Hold Prasugrel until Revascularization Decision is Made, Researchers Say

By Will Boggs MD

NEW YORK (Reuters Health) - Prasugrel treatment should be delayed until after a decision is made about revascularization in patients undergoing percutaneous coronary intervention (PCI) for non-ST-elevation myocardial infarction (NSTEMI), according to results from the ACCOAST-PCI study.

An earlier study showed that pretreatment with prasugrel offered no benefits over selective use of prasugrel at the time of PCI, but was associated with an increase in major bleeding complications. That study, however, took place before the common practice of managing NSTEMI/ACS patients invasively within 48 hours of admission.

In the ACCOAST-PCI study, Dr. Gilles Montalescot from Centre Hospitalier Universitaire Pitie-Salpetriere in Paris and colleagues compared outcomes for nearly 1,400 NSTEMI patients who received pretreatment with prasugrel with those for slightly fewer similar patients who received placebo. All patients received prasugrel at the time of PCI.

There was no difference in the primary endpoint (time to first occurrence of cardiovascular death, myocardial infarction, stroke, urgent revascularization, or GP IIb/IIIa inhibitor bailout through seven days after randomization) between the two groups (13.1% in both; p=0.93), the researchers report in the December 23 issue of the Journal of the American College of Cardiology.

The two groups also had comparable secondary outcomes; pretreatment with prasugrel was not associated with a decrease in any ischemic event, including total mortality and stent thrombosis.

Independent predictors of the primary outcome included thrombus on angiography, length of procedure, number of lesions, maximum length of stent and CRUSADE risk score.

Compared with placebo, pretreatment with prasugrel was associated with a three-fold increase in non-CABG major bleeding and a six-fold increase in non-CABG life-threatening bleeding events.

TIMI minor bleeding events were also about three times more common with prasugrel pretreatment than with placebo (2.01% vs. 0.65%).

"In patients with NSTEMI, our data support deferring a loading dose of prasugrel until a decision is made about revascularization," the researchers conclude. "This strategy allows flexibility in the management of patients by providing prasugrel, with its rapid onset of action, to patients who proceed to PCI without risking bleeding complications in patients who do not proceed to PCI."

Dr. George Dangas from Mount Sinai School of Medicine in New York, who co-wrote a related editorial in the journal, told Reuters Health by email, "The fast-acting oral antiplatelet agent prasugrel provides adequate level of activity when given at time of PCI in a way that pretreatment (i.e., in the ED or the cardiology unit ahead of the procedure) is not needed, as it is futile and may cause more bleeding."

"This enables a practice of not treating ahead of cardiac cath and PCI patients who may not end up undergoing a PCI (typically 30-40% of unstable angina (UA) or acute coronary syndrome case (ACS) may not have a PCI); such patients would have nothing important to gain and may sustain some bleeding risk," Dr. Dangas explained. "Avoidance of this unnecessary treatment in such patients will improve the overall clinical outcomes in patients who enter a hospital with a diagnosis of UA/ACS."

He added, "It is encouraging to find out sometimes how to best trim our treatments in order to avoid complications that may arise from side effects in certain types of patients in whom a particular therapy would be futile. In medicine we often find out from clinical trials what we can do 'in addition' to what we are already doing. The message from this particular trial is that in certain cases 'less is more,' indeed."

Dr. Victor L. Serebruany from HeartDrug Research Laboratories, Johns Hopkins University, Towson, Maryland, has published widely on prasugrel and other antiplatelet treatments.

"(I)t was somewhat naive to expect any extra prasugrel benefit in NSTEMI patients dependent on the timing of loading," Dr. Serebruany, who was not involved in the new study, told Reuters Health by email. "The marketing goal was obvious, but not supported by previous facts."

"Indeed, short-term prasugrel wins big in STEMI, but not NSTEMI or unstable angina," Dr. Serebruany said. "In TRITON, where delayed loading and dose advantage over clopidogrel were well established, prasugrel caused a small but consistent trend to cause more deaths, as clearly indicated in the FDA reviews."

Daiichi Sankyo Co., Ltd. and Eli Lilly and Co. sponsored the trial, employed three of the 14 authors, and had various relationships with all but one of the other authors and with Dr. Dangas.

Dr. Montalescot did not respond to a request for comments.

SOURCE: https://bit.ly/1w2Hbs6 and https://bit.ly/1GUY6Dq

J Am Coll Cardiol 2014;64:2563-2571,2572-2574.

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