ACCOAST: More Bleeds, No Benefit, With Early Prasugrel in NSTE-ACS

Shelley Wood

September 01, 2013

AMSTERDAM, THE NETHERLANDS — Pretreating non-ST-segment-elevation ACS (NSTE-ACS) patients with prasugrel (Effient, Lilly/Daiichi-Sanyo) at the time of diagnosis, rather than after angioplasty, does not improve ischemic events but does drive up major bleeding complications, results from the ACCOAST trial show [1].

Dr Gilles Montalescot (Pitié-Salpêtrière University Hospital, Paris, France) will present the full results here later this morning at the European Society of Cardiology (ESC) 2013 Congress; they are published now in the New England Journal of Medicine.

Clopidogrel preloading is a class I recommendation in patients with NSTE-ACS undergoing PCI, but it was unknown whether the more potent and rapidly acting prasugrel would also be best delivered early in this setting.

ACCOAST was designed to randomize 4100 patients to an early or standard strategy (with placebo pretreatment given in the standard group). As reported by heartwire , the trial's data and safety monitoring committee stopped enrollment at 4033 patients last November after noticing an increase in major and life-threatening bleeding and no reduction in CV events.

The primary efficacy end point (a composite of CV death, MI, stroke, urgent revascularization, or GP IIb/IIIa bailout) was not significantly different between the two treatment groups at seven or 30 days. TIMI major bleeding (either related to CABG or not) was significantly higher in the pretreatment group at both time points, as were rates of non-CABG TIMI major bleeding and life-threatening bleeding.

Differences Between Prasugrel Pretreatment and No Pretreatment

End point Pretreatment, n (%) No pretreatment, n (%) Hazard ratio p
Primary end point, 7 d 203 (10) 195 (9.8) 1.02 0.81
Primary end point, 30 d 219 (10.8) 216 (10.8) 0.997 0.98
All CABG or non-CABG TIMI major bleeding, 7 d 52 (2.6) 27 (1.4) 1.90 0.006
All CABG or non-CABG TIMI major bleeding, 30 d 58 (2.8) 29 (1.5) 1.97 0.002
Life-threatening bleeding 22 (1.1) 4 (0.2) 5.40 <0.001

 

"Among patients with NSTE-ACS who were scheduled to undergo catheterization, pretreatment with prasugrel did not reduce the rate of major ischemic events up to 30 days but increased the rate of major bleeding complications," the ACCOAST authors conclude.

The Price to Be Paid

Commenting on the study for heartwire , Dr Spencer King (St Joseph's Hospital, Atlanta, GA) said it was unlikely the findings will have an impact on off-label use of prasugrel in practice, because very few--if any--operators would have been trying this kind of pretreatment strategy, at least in this group of nonurgent, NSTE-ACS patients.

"Most people, I think, still give prasugrel in the lab," and not beforehand, he said. "There has been some pressure particularly with STEMI to give it in the emergency department, and even, in some places around the world, people who talk about giving these drugs in the ambulance. So it's not a strange concept that upstream antiplatelets could be helpful, and it could be helpful in certain kinds of patients."

But in this population, "who were not urgently in need of something," this clearly was of no use, King said.

In all likelihood, said King, an antiplatelet drug given at the time of diagnosis in NSTE-ACS patients just isn't going to reduce the infarct rate very much, because the window of time to treatment is typically quite short (two to 48 hours) and the patients are relatively stable. Of note, even the absolute numbers of bleeding events in both groups were very low. "I'm surprised it was enough to stop the trial," King observed.

"Infarction in these patients is really microembolization during the procedure: when you place stents you shower things downstream, and that's not going to change very much whether you have a potent antiplatelet on board or not. That's just the price you pay for opening the artery."

Whether a fast-acting, higher-potency drug like prasugrel could play a role upstream in higher-risk patients, including STEMI patients, remains to be seen, he added.

heartwire will update this story following the ACCOAST presentation at the ESC hot-line session.

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