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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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Related in: MedlinePlus

Study flow. A total of 40 subjects were randomly assigned to a treatment sequence, of which 39 completed at least one follow-up visit and of which 38 completed at least 7 days of the maintenance dosing phase for both study drugs
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Fig2: Study flow. A total of 40 subjects were randomly assigned to a treatment sequence, of which 39 completed at least one follow-up visit and of which 38 completed at least 7 days of the maintenance dosing phase for both study drugs

Mentions: Study flow is shown in Fig. 2. A total of 40 subjects were randomised. All subjects received at least one dose of ticagrelor and 39 subjects received at least one dose of clopidogrel. A total of 38 subjects completed the study. Clinical characteristics and demographics of the randomised subjects are shown in Table 1. The mean age was 63.8 ± 8.8 years, 28 subjects (70 %) were male, 21 (53 %) had diabetes mellitus, and 26 (65 %) had a prior myocardial infarction. Data from three subjects with baseline on-treatment reactivity <150 PRU were excluded from the primary analysis, as this observation was felt to be consistent with an incomplete washout from a P2Y12 antagonist and/or the presence of an interfering agent. These values were included in a post hoc sensitivity analysis.Fig. 2


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 flow. A total of 40 subjects were randomly assigned to a treatment sequence, of which 39 completed at least one follow-up visit and of which 38 completed at least 7 days of the maintenance dosing phase for both study drugs
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig2: Study flow. A total of 40 subjects were randomly assigned to a treatment sequence, of which 39 completed at least one follow-up visit and of which 38 completed at least 7 days of the maintenance dosing phase for both study drugs
Mentions: Study flow is shown in Fig. 2. A total of 40 subjects were randomised. All subjects received at least one dose of ticagrelor and 39 subjects received at least one dose of clopidogrel. A total of 38 subjects completed the study. Clinical characteristics and demographics of the randomised subjects are shown in Table 1. The mean age was 63.8 ± 8.8 years, 28 subjects (70 %) were male, 21 (53 %) had diabetes mellitus, and 26 (65 %) had a prior myocardial infarction. Data from three subjects with baseline on-treatment reactivity <150 PRU were excluded from the primary analysis, as this observation was felt to be consistent with an incomplete washout from a P2Y12 antagonist and/or the presence of an interfering agent. These values were included in a post hoc sensitivity analysis.Fig. 2

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