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2025 PACUPrep BCCCP Preparatory Course

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  1. Pulmonary

    ARDS
    4 Topics
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    1 Quiz
  2. Asthma Exacerbation
    4 Topics
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  3. COPD Exacerbation
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    1 Quiz
  4. Cystic Fibrosis
    6 Topics
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  5. Drug-Induced Pulmonary Diseases
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  6. Mechanical Ventilation Pharmacotherapy
    5 Topics
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  7. Pleural Disorders
    5 Topics
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  8. Pulmonary Hypertension (Acute and Chronic severe pulmonary hypertension)
    5 Topics
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    1 Quiz
  9. Cardiology
    Acute Coronary Syndromes
    6 Topics
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    1 Quiz
  10. Atrial Fibrillation and Flutter
    6 Topics
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    1 Quiz
  11. Cardiogenic Shock
    4 Topics
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  12. Heart Failure
    7 Topics
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  13. Hypertensive Crises
    5 Topics
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  14. Ventricular Arrhythmias and Sudden Cardiac Death Prevention
    5 Topics
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  15. NEPHROLOGY
    Acute Kidney Injury (AKI)
    5 Topics
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    1 Quiz
  16. Contrast‐Induced Nephropathy
    5 Topics
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    1 Quiz
  17. Drug‐Induced Kidney Diseases
    5 Topics
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    1 Quiz
  18. Rhabdomyolysis
    5 Topics
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    1 Quiz
  19. Syndrome of Inappropriate Antidiuretic Hormone (SIADH)
    5 Topics
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    1 Quiz
  20. Renal Replacement Therapies (RRT)
    5 Topics
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    1 Quiz
  21. Neurology
    Status Epilepticus
    5 Topics
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    1 Quiz
  22. Acute Ischemic Stroke
    5 Topics
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    1 Quiz
  23. Subarachnoid Hemorrhage
    5 Topics
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    1 Quiz
  24. Spontaneous Intracerebral Hemorrhage
    5 Topics
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    1 Quiz
  25. Neuromonitoring Techniques
    5 Topics
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    1 Quiz
  26. Gastroenterology
    Acute Upper Gastrointestinal Bleeding
    5 Topics
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    1 Quiz
  27. Acute Lower Gastrointestinal Bleeding
    5 Topics
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    1 Quiz
  28. Acute Pancreatitis
    5 Topics
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    1 Quiz
  29. Enterocutaneous and Enteroatmospheric Fistulas
    5 Topics
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    1 Quiz
  30. Ileus and Acute Intestinal Pseudo-obstruction
    5 Topics
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    1 Quiz
  31. Abdominal Compartment Syndrome
    5 Topics
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    1 Quiz
  32. Hepatology
    Acute Liver Failure
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  33. Portal Hypertension & Variceal Hemorrhage
    5 Topics
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    1 Quiz
  34. Hepatic Encephalopathy
    5 Topics
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  35. Ascites & Spontaneous Bacterial Peritonitis
    5 Topics
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    1 Quiz
  36. Hepatorenal Syndrome
    5 Topics
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    1 Quiz
  37. Drug-Induced Liver Injury
    5 Topics
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    1 Quiz
  38. Dermatology
    Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis
    5 Topics
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    1 Quiz
  39. Erythema multiforme
    5 Topics
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    1 Quiz
  40. Drug Reaction (or Rash) with Eosinophilia and Systemic Symptoms (DRESS)
    5 Topics
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    1 Quiz
  41. Immunology
    Transplant Immunology & Acute Rejection
    5 Topics
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    1 Quiz
  42. Solid Organ & Hematopoietic Transplant Pharmacotherapy
    5 Topics
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    1 Quiz
  43. Graft-Versus-Host Disease (GVHD)
    5 Topics
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    1 Quiz
  44. Hypersensitivity Reactions & Desensitization
    5 Topics
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    1 Quiz
  45. Biologic Immunotherapies & Cytokine Release Syndrome
    5 Topics
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    1 Quiz
  46. Endocrinology
    Relative Adrenal Insufficiency and Stress-Dose Steroid Therapy
    5 Topics
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    1 Quiz
  47. Hyperglycemic Crisis (DKA & HHS)
    5 Topics
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    1 Quiz
  48. Glycemic Control in the ICU
