> Table of Contents > Acute Coronary Syndromes: NSTE-ACS (Unstable Angina and Nstemi)
Acute Coronary Syndromes: NSTE-ACS (Unstable Angina and Nstemi)
Brendan Merchant, MD
Louis J. Berk, MD
image BASICS
DESCRIPTION
  • Unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI) are acute coronary syndromes (ACS) without ST-segment elevation (NSTE-ACS).
  • NSTEMI is defined by the rise and fall of cardiac biomarker values (preferably cardiac troponin) higher than the 99th percentile upper reference limit and accompanied by one of the following: symptoms of ischemia, new ST-segment T-wave changes, development of pathologic Q waves on ECG, or imaging evidence of new regional wall motion abnormality (1).
  • UA, although clinically indistinguishable from NSTEMI (in an appropriate clinical setting, new-onset anginal chest pain, or change in typical anginal pattern, or development of angina at rest, or change in typical anginal equivalent), can be differentiated from NSTEMI by a lack of elevation in cardiac biomarkers based on two or more samples collected at least 6 hours apart. Just as with NSTEMI, nonspecific ECG changes, such as ST-segment depressions or T-wave inversions, may be present (1).
EPIDEMIOLOGY
  • Incidence of UA/NSTEMI increases with age (2).
  • Presentation of coronary events in women is, on average, 10 years later than in men, with comparable rates of occurrence (2).
Incidence
Age-adjusted coronary heart disease (CHD) incidence rates (per 1,000 person-years): white men, 12.5; black men, 10.6; white women, 4.0; and black women, 5.1 (2)
Prevalence
For adults ≥20 years of age: 8.3% for men and 6.1% for women (2)
ETIOLOGY AND PATHOPHYSIOLOGY
  • Platelet-rich thrombus forming on a disrupted plaque
  • Dynamic obstruction triggered by intense spasm of a coronary artery, for example, Prinzmetal angina or coronary spasm induced by cocaine or methamphet-amine abuse
  • Progressive mechanical limitation of coronary flow
  • Coronary arterial inflammation
  • Coronary dissection/rupture and thrombogenesis
  • Myocardial oxygen demand exceeds supply
  • UA/NSTEMI is usually caused by acute rupture of an atherosclerotic plaque, causing thrombosis and partial or total occlusion of a coronary artery (1).
RISK FACTORS
  • Age
  • Hypertension
  • Tobacco use
  • Diabetes mellitus
  • Dyslipidemia
  • Family history of early coronary artery disease (CAD)
  • Sedentary lifestyle
  • Overweight/obesity
  • Psoriasis and other systemic inflammatory conditions
GENERAL PREVENTION
  • Smoking cessation, healthy diet, weight control, physical activity
  • If risk factors are present: BP control, lipid-lowering therapy, daily aspirin (in select patients)
COMMONLY ASSOCIATED CONDITIONS
  • Cardiovascular disease (atherosclerotic, aneurysmal, autoimmune, peripheral)
  • Other forms of heart disease (myocardial, valvular, high-output states)
image DIAGNOSIS
PHYSICAL EXAM
  • General: abnormal vital signs including tachycardia or bradycardia, hypertension or hypotension, widened pulse pressure, tachypnea, fever
  • Neurologic: dizziness, syncope, fatigue, weakness, altered mental status
  • Cardiovascular: dysrhythmia, jugular venous distention (JVD), new murmur, rub or gallop, diminished peripheral pulses, carotid bruits
  • Respiratory: tachypnea, increased work of breathing, crackles
  • Musculoskeletal: Sharp pain reproducible with movement or palpation is unlikely to be cardiac.
  • Skin: cool skin, pallor, diaphoresis, signs of dyslipidemia (xanthomas, xanthelasma)
DIFFERENTIAL DIAGNOSIS
  • Aortic dissection
  • Pulmonary embolism
  • Pleuropericarditis
  • Perforating ulcer
  • Gastroesophageal reflux disease (GERD) and spasm
  • Esophageal perforation
  • Biliary or pancreatic pain
  • Dysrhythmia
Geriatric Considerations
Elderly patients, as well as women and those with diabetes, may have an atypical presentation without classic anginal symptoms.
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • 12-lead ECG (1)[A]: applies to both UA and NSTEMI
    • ST-segment depression and/or T-wave inversion:
      • ≥ 1-mm ST depression in ≥2 contiguous leads
      • T-wave inversions, other changes
      • ST depression and/or tall R wave in V1/V2 with upright T waves may indicate transmural STEMI of posterior wall.
      • If initial ECG is nondiagnostic but symptoms persist with suspicion for ACS, perform serial ECGs at 15- to 30-minute intervals.
  • Serum biomarkers (negative by definition in UA)
    • NSTEMI is strictly defined as a rise and fall in serum biomarkers (usually troponin I or T, as they are more sensitive for detecting NSTEMI) exceeding the 99th percentile of a normal reference population. Troponin concentration rises 3 to 6 hours after onset of ischemic symptoms but can be delayed from 8 to 12 hours (troponin T is not specific in patients with renal dysfunction).
