CRT: Give prasugrel or ticagrelor a chance for ACS patients

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WASHINGTON, D.C.--While the decision about which antiplatelet drug to use for PCI may vary, Stephen D. Wiviott, MD, of Brigham and Women’s Medical Center in Boston, suggested that the third-generation options of prasugrel (Effient, Eli Lilly/Daiichi Sankyo) or ticagrelor (Brilinta, AstraZeneca) may be the best options for patients with acute coronary syndromes (ACS). He made this case during a Feb. 5 presentation at the annual Cardiovascular Research Technologies (CRT) meeting.

To achieve the intended goals of antiplatelet drugs, physicians need to choose their patients carefully and appropriately. Particularly, he spoke about the high-risk, non-STEMI or STEMI patients who will need to receive rapid PCI treatment.

“For instance, with prasugrel, there is more rapid onset of more potent action. By 15 minutes, the level of inhibition with prasugrel is greater than that achieved at steady state with clopidogrel at six hours. These findings with prasugrel are very similar with ticagrelor.” This understanding informs how these agents should be used, according to Wiviott.

The TRITON-TIMI 38 data have shown that prasugrel had significant reduction of cardiovascular events, compared with the standard dose of clopidogrel, but had a greater number of bleeding, including serious bleeding (life-threatening and fatal bleeds, particularly in high-risk subgroups). Based on all of the results to date, Wiviott said prasugrel has more rapid speed of onset, greater extent of inhibition, fewer poor responders, fewer genetic interactions, fewer incidence of stent thrombosis, but with greater incidence of bleeding.

In July 2009, prasugrel was approved for ACS with PCI, but is contraindicated in patients with known stroke and transient ischemic attack because of an excess of intracranial hemorrhage in this population. Prasugrel is not recommended for use in patients older than 75 years, because there is a boxed warning in these patients who may have a higher risk of bleeding. Also, there is not a clear understanding of which dose is appropriate for those patients with low body weight. However, the guidelines have now designated the drug for a Class I indication for ACS patients undergoing PCI.

Also, ticagrelor, which received FDA approval in July 2011, has high levels of platelet inhibition achieved very rapidly compared with clopidogrel at standard or even higher dose, noted Wiviott. “It is a reversible agent, but because of the high level of inhibition, the offset takes several days to be lower than clopidogrel,” he explained.

The PLATO trial showed a reduction in cardiovascular events, particularly reductions in MI and cardiovascular death with ticagrelor over clopidogrel. “Overall in PLATO, there was a high rate of cardiovascular death in trial because it was a high risk cohort, not because there was malfeasance in the trial,” said Wiviott, who also mentioned the 30 percent bleeding increase with ticagrelor.

“Ticagrelor, like prasugrel has a faster speed of offset, higher level of inhibition, fewer poor responders and lower rates of stent thrombosis,” said Wiviott. “Ticagrelor has slightly lower rates of bleeding than prasugrel.”

Considering the costs, ticagrelor and prasugrel are more expensive, especially compared with clopidogrel, when it becomes generic, said Wiviott, adding that prasugrel and clopidogrel may be more convenient because they have daily dose, as opposed to the twice daily dose with ticagrelor.

Thus, he concluded that third-generation antiplatelet drugs are more potent, but have more bleeding risks. Based on their profiles, Wiviott said that the newer antiplatelets may hold particular importance for primary PCI for the STEMI population because these patients require rapid onset therapy, have a high thrombotic risk and a low risk for bleeding.