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Carciotto et al. Vessel Plus 2024;8:33 https://dx.doi.org/10.20517/2574-1209.2024.01 Page 7 of 13

HOW DE-ESCALATION FITS IN THE NOVEL PARADIGM OF DAPT SHORTENING AND
P2Y INHIBITOR MONOTHERAPY?
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Several bleeding reduction strategies have demonstrated promising outcomes compared to the standard 12-
month DAPT in the context of ACS patients treated with PCI [12,17] .

The initial bleeding reduction strategies tested in the setting of ACS undergoing PCI involved shortening
DAPT by discontinuing the P2Y inhibitor 3-6 months after ACS [31-33] . However, due to a numerical
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increase in MI and ST in the short DAPT followed by aspirin group, this strategy was only recommended
for ACS patients at high bleeding risk who cannot undergo standard 12-month DAPT with potent P2Y
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inhibitors [31,32,34,35] . Therefore, the focus has shifted to shortening DAPT by interrupting aspirin and
maintaining a P2Y inhibitor [36,37] . In this setting, a strategy of clopidogrel monotherapy for 1-2 months
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(median of 39 days) after standard DAPT did not succeed in reaching non-inferiority to standard 12
months of DAPT in terms of net clinical benefit with a numerical increase in CV events despite a decrease
in bleeding complications . On the other hand, two RCTs showed that a strategy of ticagrelor
[38]
monotherapy for 1 or 3 months after standard DAPT is safer and equally effective compared to a standard
12-month DAPT with ticagrelor [39,40] . Collectively, although some residual concern exists due to the
inclusion of low-ischemic risk and East Asian patients in many of these trials, it seems that a strategy of
short DAPT followed by ticagrelor monotherapy may represent a successful strategy in ACS patients, being
also possibly advantageous compared with a de-escalation strategy.

However, it is important to note that there is currently no direct comparison of these strategies available.
Therefore, it is crucial to recognize both the strengths and limitations of each approach when providing
guidance for their use in clinical practice. Notably, shortening or modulating the standard 12-month DAPT
with a potent P2Y inhibitor is expected to decrease bleeding risk, but there is a potential trade-off in
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efficacy . This concern should be addressed through adequately powered RCTs.
[41]
Currently, three recent network meta-analyses have evaluated an indirect comparison among multiple
bleeding reduction strategies in ACS patients, and two of them concluded that while a short DAPT strategy
is safer in terms of bleeding, a DAPT de-escalation strategy reduces the risk for NACE [42-44] . The one
conducted by Laudani et al. included twenty-nine studies with a total of 50,602 participants . The study
[42]
compared short DAPT, characterized by halting the P2Y i or aspirin within 1-6 months, with DAPT de-
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escalation, which involves switching to clopidogrel or a lower dose of potent P2Y i. The study found that
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short DAPT strategies and de-escalation strategies did not differ in a significant way in terms of risk of
death and death from CV causes. Short DAPT guaranteed a lower risk of major bleeding but increased the
rate of NACE. Conversely, de-escalation was associated with a higher risk of major bleeding but reduced the
risk of NACE, mainly due to the reduction of MACE, MI, cerebrovascular events, and ST (resulting in a
[42]
reduction of these events) . The study results indicate that using two antiplatelet drugs throughout the
study period, rather than discontinuing one of them, has a synergistic effect. This suggests that a short
DAPT strategy may be safer for patients with a high PRECISE-DAPT score or who meet the HBR criteria.
Current guidelines recommend a short DAPT strategy as a class IIa recommendation and a de-escalation
strategy as a class IIb recommendation when the primary concern is preventing bleeding risk . However,
[42]
the authors concluded that based on network meta-analyses, a DAPT de-escalation strategy was linked to a
similar risk of death and reduced risk of NACE compared to short-term DAPT. Therefore, the class of
recommendation should be at least the same .
[42]

Kuno et al. conducted a network meta-analysis that included 32 RCTs with 103,497 ACS patients treated
with 12 months of DAPT (clopidogrel, ticagrelor or prasugrel), prolonged DAPT, short DAPT pursued by