    5 Topics
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    1 Quiz
  49. Thyroid Emergencies: Thyroid Storm & Myxedema Coma
    5 Topics
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    1 Quiz
  50. Hematology
    Acute Venous Thromboembolism
    5 Topics
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    1 Quiz
  51. Drug-Induced Thrombocytopenia
    5 Topics
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    1 Quiz
  52. Anemia of Critical Illness
    5 Topics
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    1 Quiz
  53. Drug-Induced Hematologic Disorders
    5 Topics
    |
    1 Quiz
  54. Sickle Cell Crisis in the ICU
    5 Topics
    |
    1 Quiz
  55. Methemoglobinemia & Dyshemoglobinemias
    5 Topics
    |
    1 Quiz
  56. Toxicology
    Toxidrome Recognition and Initial Management
    5 Topics
    |
    1 Quiz
  57. Management of Acute Overdoses – Non-Cardiovascular Agents
    5 Topics
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    1 Quiz
  58. Management of Acute Overdoses – Cardiovascular Agents
    5 Topics
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    1 Quiz
  59. Toxic Alcohols and Small-Molecule Poisons
    5 Topics
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    1 Quiz
  60. Antidotes and Gastrointestinal Decontamination
    5 Topics
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    1 Quiz
  61. Extracorporeal Removal Techniques
    5 Topics
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    1 Quiz
  62. Withdrawal Syndromes in the ICU
    5 Topics
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    1 Quiz
  63. Infectious Diseases
    Sepsis and Septic Shock
    5 Topics
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    1 Quiz
  64. Pneumonia (CAP, HAP, VAP)
    5 Topics
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    1 Quiz
  65. Endocarditis
    5 Topics
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    1 Quiz
  66. CNS Infections
    5 Topics
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    1 Quiz
  67. Complicated Intra-abdominal Infections
    5 Topics
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    1 Quiz
  68. Antibiotic Stewardship & PK/PD
    5 Topics
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    1 Quiz
  69. Clostridioides difficile Infection
    5 Topics
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    1 Quiz
  70. Febrile Neutropenia & Immunocompromised Hosts
    5 Topics
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    1 Quiz
  71. Skin & Soft-Tissue Infections / Acute Osteomyelitis
    5 Topics
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    1 Quiz
  72. Urinary Tract and Catheter-related Infections
    5 Topics
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    1 Quiz
  73. Pandemic & Emerging Viral Infections
    5 Topics
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    1 Quiz
  74. Supportive Care (Pain, Agitation, Delirium, Immobility, Sleep)
    Pain Assessment and Analgesic Management
    5 Topics
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    1 Quiz
  75. Sedation and Agitation Management
    5 Topics
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    1 Quiz
  76. Delirium Prevention and Treatment
    5 Topics
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    1 Quiz
  77. Sleep Disturbance Management
    5 Topics
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    1 Quiz
  78. Immobility and Early Mobilization
    5 Topics
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    1 Quiz
  79. Oncologic Emergencies
    5 Topics
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    1 Quiz
  80. End-of-Life Care & Palliative Care
    Goals of Care & Advance Care Planning
    5 Topics
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    1 Quiz
  81. Pain Management & Opioid Therapy
    5 Topics
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    1 Quiz
  82. Dyspnea & Respiratory Symptom Management
    5 Topics
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    1 Quiz
  83. Sedation & Palliative Sedation
    5 Topics
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    1 Quiz
  84. Delirium Agitation & Anxiety
    5 Topics
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    1 Quiz
  85. Nausea, Vomiting & Gastrointestinal Symptoms
    5 Topics
    |
    1 Quiz
  86. Management of Secretions (Death Rattle)
    5 Topics
    |
    1 Quiz
  87. Fluids, Electrolytes, and Nutrition Management
    Intravenous Fluid Therapy and Resuscitation
    5 Topics
    |
    1 Quiz
  88. Acid–Base Disorders
    5 Topics
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    1 Quiz
  89. Sodium Homeostasis and Dysnatremias
    5 Topics
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    1 Quiz
  90. Potassium Disorders
    5 Topics
    |
    1 Quiz
  91. Calcium and Magnesium Abnormalities
    5 Topics
    |
    1 Quiz
  92. Phosphate and Trace Electrolyte Management
    5 Topics
    |
    1 Quiz
  93. Enteral Nutrition Support
    5 Topics
    |
    1 Quiz
  94. Parenteral Nutrition Support
    5 Topics
    |
    1 Quiz
  95. Refeeding Syndrome and Specialized Nutrition
    5 Topics
    |
    1 Quiz
  96. Trauma and Burns
    Initial Resuscitation and Fluid Management in Trauma
    5 Topics
    |
    1 Quiz
  97. Hemorrhagic Shock, Massive Transfusion, and Trauma‐Induced Coagulopathy
    5 Topics
    |
    1 Quiz
  98. Burns Pharmacotherapy
    5 Topics
    |
    1 Quiz
  99. Burn Wound Care
    5 Topics
    |
    1 Quiz
  100. Open Fracture Antibiotics
    5 Topics
    |
    1 Quiz

