Modified ticagrelor loading doses according to the vasodilator-stimulated phosphoprotein phosphorylation index improve the clinical outcome in ST-elevation myocardial infarction patients with high on-treatment platelet reactivity

Abstract

Background: Current guidelines recommend a standard ticagrelor loading dose (LD) in ST-segment elevation myocardial infarction (STEMI) patients. However, antiplatelet therapy in STEMI patients at high risk of thrombotic events is suboptimal. The study was conducted to validate whether vasodilator-stimulated phosphoprotein (VASP)-guided ticagrelor dosing individual therapy may result in more effective platelet inhibition and better clinical outcomes. Methods: This trial included 374 STEMI patients with a low platelet response after ticagrelor LD. The patients were randomized into a control group and a VASP-guided group, where the ticagrelor pretreat-ment was individually adjusted before and after percutaneous coronary intervention (PCI) to obtain a VASP index < 50%. Up to 2 additional boluses of ticagrelor (every additional dosing was 90 mg) were prescribed after the first LD, and the VASP index was assessed 2 hours after each administration until a VASP index < 50% was obtained or up to 3 dosages (360 mg). The primary endpoint was major adverse cardiovascular events (MACEs) at 30 days. The secondary endpoints were thrombolysis in myocardial infarction (TIMI) major and minor bleeding. Results: The characteristics were similar in the two groups. After the ticagrelor doses increased, the platelet reactivity index (PRI) decreased, and 98.4% of patients reached PRI < 50% in the VASP-guided group. The adenosine concentration increased, and the rate of MACE was significantly lower in the VASP-guided group (10 [5.3%] vs. 20 [10.8%], hazard ratio 2.38, 95% confidence interval 1.21–3.28, p = 0.007). There were no major hemorrhagic complications (0 vs. 0, p = 1.0). The rate of minor bleeding in the VASP-guided group was higher than that in the control group, but the difference was not significant (24 [12.8%] vs. 16 [8.6%], p = 0.068). Conclusions: The incremental ticagrelor dosing strategy decreases the rate of MACE after PCI without increasing major and minor bleeding.