Insights into the role of thrombin in the pathogenesis of recurrent ischaemia after acute coronary syndrome

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245

Theme Issue
Coagulation proteases and cardiovascular disease

Issue: 2014: 112/5 (Nov) pp. 843–1075
Pages: 924-931
Ahead of Print: 2014-07-17

Insights into the role of thrombin in the pathogenesis of recurrent ischaemia after acute coronary syndrome

J. I. Weitz (1)

(1) McMaster University and the Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada


thrombosis, Acute coronary syndrome, factor Xa, thrombin, rivaroxaban


Acute coronary syndrome (ACS) is a medical emergency. Patients who survive the initial event remain at risk of recurrent cardiovascular events. In most cases, ACS is triggered by thrombosis after rupture of an atherosclerotic plaque. Key to thrombus formation at this site is the generation of thrombin, which not only converts fibrinogen to fibrin but also serves as a potent platelet agonist and induces platelet aggregation at the site of vascular injury. Although dual antiplatelet therapy is more effective for the prevention of recurrent events than aspirin alone after ACS, there remains an approximately 10 % risk of recurrent ischaemic events at one year. Recent studies have evaluated whether the addition of an anticoagulant to antiplatelet therapy reduces the risk of recurrent ischaemia after an ACS event. Rivaroxaban, an oral factor Xa inhibitor, attenuates thrombin generation. When used in conjunction with dual antiplatelet therapy in patients with stabilised ACS, rivaroxaban 2.5 mg twice daily significantly reduced the risk of the composite endpoint of cardiovascular death, myocardial infarction and stroke compared with placebo. Although it increased the risk of bleeding, rivaroxaban was associated with a reduction in mortality; a finding that supports the use of a dual-pathway approach that combines anticoagulant and antiplatelet therapy. This review explores the pathophysiology of ACS to provide perspective on the results of recent clinical trials with novel oral anticoagulants for ACS and to identify their potential role in this setting.

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