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Carciotto et al. Vessel Plus 2024;8:33 https://dx.doi.org/10.20517/2574-1209.2024.01 Page 11 of 13

label, parallel assignment design. Patients in the genotyping arm will receive antiplatelet therapy
(clopidogrel or ticagrelor) based on their CYP2C19 genotype, which will be identified through blood tests
within 48 h of randomization. The control group will receive treatment based on clinical and procedural
characteristics, without genotyping. The primary outcome measures at the one-year follow-up will include
major adverse cardiovascular and cerebrovascular events (MACCE), such as death from all causes, nonfatal
stroke, nonfatal MI, and ischemia-driven revascularization.

Finally, standardizing the implementation of treatment de-escalation in routine clinical practice is
necessary. Clinical practice guidelines and investigators should focus more on defining patient profiles and
standardized treatment strategies based on individual patient risk for both ischemic and bleeding events.
Even the so-called “unguided” de-escalation strategy, despite its introduction in the literature and
widespread use, is never truly unguided. It is always grounded in clinical judgment and physician discretion.
Including a patient in a study of “unguided” de-escalation involves a deliberate decision to select that
patient for treatment - a choice that would not be made if the patient were deemed ineligible for the
strategy. Many bleeding or ischemic risk scores are currently available to inform decision making for DAPT
duration, but aside from the previously mentioned genetic testing or PFT, no risk score or specific decision-
making criteria have been proposed to guide other de-escalation strategies. Additionally, no studies have
thoroughly evaluated clinical markers that inform the decision-making process for patient selection or the
timing of de-escalation. Considering that risk factors for both ischemic and bleeding events often overlap,
further evidence is needed to better understand the potential barriers and facilitators for implementing de-
escalation in routine clinical practice.

CONCLUSION
In conclusion, DAPT de-escalation strategies represent a promising approach to minimizing the risk of
bleeding complications without hampering the ischemic benefits of DAPT, in ACS patients treated with
prasugrel or ticagrelor; however, further evidence is needed to compare different types of antiplatelet agent
modulation. Furthermore, a standardized approach based on individual patient risk needs to be investigated
to implement these strategies in routine clinical practice.

DECLARATIONS
Authors’ contributions
Made substantial contributions to conceive the review, draft and critically revise the text: Carciotto G, Galli
M, Costa F, Garcia-Ruiz V, Soraci E, Magliarditi A, Liotta P, Teresi L, Franzino M, Zecchino S, Bonfiglio D,
Porto I, Vergallo R, Versace AG, Oliva F, Montalto C, Quadri G, Musumeci G, Vizzari G, Capranzano P,
Varbella F, Castriota F, Micari A

Availability of data and materials
Not applicable.

Financial support and sponsorship
Costa F, Vizzari G and Quadri G declare institutional support with research funding from the Italian
Ministry of Health (RFGR-2021-12374500).

Conflicts of interest
All authors declared that there are no conflicts of interest.