What is the preferred antiplatelet therapy, ticagrelor (ticagrelor) or clopidogrel (clopidogrel), for Acute Coronary Syndrome (ACS) patients not undergoing revascularization intervention?

From the Guidelines

Ticagrelor is generally preferred over clopidogrel for Acute Coronary Syndrome (ACS) patients not undergoing revascularization intervention. The recommended dosage for ticagrelor is a 180 mg loading dose followed by 90 mg twice daily, administered with low-dose aspirin (75-100 mg daily) 1. This dual antiplatelet therapy should typically be continued for 12 months after the ACS event.

Key Considerations

• Ticagrelor demonstrates superior efficacy in reducing cardiovascular death, myocardial infarction, and stroke compared to clopidogrel, with a more predictable antiplatelet effect as it does not require hepatic activation 1.
• However, ticagrelor is associated with increased non-CABG-related bleeding risk and may cause dyspnea in some patients.
• It is contraindicated in patients with history of intracranial hemorrhage, severe hepatic impairment, or those taking strong CYP3A inhibitors/inducers.

Alternative Options

• For patients with high bleeding risk, financial constraints, or compliance concerns with twice-daily dosing, clopidogrel (300-600 mg loading dose followed by 75 mg daily) remains a reasonable alternative 1.
• The choice between these medications should ultimately consider individual patient factors including bleeding risk, compliance ability, comorbidities, and cost considerations.

Guideline Recommendations

• The 2020 ESC guidelines recommend ticagrelor over clopidogrel for patients with ACS managed with medical therapy alone, unless the bleeding risk outweighs the potential ischemic benefit 1.
• The 2024 ESC guidelines suggest that in patients without prior MI or revascularization but with evidence of significant obstructive CAD, aspirin 75–100 mg daily is recommended lifelong, and adding a second antithrombotic agent to aspirin for extended long-term secondary prevention should be considered in patients at enhanced ischemic risk and without high bleeding risk 1.

From the Research

Comparison of Ticagrelor and Clopidogrel

• Ticagrelor has a faster onset and more potent antiplatelet effect compared to clopidogrel 2, 3, 4.
• The PLATO trial showed that ticagrelor had a significantly greater reduction in death rate from vascular causes, myocardial infarction, or stroke compared to clopidogrel, without a significant increase in major bleeding 5.
• However, ticagrelor was associated with a higher rate of non-procedure-related bleeding, dyspnea, and ventricular pauses in the first week of treatment 4, 5.

Patient-Specific Considerations

• Ticagrelor is recommended for moderate-to-high risk ACS patients, including those with chronic kidney disease, history of stroke or transient ischemic attack, and the elderly 2.
• Patients with a history of intracranial hemorrhage, moderate-to-severe hepatic impairment, high bleeding risk, or those treated with oral anticoagulants should avoid ticagrelor 2.
• Dyspnea is a common side effect of ticagrelor, and clinicians should consider other potential causes before discontinuing the medication 2.

Real-World Evidence

• A single-institution registry study found similar rates of 1-year all-cause mortality between ticagrelor and clopidogrel in patients undergoing percutaneous coronary intervention, with treatment not being a predictor of death or cardiovascular death 6.
• The study suggests that real-world outcomes may differ from clinical trial results, and that patient-specific factors such as age, end-stage renal disease, and pre-existing heart failure may have a greater impact on mortality 6.