Acute Coronary Syndromes

Background

• Acute coronary syndrome(s) (ACS) includes a spectrum of conditions associated with acute myocardial ischemia and/or necrosis usually secondary to reduction in coronary blood flow, including:
  • unstable angina (UA)
  • non-ST-elevation myocardial infarction (NSTEMI)
  • ST-elevation myocardial infarction (STEMI) (not discussed in the current topic)
• The most common cause of ACS is plaque rupture in the setting of underlying coronary artery disease (CAD)
• Common risk factors for the development of ACS include known CAD or risk factors for CAD including tobacco abuse, dyslipidemias, hypertension, diabetes mellitus, and family history of CAD.

Evaluation

• Suspect acute coronary syndrome(s) (ACS) in patients based on history and physical exam consistent with diagnosis, such as angina in the retrosternal area occurring at rest or with minimal exertion, and/or patients with signs of heart failure or hemodynamic instability.
• See differential diagnosis for conditions associated with signs and symptoms that may overlap with those for patients with ACS
• In patients presenting with suspected ACS, obtain a 12-lead electrocardiogram (ECG) within 10 minutes of arrival (Strong recommendation).
• Repeat ECG at 15- to 30-minute intervals if the initial ECG is nondiagnostic and the patient remains symptomatic, or when symptoms change (Strong recommendation).
• Measure cardiac troponin I or T in all patients with chest pain consistent with ACS (Strong recommendation).
  • If high-sensitivity cardiac troponin test (expressing results as concentrations; currently only high-sensitivity test approved by FDA is Elecsys assay with 99^th percentile cutoff of 14 ng/L) available, use
    • rapid rule out protocol at 0 and 3 hours (Strong recommendation); use rapid rule out protocol at 0 and 1 hours if specific troponin test with validated 0 hour/1 hour algorithm available (Elecsys, Architect, Dimension Vista) (Strong recommendation).
    • repeat after 3-6 hours if first two troponin measurements do not have clear diagnostic pattern (Strong recommendation)
  • If high-sensitivity cardiac troponin is not available, repeat cardiac troponin measurement 3-6 hours after symptom onset (Strong recommendation).
• Perform urgent coronary angiography, unless contraindicated, in patients with non-ST-elevation ACS with refractory angina, hemodynamic instability, or electrical instability (Strong recommendation).
• Other testing may guide management and identify comorbidities
• If initial testing (ECG, cardiac biomarkers) is inconclusive for ACS diagnosis consider:
  • observation with cardiac monitoring, and repeat ECG and cardiac biomarker levels (Weak recommendation)
  • stress testing prior to discharge from emergency room/observation unit, or ≤ 72 hours after discharge (Weak recommendation)

Management

Early hospital care

• Administer the following medications to patients with definite or highly likely acute coronary syndrome(s) (ACS):
  • aspirin 162-325 mg (chewed) as soon as possible after presentation (Strong recommendation); consider in suspected ACS (Weak recommendation)
  • add anticoagulant therapy (such as one of unfractionated heparin, enoxaparin, bivalirudin, or fondaparinux) to antiplatelet therapy as soon as possible (Strong recommendation)
  • add ticagrelor (180 mg then 90 mg twice daily) or clopidogrel (300 or 600 mg then 75 mg once daily) to aspirin and anticoagulant therapy as soon as possible, unless patient has contraindications (such as excessive risk of bleeding) (Strong recommendation); consider using ticagrelor over clopidogrel (Weak recommendation)
  • nitroglycerin 0.3-0.4 mg sublingually every 5 minutes for up to 3 doses to all patients with suspected ACS for ongoing ischemic discomfort (Strong recommendation)
  • IV nitroglycerin in the first 48 hours if the patient has persistent ischemia, heart failure, or uncontrolled hypertension (Strong recommendation)
  • beta blocker orally within the first 24 hours unless contraindicated or patient is at risk of shock (Strong recommendation)
  • oral angiotensin-converting enzyme (ACE) inhibitor (if no hypotension or contraindications) within the first 24 hours in patients with hypertension or left ventricular ejection fraction (LVEF) ≤ 40% (Strong recommendation)
• Give oxygen only if the patient has arterial saturation < 90%, respiratory distress, or if other high-risk features for hypoxemia are present (Strong recommendation).
• For patients with persistent or recurrent ischemic symptoms after beta blockers and nitrates:
  • give oral long-acting nondihydropyridine calcium channel blockers (such as verapamil or diltiazem) (Strong recommendation)
  • consider IV morphine sulfate (Weak recommendation)
• Do not give nonsteroidal anti-inflammatory drugs (NSAIDs) (except aspirin) (Strong recommendation).
• Risk assessment for likelihood of ACS and adverse outcomes to determine need for hospitalization and guide treatment may be performed using multiple scores, including
  • Global Registry of Acute Coronary Events (GRACE) score
  • Thrombolysis in Myocardial Infarction (TIMI) score
  • Acute Myocardial Infarction in Switzerland (AMIS) score
  • CRUSADE Bleeding Score

