CHICAGO – Coronary angiography within 2 hours of a diagnosis of non–ST-segment elevation acute coronary syndrome (NSTE-ACS) significantly reduced the risk of recurrent ischemic events as compared to angiography delayed for 12 hours or more, based on the results of the EARLY trial presented at the American Heart Association scientific sessions.
Dr. Laurent Bonello
EARLY examined the impacts of not pretreating with a P2Y12-ADP antagonist and of delay before coronary angiography; all study participants received the loading dose of a P2Y12-ADP antagonist at the time of intervention. The early group received angiography within 2 hours, and a delayed group received angiography 12 or more hours after NSTE-ACS.
“Regarding the primary endpoint at 30 days, which is a composite of cardiovascular death and recurrent ischemic event, there is a fivefold lower rate of MACE [major adverse cardiovascular events] in the very-early [group as] compared to the control group,” said Laurent Bonello, MD, PhD, of University Hospital North in Marseilles, France.
The MACE rate was 4.4% in the early group and 21.3% in the delayed group. However, the reduction in MACE was largely because of a reduction in recurrent ischemic events; death rates were similar in the two groups.
The EARLY trial randomized 740 patients at 16 hospitals in France with NSTE-ACS to one of two timing strategies for intervention: within 2 hours of diagnosis, the early-intervention group, and between 12 and 72 hours after diagnosis, the delayed group. Intermediate- and high-risk patients did not receive pretreatment with a P2Y12-ADP antagonist such as clopidogrel before angiography; they received the loading dose at the time of the intervention.
On average, angiography was done within 1 hour in the early group and at 18 hours in the delayed group. Percutaneous coronary intervention (PCI) was performed on 75% of the study population; 3% underwent coronary artery bypass grafting; and 20% received medical therapy.
Dr. Bonello said the purpose of the trial was to settle some uncertainties over the management of NSTE-ACS patients regarding the benefit of pretreatment with P2Y12-ADP antagonists – namely, to evaluate the impact of the lack of pretreatment on the optimal timing of the intervention. “There are no randomized clinical trials available on this specific group of non-ST elevation acute coronary syndrome patients not pretreated for the timing of the invasive strategy,” he said.
Both groups had similar baseline characteristics, such as history of MI, PCI, and aspirin and P2Y12-ADP use, although the delayed group had a higher rate of diabetes (35% vs. 28.3%).
Regarding secondary endpoints, rates of recurrent ischemic events were 2.9% for the early group and 19.8% for the delayed group during hospitalization, and 4.1% vs. 20.7% at 30 days.
Dr. Bonello noted that rates of cardiovascular death were similar for both groups: 0.3% and 0.8% in-hospital deaths, and 0.6% and 1.1% deaths at 30 days.
The disparity in MACE between all subgroups paralleled that of the overall results with two exceptions, Dr. Bonello said: The positive effect of early intervention was less pronounced in women, and there were no differences in MACE rates among those who had interventions other than PCI.
In his discussion of the trial, Gilles Montalescot, MD, PhD, of the Institute of Cardiology at Pitié-Salpêtrière Hospital in Paris, said the EARLY trial with no P2Y12-ADP pretreatment confirms findings of studies before the ACCOAST trial (N Engl J Med. 2013;369:999-1010), that early angiography has no benefit on survival, recurrent MI, revascularization, or bleeding. While the ACCOAST trial, of which Dr. Montalescot was a principal investigator, found no benefit of pretreatment with prasugrel in patients with NTSE-ASC, the EARLY trial extends those findings to other P2Y12-ADP antagonists. “With the immediate angiography strategy, there is a trivial benefit on recurrent ischemia and length of stay, like in the previous studies, thus not related to pretreatment,” he said.
Dr. Montalescot cautioned against embracing this early-intervention strategy with no P2Y12-ADP pretreatment in all situations.
“If you have a conservative strategy for managing the NTSE-ASC patient or if you are in a center far away from a cath lab and your patients have to wait days for a test, yes, you should consider administration of the P2Y12-ADP antagonist,” Dr. Montalescot said.
Dr. Montalescot disclosed receiving grants or honoraria from ADIR, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Beth Israel Deaconess Medical, and Action Coeur Academic Research Organization.
Dr. Bonello reported financial relationships with AstraZeneca, Boston Scientific, Abbott, and Biotronik. The EARLY trial received funding from the French Ministry of Health.
SOURCE: Bonello B et al. AHA scientific sessions, Session LBS.04 19343.
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