MULTISTARS AMI: Immediate Complete PCI in STEMI as Safe as Staged Revascularization

AMSTERDAM, the Netherlands—For hemodynamically stable patients with STEMI and multivessel coronary artery disease, those who receive immediate complete revascularization fare just as well as those who undergo primary PCI then later receive treatment of non-infarct-related lesions, new results from MULTISTARS AMI show.

The study, which was presented during a Hot Line session this week at the European Cardiology Society (ESC) Congress 2023 and published simultaneously in the New England Journal of Medicine, should help provide some direction when it comes to the optimal timing of complete revascularization in STEMI, say investigators.

Barbara Stähli, MD (University Heart Center, Zurich, Switzerland), who led the randomized trial, was careful when interpreting the results, noting that while they also showed immediate PCI was better than staged PCI in a superiority analysis, the trial was designed as a noninferiority study.

“We have to be cautious,” Stähli told TCTMD. “It was powered for inferiority and that is what we are showing.” The data do provide operators, as well as patients, with more information to allow them a choice between complete revascularization during the index procedure or coming back at a later date. “It wasn’t clear [before],” she noted. “We had observational data pointing toward increased event rates when you did immediate multivessel PCI in STEMI patients. We showed you can do it.”

Overall, immediate PCI was associated with less use of contrast material and shorter fluoroscopy times, she said, adding that it also would likely be associated with less use of healthcare resources. 

Shamir Mehta, MD (McMaster University/Population Health Research Institute, Hamilton, Canada), who wasn’t involved in the trial, said MULTISTARS AMI should not be viewed as a green light for operators to proceed wholesale with this strategy.

It was powered for inferiority and that is what we are showing. Barbara Stähli

“The most important goal of primary PCI is to open the infarct-related artery and establish perfusion to the ischemic myocardium,” he told TCTMD. “It’s not to open the nonculprit artery. We know that primary PCI is a lifesaving procedure and that should be the focus.”

There can be complications with primary PCI that prolong the procedure, such as slow-flow or no-flow phenomenon, he pointed out. The case may be technically challenging or the patient slightly unstable, and in these scenarios it’s best not to attempt to treat the nonculprit lesion, especially since operators may be dealing with these patients in the middle of the night. 

MULTISTARS, he stressed, shows that in select cases where operators have successfully opened the culprit artery it may be safe to open a “straightforward” nonculprit lesion during the same procedure. The nonculprit lesion isn’t always obliging, however.  

“The nonculprit lesion can often be complex,” said Mehta. “It might be a calcified lesion, or it might be a complex bifurcation lesion. It may be in a very torturous artery that requires a prolonged procedure to open that nonculprit lesion. After just doing a primary PCI, I am concerned that the time and effort it would take to open the nonculprit lesion might not be in the patient’s best interest, especially since they just had a STEMI.”

New ACS Guidelines Support Complete PCI

The 2023 European guidelines for the management of ACS, published this week to coincide with the ESC Congress, strongly recommend complete revascularization for hemodynamically stable STEMI patients with multivessel disease undergoing primary PCI (class IA recommendation). The recommendation is based on numerous trials, the largest among them being the COMPLETE trial, which was led by Mehta. In that study, treatment of the nonculprit lesions took place either during the index hospitalization or after discharge. Investigators observed no treatment effect based on the timing of revascularization of the non-infarct-related lesions.

The new ESC guidelines state that PCI of the nonculprit lesions can take place during the index PCI procedure or within 45 days. The ACS guidelines make no recommendation in favor of immediate or delayed complete revascularization because there have been no “adequately sized randomized trials with a superiority design.”

MULTISTARS AMI helps provide some evidence on the optimal timing of complete revascularization in STEMI patients with multivessel disease, but it is a relatively small, noninferiority trial.

Conducted at 37 sites in Europe, the study included 840 patients (mean age 65 years; approximately 80% male) with STEMI who underwent primary PCI of the culprit lesion plus revascularization of nonculprit lesions either during the index procedure or after a period of 19 to 45 days. In the immediate- and staged-PCI arms, 83.2% and 80.4%, respectively, had a single significant nonculprit coronary lesion necessitating PCI while 16.8% and 19.6%, respectively, had two or more nonculprit lesions. For those who underwent staged PCI, the median time to the second intervention was 37 days, with limited use of intravascular imaging.

The composite endpoint of all-cause mortality, nonfatal MI, stroke, unplanned ischemia-driven revascularization, or hospitalization for heart failure at 1 year occurred in 8.5% of those randomized to immediate PCI and 16.3% of those in the staged-PCI arm (P < 0.0001 for noninferiority and P < 0.001 for superiority). The rate of nonfatal MI was cut by more than half with immediate PCI (2.0% vs 5.3%), as was the rate of unplanned ischemia-driven revascularization (4.1% vs 9.3%). There was no difference in rates of stent thrombosis, acute kidney failure, or BARC 3 or 5 major bleeding.

Commenting on the results for TCTMD, Deepak Bhatt, MD (Mount Sinai Heart, New York, NY), said the immediate complete revascularization strategy appeared “better” than the staged approach, noting the trial will likely change how operators do things.

“Of course, the individual patient characteristics need to be incorporated in the decision of whether to apply the MULTISTARS results,” he said via email. “A patient with bad kidney function, for example, may not be a good candidate for this immediate approach. Also, if it is the middle of the night and the cath lab team is exhausted, it may not be wise to embark upon a very long case of nonculprit PCI.” 

Two Distinct Phases of ACS

Speaking with the media, Stähli said investigators performed staged PCI between 19 to 45 days—as opposed to within 2 or 3 days—because they wanted to investigate PCI performed during two distinct pathological phases of ACS. “PCI performed in the acute phase where inflammation and coagulation is activated to a maximal extent compared with a staged procedure in an elective setting where the patient has recovered and markers have normalized,” she said.

Mehta said staged revascularization of the non-infarct-related artery is most commonly performed during the index hospitalization. In COMPLETE, the median time from randomization to PCI of the nonculprit lesion in those randomized to complete revascularization was 1 day in the majority of patients treated during the index hospitalization (it was 23 days for the minority of patients who returned to hospital for the staged procedure). “That option, the most common option of PCI during the index hospitalization, wasn’t available in [MULTISTARS AMI],” he said. “Usually, the patient will come back the next day or day after if they’re stable, but that scenario wasn’t evaluated in this trial.”

The most important goal of primary PCI is to open the infarct-related artery. Shamir Mehta

Robert Byrne, MBBCh, PhD (Mater Private Hospital, Dublin, Ireland), the scheduled discussant following the Hot Line presentation, congratulated the researchers for the trial, adding that it’s difficult to perform randomized trials in STEMI patients. Observational data on practice patterns suggests operators seem a little “confused” about when to perform PCI on non-culprit-related lesions, adding there is variation across centers when it comes to timing.   

“MULTISTARS AMI adds important information on this,” said Byrne.

The trial, he said, suggests there is “no signal of harm” with the immediate PCI during the index procedure compared with the staged approach.

With respect to superiority, Byrne was more skeptical, noting that the reduction in the primary endpoint was driven by nonfatal MI and unplanned revascularization. The reduction in MI was largely an imbalance in procedural MIs, with zero in the immediate-PCI arm and 12 cases in the staged-PCI group, raising concerns about ascertainment bias, said Byrne. There was no difference in the rate of type 1 spontaneous MI between strategies. Fewer unplanned revascularizations with immediate PCI must be considered in the context of the open-label study design, he added.

In general, Byrne said that the decision to perform immediate complete revascularization must be individualized, noting that it will come down to the patient’s clinical risk and logistical considerations.