Effect of chewing vs swallowing ticagrelor on platelet inhibition in patients with ST-Segment elevation myocardial infarction: A randomized clinical trial

IMPORTANCE Dual anti-platelet therapy represents standard care for treating patients with ST-segment elevationmyocardial infarction (STEMI). Ticagrelor is a direct-acting P2Y12 inhibitor and, unlike clopidogrel and prasugrel, does not require metabolic activation. OBJECTIVE To evaluate whether chewing a loading dose (LD) of ticagrelor, 180mg, vs traditional oral administration of an equal dose enhances platelet inhibition at 30 minutes and 1 hour after LD administration in patients with STEMI. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trialwas conducted in adults aged 30 to 87 years from May to October 2016 in a large tertiary care center. Analyses were intention-to-treat. INTERVENTIONS Fifty patients with STEMI were randomized to either chewing an LD of ticagrelor, 180mg, or standard oral administration of an equal dose. MAIN OUTCOMES AND MEASURES P2Y12 reaction unitswere evaluated using VerifyNow (Accumentrics) at baseline, 30 minutes, 1 hour, and 4 hours after LD. RESULTS Baseline characteristics were similar in both groups. The mean (SD) of P2Y12 reaction units in the chewing group compared with the standard group at baseline, 30 minutes, 1 hour, and 4 hours after ticagrelor LD were 224 (33) vs 219 (44) (95%CI, -16.77 to 27.73; P = .26), 168 (78) vs 230 (69) (95%CI, -103.77 to -19.75; P = .003), 106 (90) vs 181 (89) (95%CI, -125.15 to -26.29; P = .005), and 43 (41) vs 51 (61) (95%CI, -36.34 to 21.14; P = .30), respectively. Platelet reactivity in the chewing group was significantly reduced by 24%at 30 minutes after LD (95%CI, 19.75 to 103.77; P = .001). The relative inhibition of platelet aggregation in the chewing vs the standard group were 51%vs 10% (95%CI, 13.69 to 67.67; P = .005) at 1 hour and 81%vs 76%(95%CI, -12.32 to 16.79; P = .24) at 4 hours, respectively. Major adverse cardiac and cardiovascular event rate at 30 days was low (4%) and occurred in 1 patient in each group (95%CI, 0.06 to 16.93; P > .99). CONCLUSIONS AND RELEVANCE Chewing an LD of ticagrelor, 180mg, in patients with STEMI is feasible and facilitates better early platelet inhibition compared with a standard oral LD. Larger studies are warranted to see if our preliminary findings translate into clinical outcomes. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02725099.