title: A randomised trial of the pharmacodynamic and pharmacokinetic effects of ticagrelor compared with clopidogrel in Hispanic patients with stable coronary artery disease.
abstract: The objective was to compare the pharmacodynamic (PD) and pharmacokinetic (PK) effects of ticagrelor with clopidogrel among subjects of Hispanic ethnicity, as the PD and PK effects of antiplatelet agents among Hispanics are not specifically known. This was a randomised, open-label, crossover PD/PK study of 40 Hispanic subjects with stable coronary artery disease (CAD). Subjects were allocated to either ticagrelor 180 mg loading dose (LD)/90 mg twice-daily maintenance dose (MD) followed by clopidogrel 600 mg LD/75 mg once-daily MD with an intervening washout period, or vice versa. The primary endpoint was on-treatment reactivity (OTR) at 2 h post-LD according to the VerifyNow P2Y12 test. OTR was significantly lower at 2 h post-LD with ticagrelor compared with clopidogrel (34 PRU vs. 201 PRU, least square means difference = -167 PRU [95 % CI, -197, -137], P < 0.001). OTR was also lower with ticagrelor at 30 min and 8 h post-LD (P < 0.001). The greater magnitude of antiplatelet effect with ticagrelor persisted after 7 days of MD (52 PRU [95 % CI, 30, 73] vs. 182 PRU [95 % CI, 160, 205], P < 0.001). Mean plasma concentration of ticagrelor and its active metabolite were greatest at 2 h post-LD, with similar levels at 2 h post-MD after 7 days of MD. Among Hispanic subjects with stable CAD, ticagrelor provides a more rapid onset of platelet inhibition and a significantly greater antiplatelet effect compared with clopidogrel during both the loading and maintenance phases of treatment.
authors.affiliation: , 10666 North Torrey Pines Road, Maildrop S1056, La Jolla, CA, 92037, USA, price.matthew@scrippshealth.org.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Price
authors.forename: Leonardo
authors.initials: L
authors.lastname: Clavijo
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
authors.forename: Glenn
authors.initials: G
authors.lastname: Carlson
authors.forename: Richard
authors.initials: R
authors.lastname: Caplan
authors.forename: Renli
authors.initials: R
authors.lastname: Teng
authors.forename: Juan
authors.initials: J
authors.lastname: Maya
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000368:Aged; D001792:Blood Platelets / Q000378:metabolism; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy; D006630:Hispanic or Latino; D006801:Humans; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics; D000077486:Ticagrelor; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D058921:Purinergic P2Y Receptor Antagonists; D000077144:Clopidogrel; D000077486:Ticagrelor; D000241:Adenosine; D013988:Ticlopidine