VERDICT: Very Early Invasive Angiography No Help Overall for NSTE ACS

MUNICH, Germany—Patients with NSTE ACS do not have better outcomes when they are routinely taken for invasive coronary angiography within 12 hours of diagnosis as opposed to 2 to 3 days later, but risk profile may come into play, the VERDICT trial shows.

Overall, a composite of all-cause death, nonfatal recurrent MI, hospitalization for heart failure, or hospitalization for refractory myocardial ischemia—the primary endpoint—occurred in 27.5% of those taken to the cath lab very early and 29.5% of those taken later (HR 0.92; 95% CI 0.78-1.08), Thomas Engstrøm, DMSci, PhD (Rigshospitalet, University of Copenhagen, Denmark), reported here during a Tuesday Hot Line session at the European Society of Cardiology (ESC) Congress 2018.

However, the patients with a GRACE score > 140, about half of the cohort, did seem to have better outcomes with the early invasive approach (HR 0.81; 95% CI 0.67-1.00), the findings, published simultaneously online in Circulation, showed.

“You could say that a very early invasive lookup in non-STEMI ACS is safe—complications were equally distributed between the two groups—and it’s possibly favorable for some of the patients,” Engstrøm said at a press conference.

Offering very early angiography to all patients with NSTE ACS would be logistically challenging, he said, so it’s important to choose the right patients. Patients with an elevated GRACE score would be one group to target, he said, pointing out that in that subset, the number needed to treat to prevent one primary endpoint event was 73.

American College of Cardiology spokesperson Frederick Masoudi, MD (University of Colorado Hospital, Aurora), said that even though the benefit seen in high-risk patients comes from a subgroup analysis, it is consistent with findings from the TIMACS trial, which similarly had a neutral result on the primary endpoint but a significant benefit in patients with high GRACE scores, and also has biological plausibility.

“It emphasizes, to me at least, a time-honored approach that isn’t always used, which is trying to calibrate the intensity of therapy to the underlying risk of the patient,” Masoudi told TCTMD. “The findings of this study seem to correlate well with that general approach, namely that people who are at higher risk are the ones that you consider performing early angiography in.”

As for the other patients, “obviously in the interest of getting them home as soon as you can you may want to perform angiography and PCI in as timely a manner as possible, but it relieves some of the time pressure around getting patients like that to the lab,” he said, adding that this approach is consistent with his current practice.

A Question of Timing

Both European and US guidelines recommend early invasive angiography—within 24 hours—in high-risk patients with NSTE ASC. ESC guidelines define high-risk as a GRACE score over 140, a change in troponin, or ECG changes indicative of ischemia.

Those recommendations are based primarily on the TIMACS trial, however, and the ideal timing of invasive angiography and revascularization in patients with NSTE ACS is not clear.

“An early invasive strategy conducted within 12 hours of diagnosis could be helpful to identify patients with imminent or established vessel closure, in whom prompt revascularization might result in salvage of ischemic myocardium,” the VERDICT investigators write in their paper. “On the other hand, a prolonged antithrombotic and lipid-lowering pretreatment could stabilize the coronary plaques and thus optimize conditions for a subsequent revascularization.”

To explore the issue, the researchers randomized 2,147 patients with clinical suspicion of NSTE ACS, along with ischemic ECG findings and/or elevated troponin, to undergo coronary angiography within 12 hours of diagnosis or 48 to 72 hours after diagnosis. All patients were treated with aspirin, a P2Y12 inhibitor, fondaparinux, and a beta-blocker before randomization.

Angiography was performed a median of 4.7 hours after randomization in the very early group and 61.6 hours after randomization in the deferred group. Roughly 30% of patients didn’t have a coronary stenosis. Of those with significant CAD, revascularization was performed slightly more often in the patients who received angiography very early (88.4% vs 83.1%).

Although there was no difference between groups in the primary endpoint through a median follow-up of 4.3 years, risk of nonfatal MI was significantly lower in the very early group (8.4% vs 11.2%; HR 0.73; 95% CI 0.56-0.96), with a nonsignificant trend toward less hospitalization for heart failure (9.2% vs 11.8%; HR 0.78; 95% CI 0.60-1.01). The MI finding is only hypothesis-generating because of the neutral primary endpoint, the authors note.

They point out that even though VERDICT differed from TIMACS in terms of sample size, the timing of invasive angiography in the trial arms, the components of the primary endpoint, and duration of follow-up, the findings were similar in both trials.

“These consistent observations support an individualized approach to timing of invasive therapy in NSTE-ACS, in which the highest-risk patients are considered for very early intervention in the absence of contraindications,” they say.

‘Nothing Gained by Delaying Intervention’

Serving as a discussant following Engstrøm’s presentation during the ESC session, Franz-Josef Neumann, MD (University Heart Centre Freiburg-Bad Krozingen, Germany), said the benefits of an early invasive strategy include a reduction in recurrent or refractory ischemia and a shorter hospital stay, which potentially impacts cost.

The primary endpoint may have been neutral in VERDICT, he said, because the trial was performed in a highly efficient MI network that allowed operators to intervene promptly, which may have prevented large infarctions. It’s possible, too, that there could have been “statistical noise” stemming from the lack of significant CAD in about one-third of patients and from the fact that some of the patients in the deferred group underwent early invasive angiography.

Even though no difference was seen on the primary endpoint—and thus, all further analyses are exploratory—the trial can help provide insight into whether it is safe to delay intervention in these patients, Neumann indicated.

After reviewing the reduction in MI, the trend toward less heart failure, and the benefit seen in the high-risk subgroup—which is consistent with prior studies—Neumann concluded: “In patients with non-ST-elevation acute coronary syndromes, first of all, nothing is gained by delaying intervention. And second . . . the message from previous studies is strengthened that in high-risk subsets, intervention should be performed swiftly. And I may add, 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.”

When the attendees of the Hot Line session were polled about whether VERDICT would change their practice in patients with NSTE ACS and an elevated GRACE score, the majority (67%) said the results would not because they confirm what they normally do already. Another 34%, however, said they would ask for angiography sooner than before because the subgroup analysis was convincing.