Participants 432

  • Allison Clemens
  • April
  • ababaabhay
  • achoi2392
  • adhoward1
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Lesson 9, Topic 3
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Antiplatelet Therapy in ACS: Selection, Loading, and Duration

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Selection, Loading, and Duration of DAPT in ACS

Selection, Loading, and Duration of DAPT in ACS

Objectives Icon A checkmark inside a circle, symbolizing achieved learning goals.

Learning Objective

Optimize dual antiplatelet therapy (DAPT) strategies in acute coronary syndromes (ACS) by selecting appropriate agents, timing, and duration based on patient risk profiles and clinical context.

1. Aspirin Pharmacotherapy

Aspirin plays a crucial role in the management of acute coronary syndromes (ACS) by irreversibly inhibiting platelet cyclooxygenase-1 (COX-1). This action blocks the production of thromboxane A₂ (TXA₂), a potent mediator of platelet aggregation and vasoconstriction. Effective aspirin therapy reduces mortality and the risk of reinfarction in patients with ACS. The choice of formulation and dosing regimen is critical to balance the rapidity of onset with the potential for bleeding complications.

Mechanism & PK/PD

  • Aspirin achieves its antiplatelet effect through irreversible acetylation of serine residue on platelet COX-1.
  • This inhibition lasts for the entire lifespan of the affected platelets, typically 7–10 days.
  • Suppression of TXA₂ synthesis effectively prevents platelet aggregation and reduces vasoconstriction at the site of coronary plaque rupture.

Formulations & Onset of Action

  • Chewable/Non–Enteric-Coated Aspirin: This formulation is preferred for loading doses in ACS. It allows for rapid absorption, with peak plasma concentrations achieved within 20–30 minutes. Chewing the tablet facilitates buccal absorption and hastens onset.
  • Enteric-Coated Aspirin: This formulation is designed to protect the gastric mucosa but delays absorption by 1–3 hours. It is not recommended for acute loading in ACS due to its slower onset of antiplatelet effect.

Dosing Recommendations

  • Loading Dose: A dose of 162–325 mg of chewable, non-enteric-coated aspirin should be administered as soon as ACS is diagnosed or suspected.
  • Maintenance Dose: For secondary prevention, a daily dose of 75–100 mg (commonly 81 mg in North America) of aspirin is recommended.

