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- acute coronary syndromes
- plaque stabilisation
- angiotensin converting enzyme inhibition
- thrombolytic treatment
The large secondary prevention trials of statin treatment in coronary artery disease were characterised by separation of the survival curves in the first 6–18 months after randomisation.w1–3 This was too soon to be fully explained by changes in disease progression, so the concept of plaque stabilisation arose, described largely in terms of cap strength and lipid pool.w4 w5 This concept, however, has no direct parallel in acute coronary syndromes because the plaque has, by definition, already ruptured and thrombosis has occurred with variable obstruction of the arterial lumen.1,2 The process of plaque rupture occurs against a background of inflammation and endothelial dysfunction which are generalised throughout the coronary arteries, accounting for recent intravascular ultrasound findings of multiple ruptured plaques in patients with acute coronary syndromes, often located remotely from the index artery.3 In order to achieve plaque stabilisation, therefore, with healing of the ruptured plaque and restoration of luminal patency, the following targets must be achieved:
Dissolution of thrombus
Reduction of inflammatory activity
Passivation of the coronary endothelium.
These targets are not mutually exclusive and most of the strategies used clinically for secondary prevention are effective through several different mechanisms. Timing is critical because event rates are not a linear function of time, but are front-loaded, the period of greatest risk being the early hours and days after presentation (fig 1). Nearly all these events are caused by thrombus extension or re-thrombosis, usually in relation to the index plaque or, less often, to ruptured plaques elsewhere in the coronary circulation. Clearly, therefore, plaque stabilisation must be achieved very early after presentation if lives are to be saved, and the main target must be the thrombus itself and those mechanisms which are driving the thrombotic process.
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