Ticagrelor vs. Prasugrel: Is There a Difference in ACS Patients With HTPR Post-PCI?

A new study published on July 9 in the Journal of the American College of Cardiology (JACC) is the first to compare the antiplatelet action of ticagrelor with prasugrel in acute coronary syndrome (ACS) patients with high on-clopidogrel treatment platelet reactivity (HTPR) after percutaneous coronary intervention (PCI).


The study looked at 44 ACS patients with HTPR 24 hours post-PCI. The patients were randomly prescribed with either ticagrelor (90 mg twice daily) or prasugrel (10 mg once daily) for 15 days with a crossover directly to the alternate treatment for another 15 days.

Results showed ticagrelor produced a significantly higher platelet inhibition as compared to prasugrel. At the end of two treatment period, platelet reactivity was lower for ticagrelor (32.9 PRU, 95 percent confidence interval [CI]: 18.7 to 47.2) compared with prasugrel (101.3 PRU, 95 percent CI: 86.8 to 115.7). According to the study's authors, these findings "might affect the antiplatelet agent choice in patients with ACS and HTPR, especially in high-risk subgroups like renal failure patients" moving forward. Similarly, a high thrombotic setting like an ST-segment elevation myocardial infarction or following stent thrombosis might also represent attractive scenarios for choosing ticagrelor, they note.

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Other result highlights include the following:
  • Both drugs proved effective in treating HTPR.
  • No patient experienced a major bleeding event in either patient group.

Moving forward, the authors note that the study provides the first-ever evidence indicating that patients can be directly switched from prasugrel to ticagrelor and vice versa. In addition, they recommend that further studies are needed to better inform whether the pharmacodynamics difference observed in this specific study translates into clinical efficacy or safety differences.

Commenting on the article, Gregg W. Stone MD, FACC, co-director of Medical Research and Education for the Cardiovascular Research Foundation, notes, "this is a very nicely performed crossover study in patients with ACS and HTPR after clopidogrel, which suggests that ticagrelor may be somewhat more potent than prasugrel in this setting. However, the study does not address the following critically important issues: 

  1. Is the timing of the onset of action similar between the two drugs? In patients with ACS, both prasugrel and ticagrelor may have delayed absorption and onset of action, which is especially important as effective IPA is desirable before PCI. In contrast, in the present study the drugs weren't administered until after PCI and not tested until 15 days later.
  2. Similarly, do the approved loading doses of prasugrel and ticagrelor have similar or different potency? This was also not tested here and is highly relevant for the immediate peri-PCI period.
  3. Do the differences noted in the present study translate to any clinical differences in efficacy or in safety? This is not at all a certainty, especially as the HTPR rates on treatment were not significantly different with both agents.
  4. Would the results be similar in an all-comers patient population (i.e. without HTPR)?
  5. Are the 'off-target' effects of ticagrelor in blocking RBC adenosine reuptake important in explaining its mortality benefit? Of course, this is not addressed in a pharmacodynamic study."

Stone also added, "A large-scale, appropriately powered comparative randomized trial between prasugrel and ticagrelor with meaningful patient-oriented endpoints is desperately required to determine whether there are any clinically relevant differences between these two agents in patients with ACS." 

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