De-Escalation of Antiplatelet Treatment in Patients with Myocardial Infarction Who Underwent Percutaneous Coronary Intervention: A Review of the Current Literature

Abstract

In acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI), treatment with the P2Y12 inhibitors ticagrelor or prasugrel is recommended over clopidogrel due to a better efficacy, albeit having more bleeding complication. These higher bleeding rates have provoked trials investigating de-escalation from ticagrelor or prasugrel to clopidogrel in the hope of reducing bleeding without increasing thrombotic event rates. In this review, we sought to present an overview of the major trials investigating several different options for de-escalation; unguided, platelet function testing- and genotype-guided. Based on these results, and on other established literature sources, such as guidelines and expert consensus papers, we provide an overview to help decide when and how to de-escalate antiplatelet therapy in ACS patients undergoing PCI.

P2Y12 inhibitor de-escalation after percutaneous coronary interventions

“…1,3-5,32,33 -Most of the results of the clinical trials discussed showed an advantage only in preventing less relevant bleeding complications, not significantly interfering with the really significant ones. 1,[21][22][23][25][26][27]33 -No study was carried out that directly compared the two methods of performing guided de-escalation, i.e., there is no way to determine which guide method should be adopted as preferred. 1,2,33 -In theory, guided de-escalation would be preferred, as it would offer more security when replacing the P2Y12 inhibitor, however, as clinical studies carried out without the aid of complementary tests (non-guided strategy) have shown clinical results similar to those that were guided, there is also no way to clearly determine whether, in everyday practice, one strategy is superior to the other.…”

“…The precise timing for the effectiveness of the de-escalation is also not established. 1,2,19,32,33 -Finally, there are alternatives to the de-escalation strategy, such as the pure and simple reduction in the time of use of the dual scheme or monotherapy with P2Y12 inhibitors, and there is no clinical trial published to date that has compared these different alternatives, making it impossible to recommend one over the other. 1,[3][4][5]7…”

Diagnosis and Management of Acute Coronary Syndrome: What is New and Why? Insight From the 2020 European Society of Cardiology Guidelines

“…If the TWILIGHT regimen may not be applied, patients should be treated with a 12-month duration DAPT including prasugrel or ticagrelor especially when there are high thrombotic risk criteria. However, when facing cases of patients deemed unsuitable for potent platelet inhibition, it is also possible to consider guided de-escalation of P2Y 12 inhibitors receptors, which corresponds to switching from a potent PY12Y inhibitors (i.e., prasugrel or ticagrelor) down to clopidogrel [48]. Such de-escalation should be guided by the results of platelet function testing, as in the Testing Responsiveness to Platelet Inhibition on Chronic Antiplatelet treatment for Acute Coronary Syndromes (TROPICAL-ACS) trial, or on the results of CYP2C19-directed genotyping, which was evaluated in the Patients Outcomes after Primary PCI (Popular Genetics) trial [49][50][51].…”

A new approach to ticagrelor-based de-escalation of antiplatelet therapy after acute coronary syndrome. A rationale for a randomized, double-blind, placebo-controlled, investigator-initiated, multicenter clinical study

“…The risk of major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction (MI), and stroke, gradually decreases, reaching a stable level after 1 month, while the risk of bleeding is mainly related to the type and dosage of antiplatelet drugs and remains steady during the whole period of dual antiplatelet treatment (DAPT). Therefore, in the earliest phase after ACS, the ischemic component should be especially targeted with potent antiplatelet strategies, whereas after the clinical stabilization occurs, de-escalation of the antiplatelet therapy may be justified [1][2][3][4][5][6][7][8]. Treatment with ticagrelor or prasugrel is recommended over clopidogrel due to better efficacy, albeit with more bleeding complications.…”

“…The number of studies reporting clinical outcomes in coronary artery disease patients receiving reduced maintenance dose of ticagrelor is limited; however, available results indicate that in a stable setting this strategy offers improved safety with preserved efficacy in the prevention of thrombotic events [7]. The PEGASUS-TIMI 54 study showed comparable clinical efficacy of two ticagrelor doses (90 mg b.i.d.…”