December 03, 2018
5 min read

Early intervention beneficial in non-ST segment elevation ACS

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

We were unable to process your request. Please try again later. If you continue to have this issue please contact

Gilles Montalescot
Gilles Montalescot

CHICAGO — An early intervention strategy reduces the risk for recurrent ischemic events in patients with non-ST segment elevation ACS who were not pretreated with a P2Y12 inhibitor, according to the multicenter, randomized EARLY trial.

This trial, which was presented at the American Heart Association Scientific Sessions by Laurent Bonello, MD, PhD, from Aix Marseille University in France, compared outcomes of patients who underwent coronary angiography within 2 hours after randomization or within 12 to 72 hours after randomization.

At 30 days, the rate of the primary endpoint of MACE — a composite of CV death and recurrent ischemic events — was five times lower among patients in the early intervention group vs. the delayed intervention group (4.4% vs. 21.3%; HR = 0.17; 95% CI, 0.1-0.3).

“This highly significant difference was mainly obtained during the waiting time before coronary angiography,” Bonello said.

In prespecified subgroup analyses, the researchers found that the benefit was homogenous in all subgroups, although the benefit was less pronounced in women as compared with men. There was also no positive effect on the clinical endpoints with the early strategy in patients who did not undergo PCI, according to Bonello.

Currently, guidelines recommend invasive treatment strategies for patients with non-ST segment elevation ACS, as they have been proven to be more beneficial than conservative therapy in this patient population, according to Bonello.

However, he noted, there are no conclusive data in the literature on optimal timing of the treatment strategy, with another meta-analysis showing no difference between an early and a delayed strategy in terms of death or MI. The only difference, he said, was in the secondary endpoint of recurrent ischemic events, which were reduced with an early strategy.

Furthermore, in the randomized clinical trials included in the meta-analysis, all patients were pretreated with a P2Y12 inhibitor, according to Bonello.

“A significant proportion of patients with non-ST segment elevation ACS are not pretreated anymore before a scheduled invasive strategy. The current guidelines on the optimal timing are based on secondary endpoints of an overall negative trial in which all patients were pretreated,” he said, adding that he and his colleagues designed the EARLY trial within this context.

“The EARLY trial is the first trial on the optimal timing of the invasive strategy in intermediate- and high-risk non-ST segment elevation ACS not pretreated with P2Y12 ADP receptor antagonists,” he said. “There is a large benefit of a very early strategy on recurrent ischemic events resulting in urgent revascularization.”


Reduction in recurrent ischemic events

In addition to primary endpoint of MACE, the researchers evaluated its individual components. They found that CV death did not differ among patients in the early vs. delayed intervention groups, either in-hospital (0.3% vs. 0.8%; P = .62) or at 30 days after (0.6% vs. 1.1%; P = .69).

However, Bonello highlighted the benefit of the early intervention strategy compared with the delayed intervention strategy on recurrent ischemic events, including symptoms of ischemia, ventricular arrhythmias, acute pulmonary edema and cardiogenic shock, at 30 days (4.1% vs. 20.7%; P < .001). This difference was mainly linked to symptoms of ischemia at recurrence requiring emergent PCI, he said.

Results also showed no differences between intervention groups in peak troponin level, but the researchers observed a reduction in the mean length of hospital stay with the early intervention strategy (P = .046). The rate of BARC bleeding of 3 or more was also similar between intervention groups (P = .62).

A total of 1,142 patients with intermediate- or high-risk non-ST segment elevation ACS at 13 centers in France were screened for inclusion and 741 were ultimately randomly assigned to the early intervention strategy or the delayed intervention strategy. No P2Y12 inhibitor loading dose was allowed before the procedure. After coronary angiography, the patients could be managed medically or undergo revascularization with PCI or CABG.

Patients were generally young, with a mean age of 55 years, and had a high prevalence of diabetes. About 14% of the delayed strategy group and 16% of the early strategy group were on long-term clopidogrel therapy. More than 90% of patients had high-risk non-ST segment elevation ACS and about 70% were troponin-positive on admission.

EARLY in context

In terms of clinical outcomes, these data are on par with those seen in previous trials demonstrating no effect of an early strategy on mortality, MI, urgent revascularization and bleeding, said Gilles Montalescot, MD, PhD, from the Institut de Cardiologie, Pitié-Salpêtrière, Paris, who discussed the EARLY results at the AHA Scientific Sessions.

“In this trial, though, we have a big difference in MACE that is linked to recurrent ischemic events leading to activation of the cath lab in the delayed strategy arm, but we have to think twice here because, just like all of the other studies performed in the field, this is an open-label trial,” said Montalescot, who is a Cardiology Today’s Intervention Editorial Board Member. “This is fine as long as you look at hard endpoints, such as mortality or MI with biomarkers measured after the intervention, but for this soft endpoint of recurrent ischemic events, we run the risk of bias in this study.”


Although similar to other trials, Montalescot honed in on the 21% of patients in the delayed strategy arm that made the study positive in terms of the primary endpoint.

For instance, he noted that it is expected that a high-risk population would have more patients with recurrent ischemic events. However, the risk of this population, when compared with other trials, tended to be lower.

Time to angiography must also be considered, according to Montalescot.

“The more you wait, the more likely you are to experience an ischemic event,” he said. “Here, we have a disconnect because EARLY, for the delayed arm, is a study that has a shorter time to access the cath lab, but this study also has the highest rate of recurrent ischemic events when compared with previous studies.”

The last question, Montalescot added, is the role of P2Y12 inhibitors, or the absence of P2Y12 inhibitors in the EARLY trial, in the occurrence of new ischemic events.

“Actually, we have the answer to this question in the double-blind ACCOAST study. If you look at these data in the ACCOAST study, you have a waiting period of 48 hours. There was absolutely no impact of the treatment or no pretreatment on this accumulation of ischemic events during the waiting period,” Montalescot said.

Therefore, one can conclude that the EARLY trial confirms findings from previous studies in a lower-risk population with no P2Y12 loading, he added.

“With the immediate angiographic strategy, there was a trivial benefit on recurrent ischemic events and length of stay, but this is something we have seen also in previous studies. It is not new; this is consistent with what we know and is not related to pretreatment,” Montalescot said. “So, in the strategy of loading P2Y12 inhibitors after seeing the coronary angiography, EARLY has extended the ACCOAST data to P2Y12 antagonists other than prasugrel, and I think this is an important feature of the study.”

Finally, if a physician has a conservative strategy for patients with non-ST segment elevation ACS or if they are practicing at a center far from a cath lab, the administration of a P2Y12 antagonist should be considered, Montalescot concluded. – by Melissa Foster


Bonello L. LBS.04 – Preserving Brain and Heart in Acute Care Cardiology. Presented at: American Heart Association Scientific Sessions; Nov. 10-12, 2018; Chicago.

Disclosure s : The study was funded by the French Ministry of Health. Bonello reports he has received research grants from AstraZeneca, and he has received honoraria from AstraZeneca, Boston Scientific, Abbott and Biotronik. Montalescot reports he has received research grants or honoraria from ADIR, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb and Beth Israel Deaconess Medical, and he has received research grants from AstraZeneca, Bayer and Bristol-Myers Squibb.