What is the comprehensive management of acute coronary syndrome in adults, including initial therapy, drug of choice, mechanisms of action, major adverse effects, contraindications, monitoring parameters, and duration of therapy?

Management of Acute Coronary Syndrome

Initial Therapy and Immediate Actions

Administer aspirin 160-325 mg (chewable, non-enteric) immediately upon suspicion of ACS, as this is the single most important initial intervention that reduces mortality. 1, 2

First 10 Minutes

• Obtain a 12-lead ECG within 10 minutes of presentation to distinguish STEMI (requiring immediate reperfusion) from NSTE-ACS (requiring risk-stratified approach) 3, 2, 4
• Start continuous multi-lead ECG monitoring for arrhythmia detection and ischemia monitoring 3, 2
• Assess vital signs focusing on hemodynamic instability, signs of heart failure, and oxygen saturation 3, 2
• Administer oxygen only if oxygen saturation <94%, not routinely 1, 2

Immediate Pharmacological Management (Within First Hour)

Dual Antiplatelet Therapy (DAPT):

• Aspirin 160-325 mg loading dose (already given) 1, 2
• Add P2Y12 inhibitor immediately for NSTE-ACS; choice depends on strategy 1, 3, 2:
  • Ticagrelor 180 mg loading dose is the preferred agent for moderate-to-high risk patients (elevated troponin, GRACE score >109) 1, 3, 2
  • Prasugrel 60 mg loading dose only after coronary anatomy is known and if proceeding to PCI, not before angiography 1, 3
  • Clopidogrel 300-600 mg loading dose if ticagrelor/prasugrel contraindicated or if oral anticoagulation needed 1, 2

Parenteral Anticoagulation (start immediately):

• Enoxaparin 1 mg/kg subcutaneously every 12 hours (preferred over unfractionated heparin) 1, 2, 5
• Alternative: Unfractionated heparin 60-70 units/kg bolus (maximum 5000 units), then 12-15 units/kg/hour infusion targeting aPTT 1.5-2.0 times control 2, 5

Symptom Management:

• Nitroglycerin: Sublingual 0.4 mg every 3-5 minutes (up to 3 doses), then IV infusion if chest pain persists 1, 3, 2
• Morphine 2-4 mg IV for persistent severe chest pain unresponsive to nitrates, particularly in STEMI 1, 2
  • Caution: Use morphine cautiously in NSTEMI/unstable angina due to association with increased mortality in registry data 1

Beta-blockers: Initiate early in absence of contraindications (heart failure, hypotension, bradycardia, heart block) 1, 3, 2

Drug Mechanisms of Action

Antiplatelet Agents

Aspirin:

• Irreversibly inhibits cyclooxygenase-1 (COX-1), blocking thromboxane A2 formation and platelet aggregation 1
• Contraindications: Active peptic ulcer, active bleeding, hemophilia, severe aspirin allergy 1

P2Y12 Inhibitors:

• Ticagrelor: Reversible, direct-acting P2Y12 receptor antagonist blocking ADP-induced platelet aggregation 1
  • Contraindications: Previous intracranial hemorrhage, active bleeding 1
• Prasugrel: Irreversible P2Y12 receptor antagonist (prodrug requiring hepatic activation) 1
  • Contraindications: Previous intracranial hemorrhage, prior stroke/TIA, active bleeding, age ≥75 years (relative), weight <60 kg (relative) 1
• Clopidogrel: Irreversible P2Y12 receptor antagonist (prodrug), slower onset than ticagrelor/prasugrel 1

GP IIb/IIIa Inhibitors (Eptifibatide, Tirofiban, Abciximab):

• Block final common pathway of platelet aggregation by preventing fibrinogen binding to GP IIb/IIIa receptors 1, 5
• Reserved for high-risk patients undergoing PCI or with refractory ischemia 1

Anticoagulants

Low Molecular Weight Heparin (Enoxaparin):

• Inhibits factor Xa and IIa (thrombin), preventing thrombus propagation 1, 2, 5
• Major adverse effect: Bleeding (1.2% requiring transfusion) 1
• Monitoring: Generally no routine monitoring needed; anti-Xa levels if renal impairment or obesity 2

Unfractionated Heparin:

• Inhibits thrombin (IIa) and factor Xa via antithrombin 1, 5
• Monitoring: aPTT every 6 hours until stable at 1.5-2.0 times control 2
• Reversal: Protamine sulfate (1 mg per 100 units of heparin) 1

Risk Stratification and Invasive Strategy Timing

Very High-Risk (Immediate Invasive Strategy <2 Hours)

Proceed immediately to catheterization for: 1, 3, 2

• Hemodynamic instability or cardiogenic shock
• Recurrent/ongoing chest pain refractory to medical treatment
• Life-threatening arrhythmias or cardiac arrest
• Mechanical complications of MI (papillary muscle rupture, ventricular septal defect)
• Acute heart failure

High-Risk (Early Invasive Strategy <24 Hours)

Proceed to catheterization within 24 hours for: 1, 2

• Rise or fall in cardiac troponin compatible with MI
• Dynamic ST-segment or T-wave changes (symptomatic or silent)
• GRACE score >140

Intermediate-Risk (Invasive Strategy <72 Hours)