    • With contemporary troponin assays, CK-MB and myoglobin are not useful in the diagnosis of ACS (3)[A].
    • Patients with negative biomarkers within 6 hours of the onset of symptoms should have biomarkers remeasured 8 to 12 hours from onset of symptoms
  • Chest x-ray
  • Consider transthoracic echocardiography if not recently performed (1)[B].
Follow-Up Tests & Special Considerations
  • Patients with ischemia are recommended to undergo an assessment of left ventricle (LV) function to identify impaired function and/or need for appropriate medications such as ACE inhibitors, β-blockers, and aldosterone antagonists.
  • Fasting lipid profile, preferably within 24 hours
  • Complete blood count (CBC), basic metabolic panel, activated partial thromboplastin time (aPTT)
  • Other laboratory tests:
    • Lactate dehydrogenase: increases within 24 hours, peaks 3 to 6 days, baseline 8 to 12 days (not routinely ordered)
    • Leukocytes: increase within several hours after MI, peak in 2 to 4 days
    • Brain natriuretic peptide (BNP): increases with MI, may not indicate heart failure
Pregnancy Considerations
Findings mimicking NSTEMI in pregnancy: ST depression after anesthesia, increase in CK-MB after delivery, and mild increase in troponin in preeclampsia and gestational hypertension. Spontaneous coronary dissection is a rare cause of ST elevation in pregnancy.
Diagnostic Procedures/Other
  • Coronary angiography (discussed under “Treatment”)
  • If serial cardiac enzymes are negative and symptoms have resolved, consider stress testing, including either standard exercise treadmill test (ETT), stress echocardiography, or stress nuclear study (1)[B].
  • Transesophageal echocardiography, contrast chest CT scan, or MRI generally are reserved for differentiating ACS and other causes of chest pain from aortic dissection.
Test Interpretation
  • Subendocardial myocardial necrosis may be present.
  • Atherosclerosis
image TREATMENT
GENERAL MEASURES
  • Bed/chair rest with continuous ECG monitoring
  • Antiarrhythmics as needed
  • Anxiolytics as needed
  • Deep vein thrombosis prophylaxis
  • Continuation of aspirin, clopidogrel or prasugrel or ticagrelor, β-blockers, ACE inhibitors (or ARBs if ACE intolerant), lipid-lowering therapy
  • P.17

  • Tight BP control
  • Treatment for depression PRN (common post-MI)
  • Cardiac rehabilitation and increased physical activity
  • Smoking cessation
  • Annual influenza vaccine
MEDICATION
First Line
  • Aspirin, non-enteric-coated, initial dose of 162 to 325 mg PO or chewed to all patients (1)[A]
  • P2Y12 Inhibitors
    • Clopidogrel, loading dose 300 to 600 mg followed by 75 mg/day (1)[B]; or ticagrelor, loading dose 180 mg followed by 90 mg BID (1)[B]. Clopidogrel is favored in patients with ≥2-degree heart block, hemoglobin <10 g/dL, platelet count <100,000 cell/mm3, or liver disease.
    • Prasugrel is reserved for post-PCI patients treated with coronary stents, no history of stroke or TIA, <75 years, and weight >60 kg (1)[B].
    • Patients unable to take aspirin should receive a loading and maintenance dose of clopidogrel, ticagrelor, or prasugrel.
  • Nitroglycerin (NTG) sublingual 0.4 mg every 5 minutes for total of three doses, then assess need for intravenous (IV) NTG (1)[C].
  • Supplemental oxygen 2 to 4 L/min, maintaining arterial oxygen saturation >90% (1)[B]
  • Morphine sulfate 2 to 4 mg IV (with increments of 2 to 8 mg IV repeated at 5- to 15-minute intervals) (1)[A]
  • Oral β-blocker in patients without signs of heart failure, cardiogenic shock, or other contraindications (1)[B]. (IV β-blockers are potentially harmful when risk factors for shock are present.)
  • In patients with concomitant ACS, stabilized heart failure, and reduced systolic function (LVEF <40%), the recommended β-blockers are metoprolol succinate, carvedilol, and bisoprolol (1)[C].
  • Lipid-lowering therapy: initiate or continue high-intensity statin therapy (preferred due to nonlipid benefit on vascular function) (1)[A]; niacin or fibrate (1)[C] if statin use not possible
  • Risk stratify using the TIMI or GRACE score to select use of early invasive approach (within 12 to 24 hours of admission) versus ischemia-guided therapy.
  • Risks and benefits of the early invasive approach:
    • 33% relative risk reduction for both the end points of refractory angina and rehospitalization at 6 to 12 months (2)[A]
    • 27% and 22% relative risk reduction in rates of MI at 6 to 12 months and 3 to 5 years, respectively (2)[A]
    • Doubled risk of procedure-related MI and increased risk of minor periprocedural bleeding (1)[A]
  • Invasive management
    • Benefits are more pronounced in higher risk patients, such as those with ECG changes or diabetes (2).