Monitoring & Contraindications

  • Routine laboratory monitoring of aspirin’s antiplatelet effect is generally not required.
  • Clinicians should monitor for signs and symptoms of gastrointestinal (GI) bleeding, such as melena, hematemesis, or unexplained anemia.
  • Contraindications:
    • Active pathological bleeding (e.g., intracranial hemorrhage, active peptic ulcer).
    • Known hypersensitivity to aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs), particularly in patients with asthma and nasal polyps (aspirin-exacerbated respiratory disease).
    • Severe active peptic ulcer disease.
  • GI Prophylaxis: Consider a proton pump inhibitor (PPI) for patients at high risk of GI bleeding. Risk factors include a history of GI bleeding, concurrent use of anticoagulants or corticosteroids, advanced age, and H. pylori infection.
Key Pearls for Aspirin Therapy
  • Always use chewable, non-enteric-coated aspirin for the initial loading dose in ACS to ensure rapid and effective platelet inhibition.
  • A daily maintenance dose of 81 mg (or 75-100 mg) generally provides an optimal balance between antiplatelet efficacy and bleeding risk for long-term secondary prevention. Higher maintenance doses have not shown additional benefit and may increase bleeding.

2. P2Y₁₂ Inhibitor Pharmacotherapy

Oral P2Y₁₂ receptor inhibitors are a cornerstone of DAPT, complementing aspirin by blocking adenosine diphosphate (ADP)-mediated platelet activation and aggregation. The selection of a specific P2Y₁₂ inhibitor depends on several factors, including the type of ACS (STEMI vs. NSTEMI), planned treatment strategy (invasive vs. conservative), patient-specific pharmacokinetic and pharmacogenomic considerations, and individual ischemic and bleeding risk profiles.

A. Mechanism & PK/PD Overview

  • Clopidogrel: A thienopyridine prodrug requiring a two-step metabolic activation process primarily by the cytochrome P450 (CYP) enzyme CYP2C19. Its onset of action is relatively slow (2–6 hours after a loading dose). Antiplatelet effect can be variable due to genetic polymorphisms affecting CYP2C19 activity. It causes irreversible blockade of the P2Y₁₂ receptor.
  • Prasugrel: Another thienopyridine prodrug, but it undergoes a more efficient one-step activation, largely independent of CYP2C19. This results in a faster onset (approximately 30 minutes) and more potent, consistent, and irreversible P2Y₁₂ receptor inhibition compared to clopidogrel.
  • Ticagrelor: A direct-acting, non-thienopyridine cyclopentyltriazolopyrimidine (CPTP). It binds reversibly to the P2Y₁₂ receptor and does not require metabolic activation for its effect. Onset of action is rapid (approximately 30 minutes).

B. General Indications for P2Y₁₂ Inhibitors in ACS

  • All patients with ACS undergoing percutaneous coronary intervention (PCI) should receive DAPT, consisting of aspirin and a P2Y₁₂ inhibitor.
  • For patients with high-risk NSTEMI managed medically (i.e., without early revascularization), DAPT is generally recommended, with the choice and timing of P2Y₁₂ inhibitor initiation guided by clinical judgment and subsequent decisions regarding invasive strategy.

C. Agent Selection & Clinical Decision Points

  • Utilize validated risk scores such as the DAPT score (for ischemic risk) and PRECISE-DAPT score (for bleeding risk) to help guide the choice and duration of P2Y₁₂ inhibitor therapy.
  • STEMI: In patients presenting with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI, potent P2Y₁₂ inhibitors (prasugrel or ticagrelor) are generally preferred over clopidogrel due to their faster onset and greater platelet inhibition, leading to improved ischemic outcomes.
  • NSTEMI: In patients with non-ST-segment elevation ACS (NSTEMI), the strategy for P2Y₁₂ inhibitor loading is more nuanced. If an early invasive strategy is planned, it is often recommended to defer loading with potent P2Y₁₂ inhibitors until after coronary angiography defines the anatomy. This approach minimizes bleeding risk in patients who may not undergo PCI or may require coronary artery bypass grafting (CABG). Clopidogrel may be considered for initial loading if bleeding risk is high or if potent agents are contraindicated.

