Immediate Complete PCI May Harm STEMI Patients With Multivessel CAD

Stable STEMI patients with multivessel disease who undergo immediate complete revascularization may be at higher short-term risk when compared with those treated with a staged strategy, according to results of a new meta-analysis.

Immediate complete revascularization was associated with a more than twofold higher risk of cardiac mortality at 30 days compared with a staged procedure, although there was no significant differences in the risk of major adverse cardiovascular and cerebrovascular events (MACCE), MI, repeat revascularization, and other endpoints, report Mohammed Elbahloul, MD (Kafr El-Shaikh University, Egypt), and colleagues in a paper published recently in Circulation Cardiovascular Interventions.

Senior investigator Gregg Stone, MD (Icahn School of Medicine at Mount Sinai, New York), told TCTMD the weight of evidence is now moving towards a signal of potential harm with immediate complete revascularization, a strategy that should be reserved “only for very selected circumstances.”

“The guidelines are based on an insufficient evidence base,” said Stone. “As we get more and more randomized trials, and this is where meta-analyses are useful—we still have just barely over 4,200 patients, which is not a lot when you’re looking at mortality—there is such a strong signal towards increased mortality and it’s very consistent with CULPRIT-SHOCK.”

In that trial, immediate revascularization of all significant nonculprit lesions in patients with acute MI complicated by cardiogenic shock was associated with worse clinical outcomes, specifically a higher risk of death or severe kidney failure leading to renal-replacement therapy within 30 days.

“[Ours] are non-shock patients, so it’s a very different scenario, but I think the same concepts still apply,” said Stone.

MULTISTARS and More

In the most recent American College of Cardiology/American Heart Association (ACC/AHA) ACS guidelines, complete revascularization has a class 1 (level of evidence A) recommendation for patients with STEMI and multivessel disease. Multivessel PCI of nonculprit lesions at the time of primary PCI “may be preferred” over the staged approach to reduce the risk of cardiovascular events, with the recommendation reflecting some uncertainty around benefit (class 2b, level of evidence B).

The European Society of Cardiology endorses complete revascularization, done immediately or within 45 days, as a class 1 (level of evidence A) recommendation.

Some studies, such as MULTISTARS AMI and BIOVASC, showed that immediate multivessel PCI was noninferior to the staged approach, whereas the OPTION-STEMI trial found that immediate complete revascularization was “not noninferior” to the staged strategy. The iMODERN trial found that immediate complete PCI guided by instantaneous wave-free ratio (iFR) was not superior to deferred PCI based on stress MR imaging.  

“I think that these trials, though, have been obfuscated in their interpretation because of the incorporation of myocardial infarction as an endpoint in most of them,” said Stone. “The issue is that in patients undergoing immediate complete revascularization, it’s almost impossible to detect a procedural myocardial infarction. The biomarkers are already elevated, they’ve not yet peaked, and ST-segments are already elevated. You could do harm in the [immediate] procedure by doing another intervention in a noninfarct-related artery, but it would be very hard to pick that up with any objective test.”

As a result, these studies could be biased toward immediate complete revascularization by underestimating procedural MI risks, said Stone.

This meta-analysis included 4,213 patients from nine randomized trials. The primary outcome of all-cause mortality at 30 days, which was based on eight trials with 4,124 patients, was 2.0% in the immediate PCI group and 1.2% in those receiving staged procedures (risk ratio 1.66; 95% CI 0.99-2.78). At 1 year, the rates were 4.7% and 3.5%, respectively (incidence rate ratio 1.40; 95% CI 0.97-2.03).

With data from 1,811 patients in three trials, cardiac mortality at 30 days occurred in 2.6% and 1.2% of the patients treated with immediate versus staged revascularization, respectively (risk ratio 2.19; 95% CI 1.08-1.44). There was no significant difference in this endpoint at 1 year, nor were there any significant long- or short-term differences between PCI strategies in terms of MACCE or other secondary endpoints. 

In a Kaplan-Meier analysis of 3,369 patients from six randomized trials, increased risk of early mortality with immediate complete revascularization was present in a time-dependent hazard ratio analysis, although the difference compared with the staged strategy over 1,080 days of follow-up did not reach significance (HR 1.36; 95% CI 0.99-1.86).

Staged PCIs Mostly Performed

At his center, Stone said the default strategy for STEMI patients presenting with multivessel CAD is a staged approach. In some instances, immediate complete revascularization may be performed, such as when there is plaque rupture in two different vessels, or “if you have a second vessel that is so tight—99% stenosis—that it is impeding flow even if it hasn’t ruptured or thrombosed,” said Stone. “But usually we leave them alone and bring the patient back for complete revascularization.”

Sunil Rao, MD (NYU Langone Health System, New York), who chaired the ACC/AHA writing committee that drafted the ACS guidelines, said the 2b recommendation to perform nonculprit revascularization at the same time as primary PCI of the culprit lesion was based on MULTISTARS AMI. In that study, the primary endpoint of death from any cause, nonfatal MI, stroke, unplanned ischemia-driven revascularization, or hospitalization for heart failure at 1 year was almost halved in those treated immediately versus with staged PCI (8.5% vs 16.3%; P < 0.001 for noninferiority and superiority).

“The endpoint was driven by unplanned revascularization and MI, and recurrent MI is very challenging to adjudicate in the setting of STEMI,” Rao told TCTMD. “The current meta-analysis goes against MULTISTARS to some degree.”

Multivessel CAD in the setting of STEMI occurs in roughly 10% to 15% of patients, he said, noting that it tracks with age and other cardiovascular risk factors. At their center, the decision to completely revascularize at the time of primary PCI depends on certain factors.

“Our approach is really based on the characteristics of the nonculprit disease,” he said. “If it is high risk, then we tend to stage during hospitalization and perform the nonculprit PCI prior to hospital discharge. If it is lower risk, then we stage as an outpatient. We rarely perform nonculprit PCI during the same setting as the index culprit PCI, unless there is a compelling clinical reason, like an unclear infarct-related artery.”

At this stage, Rao said further trials investigating the timing of complete revascularization are unlikely. “I think the message is pretty clear and it’s nice to see that it’s consistent for patients with STEMI regardless of whether they have shock or not,” he said.