Impact of body mass on P2Y12-inhibitor de-escalation in acute coronary syndromes-a substudy of the TROPICAL-ACS trial.

Abstract

Clinical guidelines recommend de-escalation antiplatelet strategies to reduce bleeding risk in acute coronary syndrome (ACS) patients, albeit with a weak recommendation. This sub-study of the TROPICAL-ACS trial aimed to determine the impact of body mass on the efficacy of platelet-function testing-guided de-escalation regimen in ACS patients after PCI. Patients were randomized to prasugrel (control group) or a platelet-function testing-guided regimen with clopidogrel or prasugrel defined after one-week clopidogrel. The primary endpoint was the net clinical benefit (cardiovascular death, myocardial infarction, stroke, or BARC 2-5 bleeding) for 12 months. Overweight was defined as a body mass index (BMI) >25kg/m2.Patients without overweight showed a significant net clinical benefit from the de-escalation strategy while in overweight cases de-escalation was comparable to prasugrel treatment (HR: 0.52; 95% CI: 0.31-0.88; p=0.013, and HR: 0.95; 95%CI: 0.69-1.31, p=0.717, p-non-inferiority=0.03, respectively, p-interaction=0.053). The benefit of de-escalation in terms of the risk of bleeding or of the ischemic events did not reach statistical significance. Bleeding events with de-escalation were less frequent in non-overweight patients but comparable in overweight patients (HR: 0.55; 95% CI: 0.30-1.03; p=0.057, and HR: 0.95; 95% CI: 0.64-1.41, respectively p-interaction=0.147). Non-overweight patients had lower ischemic event rates with de-escalation, while overweight cases had slightly less. (HR: 0.47; 95%CI: 0.18-1.25, p=0.128, and HR: 0.89; 95% CI: 0.53-1.50, respectively p-interaction=0.261). The strategy of guided DAPT de-escalation was associated with a significant net clinical benefit in non-overweight patients, while the two strategies were equivalent in overweight patients.