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A randomised trial of the pharmacodynamic and pharmacokinetic effects of ticagrelor compared with clopidogrel in Hispanic patients with stable coronary artery disease.

Price MJ, Clavijo L, Angiolillo DJ, Carlson G, Caplan R, Teng R, Maya J - J. Thromb. Thrombolysis (2015)

Bottom Line: 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).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).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.

View Article: PubMed Central - PubMed

Affiliation: , 10666 North Torrey Pines Road, Maildrop S1056, La Jolla, CA, 92037, USA, price.matthew@scrippshealth.org.

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.

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Study design. Hispanic subjects with CAD and treated with aspirin therapy were randomly assigned in a 1:1 fashion to one of two treatment sequences: either ticagrelor 180 mg LD and 90 mg twice-daily MD for 7–9 days, followed by a washout period and clopidogrel 600 mg LD and 75 mg once-daily MD for 7–9 days, or clopidogrel 600 mg LD and 75 mg once-daily MD for 7–9 days, followed by a washout period and ticagrelor 180 mg LD and 90 mg twice-daily MD for 7–9 days. Platelet reactivity assessment and ticagrelor plasma concentrations were measured at several timepoints around the LD and at the end of the MD phase. CAD coronary artery disease, LD loading dose, MD maintenance dose
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Fig1: Study design. Hispanic subjects with CAD and treated with aspirin therapy were randomly assigned in a 1:1 fashion to one of two treatment sequences: either ticagrelor 180 mg LD and 90 mg twice-daily MD for 7–9 days, followed by a washout period and clopidogrel 600 mg LD and 75 mg once-daily MD for 7–9 days, or clopidogrel 600 mg LD and 75 mg once-daily MD for 7–9 days, followed by a washout period and ticagrelor 180 mg LD and 90 mg twice-daily MD for 7–9 days. Platelet reactivity assessment and ticagrelor plasma concentrations were measured at several timepoints around the LD and at the end of the MD phase. CAD coronary artery disease, LD loading dose, MD maintenance dose

Mentions: Subjects were randomised 1:1 to receive one of two possible treatment sequences: either open-label clopidogrel in the first period followed by open-label ticagrelor in the second period or vice versa (Fig. 1). There was a 10–14 days washout between periods. Clopidogrel was administered as a 600 mg loading dose (LD) followed by a 75 mg once-daily MD for 7–9 days, and ticagrelor was administered as a 180 mg LD followed by a 90 mg twice-daily MD for 7–9 days. Subjects received aspirin 75–100 mg once-daily, which was maintained at a constant dose throughout the study. To evaluate the onset of anti-platelet effect, platelet reactivity was assessed at baseline prior to the LD and at 0.5, 2 and 8 h after the LD; to evaluate the effect of the MD, platelet reactivity was assessed just prior to, 2, and 8 h after the last morning dose, and 12 h after the last evening dose of ticagrelor and 24 h after the last morning dose of clopidogrel. Blood samples to analyse the plasma concentrations of ticagrelor and its active metabolite, AR-C124910XX, were drawn at the same time as platelet reactivity assessment.Fig. 1


A randomised trial of the pharmacodynamic and pharmacokinetic effects of ticagrelor compared with clopidogrel in Hispanic patients with stable coronary artery disease.

Price MJ, Clavijo L, Angiolillo DJ, Carlson G, Caplan R, Teng R, Maya J - J. Thromb. Thrombolysis (2015)

Study design. Hispanic subjects with CAD and treated with aspirin therapy were randomly assigned in a 1:1 fashion to one of two treatment sequences: either ticagrelor 180 mg LD and 90 mg twice-daily MD for 7–9 days, followed by a washout period and clopidogrel 600 mg LD and 75 mg once-daily MD for 7–9 days, or clopidogrel 600 mg LD and 75 mg once-daily MD for 7–9 days, followed by a washout period and ticagrelor 180 mg LD and 90 mg twice-daily MD for 7–9 days. Platelet reactivity assessment and ticagrelor plasma concentrations were measured at several timepoints around the LD and at the end of the MD phase. CAD coronary artery disease, LD loading dose, MD maintenance dose
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4300410&req=5

Fig1: Study design. Hispanic subjects with CAD and treated with aspirin therapy were randomly assigned in a 1:1 fashion to one of two treatment sequences: either ticagrelor 180 mg LD and 90 mg twice-daily MD for 7–9 days, followed by a washout period and clopidogrel 600 mg LD and 75 mg once-daily MD for 7–9 days, or clopidogrel 600 mg LD and 75 mg once-daily MD for 7–9 days, followed by a washout period and ticagrelor 180 mg LD and 90 mg twice-daily MD for 7–9 days. Platelet reactivity assessment and ticagrelor plasma concentrations were measured at several timepoints around the LD and at the end of the MD phase. CAD coronary artery disease, LD loading dose, MD maintenance dose
Mentions: Subjects were randomised 1:1 to receive one of two possible treatment sequences: either open-label clopidogrel in the first period followed by open-label ticagrelor in the second period or vice versa (Fig. 1). There was a 10–14 days washout between periods. Clopidogrel was administered as a 600 mg loading dose (LD) followed by a 75 mg once-daily MD for 7–9 days, and ticagrelor was administered as a 180 mg LD followed by a 90 mg twice-daily MD for 7–9 days. Subjects received aspirin 75–100 mg once-daily, which was maintained at a constant dose throughout the study. To evaluate the onset of anti-platelet effect, platelet reactivity was assessed at baseline prior to the LD and at 0.5, 2 and 8 h after the LD; to evaluate the effect of the MD, platelet reactivity was assessed just prior to, 2, and 8 h after the last morning dose, and 12 h after the last evening dose of ticagrelor and 24 h after the last morning dose of clopidogrel. Blood samples to analyse the plasma concentrations of ticagrelor and its active metabolite, AR-C124910XX, were drawn at the same time as platelet reactivity assessment.Fig. 1

Bottom Line: 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).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).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.

View Article: PubMed Central - PubMed

Affiliation: , 10666 North Torrey Pines Road, Maildrop S1056, La Jolla, CA, 92037, USA, price.matthew@scrippshealth.org.

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.

Show MeSH
Related in: MedlinePlus