Benefit of Switching Dual Antiplatelet Therapy After Acute Coronary Syndrome According to On-Treatment Platelet Reactivity: The TOPIC-VASP Pre-Specified Analysis of the TOPIC Randomized Study

Abstract

Objectives: This study sought to evaluate the impact of initial platelet reactivity on the benefit of switched strategy.

Background: TOPIC (Timing Of Platelet Inhibition after acute Coronary Syndrome) study suggested that switched dual antiplatelet therapy (DAPT) could improve net clinical benefit after acute coronary syndrome by preventing bleeding.

Methods: Acute coronary syndrome patients, 1 month after coronary stenting and event free, were randomly assigned to aspirin and clopidogrel (switched DAPT) or continuation of drug regimen (unchanged DAPT). All patients underwent platelet function testing at this time and were classified as low on-treatment platelet reactivity (LTPR) (platelet reactivity index vasodilator-stimulated phosphoprotein ≤20%) or non-LTPR (platelet reactivity index vasodilator-stimulated phosphoprotein >20%). The primary endpoint aimed to evaluate the impact of platelet reactivity on clinical outcomes and benefit of switched DAPT strategy.

Results: A total of 645 patients were included, 305 (47%) of whom were classified as LTPR. LTPR patients were less often diabetic (p = 0.01), had lower body mass index (p < 0.01), and were more often on ticagrelor (p < 0.01). Patients defined as LTPR and randomized to unchanged DAPT were at the highest risk of primary endpoint occurrence (31%; p < 0.01). Conversely, in the switched arm, LTPR patients had no significant difference in primary outcome incidence compared with non-LTPR patients (hazard ratio [HR]: 0.78; 95% confidence interval [CI]: 0.40 to 1.49; p = 0.45). The switched strategy was associated with important reduction in primary endpoint incidence in LTPR patients (HR: 0.29; 95% CI: 0.17 to 0.51; p < 0.01) and only numerically lower incidence in non-LTPR patients (HR: 0.79; 95% CI: 0.46 to 1.35; p = 0.39).

Conclusions: Switched DAPT was superior regardless of initial platelet reactivity but the benefit was greater in LTPR patients. Indeed, the switched strategy was highly effective in this group, which had impaired prognosis with unchanged DAPT but similar prognosis after switching.

Keywords: P2Y(12) blockers; acute coronary syndrome(s); platelet inhibition; switch.