Complete Revascularization May Top Culprit-Only PCI Across ACS Types

Intervening on significant nonculprit lesions in addition to the culprit lesion in patients with STEMI and multivessel PCI improves hard clinical outcomes, an updated meta-analysis shows. And a registry study suggests that patients with NSTEMI and unstable angina might also derive those same benefits.

Several randomized trials in recent years have demonstrated that complete revascularization has an advantage over culprit-only PCI in patients with STEMI, although the impact has been seen mostly for repeat revascularization. That changed with the 4,041-patient COMPLETE trial, in which multivessel PCI cut the risk of CV death or MI.

A meta-analysis that includes COMPLETE and nine prior trials, reported by lead author Varunsiri Atti, MD (Michigan State University, Lansing), and colleagues, now shows that complete revascularization in STEMI patients with multivessel disease is associated with lower risks of reinfarction, CV mortality, and repeat revascularization over about 2 years of follow-up.

In a separate analysis of the Alberta COAPT registry, lead author Kevin Bainey, MD (Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada), and colleagues report that in the broader group of ACS patients with multivessel disease, complete revascularization is associated with lower risks of all-cause and CV death, new MI, and repeat revascularization.

Both studies were published online ahead of the July 13, 2020, issue of JACC: Cardiovascular Interventions.

“Complete revascularization in patients with STEMI and multivessel disease is something that we should be doing,” Poonam Velagapudi, MD (University of Nebraska Medical Center, Omaha), senior author of the meta-analysis, told TCTMD, noting that the findings do not apply to patients with late-presenting STEMI, cardiogenic shock, or more-complex lesions. She added that it’s probably the way to go for patients with NSTEMI and unstable angina, too, but that trials are needed for confirmation.

Bainey agreed that for STEMI, “it’s a no-brainer,” and that for NSTEMI and unstable angina, the findings are hypothesis-generating and need to be confirmed in large trials. Nevertheless, the results will push clinicians to perform more-complete revascularization in these patient subsets, he said, noting that at his center they “really have adopted and embraced complete revascularization for all ACS patients.”

During the Index Procedure or Staged?

For the meta-analysis, Atti, et al pooled data from 10 trials with a total of 7,030 patients. Mean patient age ranged from 52.2 to 66.5 years, and most of the participants (80.8%) were men. The timing of when nonculprit PCI was performed—during the index procedure, staged during the initial hospitalization or after discharge, or a combination—varied across studies. Median follow-up was 25 months.

Over that span, multivessel versus culprit-only PCI was not associated with an improvement in all-cause mortality, but it had an advantage for other clinical outcomes. Safety endpoints, including major bleeding, stroke, and contrast-induced nephropathy, were similar in both groups.

Outcomes of Multivessel Versus Culprit-Only PCI

When to perform PCI on the nonculprit lesions has been debated, and data from COMPLETE have suggested that it doesn’t matter. Sensitivity analyses performed as part of the meta-analysis indicate that it might be better to perform all of the interventions during the index procedure, as that was associated with lower risks of all-cause mortality, reinfarction, CV mortality, and repeat revascularization. Staged multivessel PCI, on the other hand, was associated with a lower risk of repeat revascularization only.

“On the basis of these data, we suggest that the updated guidelines should take into consideration the benefits of multivessel PCI during index hospitalization in patients presenting with STEMI,” the authors write.

Alberta COAPT Registry

Bainey et al examined real-world data from the Alberta COAPT registry on 9,094 patients with ACS and multivessel disease who underwent PCI between April 2007 and March 2013. Nearly half had STEMI, about 40% had NSTEMI, and about 10% had unstable angina. Revascularization was deemed complete in two-thirds of patients, defined as a residual angiographic jeopardy score of less than 10% (percentage of myocardium at risk).

Complete versus incomplete revascularization was associated with lower rates of a variety of composite and individual clinical outcomes.

5-Year Outcomes: Complete vs Incomplete Revascularization

^*Inverse probability-weighted hazard ratio

The findings regarding all-cause death/new MI were generally consistent across subgroups, including by ACS presentation. However, the benefits of multivessel PCI appeared to be greater in patients younger than 75 years (P = 0.02 for interaction), “which is likely reflective of unmeasured confounders (ie, frailty) leading to incomplete revascularization,” the investigators say.

Unique to this study, they note, is an analysis showing a continuous relationship between the angiographic jeopardy score and risk of all-cause death/new MI, with risk increasing along with the percentage of residual myocardium at risk.

“It’s nice to have a big observational cohort study that basically validates what we’ve seen in RCT data in STEMI,” Bainey said, “and I really do think it will help reinforce a change in guidelines pertaining specifically to STEMI. But now it gives us an opportunity to extend complete revascularization across the spectrum of ACS.”

The Timing Debate

Bainey et al also assessed the impact of the timing of the nonculprit interventions and found that multivessel PCI was associated with a lower risk of all-cause death/new MI regardless of when they were performed (P = 0.11 for interaction).

That appears to be at odds with the findings from the meta-analysis, but Velagapudi pointed out that a prior meta-analysis from Bainey’s group also indicated that performing all of the interventions during the index procedure might provide better outcomes. In subgroup analyses, same-sitting multivessel PCI was associated with a relative 59% lower risk of CV death/new MI, while staged PCI was associated with a relative 27% lower risk. That first figure “is impressive despite the low [patient] numbers,” she said. “The staged-PCI group is mostly driven by the COMPLETE trial with over 2,000 patients” in each trial arm.

Velagapudi said the sensitivity analysis suggesting an advantage for same-sitting PCI is “not definitive, but it kind of points us in that direction.”

Bainey said that even though his group’s analyses have indicated that the timing doesn’t matter, he feels that staged procedures are safer for patients, especially considering the fact that the benefits of complete revascularization aren’t apparent until 6 months of follow-up or beyond.

Now, the bigger question is how to choose the nonculprit lesions that need to be treated, Velagapudi said, noting that the trials differed in this respect, with some using fractional flow reserve (FFR) and others using angiographic guidance. It could be that imaging modalities like IVUS, which can identify vulnerable plaques, might come into play, she said. “We have to really come up with trials that will help us pick which lesions to revascularize.”

Khaldoon Alaswad, MD, and Mohammad Alqarqaz, MD (both Henry Ford Hospital and Health System, Detroit, MI), pick up this thread in an accompanying editorial. “One wonders: what if plaque stabilization with stenting was more important than relieving the obstructive coronary lesion as determined by angiography or FFR? Assessment of plaque instability with intravascular imaging using markers like plaque burden, cap thickness, and lumen area could play a rule in future trials to determine the outcome of complete revascularization versus only infarct-related-artery PCI,” they write.

In an editorial responding to the registry study, Shamir Mehta, MD (Population Health Research Institute, Hamilton, Canada), and Matthias Bossard, MD (Luzerner Kantonsspital, Lucerne, Switzerland), say only well-designed randomized trials will be able to provide an answer to the question of how to best identify nonculprit lesions that require treatment. “Until these comparisons are available, clinicians should aim for complete revascularization in suitable patients utilizing either an angiography- or a physiology-guided strategy,” they advise.