D. Agent Profiles

Comparative Profiles of Oral P2Y₁₂ Inhibitors in ACS
Agent Loading Dose Maintenance Dose Potential Advantages Potential Disadvantages/Cautions
Clopidogrel 600 mg PO (300 mg if presentation <6 h or fibrinolysis given) 75 mg QD Lower bleeding risk compared to potent agents; cost-effective; standard of care in conjunction with fibrinolytic therapy. Slower onset of action; significant inter-individual variability in response due to CYP2C19 genetic polymorphisms; less potent platelet inhibition.
Prasugrel 60 mg PO 10 mg QD (reduce to 5 mg QD if age ≥75 years OR body weight <60 kg) Rapid onset; potent and consistent platelet inhibition; demonstrated reduction in MI and stent thrombosis compared to clopidogrel in PCI patients. Increased risk of major and fatal bleeding compared to clopidogrel; contraindicated in patients with a history of stroke or transient ischemic attack (TIA). Use with caution in elderly (≥75 years) and low body weight (<60 kg) patients.
Ticagrelor 180 mg PO 90 mg BID Rapid onset; consistent platelet inhibition without need for metabolic activation (no known major genetic variability in response); demonstrated reduction in vascular death and overall mortality compared to clopidogrel in ACS. Dyspnea is a common side effect (10–15%); can cause asymptomatic bradyarrhythmias; potential for interactions with strong CYP3A4 inhibitors or inducers; higher cost than clopidogrel. Twice daily dosing may affect adherence.

E. Monitoring & Interactions

  • Proton Pump Inhibitors (PPIs): If a PPI is indicated for gastroprotection in patients receiving clopidogrel, pantoprazole or rabeprazole are often preferred due to a potentially lower risk of inhibiting CYP2C19, although the clinical significance of this interaction remains debated. This is less of a concern with prasugrel or ticagrelor.
  • Ticagrelor Interactions: Avoid co-administration of ticagrelor with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir) which can increase ticagrelor levels and bleeding risk, or strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine) which can decrease ticagrelor efficacy. Monitor for dyspnea and bradycardia.
  • Platelet Function Testing/Genotyping: Routine platelet function testing or CYP2C19 genotyping is not generally recommended for all patients. However, it may be considered in select high-risk patients (e.g., those with recurrent ischemic events despite DAPT, or prior to elective PCI) to guide P2Y₁₂ inhibitor selection or adjustment, particularly if clopidogrel is being considered or used.
Key Pearls for P2Y₁₂ Inhibitor Therapy
  • For prasugrel, dose reduction (5 mg daily maintenance) is crucial in elderly patients (≥75 years) or those with low body weight (<60 kg) to mitigate bleeding risk, unless a compelling ischemic benefit outweighs this risk. Prasugrel is contraindicated in patients with a history of stroke/TIA.
  • Emerging strategies, such as ticagrelor monotherapy after a short course of DAPT (e.g., 1-3 months of aspirin), aim to leverage the rapid offset of ticagrelor’s reversible binding and potentially reduce long-term bleeding complications without compromising ischemic protection in select patients.

3. Loading Strategies and Timing of P2Y₁₂ Inhibitors

The timing of P2Y₁₂ inhibitor loading dose administration—whether “upstream” (e.g., in the prehospital setting or emergency department before angiography) or “in-lab” (at the time of PCI after coronary anatomy is defined)—can significantly influence both ischemic and bleeding outcomes. The optimal strategy often varies depending on the ACS subtype (STEMI vs. NSTEMI).

