β-Adrenergic Blockers, Calcium Channel Blockers, and Nitrates

Abstract

During the past two decades the pathophysiologic mechanisms considered responsible for the acute coronary syndromes (ST-segment elevation myocardial infarction [MI], ST-segment depression MI, and unstable angina) have been evolving dramatically. In the mid-to-late 1970s, episodic coronary vasospasm was thought to be responsible for the development of unstable angina and acute MI (AMI) (1,2). In the mid-to-late 1980s and mid-1990s, plaque rupture and subsequent thrombus formation were considered paramount (3,4), and coronary vasoconstriction was considered quite inconsequential. The different acute coronary syndromes were perceived simply to represent different points on a single continuum of plaque rupture and thrombus formation: the continuum ranged from a ruptured plaque with little or no thrombus (often asymptomatic), to a ruptured plaque with moderate thrombus leading to only partial coronary occlusion (unstable angina and MI associated with ST-segment depression), to a ruptured plaque with extensive thrombus and complete occlusion of the artery (MI associated with ST-segment elevation). In the mid-to-late 1990s, however, it has been appreciated that this two-component pathophysiologic model of the acute coronary syndromes may be simplistic and inadequate for some patients. Recent evidence from atherectomy samples, for example, indicate that a substantial number of patients with unstable angina, and perhaps a subset of patients with ST-segment deviation MI as well, may be manifesting disease due to a rapid cellular proliferation of the atherosclerotic plaque itself, with little contribution from either major thrombus formation or vasoconstriction (5,6). These three mechanisms (ruptured plaque, thrombus formation, and rapid cellular proliferation) may also be closely interrelated in a given patient, with a substantial contribution from each.