Coronary Artery Disease and Acute Coronary Syndrome

Atherosclerotic coronary artery disease (CAD) is a leading cause of mortality and morbidity worldwide. While many patients with CAD are asymptomatic, chest pain is a common presentation. An initial evaluation of chest pain should identify whether the patient is presenting with acute coronary syndrome (ACS), which is an emergency condition characterized by acute myocardial injury (most commonly due to atherosclerotic plaque rupture or plaque erosion followed by thrombus formation).

In this section, we will discuss the diagnosis and management of:

• Coronary Artery Disease

• Acute Coronary Syndrome

Coronary Artery Disease

Evaluation

All patients who present with chest pain should receive a thorough history and physical examination to determine whether the pain is cardiac related and whether the patient is stable versus unstable. However, a review of the full evaluation of chest pain is beyond the scope of this guide.

Features of chest pain: Typical cardiac chest pain or angina is characterized by retrosternal chest discomfort that is provoked by physical exertion or emotional stress and relieved promptly (i.e., <5 minutes) with rest or nitroglycerin treatment. Other symptoms associated with myocardial ischemia include dyspnea, nausea, epigastric discomfort, presyncope, or syncope. Women, elderly patients, and those with diabetes may present with nonclassic chest-pain qualities, and more attention needs to be paid to these populations.

• High-risk features: The following table lists features of chest pain presentation suggestive of ACS (discussed below) that necessitates more-urgent evaluation and management.

(Source: 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease. J Am Coll Cardiol 2012.)

• Probable CAD and low-risk features: Patients deemed to have probable CAD and low-risk features should undergo evaluation to determine the severity of CAD and the risk for myocardial infarction (MI) and its complications.

Tests for CAD can be classified as functional or anatomical. Functional tests use a stressor to illicit myocardial oxygen demand-and-supply mismatch, leading to reversible ischemia, which can be detected by electrocardiogram (ECG), imaging, or both. Anatomical tests directly examine for the presence and severity of plaque(s).

• Functional tests

  • Stressors include exercise on a treadmill or stationary bicycle.

    • Continuous infusion of dobutamine or injection of coronary vasodilators (e.g., regadenoson) can be used in patients who cannot exercise.

  • Imaging modalities include echocardiography, nuclear myocardial perfusion imaging, and less frequently, cardiac magnetic resonance imaging.

    • Imaging is typically required for patients who have baseline ECG findings (e.g., left bundle branch block, ventricular pacing, or resting ST-segment abnormalities, such as ST changes from left ventricular hypertrophy or digoxin use) that interfere with ECG interpretation.

• Anatomical tests

  • Coronary angiography, the gold standard test for CAD, is associated with procedural risks (e.g., bleeding, infection, MI, or stroke) and may be necessary to guide management (see below) based on findings from other tests.

  • Coronary computed tomography angiography (CCTA) is a noninvasive alternative to angiography but typically requires patients to have a slow-enough heart rate to acquire adequate quality images that are timed to the cardiac cycle.

• Coronary artery calcium (CAC)

  • For patients at low-to-intermediate risk for CAD, a targeted CT scan can quantify the amount of CAC present, which can identify individuals at low risk for adverse outcomes.

Each test is associated with different sensitivity, specificity, and prognostic values that depend on the patient’s overall clinical likelihood of having CAD. Choosing an appropriate test can avoid false-positive or -negative results. In patients with an established diagnosis of CAD, testing can guide management when symptoms or clinical status change.

Predictors of morbidity and mortality include:

• maximum exercise capacity

• ECG changes during exercise

• amount of cardiac dysfunction detected by imaging

• severity of coronary stenoses

For more information on choosing cardiac testing, please see the 2021 ACC/AHA guideline for the evaluation and diagnosis of chest pain and the 2014 ACC/AHA guideline for management of stable ischemic heart disease.

Management

In all patients with CAD, the cornerstones of treatment are lifestyle changes and risk-factor management.

Medical therapies include:

• lipid lowering with statins, ezetimibe, and/or proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors; goal for treatment will be tailored based on a patient’s risk for adverse cardiac events. Bempedoic acid, an ATP citrate lyase inhibitor, is a novel LDL cholesterol-lowering medication that can reduce the risk for adverse events.

• blood pressure control with goal of <130/80 mm Hg; drugs with concurrent indications in CAD are preferred (e.g., beta-blockers, angiotensin-converting-enzyme [ACE] inhibitors, and angiotensin-receptor blockers); of note, beta-blockers can be stopped 3 years after MI or ACS in favor of a more effective drug for blood pressure control if a patient has no other indications for beta-blockers (i.e., ejection fraction [EF] ≤40%)

• diabetes control with goal hemoglobin A1c (HbA1c) <7% in patients with long life expectancy and goal 7% to 9% in patients with comorbidities

• low-dose aspirin indefinitely, with clopidogrel (75 mg daily) as an alternative for patients who cannot tolerate aspirin

• control of chronic stable angina with beta-blockers, calcium-channel blockers, long-acting nitrates, and/or ranolazine

• annual influenza vaccination

Revascularization: Based on testing, certain patients may have high-risk features that warrant coronary revascularization, either with coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). The decision for CABG versus PCI should be made by an interdisciplinary heart team based on the patient’s preferences, comorbidities, and procedural risks. Several clinical trials have shown that routine revascularization in patients with stable CAD does not improve mortality. In general, revascularization should be considered for patients with:

• ≥50% diameter stenosis in the left main coronary artery

• ≥70% stenoses in three major coronary arteries

• unacceptable angina despite maximum medical therapy

After PCI for revascularization of stable coronary disease, patients are typically treated with low-dose aspirin and clopidogrel (i.e., dual antiplatelet therapy [DAPT]) for ≥1 month after bare metal stent (BMS) placement and for ≥6 months after drug-eluting stent (DES) placement. Aspirin can be omitted for patients prescribed anticoagulation treatment (e.g., warfarin or non-vitamin K antagonist oral anticoagulants [NOACs]) for another indication.

