Managing acute coronary syndromes: Decades of progress
ABSTRACTIn managing acute coronary syndromes, physicians can draw on a large body of evidence from clinical trials. This article reviews clinical trials that inform current standards of practice regarding reperfusion, aggressive vs conservative initial approaches, and the appropriate use of aspirin, dual antiplatelet therapy, glycoprotein IIb/IIIa antagonists, anticoagulants, and statins.
KEY POINTS
- For acute ST-elevation myocardial infarction, primary percutaneous coronary intervention is preferred over fibrinolytic therapy if it is available within 90 minutes of first medical contact.
- For non-ST-elevation acute coronary syndromes, either an early invasive or conservative strategy is recommended depending on patient risk and whether intensive medical therapy is available and appropriate.
- Daily aspirin therapy is indicated for all patients with acute coronary syndromes unless they have a true aspirin allergy.
- Adenosine diphosphate receptor inhibitors—clopidogrel, prasugrel, and ticagrelor—reduce ischemic events but increase bleeding risk and should be used only for patients with no history of stroke or transient ischemic attack.
Most decisions for managing acute coronary syndromes can be based on ample data from large randomized trials with hard clinical end points, so there is little reason to provide care that is not evidence-based.
This article reviews some of the trials that provide guidance on diagnosing and managing acute coronary syndromes, including the timing of reperfusion and adjunctive therapies in different situations.
MOST ACUTE CORONARY SYNDROMES ARE NON-ST-ELEVATION CONDITIONS
Acute coronary syndromes range from unstable angina and non-ST-elevation myocardial infarction (NSTEMI) to ST-elevation MI (STEMI), reflecting a continuum of severity of coronary stenosis. The degree of coronary occlusion may ultimately determine whether a patient has unstable angina or MI with or without ST elevation.1
The substrate for all of these is vulnerable plaque. Angiographic studies have indicated that in many cases medium-size plaques (30%–40% stenosis) are more likely to rupture than larger, more obstructive ones. Moderate plaques may be vulnerable because they are less mature, with a large lipid core and a thin cap prone to rupture or erode, exposing the thrombogenic subendothelial components.2
Because the vulnerability of a coronary plaque may not correlate with the severity of stenosis before the plaque ruptures, stress tests and symptoms may not predict the risk of MI. The key role of thrombosis in the pathogenesis also highlights the importance of antithrombotic therapy in the acute phases of acute coronary syndromes, which can significantly reduce mortality and morbidity rates.
Perhaps because of the widespread use of aspirin and statins, most patients who currently present with an acute coronary syndrome have either unstable angina or NSTEMI: of about 1.57 million hospital admissions in 2004 for acute coronary syndromes, for example, only 330,000 (21%) were for STEMI.3
DIAGNOSING ACUTE CORONARY SYNDROME
Symptoms may not be classic
The classic symptoms of acute coronary syndromes are intense, oppressive chest pressure radiating to the left arm, but nearly any discomfort “between the nose and navel” (eg, including the jaw, arm, and epigastric and abdominal areas) may be an acute coronary syndrome. Associated symptoms may include chest heaviness or burning, radiation to the jaw, neck, shoulder, back, or arms, and dyspnea.
Particularly in older, female, postoperative, or diabetic patients, the presentation may be atypical or “silent,” including nausea or vomiting; breathlessness; sweating; arrhythmias; or light-headedness. Especially in these groups, symptoms may be mild or subtle, and acute coronary syndrome may manifest only as “not feeling well.”
The differential diagnosis of acute coronary syndromes is broad. Most important to immediately consider are pulmonary embolism and aortic dissection, as they are life-threatening and are treated differently from acute coronary syndromes. Otherwise, it is best to err on the side of caution and treat for an acute coronary syndrome until it is proven otherwise.
Electrocardiography is critical
Electrocardiography (ECG) gives valuable information about the location, extent, and prognosis of infarction, and it is critically important for distinguishing STEMI from NSTEMI, with ST elevation classically diagnostic of complete coronary occlusion. Q waves can occur early and do not necessarily signify completed infarction, as traditionally thought. ST depression or T inversion indicates that total coronary occlusion is unlikely unless they are in a pattern of circumflex infarct associated with an enlarging R wave in lead V1. An ST elevation in RV4 indicates right ventricular infarction.
The appearance on ECG may evolve over time, so a patient with atypical symptoms and a nonspecific electrocardiogram should be observed for 24 hours or until more specific criteria develop.
Biomarkers in NSTEMI
In MI, cardiac troponin levels begin to rise about 3 hours after the onset of chest pain, and elevations can last for up to 14 days. Levels can also be mildly elevated chronically in patients with renal dysfunction, so positive biomarker tests in that population should be interpreted cautiously.
For STEMI, the opportunity to reperfuse is lost if one waits for cardiac biomarkers to become elevated. But for NSTEMI, they are highly sensitive and specific for identifying patients at high risk and determining who should be treated aggressively. Patients who are biomarker-negative have a better prognosis than patients with identical symptoms and electrocardiograms who are biomarker-positive.
MI is currently defined as a rise in any biomarker (usually troponin) above the 99th percentile for a reference population, with at least one of the following:
- Ischemic symptoms
- New ST/T changes or left bundle branch block
- Pathologic Q waves
- Loss of myocardium or abnormal wall motion seen by imaging
- Intracoronary thrombus.
