September 1st, 2013
Pretreatment with Prasugrel Not Indicated in NSTEMI
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Although current guidelines strongly recommend that dual antiplatelet therapy be administered early in treating patients with non-ST-segment-elevation acute myocardial infarction (NSTEMI), it is unclear whether pretreatment is beneficial,especially with the newer, more potent and more rapidly acting antiplatelet agents prasugrel and ticagrelor. Now a large new study, ACCOAST, presented at the European Society of Cardiology in Amsterdam and published simultaneously in the New England Journal of Medicine, offers strong evidence that pretreatment with prasugrel should not be performed in this situation.
Near the end of the enrollment period, the trial was stopped prematurely on the advice of the independent data and safety monitoring committee because of an increase in major and life-threatening bleeding, but no reduction in cardiovascular events, among patients in the pretreatment group.
A total of 4033 patients scheduled for coronary angiography were randomized to receive pretreatment with prasugrel or no prasugrel. There were no significant differences in the primary endpoint, (death from CV causes, MI, stroke, urgent revascularization, or glycoprotein IIb/IIIa bailout at 7 days). However, TIMI major bleeding was significantly more common in the pretreatment group at 7 days. Similar findings were observed at 30 days.
- Primary endpoint: 10.0% in the pretreatment group versus 9.8% in the control group (hazard ratio, 1.02; 95% CI, 0.84-1.25; P=0.81)
- TIMI major bleeding: 2.6% versus 1.4% (HR, 1.90; 95% CI, 1.19-3.02; P=0.006)
No benefit of pretreatment was observed in the subgroup of patients who underwent PCI. The pretreatment group had a 3-fold excess in major bleeding not related to CABG and a 6-fold increase in life-threatening bleeding not related to CABG.
That authors write, “Our results support the administration of prasugrel when the coronary anatomy is known and after PCI is selected as the treatment strategy.” They noted that prior to catheterization the risk for ischemic complications is very low.
In an accompanying editorial, John Keaney, Jr, writes that ACCOAST “may streamline the care of patients with NSTEMI in the hospital” and allow cardiologists to “safely pursue a more parsimonious approach of reserving prasugrel adminstration until after angiography.” By delaying administration of a P2Y12 inhibitor, patients who require CABG will no longer suffer long delays and “P2Y12 treatment can be limited to patients who will be undergoing PCI.”
For an interview with the lead investigator of the ACCOAST trial, click here.