Medical Treatment of Unstable Angina and Acute Non-ST-Elevation Myocardial Infarction

Abstract

Unstable angina, acute non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI) are a continuum following rupture or fissuring of a non-occlusive atherosclerotic plaque and the development of thrombosis and enhanced vasoconstriction at that site. If the period of coronary artery obstruction and enhanced vasoconstriction lasts for less than 20 min and is recurrent, as the thrombus forms and lyses and reforms again, one has unstable angina. If the period of coronary artery occlusion resulting from thrombosis and enhanced vasoconstriction at the site of coronary artery injury lasts for more than 20 min to approximately 2 h, or results in a subtotal coronary artery obstruction, the infarct is limited to the subendocardium and is an NSTEMI. If the period of coronary artery obstruction lasts for more than 2 h, the infarct progresses outward vertically and becomes a STEMI. Mediators of the enhanced vasoconstriction and thrombosis are largely platelet-derived and include thromboxane A 2, serotonin, adenosine diphosphate (ADP), platelet-activating factor, and thrombin and oxygen-derived free radicals. At sites of vascular injury, production of endothelium-derived antithrombotic substances and local vasodilators is attenuated, limiting the availability of nitric oxide, tissue plasminogen activator, and prostacyclin. Thus, an intensively prothrombotic-enhanced vasoconstrictor environment is created locally at sites of plaque fissuring and ulceration. Therefore, the medical treatment of unstable angina and NSTEMI rests in inhibiting thrombosis and vasoconstriction at the local vascular site, using nitrates (often intravenous nitroglycerin) and inhibitors of thromboxane, ADP, thrombin, and serotonin. Aspirin, clopidogrel or another ADP antagonist, a heparin, or a direct thrombin inhibitor, and occasionally an inhibitor of the platelet glycoprotein IIb/IIIa receptors are often used in the initial treatment of these patients. A statin should be administered to lower the low-density lipoprotein (LDL) concentration to values less than 100 mg/ml, unless otherwise contraindicated. Those with elevated risk factors, biomarkers of a poor prognosis, and those with continuing chest pain, congestive heart failure, and/or left ventricular dysfunction are generally referred for coronary arteriography and either percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery, depending on the coronary artery anatomy. Randomized trials have shown that the best treatment of these patients who are at higher risk is an aggressive one with PCI or CABG, whichever is most appropriate for the individual patient.