News | TCTAP 2022

Tailored de-escalation strategy in PCI and ACS: platelet function test and genetic test guidance

At TCTAP 2022, Dominick J. Angiolillo, MD outlines de-escalation strategies with PFT, genetic tests for PCI-ACS

Early de-escalation guided by platelet function testing (PFT) and genetic testing is a reasonable approach to reduce bleeding events related to dual antiplatelet therapy (DAPT), an expert said.

¡°The question is whether we can afford to frontload the benefits of DAPT with more potent P2Y12 inhibitors and then de-escalate to minimize the risk of bleeding complications,¡± said Dominick J. Angiolillo, MD, PhD (University of Florida College of Medicine, Jacksonville, USA) at TCTAP 2022 on Apr 27.

¡°Although routine and early de-escalation within 30-days cannot be recommended, particularly unguided, the strategy of de-escalating P2Y12 inhibiting therapy is reasonable to reduce the risk of bleeding in patients that need DAPT,¡± he said.

DAPT is a medication strategy comprised of a P2Y12 inhibitor (ticagrelor, prasugrel or clopidogrel) and aspirin administered to patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI) to prevent blood clots.

A de-escalation strategy involves either reducing the intensity or duration of therapy. Reducing the intensity of DAPT entails switching from a potent P2Y12 inhibitor (ticagrelor or prasugrel) to a weaker one (clopidogrel).

The strategy aims to reduce bleeding complications related to DAPT without losing the benefits of ischemic protection. De-escalation also helps reduce medication costs or side effects not related to bleeding like ticagrelor-related dyspnea.

Based on trials like TOPIC, TROPICAL-ACS and POPular Genetics , Angiolillo recommended:

  • Identifying ACS patients at high bleeding risk or low ischemic risk.
  • Avoid early switching (<30 days), particularly if ¡°unguided.¡±
  • If an early switch is needed, consider a guided approach with platelet function testing or CYP2C19 genotyping (genetic testing) to identify good clopidogrel response.
  • Use switching regimens recommended by guidelines (i.e., avoid drug-drug interactions)

¡°Very early de-escalation (within a few days of acute coronary event) is associated with increased thrombotic complications possibly due to ¡®hot¡¯ platelets, increased platelet turnover rate and drug-drug interactions, among others,¡± he said.

¡°One important concept is that de-escalation occurs after 30 days in many trials, so the recommendation for most ACS patients is to wait for this acute period to pass,¡± he said. ¡°And per the 2017 international expert consensus, always make the switch with a loading dose of the drug being switched to when de-escalating or escalating, particularly in the early phase.¡±

PFT, genetic testing, ABCD-GENE score to predict clopidogrel non-response

Owing to medical advances, contemporary tools like PFT and CYP2C19 genotyping have shown promise for tailoring DAPT, and major guidelines are reflecting their potential in de-escalating strategies.

The 2020 European Society of Cardiology (ESC) guidelines for ACS cautiously recommend de-escalation (Class IIb) as an alternative DAPT strategy for ACS patients deemed unsuitable for potent platelet inhibitors.

¡°De-escalation may be done unguided based on clinical judgment or guided by platelet function testing or CYP2C19 genotyping, depending on patient¡¯s risk profile and availability of respective assays,¡± the European guidelines read.

But recent studies, including a meta-analysis, showed guided antiplatelet therapy selection reduced major adverse cardiovascular events (MACE) over standard therapy (RR 0.78, 95% CI 0.63-0.95, p=0.015), strengthening the case for guided de-escalation.

Considering the updated evidence and the conservative leeway offered by the guidelines, Angiolillo suggested tailoring DAPT strategy by predicting clopidogrel response with PFT and genotype guidance, particularly for early switches:

  • First, de-escalate
  • Wait for a certain period, then conduct PFT
  • Eventually, escalate if non-responsive to clopidogrel; continue therapy if there is good response to clopidogrel (use genetic testing to identify responsiveness)

The ABCD-GENE score, developed by Angiolillo and investigators, also predicts clopidogrel response by integrating the clinical and genetic factors associated with drug response.

¡°CYP2C19 loss-of-function allele does not necessarily mean poor clopidogrel response, and wild-type gene does not always indicate good clopidogrel response,¡± he said. ¡°Since genetic testing looks at genotype, not phenotype, we asked, can we do better?¡±

¡°We developed the ABCD-GENE score as a novel tool to predict clopidogrel nonresponse like high platelet reactivity (HPR), which was evaluated in various settings like the TAILOR-PCI and CHANCE trials and proved useful,¡± he said.

¡°The consensus is to follow guidelines, but when bleeding risk outweighs thrombotic risk, there is an opportunity to consider de-escalation for ACS patients, especially since recent recommendations were made before the recent meta-analysis demonstrated the effectiveness of de-escalation in ACS.¡±


Angiolillo declared individual consulting fees/honorarium from Abbott, Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi, The Medicines Company, CeloNova, American Board of Internal Medicine and American College of Cardiology; Institutional grant support from Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, Osprey Medical and Renal Matsutani; Gift grants from Spartan, Scott R. MacKenzie Foundation; Federal grant from the National Institute of Health.

Leave a comment

Sign in to leave a comment.