Antiplatelet Drugs

Antiplatelet drugs prevent platelets from clumping together to form a blood clot. They are primarily used in the prevention and treatment of cardiovascular diseases such as heart attack, stroke, and peripheral arterial disease.

Types of Antiplatelet Drugs

  1. Aspirin
  2. P2Y12 Inhibitors
  3. Glycoprotein IIb/IIIa Inhibitors
  4. Phosphodiesterase Inhibitors
  5. PAR-1 Antagonists

1. Aspirin (Acetylsalicylic Acid)

  • Category: Nonsteroidal Anti-inflammatory Drug (NSAID)
  • Mechanism of Action: Aspirin irreversibly inhibits cyclooxygenase-1 (COX-1) enzyme, leading to decreased synthesis of thromboxane A2 (TXA2), a potent promoter of platelet aggregation.
  • Indications:
    • Prevention of myocardial infarction (heart attack)
    • Stroke prevention in patients with a history of transient ischemic attacks (TIAs) or strokes
    • Acute coronary syndrome (ACS)
  • Side Effects:
    • Gastrointestinal bleeding
    • Peptic ulcer disease
    • Tinnitus (at high doses)
    • Allergic reactions, including bronchospasm in aspirin-sensitive individuals

Dosage:

  • Acute settings: 300 mg orally for immediate effect.
  • Maintenance: 75-100 mg orally daily.

Contraindications:

  • Active peptic ulcer disease.
  • Aspirin hypersensitivity.
  • Severe hepatic or renal impairment.

Antidote: activate charcoal

2. P2Y12 Inhibitors (e.g., Clopidogrel, Prasugrel, Ticagrelor)

  • Category: ADP Receptor Inhibitors
  • Mechanism of Action: These drugs inhibit the P2Y12 receptor on platelets, preventing ADP (adenosine diphosphate)-mediated activation and aggregation of platelets.
  • Indications:
    • Acute coronary syndrome (ACS)
    • Post-percutaneous coronary intervention (PCI) to prevent stent thrombosis
    • Stroke prevention in certain patients
  • Side Effects:
    • Bleeding (major risk)
    • Thrombocytopenia
    • Dyspnea (especially with Ticagrelor)
    • Gastrointestinal disturbances

Dosage:

  • Clopidogrel: 300-600 mg loading dose, then 75 mg orally daily.
  • Prasugrel: 60 mg loading dose, then 10 mg orally daily.
  • Ticagrelor: 180 mg loading dose, then 90 mg orally twice daily.

Contraindications:

  • Active bleeding.
  • History of intracranial hemorrhage.
  • Severe hepatic impairment.
  • Thrombocytopenia

3. Glycoprotein IIb/IIIa Inhibitors (e.g., Abciximab, Eptifibatide, Tirofiban)

  • Category: Glycoprotein IIb/IIIa Receptor Antagonists
  • Mechanism of Action: These drugs block the glycoprotein IIb/IIIa receptor on platelets, preventing the final common pathway of platelet aggregation by inhibiting the binding of fibrinogen and von Willebrand factor.
  • Indications:
    • Acute coronary syndrome (ACS)
    • During percutaneous coronary intervention (PCI) to prevent ischemic complications
  • Side Effects:
    • Major bleeding
    • Thrombocytopenia
    • Hypotension (especially with Abciximab)
    • Hypersensitivity reactions.

Dosage:

  • Abciximab: 0.25 mg/kg IV bolus, followed by 0.125 mcg/kg/min IV infusion.
  • Eptifibatide: 180 mcg/kg IV bolus, followed by 2 mcg/kg/min IV infusion.
  • Tirofiban: 0.4 mcg/kg/min IV for 30 minutes, then 0.1 mcg/kg/min.

Contraindications:

  • Active internal bleeding.
  • Recent major surgery or trauma.
  • Thrombocytopenia.

4. Phosphodiesterase Inhibitors (e.g., Dipyridamole, Cilostazol)

  • Category: Phosphodiesterase Inhibitors
  • Mechanism of Action: These drugs increase cyclic AMP (cAMP) in platelets by inhibiting phosphodiesterase, leading to reduced platelet activation and aggregation.
  • Indications:
    • Secondary stroke prevention (Dipyridamole, often combined with aspirin)
    • Intermittent claudication in peripheral arterial disease (Cilostazol)
  • Side Effects:
    • Headache
    • Dizziness
    • Gastrointestinal disturbances
    • Palpitations (especially with Cilostazol)

Dosage:

  • Dipyridamole: 200 mg orally twice daily (extended-release formulation).
  • Cilostazol: 100 mg orally twice daily.

Contraindications:

  • Severe coronary artery disease.
  • Heart failure (specific to cilostazol).

5. PAR-1 Antagonists (e.g., Vorapaxar)

  • Category: Protease-Activated Receptor-1 (PAR-1) Antagonists
  • Mechanism of Action: Vorapaxar inhibits the PAR-1 receptor on platelets, which is a major receptor for thrombin, thus preventing thrombin-induced platelet aggregation.
  • Indications:
    • Prevention of thrombotic cardiovascular events in patients with a history of myocardial infarction or peripheral arterial disease
  • Side Effects:
    • Bleeding (including intracranial hemorrhage)
    • Anemia
    • Depression
    • Rash

Clinical Guidelines and Monitoring

In the UK, the use of antiplatelet drugs is guided by clinical guidelines from bodies such as the National Institute for Health and Care Excellence (NICE).

  1. Acute Coronary Syndromes (ACS):
    • Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) is recommended.
  2. Secondary Prevention of Cardiovascular Disease:
    • Aspirin is typically used, sometimes in combination with other antiplatelets depending on the patient’s risk profile.
  3. Stroke and TIA:
    • Clopidogrel or a combination of aspirin and dipyridamole is recommended for secondary prevention.

Monitoring and Adverse Effects

Regular monitoring is essential to ensure the safety and efficacy of antiplatelet drugs:

  • Complete Blood Count (CBC): To monitor for thrombocytopenia, especially with glycoprotein IIb/IIIa inhibitors.
  • Renal and Liver Function Tests: Periodic monitoring, particularly in patients with preexisting conditions.
  • Bleeding Complications: Regular assessments for signs of bleeding, both overt and occult.

References

  1. NICE Guidelines on Antiplatelet Therapy