Immediate vs Deferred PCI for Nonculprit Lesions in STEMI: Insights from the iMODERN Trial

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The iMODERN trial compared immediate iFR-guided PCI versus deferred cardiac stress MRI-guided PCI for nonculprit lesions in STEMI patients with multivessel disease after successful primary PCI. At three years, the risk of death, recurrent myocardial infarction, or heart failure hospitalization was similar between both strategies. This large randomized controlled trial suggests that immediate physiological assessment and treatment of nonculprit lesions does not confer superiority over a deferred imaging-guided approach.

Background

ST-segment elevation myocardial infarction (STEMI) is a life-threatening condition usually caused by an acute occlusion of a coronary artery. Primary percutaneous coronary intervention (PCI) targeting the culprit lesion is the established standard of care and dramatically improves survival and reduces morbidity. However, nearly half of STEMI patients have multivessel coronary artery disease, and the optimal management of nonculprit lesions remains controversial.

Previous studies have shown the benefit of complete revascularization but diverge on timing and assessment modalities. Immediate treatment of nonculprit lesions during primary PCI could potentially reduce future events but carries risks of prolonged procedures and contrast nephropathy. Deferred revascularization guided by functional or imaging-based ischemia assessment may avoid unnecessary intervention but delay treatment.

The instantaneous wave-free ratio (iFR) is a catheter-based physiological measurement conducted during cardiac catheterization to identify hemodynamically significant lesions without inducing hyperemia. Cardiac stress magnetic resonance imaging (MRI) offers a noninvasive method to detect ischemia and guide intervention decisions after stabilization.

Given these evolving techniques, the iMODERN trial set out to compare immediate iFR-guided PCI versus deferred cardiac stress MRI-guided PCI in STEMI patients with multivessel disease following successful primary PCI, addressing a key clinical question on timing and modality of nonculprit lesion treatment.

Study Design

The iMODERN study was an international, investigator-initiated, open-label, randomized controlled trial. Eligible patients were those with STEMI undergoing successful primary PCI who had at least one angiographically significant (>50%) nonculprit lesion.

Participants were randomized 1:1 to one of two groups:

• Immediate PCI group (iFR-guided): Nonculprit lesions were evaluated during the index procedure using instantaneous wave-free ratio (iFR). Lesions with iFR ≤0.89 underwent immediate PCI.
• Deferred PCI group (MRI-guided): Cardiac stress MRI was performed within 6 weeks post-randomization, and PCI was performed for lesions with ischemia on imaging.

The primary composite endpoint was death from any cause, recurrent myocardial infarction, or hospitalization for heart failure at 3 years. Safety endpoints including serious adverse events were also recorded.

Key Findings

The trial enrolled 1146 patients with a mean age of 63 years, predominantly male (78%). Among these, 558 were allocated to the immediate iFR-guided PCI group and 588 to the deferred MRI-guided PCI group.

In the iFR group, 42.6% (237/556) of patients underwent PCI of nonculprit lesions immediately, whereas in the MRI group only 18.7% (110/587) underwent PCI after the deferred imaging assessment.

At 3 years, the primary composite endpoint occurred in 9.3% of the immediate iFR group versus 9.8% of the deferred MRI group (hazard ratio 0.95, 95% confidence interval [CI] 0.65–1.40; P = 0.81), indicating no statistically significant difference between strategies.

Serious adverse events were numerically fewer in the immediate group (145 patients) compared to the deferred group (181 patients), though the clinical significance was not emphasized.

The results imply that immediate physiological assessment and intervention of nonculprit lesions in STEMI does not improve major clinical outcomes over a strategy of delayed ischemia assessment by cardiac MRI with subsequent selective PCI.

Expert Commentary

The iMODERN trial adds important evidence to the ongoing debate regarding complete revascularization timing in multivessel STEMI. Although prior trials have supported complete revascularization compared to culprit-only PCI, the present study contributes nuanced insight into how best to identify which lesions merit PCI and when.

The use of iFR as a hyperemia-independent physiological assessment during the immediate procedure contrasts with the deferred noninvasive approach of stress MRI. Both modalities have pros and cons: iFR allows instant decision-making but may lead to over-treatment of flow-limiting but clinically insignificant lesions; stress MRI offers exquisite ischemia detection but requires patient stability and resources for timely imaging.

Strengths include the large sample size, international multi-center design, and long-term follow-up. Limitations include the open-label design which can introduce bias, and the relatively low event rate, possibly limiting sensitivity to detect modest benefit differences.

Current guidelines acknowledge nonculprit lesion intervention after STEMI but differ on optimal timing and tools. This trial supports a flexible approach, allowing deferred assessment with functional imaging as a safe alternative to immediate invasive physiology-guided PCI.

Conclusion

For patients with STEMI and multivessel disease who have undergone successful primary PCI, immediate iFR-guided PCI of nonculprit lesions does not reduce death, recurrent myocardial infarction, or hospitalization for heart failure compared to deferred cardiac stress MRI-guided PCI at 3 years.

These findings endorse individualized treatment strategies incorporating functional assessment and patient factors, emphasizing that deferral of nonculprit PCI guided by cardiac MRI is a valid and safe clinical approach.

Future research may explore combining both modalities or integrating newer imaging techniques to optimize timing and selection for complete revascularization and ultimately improve patient outcomes.

Funding and Clinical Trials Registration

The iMODERN trial was funded by Philips Volcano and other supporters. The study is registered at ClinicalTrials.gov under number NCT03298659.

References

Nijveldt R, Maeng M, Beijnink CWH, Piek JJ, Al-Lamee RK, Raposo L, Baptista SB, Escaned J, Davies J, Klem I, et al. Immediate or Deferred Nonculprit-Lesion PCI in Myocardial Infarction. N Engl J Med. 2025 Oct 28. doi: 10.1056/NEJMoa2512918. Epub ahead of print. PMID: 41159879.