Guided DAPT de-escalation therapy in PCI-treated ACS patients with diabetes vs. non-diabetes
Diabetes and Outcomes following Guided De-Escalation of Antiplatelet Treatment in Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention: A Prespecified Analysis from the Randomized TROPICAL-ACS Trial
Introduction and methods
Although guidelines recommend P2Y12 inhibition up to one year after invasive procedures in ACS patients , dual antiplatelet therapy (DAPT) de-escalation strategies are commonly practiced [2-4] to obtain greatest ischemic benefit during the first weeks after PCI and reduce bleeding risk. Recently, an International Expert Consensus document was published reporting on the clinical relevance of switching P2Y12 inhibitors including a DAPT de-escalation strategy .
In the TROPICAL-ACS trial  invasively treated ACS patients were randomized to control (prasugrel) or guided de-escalation (7 days prasugrel followed by 7 days clopidogrel). Platelet function testing (agonist-induced platelet aggregation) was performed 14 days after randomization and patients in the guided de-escalation group continued on clopidogrel when platelet reactivity was not high or switched to prasugrel when platelet reactivity was high. Patients in the control group continued on prasugrel. Results of this trial demonstrated that platelet function testing guided DAPT de-escalation with early switch from prasugrel to clopidogrel was effective and safe. In response to these results, the 2018 ESC/EACTS Guidelines included recommendations on guided DAPT de-escalation that may be considered as an alternative DAPT strategy in ACS patients.
No differences in outcomes were found examining the effect of DAPT strategies in patients with and without diabetes  and current guidelines do not per se consider prolonged DAPT for diabetes patients. However, it is important to realize that diabetes patients have an increased ischemic risk and higher platelet reactivity, which may result in different effects of DAPT de-escalation therapy.
Therefore, in this pre-specified analysis of the TROPICAL-ACS trial outcomes of guided de-escalation DAPT therapy were examined in diabetes vs. non-diabetes patients.
The TROPICAL-ACS trial, an investigator-initiated and randomized multicenter trial, enrolled 2610 ACS patients after PCI, who were randomized to control (n=1306) or guided de-escalation group (n=1304). For this pre-specified sub-study patients were stratified into diabetes (n=527, 20.2%) and non-diabetes patients (n=2083, 79.8%). Primary endpoint was a net clinical benefit endpoint of CV death, MI, stroke and BARC bleeding grade ≥2 after 12 months.
- In the control group, median platelet aggregation (median [IQR]) was significantly higher in diabetes vs. non-diabetes patients (29.0 U [IQR:20.0-40.0] vs. 25.3 U [17.0-37.0], P=0.01). Similarly, in the guided de-escalation group, platelet aggregation was higher in diabetes patients vs. non-diabetes patients (44.0 U [31.0- 65.] vs. 38.0 U [25.0-59.0], P=0.005).
- In diabetes patients, 1-year incidence of primary endpoint did not differ between guided de-escalation and control groups (12.5% vs. 10.8%; HR 1.17; 95%CI:0.71–1.93, P=0.55). Incidence of BARC≥2 bleedings was not different between groups, nor was all-cause mortality at 1-year.
- In non-diabetes patients, 1-year incidence of the primary endpoint was lower in the guided de-escalation vs. control group (6.1% vs. 8.5%; HR 0.71; 95%CI: 0.52– 0.99, P=0.04). Interaction between diabetes status and treatment effects was not significant (P=0.10). Incidence of BARC≥2 bleedings and 1-year all-cause mortality were not different between groups.
No interaction between diabetes status, guided de-escalation vs. control therapy and outcome was observed in ACS patients after PCI in a pre-specified analysis of the TROPICAL-ACS trial. However, results suggest that in non-diabetes patients primary outcome was reduced in those who received guided de-escalation therapy vs. control therapy, whereas no difference in outcomes were seen with guided de-escalation therapy vs. control in patients with diabetes.