  • Subsequent recommendations (1)[A]: For patients with elevated risk for clinical events or refractory angina or hemodynamic or electrical instability, initiate anticoagulant: enoxaparin or unfractionated heparin (UFH) or bivalirudin. Prior to angiography, add GP IIb/IIIa inhibitor (eptifibatide or tirofiban) or thienopyridine (clopidogrel or ticagrelor).
  • Ischemia-guided therapy
    • For low-risk or selected intermediate-risk patients, based on patient or physician preference, or in chronic renal insufficiency stage IV: Initiate anticoagulant therapy: enoxaparin or UFH or fondaparinux; enoxaparin or fondaparinux preferable. Initiate clopidogrel or ticagrelor (1)[B].
  • Contraindications: Prasugrel contraindicated in patients ≥75 years or those with history of CVA/TIA or increased bleeding risk. Ticagrelor contraindicated in ≥2-degree heart block.
Second Line
  • ACE inhibitor in patients with pulmonary congestion or left ventricular ejection fraction (EF) ≤40%. Substitute ARB for ACE-intolerant patients (1)[A].
  • Nondihydropyridine calcium channel blocker (CCB) (verapamil or diltiazem) to reduce myocardial oxygen demand when β-blockers are contraindicated if normal EF (1)[B]. Use oral long-acting CCB only after β-blockers and nitrates have been fully used (1)[C].
  • Long-term nitrate therapy for recurrent angina/ischemia or heart failure (1)[C].
  • Sublingual NTG at discharge (1)[C]
ISSUES FOR REFERRAL
Cardiology consultation is appropriate for likely UA/NSTEMI, particularly regarding the complexities of anticoagulation/antiplatelet therapy.
SURGERY/OTHER PROCEDURES
  • Coronary reperfusion
    • PCI with stent placement
    • CABG surgery
  • Intra-aortic balloon pump for severe ischemia, hypotension, refractory pain
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
  • All patients with definite or suspected acute MI, ongoing pain, positive cardiac markers, ST deviations, hemodynamic abnormalities, probable or definite ACS
  • Bed rest with continuous ECG monitoring, assess for reperfusion therapy, relieve ischemic pain, treat life-threatening complications, admit to coronary care unit.
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
  • It is reasonable in patients with possible ACS who have normal serial ECGs and cardiac troponins to have a treadmill ECG, stress myocardial perfusion imaging, or stress echocardiography before discharge or within 72 hours after discharge (2)[A],(3)
  • Follow up within 2 to 6 weeks (low risk) and 14 days (high risk).
  • Refer to cardiac rehabilitation.
DIET
  • Diet low in saturated fat, cholesterol, and sodium
  • Request dietary consult.
PATIENT EDUCATION
  • Education on new medications, diet, exercise, smoking cessation, lifestyle modification
  • Resume exercise, sexual activity after outpatient reevaluation
PROGNOSIS
UA/NSTEMI patients have lower in-hospital mortality than those with STEMI but a similar or worse longterm outcome.
REFERENCES
1. Anderson JL, Adams CD, Antman EM, et al. 2012 ACCF/AHA focused update incorporated into the ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127(23):e663-e828.
2. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics—2012 update: a report from the American Heart Association. Circulation. 2012;125(1):e2-e220.
3. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;64(24): e139-e228. doi:10.1016/j.jacc.2014.09.017.
Additional Reading
  • Cayla G, Silvain J, Collet JP, et al. Updates and current recommendations for the management of patients with non-ST-elevation acute coronary syndromes: what it means for clinical practice. Am J Cardiol. 2015;115(Suppl 5):10A-22A.
  • Hoenig MR, Aroney CN, Scott IA. Early invasive versus conservative strategies for unstable angina and non-ST elevation myocardial infarction in the stent era. Cochrane Database Syst Rev. 2010;(3):CD004815.
Codes
ICD10
  • I24.9 Acute ischemic heart disease, unspecified
  • I20.0 Unstable angina
  • I21.4 Non-ST elevation (NSTEMI) myocardial infarction
Clinical Pearls
  • Discontinue NSAIDs, nonselective or selective cyclo-oxygenase (COX)-2 agents, except for ASA, due to increased risks of mortality, reinfarction, hypertension, heart failure, and myocardial rupture.
  • Discontinue clopidogrel or prasugrel or ticagrelor 5 to 7 days before elective CABG.
  • Do not use nitrate products in patients who recently used a phosphodiesterase-5 inhibitor (24 hours of sildenafil or vardenafil, or 48 hours of tadalafil).
  • Duration of antithrombotic therapy after NSTEMI depends on type of stent received and medications administered.
  • Avoid β-blockers in cocaine or methamphetamine user.