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Page 6 of 13 Carciotto et al. Vessel Plus 2024;8:33 https://dx.doi.org/10.20517/2574-1209.2024.01
[25]
potential to improve the precision of these tests .
There are three major RCTs that tested a PFT-guided de-escalation therapy in ACS patients [26-28] .
The ANTARCTIC, a multicenter, randomized controlled superiority study, enrolled 877 elderly patients
who underwent coronary stenting for ACS. The patients were randomly assigned in a 1:1 ratio to receive
either 5 mg of prasugrel with dose adjustment or drug switching in case of insufficient response, or 5 mg of
[26]
prasugrel without monitoring . PFT was performed 2 weeks after randomization. Patients were
maintained on prasugrel 5 mg if the results of the VerifyNow assay results showed normal platelet reactivity
(PRU 85-208). If PFT showed high platelet reactivity, the dosage was escalated to prasugrel 10 mg. If the
patient had low platelet reactivity, the dosage was de-escalated to clopidogrel 75 mg. The primary endpoint,
a composite of CV death, MI, stroke, ST, urgent revascularization, and bleeding complications BARC 2, 3 or
5, at 12 months occurred in 120 patients in the de-escalation group and 123 patients in the standard group
(28% vs. 28%). There was no significant difference in terms of the rate of bleeding events .
[26]
The TROPICAL-ACS is another RCT that evaluated PFT-guided de-escalation therapy. This larger
randomized, multicenter trial enrolled 2,610 ACS patients who underwent successful PCI and had an
indication for 12 months of DAPT . The study randomly assigned patients (1:1) to either standard DAPT
[27]
with prasugrel 10 mg or to a PFT-guided de-escalation therapy. The de-escalation group was administered
prasugrel for 1 week, followed by 1 week of clopidogrel. Subsequently, the patients underwent PFT to decide
whether to maintain therapy with clopidogrel or to switch again to prasugrel, 14 days after the hospital
discharge. The de-escalation strategy was found to be non-inferior for the primary composite endpoint of
net clinical benefit at 12 months (7% vs. 9%), with no differences in the combined risk of CV death, MI, or
stroke and no differences in terms of bleeding .
[27]
The POPular Genetics randomized trial studied a de-escalation strategy based on genetic tests in 2,488
patients with STEMI who underwent coronary stenting. The patients were randomly assigned in a 1:1 ratio
to either genotype-guided-descalation, receiving clopidogrel when CYP2C19 LoF alleles were not found, or
DAPT with potent P2Y inhibitors (mainly ticagrelor), within 48 h after PCI, for 12 months . The de-
[28]
12
escalation strategy proved to be non-inferior for the primary endpoints of net adverse clinical events at 1
year (with rates of 5.1% in the genotype-guided group and 5.9% in the standard treatment group). PLATO
major or minor bleeding at 12 months occurred less often in the genotype-guided group, with no apparent
increase in the rate of ischemic events .
[28]
A recent comprehensive meta-analysis, which included 11 RCTs and 3 observational studies with data for
20,743 patients, improved statistical power for hard ischemic and bleeding outcomes. The analysis showed
that guided de-escalation therapy reduced the rate of bleeding by 19% without increasing the incidence of
ischemic events .
[29]
Another network meta-analysis was conducted on 61,898 patients from 15 different RCTs comparing
various oral P2Y12 inhibitors recommended for patients with ACS. Trials testing a guided versus a standard
approach were also included. This analysis concluded that, compared to clopidogrel, the only strategy that
reduced MACE without a significant difference in terms of all bleeding was the guided de-escalation
approach .
[30]