angina at 7 days compared with UH (3.0% vs 6.5%; P = 0.047), although the incidence of minor bleeding was increased (7.6% vs 4.5%; P < 0.05). Bivalirudin was as effective as UH in preventing complications after percutaneous coronary intervention (11.4% vs 12.2%; NS) and carried a lower bleeding risk (7.8% vs 19.2%; NS); however, its use in the management of ACS has not been studied. Desirudin used at low doses (0.1-mg/kg bolus + 0.1 mg/kg/h) in large-scale clinical trials in patients with acute MI treated with alteplase or streptokinase appeared to be at least as effective as UH (8.9% vs 9.8% at 30 days; NS). However, its therapeutic index was narrow, since it was associated with significantly more moderate bleeding (8.8% vs 7.7%; P < 0.05).
Conclusions:
All clinical trials to date have studied relatively short-term use (3-5 days) of direct thrombin inhibitors, and long-term benefits on morbidity and mortality have not been demonstrated. Until further data are available, direct thrombin inhibitors should be restricted to use as a possible alternative in patients who require anticoagulant therapy but experience UH-induced thrombocytopenia.