Immediate or Deferred Nonculprit-Lesion PCI in Myocardial Infarction (iMODERN)

Authors, Journal, Affiliations, Type, DOI

• Lead authors: Robin Nijveldt (Radboud UMC, Nijmegen), Michael Maeng (Aarhus University Hospital), Niels van Royen (Radboud UMC)
• Journal: New England Journal of Medicine, 2026;394:958–68. Published online October 28, 2025.
• Affiliations: 41 sites worldwide (Netherlands, Denmark, UK, Portugal, Spain, Belgium, Slovenia, Switzerland, Thailand, Italy, Luxembourg, France, US)
• Type: International, investigator-initiated, prospective, open-label, superiority, randomized controlled trial (iMODERN trial; NCT03298659)
• DOI: 10.1056/NEJMoa2512918
• Funding: Philips Volcano (iFR pressure wire) and Biotronik Scientific (unrestricted grants); Dutch Ministry of Economic Affairs (public–private partnership). Funders had no role in design, conduct, or reporting.

Overview

The iMODERN trial enrolled 1,146 STEMI patients with multivessel CAD who had undergone successful primary PCI, randomizing them to immediate iFR-guided PCI of nonculprit lesions (iFR ≤0.89) versus deferred cardiac stress MRI-guided PCI within 6 weeks. At 3-year follow-up, the primary composite of death, recurrent MI, or HF hospitalization occurred in 9.3% versus 9.8% of patients (HR 0.95; P=0.81), failing to demonstrate superiority of the immediate strategy. The iFR strategy treated far more lesions (42.6% vs 18.7% of patients), reflecting the inherent differences between iFR (epicardial pressure-drop surrogate) and MRI (myocardial perfusion). HF hospitalization and stroke/TIA were lower in the iFR group, while stent thrombosis was higher; the primary composite was not significantly different.

Keywords

STEMI, multivessel coronary artery disease, nonculprit lesion PCI, instantaneous wave-free ratio (iFR), cardiac stress MRI, complete revascularization, primary PCI, iFR-guided revascularization, physiologic guidance

Key Takeaways

Background and Rationale

• Current guidelines recommend complete revascularization (culprit + nonculprit lesions) in STEMI with multivessel CAD — Class I/A per 2025 ACC/AHA/SCAI guidelines
• The timing of nonculprit-lesion PCI remains debated: immediate (index procedure) vs staged (separate admission)
• Previous trials (MULTISTARS AMI, BIOVASC) used angiographic guidance and included unplanned revascularization as a primary endpoint — potentially a subjective endpoint
• iMODERN is the first trial to use physiologic guidance (iFR) for immediate nonculprit PCI versus noninvasive imaging (cardiac stress MRI) for deferred selective PCI

Trial Design

• Population: STEMI patients ≥18 years, successful primary PCI (TIMI 3 flow, minimal residual stenosis) within 12 hours of symptom onset, ≥1 nonculprit lesion with >50% stenosis amenable to PCI
• Exclusions: Prior STEMI, chronic total occlusion, complex nonculprit lesions, >50% left main stem stenosis, hemodynamically unstable (Killip III/IV/cardiogenic shock)
• Randomization 1:1: Immediate iFR-guided PCI vs deferred cardiac stress MRI-guided PCI
• Stratification: Nonculprit lesion in LAD segment 6 or 7
• Sites: 41 worldwide; 1,146 patients enrolled December 2017–February 2022; final follow-up May 2025
• Mean age: 63±11 years; 78% men

iFR Arm (n=558)

• iFR measured at time of primary PCI using Philips Volcano pressure wire
• PCI performed if iFR ≤0.89 (cutoff for hemodynamically significant stenosis)
• For stenosis >90%, PCI without iFR was permitted per protocol
• 42.6% (237/556) of patients underwent nonculprit PCI; iFR positive in 44.9% of assessed lesions
• Mean procedure duration: 75.4±33.3 min; mean stents/patient: 2.1±1.4

MRI Arm (n=588)

• Cardiac stress MRI within 6 weeks of index PCI (median 27 days; IQR 15–37)
• Vasodilator stress (adenosine or regadenoson) + gadolinium contrast; late gadolinium enhancement for infarct size
• MRI performed in 81.1% (476/587); 11.1% (65 patients) had bailout iFR-guided PCI instead (median 34 days)
• MRI positive for ischemia: 20.2% (96/476 who had MRI); overall 21.8% (128 patients) had ischemia detected
• 18.7% (110/587) underwent nonculprit PCI at median 40 days; mean stents/patient: 1.8±1.1

