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Ticagrelor Tops Prasugrel in Pharmacodynamic Study


July 9, 2012 (Patras, Greece) — The first direct pharmacodynamic comparison of two new antiplatelet agents, prasugrel (Effient, Lilly/Daiichi-Sanyo) and ticagrelor (Brilinta/Brilique, AstraZeneca), has found that ticagrelor produces greater platelet inhibition than prasugrel but that both agents would be effective alternatives if a patient is resistant to clopidogrel [1].
"We found that ticagrelor is stronger than prasugrel; it provides lower platelet reactivity. However, both agents overcome clopidogrel resistance quite well," lead author Dr Dimitrios Alexopoulos (Patras University Hospital, Patras, Greece) told heartwire . He and his colleagues report their findings in the July 17, 2012 issue of theJournal of the American College of Cardiology.
The results of the small crossover study, which lasted only 30 days, also show that patients can be switched from prasugrel to ticagrelor, and vice versa, which has not previously been investigated, says Alexopoulos.
In certain situations, we may choose the stronger agent [ticagrelor], but we can achieve very low levels of platelet reactivity with both.
He says the findings will not really change his practice. "In certain situations, we may choose the stronger agent [ticagrelor]--for example, in those patients with renal failure or those with ST-elevation myocardial infarction [STEMI] with a high thrombus burden. But we can achieve very low levels of platelet reactivity with both, and we did not see any bleeding events. It's difficult from a pharmacodynamic study to draw any clear clinical implications."
He adds that he will still opt for a particular new agent "based mostly on what we know from the big [pivotal] trials, TRITON TIMI 38 and PLATO. Each agent has specific contraindications--you cannot use prasugrel in patients with low weight or in older patients." On the other hand, he continues, doctors are cautioned against the use of ticagrelor in those with bradycardia or severe chronic obstructive pulmonary disease [COPD].
New Platelet Reactivity Thresholds for Ischemia and Bleeding Required
In the study, 44 patients with ACS who had high on-treatment platelet reactivity (HTPR) while on clopidogrel 24 hours after PCI were randomized to either 90 mg of ticagrelor twice daily or prasugrel 10 mg once daily for 15 days with a crossover directly to the alternative treatment for another 15 days. HTPR was defined as platelet reactivity units (PRU) of >235 as assessed by the VerifyNow P2Y12-function assay (Accumetrics).
The primary end point of platelet reactivity at the end of the two treatment periods was lower for ticagrelor, at 32.9 PRU, compared with prasugrel, at 101.3 PRU (p<0.001). No patient exhibited a major bleeding event in either treatment group; ticagrelor was more frequently accompanied by mild side effects such as allergic reactions, dyspepsia, and new-onset/worsening dyspnea.
The fact that both new agents can achieve very low levels of platelet reactivity "means we should probably search for new, lower thresholds for both ischemia and bleeding," says Alexopoulos.
Currently, the ischemic threshold is considered to be 208 PRU, and "almost all our patients achieved values below this threshold, but still the patients did get some ischemic events," he noted.
Meanwhile, bleeding thresholds in clopidogrel-treated patients are considered to be <190 PRU preintervention and <85 at one month postintervention to predict bleeding outcomes. "But we got very low values, around 30 to 40, and nobody had bleeding. I think that new thresholds need to be identified for these agents."
Alexopoulos and colleagues add that "further studies are needed to elucidate whether the pharmacodynamic difference observed translates into differences in clinical efficacy or safety." To heartwire , however, Alexopoulos acknowledged "a real clinical comparison of the two agents"--a head-to-head clinical trial--would probably not be funded by either manufacturer and therefore is unlikely to happen unless an alternative sponsor can be found.
Alexopoulos has received speaker fees from Sanofi, Pharmaserve/Eli Lilly, AstraZeneca, and Boehringer Ingelheim. All other authors have no disclosures.

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