ACCOAST: Pretreatment With Prasugrel in NSTEMI Patients Does Not Reduce Major CV Risks; Increases Bleeding Risks

"This trial, importantly, did not send people urgently to the cath lab, but it was between two hours and 48 hours that they had to go to the cath lab," said Spencer King, MD, MACC.
While pretreatment using prasugrel in patients with non-ST-segment elevation acute coronary syndromes (NSTEMI) scheduled to undergo catheterization did not reduce the rate of major ischemic events up to 30 days, the rate of major bleeding complications did increase, according to results from the ACCOAST Trial presented at the ESC Congress 2013 and simultaneously published in the New England Journal of Medicine.

The study randomly assigned 4,033 NSTEMI patients to receive 30 mg of prasugrel (pretreatment group) or placebo (control group) before their scheduled coronary angiography. When PCI was indicated, an additional 30 mg dose of prasugrel was given to those in the pretreatment group, while 60 mg of prasugrel was given to those in the control group.

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According to the study, death from cardiovascular causes, including myocardial infarction, stroke, urgent revascularization or the need for rescue therapy with glycoprotein IIB/IIIA inhibitors, did not differ significantly between patients in the pretreatment group (10 percent) and those receiving the placebo (9.8 percent) at seven days after randomization. In addition, there was no significant difference between the two groups in terms of death from cardiovascular causes after 30 days. Further, the investigators noted no significant differences in cardiovascular mortality risk between the pretreatment and control groups in the cohort of patients who underwent PCI.

In terms of safety, however, the study found significantly higher incidences of TIMI major and life-threatening bleeding complications in the pre-treatment group as compared to the control group. According to the study investigators, bleeding events were largely associated with PCI or CABG and occurred early in those patients that underwent PCI, with the most frequent complications involving bleeding at the access site, pericardial bleeding and retroperitoneal bleeding. While the study investigators did note that bleeding was less frequent in those patients who were younger, had a high body weight and/or had PCI performed through radial access, pretreatment with prasugrel was still consistently linked to excess bleeding in these subgroups.

Overall, the ACCOAST findings suggest that "stronger antiplatelet therapy does not prevent the occurrence of myocardial infarction before catheterization or after PCI," the investigators note. "Our results support the administration of prasugrel when the coronary anatomy is known and after PCI is selected as the treatment strategy."

In an accompanying commentary, John Keaney, Jr., MD, writes that the findings "indicate that one can safely pursue a more parsimonious approach of reserving prasugrel administration until after angiography. With this strategy, P2Y12 treatment can be limited to patients who will be undergoing PCI, and patients with NSTEMI who require CABG will be able to avoid unnecessary delays." Kearny urges news studies to determine whether newer agents, administered only post-angiography, can improve efficiency in treatment of NSTEMI patients.


Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Interventions and ACS, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: Myocardial Infarction, Acute Coronary Syndrome, Stroke, Coronary Angiography, Thiophenes, Catheterization, Body Weight, Hemorrhage, New England


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