VERDICT: No Advantage of Early Invasive Strategy in NSTE-ACS

Susan Jeffrey

August 29, 2018

MUNICH — A randomized trial comparing very early invasive evaluation of patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) within about 5 hours, with a strategy of less urgent evaluation within 2 to 3 days, shows the early invasive approach did not improve overall long-term clinical outcomes: a composite of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or hospital admission for heart failure.

However, secondary analysis showed a significant benefit of the early invasive strategy for the highest-risk patients, those with a Global Registry of Acute Coronary Events (GRACE) risk score greater than 140, the researchers said.

Senior author Thomas Engstrøm, MD, from the Department of Cardiology, Glostrup Hospital, University of Copenhagen, Denmark. concluded that the very early invasive strategy did not improve the primary outcome, but he added that it "is safe, complications were equally distributed between the two groups, and it's possibly favorable for some of the patients."

"If you assume that acute investigation should be offered everybody, there is a clear logistical challenge, and it is potentially not also cost-effective," he added. "Nonetheless," he concluded, the researchers feel that "patients that present with symptoms of ACS, have troponin rise, and have a high GRACE score should be examined within 12 hours."

Results of the Very EaRly vs Deferred Invasive evaluation using Computerized Tomography (VERDICT) trial were presented here at the European Society of Cardiology (ESC) Congress 2018 to coincide with their publication online August 28 in Circulation.

Commenting for theheart.org | Medscape Cardiology, Manesh Patel, MD, an interventional cardiologist and chief of the Division at Duke University, Durham, North Carolina, speaking on behalf of the American Heart Association (AHA), called VERDICT "an important trial for how we take care of patients."

The finding that high-risk patients may derive benefit from the early strategy should be viewed with caution but are consistent with results of a previous trial called Timing of Intervention in ACS (TIMACS), Patel noted.  

"So the TIMACS trial and the VERDICT trial now probably tell us that patients who are having ongoing symptoms, or high-risk patients with NSTEMI should generally go pretty early to the cath lab, but in general, it's consistent with what we knew before," as well as with current AHA/ESC guidelines that say an early invasive strategy may be considered in high-risk patients, he said.

"It's probably good news for most of the cath lab interventional cardiologists and personnel because taking every NSTEMI to the cath lab within  4 hours would be complicated," Patel added. "It doesn't mean we wouldn't do it if it clearly improved outcomes, but it looks like the high-risk patients could still benefit if we could identify those patients using the GRACE score."

Joep Perk, MD, Linnaeus University, Sweden, member of the board for the European Association of Preventive Cardiology and a spokesperson for the ESC, was pleased with the results.

"One good thing is that at the end of the day, it's the gut feeling of the doctor that really makes it, and with all the exact measurements that we have, it's good to see there is still an art to our profession, a judgment that this is a really serious patient," Perk said in an interview.

"It's a consolation also because we have a lot of elderly people in Scandinavia that wait too long, and this gives you a feeling that this is maybe not too dangerous," he added. "We'll take proper care of them if we don't panic too much, and I think that's the real bottom line of this good study."

Early Invasive Strategy

The aim of the VERDICT trial was to compare a strategy of very early invasive coronary angiography (ICA) and possible revascularization within 12 hours of diagnosis, with an invasive strategy performed within 48 to 72 hours in terms of clinical outcomes.

Patients admitted with clinical suspicion of NSTE-ACS to one of nine hospitals in the Capital Region of Copenhagen were screened for inclusion, Engstrøm said. Those with electrocardiographic  changes indicating new ischemia and/or elevated troponin, for whom ICA was clinically indicated and deemed feasible within 12 hours, were randomly assigned 1:1 to the early invasive or standard invasive strategy. All received aspirin, a P2Y12 inhibitor, fondaparinux, and β-blockers before randomization.

Percutaneous coronary intervention (PCI) was the preferred revascularization strategy, but patients not eligible for PCI were allowed coronary artery bypass grafting (CABG), he noted.

The primary endpoint was a combination of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or hospital admission for heart failure.

A total of 2147 patients were randomly assigned to very early invasive evaluation (1075 patients), with ICA performed at a median of 4.7 hours after randomization, or to standard invasive care (1072 patients), with ICA performed a median of 61.6 hours after randomization.

Coronary findings showed that "notably, about one third of patients did not actually have significant coronary artery disease," Engstrøm said. Another third had one-vessel disease, and the other third was divided between those with two- and three-vessel disease, "with a minority of patients having left main stenosis."

Among patients with significant coronary artery disease identified by ICA, coronary revascularization was performed in 88.4% of patients in the very early strategy group and 83.1% of those in the standard invasive care group.

Within a median follow-up of 4.3 years, a primary endpoint occurred in 296 (27.5%) of those randomly assigned to the early strategy and 316 (29.5%) of those assigned to the standard care group, not a significant difference.

There were signs of benefit, though, on components of the primary endpoint, including a significant reduction in nonfatal MI and a trend toward benefit for heart failure with the very early strategy, he noted.

Table. VERDICT: Outcome in NSTE-ACS With Early Invasive vs Standard Strategy

Endpoint Hazard Ratio (95% Confidence Interval) P Value
Primary endpoint 0.92 (0.78 - 1.08) .29
Nonfatal MI 0.73 (0.56 - 0.96) .025
Heart Failure 0.78 (0.60 - 1.01) .06

 

Among patients with a GRACE risk score greater than  140, also a prespecified subgroup analysis, the early invasive strategy improved the primary outcome compared with the standard invasive treatment (hazard ratio,  0.81; 95% confidence interval,  0.67 - 1.01; P for interaction = .023).

Invited discussant for the presentation here was Franz-Josef Neumann, MD, from University Heart Centre Freiburg–Bad Krozingen, Germany, chair of the task force for new ESC/European Association for Cardio-Thoracic Surgery (EACTS) guidelines on myocardial revascularization released at this meeting.

He congratulated the investigators on a trial with a "clinically highly relevant question, that was well designed and well performed," with adequate power for the primary endpoint. "There was complete long-term follow up and the trial was performed in a highly efficient myocardial infarction network by a research group with an excellent track record for studies in acute coronary syndromes," Neumann said.

"The bottom line is that from VERDICT there's no proof of benefit of very early intervention because the primary endpoint was not met, and therefore, any further analyses are exploratory," he said. "Nevertheless, we may also ask the question, 'Is it then safe to delay intervention?"

Factored in should be the positive results on secondary outcomes, such as the reduction in nonfatal MI and heart failure in this trial, the fact that there were more revascularizations with early intervention, and the apparent benefit in high-risk subgroups of patients, he said.

"So my take-home messages from VERDICT are that in patients with non-ST elevation acute coronary syndromes, first of all, nothing is gained by delaying intervention, and second, that the message from previous studies is strengthened, that in high-risk subsets, intervention should be performed swiftly, and I may add that there is an even higher need in settings where you don't have the ability to interfere immediately, as in the setting of the VERDICT trial," Neumann concluded.

This study was funded by the Danish Agency for Science, Technology and Innovation and the Danish Council for Strategic Research and The Research Council of Rigshopitalet.  Engstrøm reports personal fees from Boston Scientific, Abbott, Bayer, Novo and Astra Zeneca, outside the submitted work. Patel has no disclosures.

European Society of Cardiology (ESC) Congress 2018.  Presented August 28, 2018.

Circulation. Published online August 28, 2018. Full text

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