Acute coronary syndromes: Virchow's triad revisited

Abstract

In 1996, the over-a-century-old hypothesis presented by Rudolf Virchow that vascular thrombosis is caused by vessel-wall injury, alterations in blood flow, and abnormal blood coagulability, continued to spawn research. In atherosclerosis research, the role of statins was further emphasised in the CARE trial, which showed a significant reduction in death from coronary causes and stroke in patients with myocardial infarction and an average cholesterol (<6.2mmol/L [<240mg/dL]). Benefit was also found with antioxidant vitamin E in patients with established ischaemic heart disease, consistent with the lipidoxidation theory of coronary artery disease. Improved thrombolytic and anti thrombotic regimens, and technological advances in invasive cardiology, substantially increased survival among patients admitted with acute coronary syndromes. New plasminogen activators with reduced clearance and more pronounced fibrin specificity, including recombinant staphylokinase and T N K tissue plasminogen activator compared favourably with standard accelerated aheplase in achieving early recanalisation. The G U S T O IIb angiographic substudy found a moderate but significant benefit for immediate percutaneous coronary angioplasty (PTCA) over thrombolytic therapy in patients with acute myocardial infarction, but cost will be an obstacle to widespread use of PTCA. A provocative study (N Engl J Med 1996; 334: 7) that reported better reperfusion (86% TIMI III flow at 90 min) and smaller infarcts after thrombolysis in patients with preceding unstable angina may help to individualise treatment for patients. Recognition of the role of thrombin and platelets has spurred the use of hirudin as a direct antithrombin agent and the introduction of more potent platelet inhibitors, such as glycoprotein IIb/IIIa-receptor blockers and ticlopidine. Ticlopidine virtually eliminated immediate stent thrombosis and the serious bleeding complications often observed with the combination of aspirin and anticoagulants. An early risk reduction of non-fatal (re)infarction with recombinant hirudin in GUSTO IIb was not sustained over time, probably because of continuing or rebound thrombin generation (N Engl J Med 1996; 334: 775). Glycoprotein IIb/IIIa-receptor blockers (c7E3), in contrast, improved early vessel patency after PTCA and had prolonged clinical benefit, suggests an effect beyond reduction of platelet