Limits...
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.

Show MeSH

Related in: MedlinePlus

On-treatment platelet reactivity on ticagrelor and clopidogrel in Hispanic subjects with CAD receiving low-dose aspirin. a On-treatment reactivity at baseline and after a ticagrelor 180 mg LD or clopidogrel 600 mg LD and after 7–9 days of MD therapy with ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily. b Percentage reduction from baseline in on-treatment reactivity after a ticagrelor 180 mg LD or clopidogrel 600 mg LD and after 7–9 days of MD with ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily. Values are expressed as the least square means and 95 % confidence intervals. LD loading dose, MD maintenance dose. ***P < 0.001
© Copyright Policy - OpenAccess
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4300410&req=5

Fig3: On-treatment platelet reactivity on ticagrelor and clopidogrel in Hispanic subjects with CAD receiving low-dose aspirin. a On-treatment reactivity at baseline and after a ticagrelor 180 mg LD or clopidogrel 600 mg LD and after 7–9 days of MD therapy with ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily. b Percentage reduction from baseline in on-treatment reactivity after a ticagrelor 180 mg LD or clopidogrel 600 mg LD and after 7–9 days of MD with ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily. Values are expressed as the least square means and 95 % confidence intervals. LD loading dose, MD maintenance dose. ***P < 0.001

Mentions: The antiplatelet effect of study drug LD is shown in Table 2 and Fig. 3. At 2 h post-LD, the primary endpoint of the study, on-treatment reactivity was significantly lower after ticagrelor compared with clopidogrel (LS means difference, −167 PRU [95 % CI −197, −137], P < 0.001). This greater anti-platelet effect was evident within 30 min after the LD and persisted at 8 h after the LD (Table 2). The antiplatelet effects of ticagrelor 90 mg twice-daily MD and clopidogrel 75 mg once-daily MD after 7–9 days of dosing are shown in Table 3 and Fig. 3. On-treatment reactivity was significantly lower with ticagrelor compared with clopidogrel 2 h and 8 h after the MD, and was significantly lower at the end of the dosing interval (12 h after the last ticagrelor MD and 24 h after the last clopidogrel MD). On sensitivity analysis, the primary results were similar when data from the three subjects with abnormally low baseline reactivity were included (LS means difference at 2 h post-LD between ticagrelor and clopidogrel, –154.4 PRU [95 % CI −187.4, −121.4], P < 0.001). The results of other sensitivity analyses were also similar to the primary analysis (see Online Appendix.)Table 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)

On-treatment platelet reactivity on ticagrelor and clopidogrel in Hispanic subjects with CAD receiving low-dose aspirin. a On-treatment reactivity at baseline and after a ticagrelor 180 mg LD or clopidogrel 600 mg LD and after 7–9 days of MD therapy with ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily. b Percentage reduction from baseline in on-treatment reactivity after a ticagrelor 180 mg LD or clopidogrel 600 mg LD and after 7–9 days of MD with ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily. Values are expressed as the least square means and 95 % confidence intervals. LD loading dose, MD maintenance dose. ***P < 0.001
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig3: On-treatment platelet reactivity on ticagrelor and clopidogrel in Hispanic subjects with CAD receiving low-dose aspirin. a On-treatment reactivity at baseline and after a ticagrelor 180 mg LD or clopidogrel 600 mg LD and after 7–9 days of MD therapy with ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily. b Percentage reduction from baseline in on-treatment reactivity after a ticagrelor 180 mg LD or clopidogrel 600 mg LD and after 7–9 days of MD with ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily. Values are expressed as the least square means and 95 % confidence intervals. LD loading dose, MD maintenance dose. ***P < 0.001
Mentions: The antiplatelet effect of study drug LD is shown in Table 2 and Fig. 3. At 2 h post-LD, the primary endpoint of the study, on-treatment reactivity was significantly lower after ticagrelor compared with clopidogrel (LS means difference, −167 PRU [95 % CI −197, −137], P < 0.001). This greater anti-platelet effect was evident within 30 min after the LD and persisted at 8 h after the LD (Table 2). The antiplatelet effects of ticagrelor 90 mg twice-daily MD and clopidogrel 75 mg once-daily MD after 7–9 days of dosing are shown in Table 3 and Fig. 3. On-treatment reactivity was significantly lower with ticagrelor compared with clopidogrel 2 h and 8 h after the MD, and was significantly lower at the end of the dosing interval (12 h after the last ticagrelor MD and 24 h after the last clopidogrel MD). On sensitivity analysis, the primary results were similar when data from the three subjects with abnormally low baseline reactivity were included (LS means difference at 2 h post-LD between ticagrelor and clopidogrel, –154.4 PRU [95 % CI −187.4, −121.4], P < 0.001). The results of other sensitivity analyses were also similar to the primary analysis (see Online Appendix.)Table 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