Acute coronary syndrome (ACS), which is associated with high rates of morbidity and mortality, refers to the spectrum of acute myocardial ischemia, including unstable angina (UA), ST-segment elevation myocardial ischemia, and acute myocardial ischemia without ST-segment elevation. The risk of recurrent ischemic events is greatest in the weeks and months immediately following ACS. Despite the widespread use of conventional therapies aimed at modifying platelet function and the coagulation cascade to reduce the risk of further ischemia, patients who have experienced an ACS continue to be at high cardiac risk. Nearly 25% of men and 38% of women die within 1 year of having a first myocardial infarction (MI). These statistics highlight the need for improved strategies that target the pathophysiologic mechanisms operating in ACS and treat the underlying atherosclerotic disease.
Evidence from numerous large, randomized, controlled trials- unequivocally demonstrates the ability of statins to reduce coronary morbidity and mortality. However, while the benefits of statin therapy in patients with stable coronary artery disease (CAD) are clearly recognized, it is only recently that the positive impact of initiating statin treatment immediately following the occurrence of ACS has emerged.” This review will present evidence supporting early initiation of statin therapy in ACS, including results from hospital-based initiatives that guide physicians to prescribe statins prior to patient discharge in order to improve treatment rates, patient adherence, and clinical outcomes reached with concern of My Canadian Pharmacy.
Atherothrombosis is the major cause of ACS. It has now become clear that coronary atherosclerosis is not simply an inevitable consequence of aging but rather a chronic inflammatory process that can be converted into an acute clinical event by plaque rupture and arterial thrombosis. Contemporary models, suggest that atherosclerotic plaques are not merely passive structures but dynamic inflammatory lesions. Fatty streaks, which can be detected in the arterial intima as early as adolescence, progress into more complicated raised lesions composed of inflammatory cellular material, along with cholesterol ester. Lesions develop into mature atheroma containing fibrous tissue elements, inflammatory elements, and extracellular deposits of cholesterol and are vulnerable to rupture. Although the exact inciting factors of the vulnerable plaque rupture are not fully understood, inflammation is accepted to be a pivotal event. The rupture of an unstable atherosclerotic plaque results in the lipid core coming into contact with circulating blood, which triggers platelet activation and coagulation, leading to thrombosis.
While the underlying molecular processes of atherogenesis are complex, they are amenable to therapeutic intervention. After an ACS, the primary goal of therapy is to reduce the risk of further ischemic complications., Antiplatelet therapy is the foundation of immediate ACS management. Therapies to decrease platelet aggregation include aspirin, the thienopyridine agent clopidogrel, and platelet glycoprotein Ilb/IIIa antagonists. In addition, a fundamental aspect of treatment involves the use of anticoagulant agents such as unfractionated heparin and newer low-molecular-weight heparins. Anti-ischemic treatments include the use of nitrates and (3-blockers. Neurohumoral agents such as angiotensin-converting enzyme (ACE) inhibitors, (3-blockers, and aldosterone antagonists are utilized for early and long-term cardioprotection.
A critical aspect of preventing future coronary events is stabilizing vulnerable lesions. Although significant therapeutic advances in the treatment of ACS have been made with antiplatelet and antithrombotic therapy during the past decade, these therapies alone do not appear to completely stabilize unstable plaques. Results from several clinical trials suggest that early administration of high-dose, potent statin therapy following an ACS may stabilize vulnerable plaques decreasing adverse outcomes in both the short-term and long-term. The likely mechanisms of benefit are not solely attributed to the lipid-lowering effects of statins but, at least in part, to the variety of antiinflammatory and antiproliferative effects, commonly described as pleiotropic effects, exerted by statins. Pleiotropic effects commonly ascribed to statins include improvements in endothelial function and vasomotion, reductions in platelet aggregability and thrombus formation, fibrinolytic and antioxidant activity, as well as decreases in matrix degradation due to reductions in macrophage met-alloproteinase production and increases in collagen content. Furthermore, statins are proposed to reduce inflammation within plaques. The most widely examined inflammatory biomarker is high-sensitivity C-reactive protein (hsCRP). Elevated levels of hsCRP have been correlated with increased cardiovascular risk and mortality. C-reactive protein binds to oxidized low-density lipoprotein cholesterol (LDL-C) and apoptotic cells but not to native LDL-C or healthy cells, signifying an association with atherosclerotic plaques. Reductions in hsCRP levels achieved with intensive statin therapy appear to correlate with increased clinical benefit in patients who have experienced an ACS.