Impact of Escalating Loading Dose Regimens of Ticagrelor in @entity1 With ST-Segment Elevation XXXX Undergoing Primary Percutaneous Coronary Intervention: Results of a Prospective Randomized Pharmacokinetic and Pharmacodynamic Investigation.

@entity1 @entity3077 @entity19319 @entity1286 @entity33511 @entity583 @entity3075
OBJECTIVES: The goal of this study was to assess the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of escalating ticagrelor loading dose (LD) regimens in primary percutaneous coronary intervention (PPCI). BACKGROUND: @entity1 with ST-segment elevation @entity583 undergoing PPCI frequently have suboptimal platelet inhibition in the early hours after ticagrelor LD. The use of high ticagrelor LD regimens has been hypothesized to optimize platelet inhibition in PPCI. METHODS: This was a prospective, randomized study of escalating ticagrelor LD regimens (180 mg, 270 mg, or 360 mg) in PPCI (N  = 52). PK/PD analyses were performed before and 30 min, 1, 2, 4, 8, and 24 h post-LD. PK assessments included exposure to @entity3077 and its metabolite ( @entity33511 ). PD assessments included @entity3075 reaction units (PRU) measured by VerifyNow @entity3075 and platelet reactivity index (PRI) measured by @entity19319 ( @entity19319 ). RESULTS: Platelet reactivity was elevated during the first 2 h post-LD. There were no differences in PRU between groups during the study time course (p  = 0.179). There were no significant differences in PRU levels across groups at all time points, except at 1 h (p  = 0.017) where platelet reactivity was lowest with a 270-mg LD. No differences were found between the 180-mg and 360-mg groups (primary endpoint; p > 0.999). High on-treatment platelet reactivity rates were not different across groups, except at 1 hour (p = 0.038). Parallel PD findings were observed with @entity19319 -PRI. PK analysis showed a delay in ticagrelor absorption and generation of @entity33511 , irrespective of dose. Although @entity1286 was associated with a delay in ticagrelor PK/PD, it was not an independent predictor of high on-treatment platelet reactivity. CONCLUSIONS: ST-segment elevation @entity583 @entity1 undergoing PPCI frequently exhibit impaired response to ticagrelor in the early hours after drug administration, which cannot be overcome by increasing LD regimens. These PD findings are largely attributed to an impaired PK profile, indicating a delay in drug absorption compared with that reported in stable clinical settings. (High Ticagrelor Loading Dose in STEMI; NCT01898442).
