What is the comparison between Clopidogrel (Plavix), Prasugrel (Effient), and Ticagrelor (Brilinta) in dual antiplatelet therapy (DAPT) post percutaneous coronary intervention (PCI) in non-ST elevation myocardial infarction (NSTEMI)?

From the Guidelines

For dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in NSTEMI patients, ticagrelor is generally preferred over prasugrel and clopidogrel due to its superior outcomes and more consistent platelet inhibition without requiring metabolic activation, as shown in the PLATO trial 1.

Comparison of P2Y12 Inhibitors

The choice of P2Y12 inhibitor for DAPT in NSTEMI patients depends on various factors, including individual bleeding risk, comorbidities, concomitant medications, and cost.

• Ticagrelor (180 mg loading dose, then 90 mg twice daily) offers more consistent platelet inhibition without requiring metabolic activation and has shown reduced cardiovascular death compared to clopidogrel 1.
• Prasugrel (60 mg loading dose, then 10 mg daily) provides more potent and rapid platelet inhibition than clopidogrel but is contraindicated in patients with prior stroke/TIA, age >75, or weight <60 kg (or requires dose reduction to 5 mg daily in these cases) 1.
• Clopidogrel (600 mg loading dose, then 75 mg daily) remains appropriate for patients who cannot tolerate the newer agents due to bleeding risk or cost concerns, or who require oral anticoagulation.

Considerations for Treatment

The 2020 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation recommend considering the individual patient's risk factors and comorbidities when selecting a P2Y12 inhibitor 1.

• Patients with high ischemic risk and low bleeding risk benefit most from the more potent agents (ticagrelor or prasugrel).
• Those with higher bleeding risk may be better suited for clopidogrel.
• The treatment algorithm and treatment duration should be individualized based on the patient's specific needs and risk factors.

Combination with Aspirin

All P2Y12 inhibitors should be combined with aspirin (81-325 mg loading dose, then 81 mg daily) for 12 months post-PCI for NSTEMI.

• The combination of aspirin and a P2Y12 inhibitor provides optimal antiplatelet therapy for patients with NSTEMI undergoing PCI.
• The choice of P2Y12 inhibitor and aspirin dose should be based on the individual patient's risk factors and comorbidities.

From the FDA Drug Label

Prasugrel significantly reduced total endpoint events compared to clopidogrel (see Figure 3 and Table 5). The reduction of total endpoint events was driven primarily by a decrease in nonfatal MIs, both those occurring early (through 3 days) and later (after 3 days). Prasugrel reduced the occurrence of the primary composite endpoint compared to clopidogrel in both the UA/NSTEMI and STEMI populations (see Table 5).

The comparison between Clopidogrel (Plavix) and Prasugrel (Effient) in dual antiplatelet therapy (DAPT) post percutaneous coronary intervention (PCI) in non-ST elevation myocardial infarction (NSTEMI) shows that:

• Prasugrel reduces the rate of thrombotic CV events, including stent thrombosis, compared to Clopidogrel.
• Prasugrel decreases nonfatal MIs, both early and late, compared to Clopidogrel.
• Prasugrel has a higher rate of clinically significant bleeding than Clopidogrel.

There is no direct comparison to Ticagrelor (Brilinta) in the provided drug labels 2 2.

From the Research

Comparison of Clopidogrel, Prasugrel, and Ticagrelor in DAPT Post PCI in NSTEMI

• The efficacy and safety of novel oral P2Y12 receptor inhibitors (prasugrel and ticagrelor) compared to clopidogrel in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) have been evaluated in several studies 3, 4, 5, 6, 7.
• Prasugrel and ticagrelor have been shown to decrease the risk of all-cause death, major adverse cardiac events, and stent thrombosis without causing more bleeding events compared to clopidogrel in patients with STEMI undergoing PCI 3.
• In real-life data, ticagrelor is more effective in reducing ischemic events during the first year after ACS, despite an increased risk of major bleedings, while prasugrel assures a better balance between ischemic and bleeding recurrent events 4.
• Current evidence suggests that prasugrel or ticagrelor plus aspirin should be the DAPT of choice in patients with ACS undergoing PCI unless they are at particularly high risk of bleeding 5.
• A network meta-analysis found that high- to low-potency DAPT and aspirin+prasugrel containing DAPT for 12 months had a significantly lower incidence of major adverse cardiovascular events at 1 year, while prasugrel and ticagrelor containing DAPT for 12 months had significantly higher rates of major bleeding 6.
• The choice of agent should be made on an individual patient basis, considering the patient's risk of bleeding and other clinical factors 5, 7.

Efficacy and Safety

• Prasugrel and ticagrelor have been shown to be more effective than clopidogrel in reducing ischemic events, but may have a higher risk of bleeding 3, 4, 6.
• Ticagrelor has been found to constantly reduce recurrent MIs despite a higher risk of BARC 3-5 events 4.
• Prasugrel has been found to have a constant equivalence between opposite risks, with a lower risk of bleeding compared to ticagrelor 4.

Clinical Implications

• The choice of DAPT agent should be individualized based on the patient's clinical characteristics and risk factors 5, 7.
• Aspirin and ticagrelor for 3 months, followed by aspirin and clopidogrel for the remaining duration, may be considered the optimal strategy for treating post-PCI patients with ACS due to a significantly reduced risk of major adverse cardiovascular events without increasing the risk of bleeding 6.