PHARMACODYNAMIC EVALUATION OF THE PLATELET ANTIAGGREGANT EFFECT OF SWALLOWED TICAGRELOR AGAINST CHEWED TICAGRELOR IN PATIENTS WITH ACUTE CORONARY SYNDROME. TICA-MASTICA-SICA TRIAL

Abstract

BACKGROUND Dual antiplatelet therapy represents the standard of care for the treatment of patients with acute coronary syndrome (ACS). Ticagrelor is a direct-acting P2Y12 inhibitor and does not require metabolic activation. The objective was to assess whether the chewed 180 mg of ticagrelor loading dose (LD), compared to conventional oral administration, increases platelet inhibition and reduces high on-treatment platelet reactivity (HTPR) in patients with ACS. METHODS AND RESULTS Single-center randomized clinical trial in patients with ACS. We measured platelet reactivity and % platelet aggregation (%IPA) using VerifyNow P2Y12 (Accumetrics) at baseline, 30 minutes, 1, 4 and 24 hours after LD. HTPR was defined as ≥208 PRU and/or % platelet inhibition ≤15%. We studied 40 consecutive patients (Pts.), 21 Pts. in the swallowed ticagrelor group and 19 Pts. in the chewed ticagrelor group. At 30 minutes, platelet reactivity was 180.81 ± 64.16 PRU vs. 117 ± 58.62 PRU p < 0.01 (95%CI 24.3 to 103.3); At one hour 154.29 ± 84.55 PRU vs 54.84 ± 59.6 PRU p < 0.001 (95%CI 52.1 to 146.7) respectively. The baseline results, at 4 and 24 hours, had no differences (p=NS). %IPA was 11.19 ±22.42 vs 42.26 ±27.3 < 0.0001, (95%CI 15.3, 47); 25.33 ±34.03 vs 75.47 ±26.27 p < 0.0001, 95%CI (27.5, 66.7) Platelet reactivity in the chewed ticagrelor group was significantly reduced by 52.65% at 30 minutes after LD, compared to 16.79% in the swallowed group (95%CI -0.63 to -0.083; p < 0.01). The frequency of HTPR at one hour was 57.14% in the swallowed group vs. 5.26% in the chewed group; p < 0.001. After 4 hours, HTPR was not observed in any group. CONCLUSION Chewed ticagrelor allowed a significant reduction in platelet reactivity and HTPR from the first 30 minutes and the first hour. Dual antiplatelet therapy represents the standard of care for the treatment of patients with acute coronary syndrome (ACS). Ticagrelor is a direct-acting P2Y12 inhibitor and does not require metabolic activation. The objective was to assess whether the chewed 180 mg of ticagrelor loading dose (LD), compared to conventional oral administration, increases platelet inhibition and reduces high on-treatment platelet reactivity (HTPR) in patients with ACS. Single-center randomized clinical trial in patients with ACS. We measured platelet reactivity and % platelet aggregation (%IPA) using VerifyNow P2Y12 (Accumetrics) at baseline, 30 minutes, 1, 4 and 24 hours after LD. HTPR was defined as ≥208 PRU and/or % platelet inhibition ≤15%. We studied 40 consecutive patients (Pts.), 21 Pts. in the swallowed ticagrelor group and 19 Pts. in the chewed ticagrelor group. At 30 minutes, platelet reactivity was 180.81 ± 64.16 PRU vs. 117 ± 58.62 PRU p < 0.01 (95%CI 24.3 to 103.3); At one hour 154.29 ± 84.55 PRU vs 54.84 ± 59.6 PRU p < 0.001 (95%CI 52.1 to 146.7) respectively. The baseline results, at 4 and 24 hours, had no differences (p=NS). %IPA was 11.19 ±22.42 vs 42.26 ±27.3 < 0.0001, (95%CI 15.3, 47); 25.33 ±34.03 vs 75.47 ±26.27 p < 0.0001, 95%CI (27.5, 66.7) Platelet reactivity in the chewed ticagrelor group was significantly reduced by 52.65% at 30 minutes after LD, compared to 16.79% in the swallowed group (95%CI -0.63 to -0.083; p < 0.01). The frequency of HTPR at one hour was 57.14% in the swallowed group vs. 5.26% in the chewed group; p < 0.001. After 4 hours, HTPR was not observed in any group. Chewed ticagrelor allowed a significant reduction in platelet reactivity and HTPR from the first 30 minutes and the first hour.