Pharmacologic prevention of coronary plaque rupture – the major cause of acute coronary syndromes

The rupture of a vulnerable coronary atherosclerotic plaque results in coronary thrombosis, the main cause of unstable angina, acute myocardial infarction, and sudden cardiac death. Usually, a culprit plaque that ultimately ruptures does not cause significant flow-limiting stenosis, but is characterized by a typical histological structure: it contains a large necrotic lipid core and a thin fibrous cap, which separates the core from the circulating blood. The formation of such thin-cap fibroatheromata results from a reactive inflammatory response of the growing plaque to continuous accumulation of lipids derived from low-density lipoprotein. Consequently, adequate control of both lipid accumulation and inflammation in the plaque are crucial in the prevention of plaque rupture. At present, these requirements are pharmacologically best fulfilled by statins. Emerging therapies with a similar dual effect on coronary plaques include intravenous infusion of synthetic high-density lipoprotein. These therapies are likely initially to stabilize inflamed plaques and, if administered sufficiently rigorously and for a sufficiently long time, they lead to regression of lipid-laden vulnerable plaques. It is becoming increasingly evident that other cardiovascular drugs may also increase plaque stability. These agents include peroxisome proliferator activated receptor a and g agonists, angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, calcium channel blockers, and aspirin. Heart Metab. 2007;36:9–14.