Usage
Aspirin + Ticagrelor is prescribed to reduce the risk of cardiovascular death, myocardial infarction (MI), and stroke in patients with acute coronary syndrome (ACS) or a history of MI. It also reduces the rate of stent thrombosis in patients who have been stented for the treatment of ACS. Additionally, it is used to reduce the risk of a first MI or stroke in high-risk patients with coronary artery disease (CAD), particularly those with type 2 diabetes mellitus. Finally, it’s used to reduce the risk of stroke in patients with acute ischemic stroke (NIH stroke scale score ≤5) or high-risk transient ischemic attack (TIA).
This drug combination falls under the pharmacological classifications of antiplatelet agents and nonsteroidal anti-inflammatory drugs (NSAIDs), specifically due to the aspirin component.
The mechanism of action involves inhibiting platelet aggregation, primarily through Ticagrelor’s reversible antagonism of the P2Y12 receptor, which prevents ADP-mediated platelet activation and aggregation. Aspirin irreversibly inhibits cyclooxygenase-1 (COX-1), reducing thromboxane A2 production, further inhibiting platelet aggregation. The combined effect significantly reduces the risk of thrombus formation.
Alternate Names
While “Aspirin + Ticagrelor” represents the generic drug combination, Ticagrelor is also known by the brand name Brilinta. Aspirin is widely recognized and doesn’t typically have other brand names used in combination with Ticagrelor.
How It Works
Pharmacodynamics: Ticagrelor reversibly binds to the P2Y12 receptor on platelets, preventing ADP-induced platelet activation and aggregation. Aspirin irreversibly inhibits COX-1, reducing thromboxane A2 synthesis, further inhibiting platelet aggregation. Together, they synergistically decrease platelet activation, reducing thrombotic events.
Pharmacokinetics: Ticagrelor is rapidly absorbed, reaching peak plasma concentration in 1.5-2 hours. It is metabolized by CYP3A4/5 enzymes in the liver to an active metabolite. Both Ticagrelor and its metabolite are primarily eliminated via hepatic metabolism and biliary excretion. Aspirin is rapidly absorbed and converted to its active form, salicylate. Salicylate is eliminated primarily by renal excretion, with some hepatic metabolism.
Mode of Action: Ticagrelor reversibly binds to the P2Y12 receptor on platelets, acting as a competitive antagonist to ADP. Aspirin irreversibly acetylates COX-1, preventing the formation of thromboxane A2, a potent platelet activator. The combined result is reduced platelet activation and aggregation.
Receptor Binding, Enzyme Inhibition: Ticagrelor: P2Y12 receptor antagonist (reversible). Aspirin: COX-1 enzyme inhibitor (irreversible).
Elimination Pathways: Ticagrelor: Hepatic metabolism (CYP3A4/5), biliary excretion. Aspirin: Renal excretion, hepatic metabolism.
Dosage
Standard Dosage
Adults:
- ACS/History of MI: Ticagrelor loading dose: 180 mg orally once, followed by 90 mg twice daily for 1 year. Maintenance dose after 1 year: 60 mg twice daily. Aspirin: Initial dose of 325 mg, then a maintenance dose of 75-100 mg daily.
- CAD (high-risk, no prior MI/stroke): Ticagrelor: 60 mg orally twice daily. Aspirin: 75-100 mg daily.
- Acute Ischemic Stroke/TIA: Ticagrelor loading dose: 180 mg orally once, followed by 90 mg twice daily for up to 30 days. Aspirin: loading dose of 300-325 mg, then 75-100 mg daily.
Children:
The safety and efficacy of Ticagrelor have not been established in pediatric patients. Aspirin should be used cautiously in children due to the risk of Reye’s syndrome.
Special Cases:
- Elderly Patients: No dosage adjustment is generally required, though close monitoring for bleeding is recommended.
- Patients with Renal Impairment: No dose adjustment is needed for Ticagrelor.
- Patients with Hepatic Dysfunction: Ticagrelor should be used with caution in moderate hepatic impairment and is contraindicated in severe hepatic dysfunction. Aspirin dosage may need adjustment.
- Patients with Comorbid Conditions: Close monitoring is recommended, particularly in patients with bleeding disorders or on anticoagulant therapy.
Clinical Use Cases
The dosages mentioned above cover typical clinical use cases including ACS, post-MI, CAD, stroke and TIA. Dosing adjustments may be necessary in specific clinical scenarios like PCI, based on the risk of thrombotic vs. bleeding events.