Acute Coronary Syndrome

The three types of ACS can be differentiated based on ECG findings and biomarkers (primarily troponin) as follows:

• STEMI (ST-segment elevation myocardial infarction): ST elevations on ECG with positive biomarkers

• NSTEMI (non-ST-segment elevation myocardial infarction): no ST elevations on ECG but positive biomarkers and symptoms consistent with acute coronary artery thrombosis (e.g., sudden onset or progressively worsening angina)

• UA (unstable angina): progressive symptoms of angina, often at rest or with minimal exertion, without ECG changes or positive biomarkers but suggestive of critical coronary artery stenosis an impending MI, or both; an increasingly rare clinical syndrome due to the high sensitivity of troponin assays

Management of Acute STEMI

Immediate PCI or “primary” PCI is the preferred management of acute STEMI (especially in patients who present within 12 hours of symptom onset). The shorter the interval between first medical contact and primary PCI, the better the outcome.

• An interval of ≤90 minutes is used as a quality measure for hospitals that perform primary PCI. Patients should be transferred to a PCI-capable hospital if time from first medical contact to PCI can be ≤120 minutes.

• Otherwise, systemic fibrinolytic therapy (e.g., tenecteplase, reteplase, or alteplase) is recommended with subsequent transfer for coronary angiography.

• Of note, PCI is also recommended for resuscitated patients after a cardiac arrest if the initial ECG is consistent with a STEMI.

Coronary angiography and revascularization:

• Patients with non-ST-segment elevation-acute coronary syndrome (NSTE-ACS) and high-risk features should also undergo immediate coronary angiography and revascularization, which includes cardiogenic shock, severe heart failure, or structural complications of myocardial infarction (e.g., papillary muscle rupture or ventricular septal defect).

• Patients with NSTE-ACS not requiring immediate PCI should undergo risk stratification to determine whether catheterization within 24 to 48 hours of admission is appropriate. The Global Registry of Acute Coronary Events (GRACE) risk model and the TIMI risk score are recommended for this purpose; patients with a TIMI risk score >2 benefit from this so-called “early invasive” approach.

The following table lists the factors associated with appropriate selection of early invasive strategy or ischemia-guided strategy:

(Source: 2014 AHA/ACC Guideline for the Management of Patients with Non-ST-Elevation Acute Coronary Syndromes, Circulation 2014. Reprinted with permission. ©2014, American Heart Association, Inc.)

Medical management of ACS includes:

• aspirin (162 to 325 mg, chewed or crushed, given immediately upon initial recognition of potential ACS)

• antiplatelet therapy with a loading dose of P2Y₁₂-receptor blocker (clopidogrel, prasugrel, or ticagrelor); ticagrelor or prasugrel (contraindicated in patients with prior stroke or transient ischemic attack) is preferred over clopidogrel in the ACS setting

• heparin or bivalirudin for patients undergoing invasive management; low-molecular-weight heparin or fondaparinux for patients not undergoing invasive management

• beta-blocker (avoid in patients with signs of acute heart failure, low cardiac output, or both)

• nitrates for relief of ischemic symptoms

• morphine for relief of chest pain in STEMI

• oxygen for patients who are hypoxemic on presentation

Post-ACS management includes:

• low-dose aspirin: for patients taking oral anticoagulant, DAPT and anticoagulation are typically continued for the first month after ACS before discontinuing aspirin

• P2Y₁₂-receptor blocker: ≥12 months at maintenance dose to prevent stent thrombosis and recurrent MI; clopidogrel is preferred for patients on concomitant oral anticoagulant; ultimate duration of DAPT may vary based on bleeding risk and type of stent

• beta-blocker: reduces frequency of ventricular arrythmia, helps with positive left ventricular (LV) remodeling in those with EF ≤40% and improves mortality

• ACE inhibitor: for patients with anterior infarction, LVEF ≤40%, hypertension, diabetes, or stable chronic kidney disease (CKD) unless contraindicated; angiotensin-receptor blocker (ARB) for patients who cannot tolerate ACE inhibitors secondary to cough or angioedema

• aldosterone blockade: for patients receiving maximum tolerated therapeutic doses of ACE inhibitor and beta-blocker and have LVEF ≤40%, diabetes mellitus, or heart failure without significant CKD or hyperkalemia

• high-intensity statin (or other agents mentioned above for CAD management in patients who cannot tolerate statins)

• nitrites as needed

• implanted cardioverter-defibrillator (ICD) placement: generally not recommended within 90 days of revascularization or within 40 days of myocardial infarction based on the DINAMIT and IRIS studies

The following table describes recommended routine medical therapies for ACS:

(Source: 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction, Circulation 2012. Reprinted with permission. ©2012, American Heart Association, Inc.)