Upstream Loading (Pre-PCI Administration)

  • Goal: To achieve therapeutic levels of platelet inhibition at the time of coronary vessel instrumentation during PCI, potentially reducing periprocedural ischemic complications.
  • STEMI: The ATLANTIC trial investigated prehospital administration of ticagrelor in STEMI patients. While prehospital ticagrelor was found to be safe and resulted in a reduction in early stent thrombosis, it did not significantly improve pre-PCI coronary reperfusion rates. Current guidelines generally support upstream loading with a potent P2Y₁₂ inhibitor (ticagrelor or prasugrel) for STEMI patients undergoing primary PCI.
  • NSTEMI: The ACCOAST trial evaluated pretreatment with prasugrel in NSTEMI patients scheduled for an invasive strategy. Prasugrel pretreatment was associated with a significant increase in bleeding complications without a corresponding reduction in ischemic events. Consequently, routine upstream loading with potent P2Y₁₂ inhibitors is generally not recommended for NSTEMI patients before coronary angiography.

In-Lab Loading (At the Time of PCI)

  • This strategy involves administering the P2Y₁₂ inhibitor loading dose after diagnostic angiography has defined the coronary anatomy and the decision to proceed with PCI has been made.
  • It is particularly relevant in NSTEMI patients where coronary anatomy is uncertain, as it minimizes bleeding risk in patients who may ultimately be managed medically, require CABG, or have non-obstructive coronary disease.

STEMI vs. NSTEMI Loading Considerations

  • STEMI: Urgent upstream loading with ticagrelor or prasugrel is generally recommended to achieve rapid and robust platelet inhibition prior to or at the time of primary PCI.
  • NSTEMI: It is generally advisable to defer P2Y₁₂ inhibitor loading until coronary anatomy is defined by angiography, especially for potent agents like prasugrel or ticagrelor. If a P2Y₁₂ inhibitor is given upstream in NSTEMI, clopidogrel may be a safer option, particularly if bleeding risk is high or if there’s a possibility of CABG.
Key Pearls for Loading Strategies
  • Do not routinely pretreat NSTE-ACS patients with potent P2Y₁₂ inhibitors (prasugrel or ticagrelor) before diagnostic angiography, as this practice has been associated with increased bleeding without clear ischemic benefit.
  • In STEMI patients receiving upstream P2Y₁₂ inhibitor loading, be mindful of potential drug-drug interactions, such as morphine-induced delay in the absorption and onset of action of oral P2Y₁₂ inhibitors. Consider strategies to mitigate this if clinically significant.

4. Maintenance Therapy and Duration of DAPT

Following an ACS event and initial loading, the duration of DAPT is a critical consideration. While a standard 12-month course has been the traditional approach, contemporary practice emphasizes individualizing therapy duration. This involves shortening DAPT for patients at high bleeding risk, potentially prolonging it for those at high ischemic risk, and considering transitions to P2Y₁₂ inhibitor monotherapy or de-escalation strategies based on evolving patient factors and risk assessments.

Standard 12-Month DAPT

  • A 12-month duration of DAPT (aspirin plus a P2Y₁₂ inhibitor, typically a potent agent like ticagrelor or prasugrel post-PCI) has been the standard of care, supported by landmark clinical trials such as CURE (clopidogrel), TRITON-TIMI 38 (prasugrel), and PLATO (ticagrelor).
  • This duration is generally recommended for most ACS patients unless there is a high risk of bleeding or other contraindications.

Shortened DAPT Duration (e.g., 3–6 Months)

  • For patients identified as having a high bleeding risk (e.g., PRECISE-DAPT score ≥25, advanced age ≥75 years, history of major bleeding, need for chronic oral anticoagulation), a shorter duration of DAPT (e.g., 1, 3, or 6 months) followed by P2Y₁₂ inhibitor or aspirin monotherapy is increasingly recommended.
  • Trials like STOPDAPT-2 and SMART-DATE have suggested that shorter DAPT durations in selected PCI populations do not significantly increase ischemic events but do lead to a reduction in bleeding complications.