Invasive versus ischemia-guided (conservative) strategy

• Further management is based on the initial decision between invasive strategy vs. ischemia-guided strategy
  • immediate invasive strategy refers to immediate angiography (≤ 2 hours), or as quickly as possible after initial presentation, with intent of revascularization procedure
  • early invasive strategy refers to angiography ≤ 24 hours after admission in patients with initial stabilization
  • delayed invasive strategy refers to coronary angiography 25-72 hours post admission in patients with initial stabilization
  • ischemia-guided strategy does not include immediate angiography, but the possibility of angiography based on additional test results
• Proceed to immediate invasive strategy if unstable (ongoing angina, hemodynamically, or electrically) after initial treatment (Strong recommendation)
• If stable after initial treatment:
  • Proceed with immediate invasive strategy if at any time instability develops after initial stablization (Strong recommendation).
  • Proceed with early invasive strategy if high risk (Strong recommendation).
• If initial invasive strategy:
  • consider ticagrelor over clopidogrel (Weak recommendation)
  • prasugrel is an option at time of percutaneous coronary intervention (PCI) and is preferred over clopidogrel in patients NOT at high risk of bleeding complications (Weak recommendation), but is not recommended if coronary anatomy is not known
  • consider giving IV glycoprotein IIb/IIIa inhibitor (eptifibatide or tirofiban) at the time of percutaneous coronary intervention (PCI) in high-risk patients (such as those with elevated troponin levels, diabetes, or significant ST-segment depression) NOT at high risk for bleeding
    • in addition to aspirin and ticagrelor or clopidogrel (Weak recommendation).
    • if not pretreated with ticagrelor or clopidogrel.
  • cangrelor may be considered as adjunct in patients undergoing percutaneous coronary intervention who are naive to P2Y₁₂ inhibitors (Weak recommendation)
• Consider delayed invasive strategy if intermediate risk for clinical events after initial stabilization (Weak recommendation).
• If low risk for clinical events, use one of the following strategies prior to hospital discharge
  • delayed invasive strategy
  • ischemia-guided strategy

Preparation for hospital discharge

• Long-term medications (in the absence of contraindications) that should be added in the hospital if patient not already taking typically include:
  • dual antiplatelet therapy with aspirin, ticagrelor, clopidogrel, or prasugrel depending on the use of stents (Strong recommendation)
  • beta blockers in those with left ventricle ejection fraction (LVEF) ≤ 40% (Strong recommendation) and possibly in those with LVEF > 40 (Weak recommendation).
  • ACE inhibitor (Strong recommendation)
    • If patient is intolerant of ACE inhibitor, use angiotensin receptor blocker if LVEF < 40% (Strong recommendation) and consider if LVEF ≥ 40% (Weak recommendation)
    • If patient has LVEF ≤ 40% despite use of therapeutic doses of ACE inhibitor and beta blocker, use aldosterone blockade if no significant renal dysfunction or hyperkalemia (Strong recommendation)
  • high-intensity statin therapy, regardless of lipid levels (Strong recommendation)
• Perform noninvasive stress testing in low-risk patients when the patient is free of ischemia and heart failure for at least 12-24 hours when an ischemia-guided approach has been chosen (Strong recommendation).
• Perform echocardiography, or other noninvasive method to assess left ventricular function, prior to discharge in patients with confirmed ACS treated with conservative (noninvasive or ischemia-guided) strategy (Strong recommendation).
• Give all patients sublingual or spray nitroglycerin prior to hospital discharge and provide instructions in its use (Strong recommendation).
• Continue medications prescribed for secondary prevention and medications required to control ischemia (Strong recommendation).
• Enroll patients in cardiac rehabilitation/secondary prevention programs, especially if they have multiple modifiable risk factors or they are moderate- to high-risk patients (Strong recommendation).