Primary Endpoint

• Composite: death from any cause + recurrent myocardial infarction + hospitalization for heart failure at 3 years
• iFR group: 50/536 (9.3%) | MRI group: 55/562 (9.8%)
• HR 0.95 (95% CI 0.65–1.40); P=0.81 — NOT SUPERIOR

Secondary Endpoints at 3 Years

• Serious adverse events: 145 patients (iFR) vs 181 patients (MRI)

Why Did iFR and MRI Detect Different Rates of Ischemia?

• iFR flagged 44.9% of lesions as ischemic; MRI flagged 20.2% — a 2× difference
• Not attributable to timing (deferred iFR in bailout group showed similar positive rates to immediate iFR group)
• Reflects fundamental technical differences:
  • iFR: pressure difference across epicardial stenosis (surrogate of flow reserve); may detect smaller ischemic territories
  • MRI: myocardial perfusion; lower sensitivity for small perfusion defects
  • STEMI physiology: elevated baseline flow may create false-positive iFR (mean ΔiFR 0.01; false positive rate ~11%)
• This overtreatment by iFR did not translate to superior outcomes at 3 years

Contextual Comparison with Other Trials

• COMPLETE (2019): Complete vs culprit-only angiography-guided revascularization — 10.5% vs 7.8% CV death/MI at 3yr (multivessel superior)
• MULTISTARS AMI (NEJM 2023): Immediate vs staged 19–45 days — 8.5% vs 16.3%; RR 0.52 (P<0.001 superiority); benefit driven by unplanned revascularization in first 45 days
• BIOVASC (Lancet 2023): Immediate noninferior to staged across ACS spectrum; benefit attenuated at 24 months
• OPTION-STEMI (Lancet 2025): Immediate did NOT show noninferiority vs in-hospital staged PCI
• iMODERN (NEJM 2026): Immediate iFR-guided NOT superior to deferred MRI-guided at 3 years — aligns with OPTION-STEMI, challenges upgrade of immediate strategy to Class I

Limitations of the Document

• Underpowered: Event rate lower than expected; follow-up extended from 1 to 3 years; wide confidence intervals (HR 0.65–1.40) — cannot exclude meaningful benefit or harm
• Open-label design: Potential for ascertainment bias in subjective endpoints
• 11.1% of MRI group did not receive MRI — instead underwent iFR bailout, contaminating the deferred-imaging strategy
• Ischemia-driven (not angiography-guided) PCI in both arms — may undertreat angiographically significant but physiologically "non-ischemic" lesions; authors argue low event rates refute undertreatment
• STEMI physiology biases iFR upward (elevated resting flow → lower, potentially false-positive iFR values in 11% of lesions)
• Industry funding: Philips Volcano manufactures the iFR pressure wire — potential conflict despite stated non-involvement
• Subgroup analyses inconclusive due to wide CIs
• Race/ethnicity not documented (Dutch law restriction)

Key Concepts Mentioned

• concepts/Multivessel-PCI-STEMI-Timing — primary topic; iMODERN challenges immediate strategy superiority
• concepts/Instantaneous-Wave-Free-Ratio — iFR defined and applied as the physiologic guide in the intervention arm
• concepts/Intracoronary-Imaging-Guided-PCI — nonculprit lesion selection and PCI guidance methods
• concepts/MINOCA — stress MRI used to distinguish ischemic perfusion defects from infarction

Key Entities Mentioned

• entities/Acute-Coronary-Syndrome — STEMI management and revascularization strategy
• entities/Chronic-Coronary-Disease — nonculprit lesions represent chronic CAD in the context of acute STEMI

Wiki Pages Updated

• wiki/sources/iFR-PPCI-iMODERN-NEJM-2026.md — created (this file)
• wiki/sourceindex.md — new entry added
• wiki/wikiindex.md — new concept entry added
• wiki/concepts/Multivessel-PCI-STEMI-Timing.md — iMODERN data added; contradictions updated; source_count updated to 2
• wiki/concepts/Instantaneous-Wave-Free-Ratio.md — new concept page created