Dual Antiplatelet Therapy De-Escalation in Stabilized Myocardial Infarction With High Ischemic Risk: Post Hoc Analysis of the TALOS-AMI Randomized Clinical Trial

Abstract

Importance: In patients with acute myocardial infarction (AMI) who have high ischemic risk, data on the efficacy and safety of the de-escalation strategy of switching from ticagrelor to clopidogrel are lacking.

Objective: To evaluate the outcomes of the de-escalation strategy compared with dual antiplatelet therapy (DAPT) with ticagrelor in stabilized patients with AMI and high ischemic risk following percutaneous coronary intervention (PCI).

Design, setting, and participants: This was a post hoc analysis of the Ticagrelor vs Clopidogrel in Stabilized Patients With Acute Myocardial Infarction (TALOS-AMI) trial, an open-label, assessor-blinded, multicenter, randomized clinical trial. Patients with AMI who had no event during 1 month of ticagrelor-based DAPT after PCI were included. High ischemic risk was defined as having a history of diabetes or chronic kidney disease, multivessel PCI, at least 3 lesions treated, total stent length greater than 60 mm, at least 3 stents implanted, left main PCI, or bifurcation PCI with at least 2 stents. Data were collected from February 14, 2014, to January 21, 2021, and analyzed from December 1, 2021, to June 30, 2022.

Intervention: Patients were randomly assigned to either de-escalation from ticagrelor to clopidogrel or ticagrelor-based DAPT.

Main outcomes and measures: Ischemic outcomes (composite of cardiovascular death, myocardial infarction, ischemic stroke, ischemia-driven revascularization, or stent thrombosis) and bleeding outcomes (Bleeding Academic Research Consortium type 2, 3, or 5 bleeding) were evaluated.

Results: Of 2697 patients with AMI (mean [SD] age, 60.0 [11.4] years; 454 [16.8%] female), 1371 (50.8%; 684 assigned to de-escalation and 687 assigned to ticagrelor-based DAPT) had high ischemic risk features and a significantly higher risk of ischemic outcomes than those without high ischemic risk (1326 patients [49.2%], including 665 assigned to de-escalation and 661 assigned to ticagrelor-based DAPT) (hazard ratio [HR], 1.74; 95% CI, 1.15-2.63; P = .01). De-escalation to clopidogrel, compared with ticagrelor-based DAPT, showed no significant difference in ischemic risk across the high ischemic risk group (HR, 0.88; 95% CI, 0.54-1.45; P = .62) and the non-high ischemic risk group (HR, 0.65; 95% CI, 0.33-1.28; P = .21), without heterogeneity (P for interaction = .47). The bleeding risk of the de-escalation group was consistent in both the high ischemic risk group (HR, 0.64; 95% CI, 0.37-1.11; P = .11) and the non-high ischemic risk group (HR, 0.42; 95% CI, 0.24-0.75; P = .003), without heterogeneity (P for interaction = .32).

Conclusions and relevance: In stabilized patients with AMI, the ischemic and bleeding outcomes of an unguided de-escalation strategy with clopidogrel compared with a ticagrelor-based DAPT strategy were consistent without significant interaction, regardless of the presence of high ischemic risk.

Figure 1.. Prevalence of the Individual High Ischemic Risk Features

The prevalence of each high ischemic risk factor is shown according to the clinical and procedural aspects for patients with high ischemic risk in the de-escalation group (de-escalation strategy of switching from ticagrelor to clopidogrel) vs the active control group (dual antiplatelet therapy with ticagrelor). CKD indicates chronic kidney disease; PCI, percutaneous coronary intervention.

Figure 2.. Clinical Outcomes of the Antiplatelet Strategy

A, In patients with high ischemic risk, there was no significant difference in the primary ischemic outcome between the de-escalation group (de-escalation strategy of switching from ticagrelor to clopidogrel) vs the active control group (dual antiplatelet therapy with ticagrelor). The difference in absolute risk differences (ARDs) between patients with high ischemic risk and those without high ischemic risk was not significant. B, In patients with high ischemic risk, the risk of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding was numerically but not signficantly lower with de-escalation. The difference in ARDs between patients with high ischemic risk and those without high ischemic risk was not significant. HR indicates hazard ratio; PCI, percutaneous coronary intervention.

Figure 3.. Associations of the Antiplatelet Strategy According to the Individual Components of High Ischemic Risk

A, Across the individual high ischemic risk factors and the number of complex percutaneous coronary intervention (PCI) features, there was no significant difference in the risk of primary ischemic outcome between the de-escalation strategy (switching from ticagrelor to clopidogrel) and the active control strategy (dual antiplatelet therapy with ticagrelor). B, The risk of Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding was numerically but not significantly lower in the de-escalation strategy compared with the active control group except in patients with chronic kidney disease (CKD). NA indicates not applicable.