ELISA-3: Early vs. Late Intervention No Different for High-Risk NSTE ACS Patients

PARIS, France—Early invasive treatment is not superior to a delayed strategy in older, high-risk patients with non-ST-segment acute coronary syndromes (NSTE ACS), researchers reported Thursday, May 23 at EuroPCR 2013. The findings, from the randomized ELISA-3 trial, were simultaneously published in the May 2013 issue of EuroIntervention.

While several trials have shown long-term reductions in cardiovascular mortality and reinfarction with the early strategy, “[o]ne of the problems is that age in these trials is often [younger] than in real life and therefore the generalizability of the results is somewhat questionable,” said Erik Badings, MD, MSc, of Deventer Hospital (Deventer, the Netherlands). Moreover, he added, recent meta-analyses have suggested modest benefit at best.

For ELISA-3, Dr. Badings and colleagues randomly assigned 542 NSTE ACS patients who presented to 1 PCI and 5 non-PCI centers to receive angiography and revascularization within 12 hours (n = 269) or after 48 hours (n = 265).

Patents had a median age of 72 years, and approximately 79% were biomarker positive. The gap between hospital admission and randomization was similar between the 2 groups at about 2 hours, while the median time from randomization to angiography was 2.6 hours (interquartile range [IQR], 1.2-6.2 hours) and 54.9 hours (IQR, 44.2-74.5 hours) with the early and delayed strategies, respectively.

At 30 days, the primary composite endpoint of death, reinfarction, and recurrent ischemia did not differ between the early and delayed groups, though there was a trend favoring immediate intervention for recurrent ischemia. Both strategies resulted in similar biomarker results and bleeding. However, hospital stays were significantly shorter for patients treated earlier (table 1).

Table 1. Outcomes by Timing of Invasive Treatment


(n = 269)

(n = 265)

P Value

Primary Composite at 30 Days




Death at 30 Days



> 0.99

MI at 30 Days




Recurrent Ischemia at 30 Days




Troponin T at 72-96 Hours, µg/La

0.31 (0.12-0.68)

0.31 (0.10-0.99)


Proportion Without CK-MB Rise




Any Bleeding




Major Bleeding




Hospital Stay, daysa

4 (2-10)

6 (4-12)

< 0.001

a Median (IQR).

Subgroup analyses showed no significant variability in the primary outcome, though there was a trend toward greater benefit from the earlier strategy in higher risk patients, such as those with greater ST depression or higher troponin T levels at admission.

“One unexpected finding,” Dr. Badings noted, is that patients randomized at non-PCI centers appeared to fare better with early treatment (RR 0.227, 95% CI 0.052-0.992) while those randomized at PCI centers did not (RR 0.849, 95% CI 0.509-1.417; P = 0.089 for interaction). “Of course, this is only a post hoc specified subgroup analysis,” he stressed, “so these results need to be taken with extreme caution.”

In addition, ELISA-3 is largely consistent with recent meta-analyses, Dr. Badings said, citing studies published in the European Heart Journal in 2011 and Annals of Internal Medicine in 2013.

One important caveat is that because the event rates were lower than expected, the trial is underpowered, he commented. Moreover, accurate assessment of periprocedural MI can be difficult in patients with elevated biomarkers.

“In this group of relatively old, high-risk patients with NSTE ACS, early angiography and revascularization was not superior to a delayed invasive strategy,” Dr. Badings concluded.

How Early Is Early?

An audience member questioned the 2-hour delay between randomization and treatment that occurred even in the early group. What would happen, he asked, “if you transfer these patients as if they were primary PCIs, utilizing the fastest possible means?” Dr. Badings replied that the delay relates to the fact that patients who presented to non-PCI centers were randomized onsite before being transferred via ambulance for treatment.

Session co-chair William Wijns, MD, PhD, of Cardiovascular Center Aalst (Aalst, Belgium), praised the study findings, particularly the difference in length of stay. “We may think [hospitalization] is trivial. It is not trivial at all,” he said. However, Dr. Wijns questioned whether the trial could have been underpowered from the beginning.

Dr. Badings said the researchers based their calculations on earlier studies suggesting that 35% of patients would have an event; in reality, the rate was 15%. “Which is great news for the patients,” Dr. Wijns added.

Study Details

All patients had ischemic symptoms at rest within 24 hours before randomization plus at least 2 of 3 high-risk characteristics:

  • Extensive myocardial ischemia (cumulative ST depression > 5 mm or temporary ST elevation < 30 mins)
  • Positive biomarkers (troponin T > 10 µg/L, myoglobin > 150 µg/L, or CK-MB fraction > 6%)
  • Age greater than 65 years.


Badings EA, The HSK, Dambrink J-H E, et al. Early or late intervention in high-risk non-ST-elevation acute coronary syndromes: Results of the ELISA-3 trial. EuroIntervention. 2013;9:54-61.



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  • Dr. Badings reports serving as a consultant to Merck Sharp &amp; Dohme and Sanofi-Aventis.