Prolonged DAPT Duration (>12 Months)

  • In patients with a high ischemic risk (e.g., DAPT score ≥2, history of recurrent MI, complex PCI, multivessel disease, diabetes) and a low bleeding risk, extending DAPT beyond 12 months may be considered.
  • The DAPT Study and PEGASUS-TIMI 54 trial demonstrated that prolonged DAPT can reduce the risk of myocardial infarction and stent thrombosis but at the cost of an increased risk of bleeding. The decision requires careful balancing of absolute risk reductions in ischemic events against the incremental bleeding risk.

P2Y₁₂ Inhibitor Monotherapy (Aspirin Discontinuation)

  • An emerging strategy involves discontinuing aspirin after an initial period of DAPT (e.g., 1–3 months post-PCI) and continuing with P2Y₁₂ inhibitor monotherapy (typically ticagrelor or clopidogrel).
  • The TWILIGHT trial, for instance, showed that in high-risk PCI patients who completed 3 months of DAPT, ticagrelor monotherapy for an additional 12 months significantly reduced clinically relevant bleeding by 44% compared to ticagrelor plus aspirin, without an increase in ischemic events.

De-Escalation Protocols

  • De-escalation involves switching from a more potent P2Y₁₂ inhibitor (ticagrelor or prasugrel) to clopidogrel after an initial period of intensive antiplatelet therapy (e.g., 1 month post-ACS).
  • This strategy may be guided by factors such as bleeding events, intolerable side effects from potent agents, patient preference, cost considerations, or results from platelet function testing/genotyping in selected cases. The goal is to maintain adequate ischemic protection while minimizing long-term bleeding risk.
Key Pearls for DAPT Duration and Maintenance
  • Utilize validated bleeding risk scores like PRECISE-DAPT to identify candidates who may benefit from a shortened duration of DAPT (e.g., ≤6 months) to minimize bleeding complications.
  • Employ ischemic risk scores like the DAPT score to help weigh the potential benefits and risks of extending DAPT beyond 1 year in patients with high ischemic risk and low bleeding risk.

References

  1. Rao SV, Newby LK, Hochman JS, et al. 2025 ACC/AHA guideline for the management of patients with acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2025;151:e771–e862.
  2. Wiviott SD, Braunwald E, McCabe CH, et al; TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357(20):2001–2015.
  3. Wallentin L, Becker RC, Budaj A, et al; PLATO Investigators. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361(11):1045–1057.
  4. Montalescot G, van ‘t Hof AW, Lapostolle F, et al; ATLANTIC Investigators. Prehospital ticagrelor in ST-segment elevation myocardial infarction. N Engl J Med. 2014;371(11):1016–1027.
  5. Montalescot G, Bolognese L, Dudek D, et al; ACCOAST Investigators. Pretreatment with prasugrel in non-ST-segment elevation acute coronary syndromes. N Engl J Med. 2013;369(11):999–1010.
  6. Costa F, van Klaveren D, James S, et al. Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and dual antiplatelet therapy (PRECISE-DAPT) score. Lancet. 2017;389(10073):1025–1034.
  7. Yeh RW, Secemsky EA, Kereiakes DJ, et al. Development and validation of a prediction rule for benefit and harm of dual antiplatelet therapy beyond 1 year after percutaneous coronary intervention. JAMA. 2016;315(16):1735–1749.
  8. Mehran R, Baber U, Sharma SK, et al; TWILIGHT Investigators. Ticagrelor with or without aspirin in high-risk patients after PCI. N Engl J Med. 2019;381(21):2032–2042.
  9. Bellemain-Appaix A, O’Connor SA, Silvain J, et al. Association of clopidogrel pretreatment with mortality, cardiovascular events, and major bleeding in patients with non-ST-segment elevation acute coronary syndrome: a systematic review and meta-analysis. JAMA. 2012;308(23):2507–2516.
  10. Steg PG, James S, Harrington RA, et al; PLATO Study Group. Ticagrelor versus clopidogrel in patients with ST-elevation acute coronary syndromes intended for reperfusion with primary percutaneous coronary intervention: A Platelet Inhibition and Patient Outcomes (PLATO) trial subgroup analysis. Circulation. 2010;122(21):2131–2141.