Dosage Adjustments
Dose adjustments may be necessary in patients with moderate hepatic impairment or when co-administered with strong CYP3A inhibitors or inducers.
Side Effects
Common Side Effects
- Dyspnea (shortness of breath)
- Bleeding (e.g., nosebleeds, easy bruising, prolonged bleeding from cuts)
- Headache
- Dizziness
- Nausea
- Gastrointestinal bleeding
- Dyspepsia
Rare but Serious Side Effects
- Major bleeding (intracranial, gastrointestinal)
- Thrombotic Thrombocytopenic Purpura (TTP)
- Ventricular pauses/asystole
Long-Term Effects
Long-term use may increase the risk of bleeding complications.
Adverse Drug Reactions (ADR)
Serious bleeding events including intracranial hemorrhage and TTP require immediate intervention.
Contraindications
- Active pathological bleeding (e.g., peptic ulcer)
- History of intracranial hemorrhage
- Severe hepatic impairment
- Concomitant use of strong CYP3A inhibitors or inducers
Drug Interactions
- Strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin) increase Ticagrelor levels.
- Strong CYP3A inducers (e.g., rifampin, phenytoin) decrease Ticagrelor levels.
- Anticoagulants (e.g., warfarin) increase bleeding risk.
- Aspirin doses above 100 mg daily can reduce the effectiveness of Ticagrelor.
Pregnancy and Breastfeeding
- Pregnancy: Ticagrelor is a pregnancy category C drug. Use only if the potential benefit justifies the potential risk to the fetus.
- Breastfeeding: Breastfeeding is not recommended while taking Ticagrelor due to potential risks to the infant.
Drug Profile Summary
- Mechanism of Action: Inhibits platelet aggregation via P2Y12 receptor antagonism (ticagrelor) and COX-1 inhibition (aspirin).
- Side Effects: Dyspnea, bleeding, headache, dizziness, nausea.
- Contraindications: Active bleeding, intracranial hemorrhage history, severe hepatic impairment, strong CYP3A inhibitors/inducers.
- Drug Interactions: CYP3A inhibitors/inducers, anticoagulants, high-dose aspirin.
- Pregnancy & Breastfeeding: Use with caution in pregnancy if benefits outweigh risks; breastfeeding not recommended.
- Dosage: See dosage section above.
- Monitoring Parameters: Signs of bleeding, hemoglobin/hematocrit, renal function, uric acid levels.
Popular Combinations
Aspirin is routinely combined with Ticagrelor in recommended doses to synergistically inhibit platelet aggregation and reduce cardiovascular events.
Precautions
Assess for bleeding risk factors, hepatic/renal function before initiating therapy. Monitor for signs of bleeding during treatment. Caution should be used in elderly patients. Patients should be advised on proper aspirin dosage to avoid reducing Ticagrelor’s effectiveness. Avoid use with strong CYP3A inhibitors/inducers.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Aspirin + Ticagrelor?
A: See detailed dosage guidelines above, as it varies depending on indication and patient-specific factors.
Q2: What is the primary mechanism of action of Ticagrelor?
A: Ticagrelor reversibly inhibits the P2Y12 receptor on platelets, preventing ADP-mediated platelet activation and aggregation.
Q3: What are the common side effects of Aspirin + Ticagrelor?
A: Common side effects include dyspnea, bleeding, headache, dizziness, and nausea.
Q4: Should Aspirin + Ticagrelor be used during pregnancy?
A: It should be used with caution during pregnancy only if the potential benefit outweighs the potential risk to the fetus. It is categorized as a pregnancy category C drug.
A: Ticagrelor is primarily metabolized by CYP3A4/5 enzymes in the liver. Concomitant medications affecting these enzymes can alter Ticagrelor levels.
Q6: Can a patient on Clopidogrel be switched to Ticagrelor?
A: Yes, Ticagrelor can be initiated 24 hours after the last dose of Clopidogrel.
Q7: How does high-dose aspirin affect Ticagrelor?
A: Aspirin maintenance doses above 100 mg can reduce the effectiveness of Ticagrelor.
Q8: What are the contraindications for using Ticagrelor?
A: Contraindications include active pathological bleeding, history of intracranial hemorrhage, severe hepatic impairment, and concomitant use of strong CYP3A inhibitors or inducers.
Q9: Is there a reversal agent for Ticagrelor?
A: No, there is currently no specific reversal agent available for Ticagrelor.
