Korean Circ J.  2018 Oct;48(10):863-872. 10.4070/kcj.2018.0255.

De-Escalation of P2Y₁₂ Receptor Inhibitor Therapy after Acute Coronary Syndromes in Patients Undergoing Percutaneous Coronary Intervention

• Kupka D
• Sibbing D

• KMID: 2420639
• DOI: http://doi.org/10.4070/kcj.2018.0255

Abstract

Dual antiplatelet therapy (DAPT) "” a combination of a P2Y₁₂ receptor inhibitor and aspirin "” has revolutionized antithrombotic treatment. Potent P2Y₁₂ inhibitors such as prasugrel and ticagrelor exhibit a strong and more consistent platelet inhibition when compared to clopidogrel. Therefore, ticagrelor and prasugrel significantly reduce ischemic events, but at an expense of an increased bleeding risk in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). These observations have engaged intensive clinical research in alternative DAPT regimens to achieve sufficient platelet inhibition with an acceptable bleeding risk. Our review focusses on P2Y₁₂ receptor therapy de-escalation defined as a switch from a potent antiplatelet agent (ticagrelor or prasugrel) to clopidogrel. Recently, both unguided (platelet function testing independent) and guided (platelet function testing dependent) DAPT de-escalation strategies have been investigated in different clinical studies and both switching strategies could be possible options to prevent bleeding complications without increasing ischemic risk. In light of the still limited data currently available, future large-scale trials should accumulate more data on various DAPT de-escalation regimens with both ticagrelor and prasugrel in unguided and guided de-escalation approaches. In the current review we aim at summarizing and discussing the current evidence on this still emerging topic in the field of antiplatelet treatment.

Keyword

Acute coronary syndrome; P2Y₁₂ Inhibitors; DAPT de-escalation

MeSH Terms

Acute Coronary Syndrome*
Aspirin
Blood Platelets
Hemorrhage
Humans
Percutaneous Coronary Intervention*
Prasugrel Hydrochloride
Aspirin
Prasugrel Hydrochloride

Figure

• 

  Figure 1 Timing of ischemic versus bleeding events after PCI. Ischemic and bleeding rates after PCI are displayed dependent on time. Whereas ischemic rates reach a plateau during the first month, bleeding rates steadily decline. In the second month, ischemic events substantially decrease resulting in an exuberant bleeding risk in the later phase post-PCI. PCI = percutaneous coronary intervention.

• 

  Figure 2 The Pros and Cons of DAPT de-escalation. Characteristics marked in red are variables that may favor a DAPT de-escalation approach and variables marked in blue could be considered as factors that argue against DAPT de-escalation as an alternative DAPT strategy after PCI. Part of the figure content and variables are adapted from the ESC 2017 DAPT guidelines12). DAPT = dual antiplatelet therapy, PCI = percutaneous coronary intervention.

• 

  Figure 3 Trials and possible strategies for un-guided and guided DAPT de-escalation. The figure shows studies and strategies on DAPT de-escalation approaches for P2Y12 receptor therapy. (A) Guided de-escalation of DAPT investigated in the TROPICAL-ACS trial. Patients were enrolled if they had biomarker-positive acute coronary syndrome with successful PCI and randomly assign to a PFT-based DAPT de-escalation arm or uniform prasugrel treatment. (B) Unguided DAPT de-escalation investigated in the TOPIC trial. Patients with ACS and undergoing coronary intervention, on aspirin and a potent P2Y12 blocker were randomly assigned to switch to aspirin and clopidogrel or continuation of their drug regimen with a potent P2Y12 inhibitor. ACS = acute coronary syndrome, DAPT = dual antiplatelet therapy, PFT = platelet function testing; TOPIC = timing of optimal platelet inhibition after acute coronary syndrome; TROPICAL-ACS = Testing Responsiveness to Platelet Inhibition on Chronic Antiplatelet Treatment for Acute Coronary Syndrome.

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