This article is more than 5 years old. Information may no longer be current.
Higher Platelet Inhibition Observed with Ticagrelor vs. Prasugrel
Click Here to Manage Email Alerts
Among patients with ACS who exhibit high on-treatment platelet reactivity while on clopidogrel 24 hours following PCI, use of ticagrelor for 15 days was associated with a significantly higher platelet inhibition compared with an equal time of prasugrel in a pharmaco-dynamic study.
Researchers of the prospective, single-center, single blind study identified 44 patients with ACS and high on-treatment platelet reactivity (HTPR) while on clopidogrel 24 hours post-PCI. Patients were randomly assigned to either ticagrelor (Brilinta, AztraZeneca) 90 mg twice daily or prasugrel (Effient, Daiichi Sankyo/Eli Lilly) 10 mg once daily for 15 days with a crossover to the alternate treatment for another 15 days.
At the end of the two treatment periods, the study’s primary endpoint of platelet reactivity was 32.9 platelet reactivity units (PRU) (95% CI, 18.7-47.2) in the ticagrelor group and 101.3 PRU (95% CI, 86.8-115.7) in the prasugrel group (P<.001). The difference in the secondary endpoint of the rate of HTPR — defined as PRU=235 according to the VerifyNow P2Y12 function assay — did not reach statistical significance (ticagrelor, 0% vs. prasugrel, 2.4%; P=.5). Researchers did not observe a major bleeding or major adverse CV event in either treatment groups.
For more information:
Alexopoulos D. J Am Coll Cardiol. 2012;60:193-199.
Perspective
Udaya S. Tantry
Paul A. Gurbel
This is a provocative study comparing the effect of maintenance doses of prasugrel and ticagrelor in patients who were determined as having HTPR during clopidogrel treatment. As previously demonstrated in the RESPOND study, Alexopoulos and colleagues again showed that ticagrelor is highly effective in overcoming HTPR in clopidogrel nonresponders. Furthermore, these investigators also demonstrated that a significantly lower level of platelet reactivity can be achieved with ticagrelor maintenance dose compared with prasugrel maintenance dose.
However, there are some issues with this study that should be addressed before coming to a conclusion about which agent has the desirable pharmacodynamic effect in the clopidogrel nonresponder. First, the HTPR status was measured 24 hours after PCI in patients who were administered different doses of clopidogrel (>7 days 75 mg; if <7 days with 75mg/day clopidogrel, a 300-mg loading dose was administered and in clopidogrel-naive patients a 600-mg loading dose was administered). However, platelet function was measured during steady state. HTPR patients were randomized to 10 mg/day prasugrel or 90 mg twice-daily ticagrelor for 15 days and platelet function was measured at the end of 15 days treatment. It has been clearly observed in previous studies, including GRAVITAS, that the platelet response to clopidogrel treatment improves in the first 30 days following PCI even during clopidogrel therapy. Therefore, some level of the improved platelet response may be attributed to time rather than ticagrelor or prasugrel therapy. To obviate this confounder, the investigators may have considered randomizing patients at least 30 days after PCI.
Second, it has been shown that the platelet response measured by VerifyNow at low levels of platelet reactivity (<100 PRU) that is achieved during more potent P2Y12 receptor blocker inhibition is not accurate. Inclusion of another method to measure platelet function, such as conventional platelet aggregation, would have strengthened their conclusions. Third, the results of the current study may not be applicable to acute scenarios such as during PCI or ACS where immediate and high levels of inhibition are desired — in the current investigation no loading dose of either ticagrelor or prasugrel was administered. And, finally, extreme low levels of platelet reactivity (PRU <75), as observed more frequently with ticagrelor than prasugrel in the current study, may not be desirable in the long term given the potential for enhanced bleeding risk.
– Udaya S. Tantry, PhD
Laboratory Director, Sinai Center for Thrombosis Research, Baltimore
– Paul A. Gurbel, MD
Director, Sinai Center for Thrombosis Research
Cardiology Today Intervention Editorial Board member
Disclosure: Dr. Tantry has received honoraria from Accumetrics; Dr. Gurbel has received research grants, honoraria and consultant fees from Accumetrics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Daiichi Sankyo/Eli Lilly, Johnson & Johnson, Medtronic, Merck, Novartis/Portola and Sanofi-Aventis.