Proceed to catheterization within 72 hours for: 1

• Diabetes mellitus
• Renal insufficiency (eGFR <60 mL/min/1.73 m²)
• LVEF <40% or congestive heart failure
• Early post-infarction angina
• Recent PCI or prior CABG
• GRACE score 109-140
• Recurrent symptoms or ischemia on non-invasive testing

STEMI-Specific Reperfusion

Primary PCI within 120 minutes is the gold standard for STEMI, reducing mortality from 9% to 7% 1, 4

If PCI unavailable within 120 minutes: 1, 4

• Administer fibrinolytic therapy (alteplase, reteplase, or tenecteplase)
• Full dose for patients <75 years
• Half dose for patients ≥75 years
• Transfer for PCI within 24 hours after fibrinolysis

Major Adverse Effects and Management

Bleeding Complications

Minor bleeding: Stop offending agent temporarily 1

Major bleeding (hematemesis, melena, intracranial hemorrhage): 1

• Discontinue all antithrombotic agents
• Protamine sulfate for unfractionated heparin (neutralizes anti-IIa but only partially neutralizes anti-Xa of LMWH)
• Platelet transfusion for severe thrombocytopenia or life-threatening bleeding on antiplatelet agents
• Risk: Rebound thrombotic phenomenon after heparin reversal 1

GP IIb/IIIa inhibitor bleeding: Increased bleeding requiring transfusion but consistent mortality benefit (4.3% vs 8.3% at 7 days in PRISM-PLUS) 1

Gastrointestinal Effects

• Aspirin: GI intolerance relatively infrequent at low doses (75-162 mg) 1
• Clopidogrel: Fewer side effects than ticlopidine, no routine monitoring needed 1

Monitoring Parameters

Antiplatelet Therapy

• No routine laboratory monitoring required for aspirin, clopidogrel, or ticagrelor 1, 2
• Platelet count if GP IIb/IIIa inhibitors used (risk of thrombocytopenia) 1

Anticoagulation

• Enoxaparin: No routine monitoring; consider anti-Xa levels in renal impairment (CrCl <30 mL/min) or extremes of body weight 2
• Unfractionated heparin: aPTT every 6 hours until therapeutic (1.5-2.0 times control), then daily 2

Cardiac Biomarkers

• High-sensitivity troponin at 0 and 1 hour (or 0 and 3-6 hours if standard assay) 3, 2
• Additional measurement at 3-6 hours if initial measurements non-diagnostic but clinical suspicion remains 1, 3

Hemodynamic Monitoring

• Continuous vital signs, oxygen saturation, cardiac rhythm monitoring 3, 2
• Echocardiography to assess LV function and rule out mechanical complications 1, 3

Renal Function

• Baseline and serial creatinine/eGFR for anticoagulant dosing adjustments 1, 3

Duration of Therapy

Acute Phase (In-Hospital)

Antiplatelet therapy:

• Aspirin: Continue indefinitely 1
• P2Y12 inhibitor: Continue through hospitalization and for 12 months 1, 3, 2

Anticoagulation:

• Continue parenteral anticoagulation until revascularization or hospital discharge (typically 2-8 days) 2, 5
• Discontinue after successful PCI unless other indication (e.g., atrial fibrillation) 5

Long-Term (Post-Discharge)

Dual Antiplatelet Therapy (DAPT):

• 12 months of DAPT (aspirin + P2Y12 inhibitor) unless excessive bleeding risk 1, 3, 2
• After 12 months: Continue aspirin 75-162 mg daily indefinitely 1, 2, 5
• Ticagrelor: 90 mg twice daily for 12 months 1, 3, 2
• Prasugrel: 10 mg daily for 12 months (5 mg daily if age ≥75 years or weight <60 kg) 1
• Clopidogrel: 75 mg daily for 12 months 1, 2

High-Intensity Statin:

• Start immediately and continue indefinitely, targeting ≥50% LDL reduction 1, 3, 2

Beta-Blockers:

• Continue indefinitely, particularly if LVEF ≤40% 3, 2

ACE Inhibitors/ARBs:

• Continue indefinitely if LVEF ≤40%, heart failure, hypertension, or diabetes 2

Critical Pitfalls and Caveats

Prasugrel timing: Never administer prasugrel before coronary anatomy is known; wait until after angiography 1, 3. This is a Class III recommendation (harm).

Clopidogrel and CABG: Discontinue clopidogrel 5 days before elective CABG to reduce bleeding risk 1, 5. For ticagrelor, discontinue 3-5 days before surgery.

Morphine in NSTEMI: Use with extreme caution due to registry data showing association with increased mortality 1. Reserve for refractory pain only.

Oxygen therapy: Do not administer supplemental oxygen routinely; only if oxygen saturation <94% 1, 2. Routine oxygen may be harmful.

Fibrinolysis contraindications: Absolute contraindications include prior intracranial hemorrhage, known structural cerebrovascular lesion, ischemic stroke within 3 months, active bleeding, and suspected aortic dissection 1, 4.

Radial vs femoral access: Radial artery access is preferred for PCI as it reduces bleeding complications and mortality compared to femoral access 1, 3.

Drug-eluting stents: Always use drug-eluting stents over bare-metal stents for any PCI in ACS 1, 3.