Multivessel PCI Timing in STEMI

Definition

In patients with STEMI and multivessel coronary artery disease (CAD), complete revascularization refers to treating both the culprit lesion (infarct-related artery) and all angiographically significant nonculprit lesions. The question of timing — whether nonculprit lesions should be treated during the index procedure (immediate) or in a separate procedure after initial stabilization (staged) — has been the subject of several major RCTs. Current evidence, including the MULTISTARS AMI trial, supports that immediate complete revascularization during the index STEMI procedure is at minimum noninferior and potentially superior to a staged approach in hemodynamically stable patients.

Key Concepts

Background: Culprit-Only vs Complete Revascularization (resolved)

• Multivessel CAD is present in approximately 40–50% of STEMI patients and independently increases mortality risk
• Multiple RCTs (PRAMI, CvLPRIT, DANAMI-3-PRIMULTI, COMPLETE) established that complete revascularization is superior to culprit-lesion-only PCI in reducing recurrent MI and ischemia-driven revascularization; the COMPLETE trial additionally showed reduction in cardiovascular death or MI (HR ~0.74) (sources/complete-pci-multistars-ami-nejm-2023, rating: high)
• This question is now considered settled; current ACS guidelines recommend complete revascularization as Class I/A

Immediate vs Staged: MULTISTARS AMI (NEJM 2023) — Primary Evidence

• Design: 840 hemodynamically stable STEMI patients with multivessel CAD; randomized after successful culprit PCI to: (a) immediate multivessel PCI or (b) staged PCI of nonculprit lesions within 19–45 days (sources/complete-pci-multistars-ami-nejm-2023, rating: high)
• Primary outcome: Composite of all-cause death, nonfatal MI, stroke, unplanned ischemia-driven revascularization, or HF hospitalization at 1 year
• Result: Immediate 8.5% vs staged 16.3%; RR 0.52 (95% CI 0.38–0.72); P<0.001 for noninferiority AND superiority (sources/complete-pci-multistars-ami-nejm-2023, rating: high)
• Driver of benefit: Primarily lower nonfatal MI (2.0% vs 5.3%; HR 0.36) and unplanned revascularization (4.1% vs 9.3%; HR 0.42) in the first 45 days; no significant difference in death, stroke, or HF hospitalization
• Landmark analysis: Entire between-group difference occurred in the 0–45-day window (HR 0.33); after day 45, groups converged (HR 0.86, NS)
• Safety: Major bleeding similar (3.1% vs 4.8%; NS); fewer serious adverse events (104 vs 145)

Immediate vs Staged: BIOVASC Trial (Lancet 2023) — ACS Spectrum

• Enrolled patients across the full ACS spectrum (UA, NSTEMI, STEMI) — first RCT to do so
• Showed immediate complete revascularization noninferior to staged strategy across all ACS presentations
• Consistent with MULTISTARS AMI findings, supporting extension of immediate strategy to non-STEMI ACS (sources/complete-pci-multistars-ami-nejm-2023, rating: high)

Mechanistic Rationale for Immediate Strategy

• Nonculprit lesions in STEMI patients frequently exhibit unstable plaque features (thin fibrous cap, large lipid core) on OCT, predisposing to plaque rupture before a staged procedure is performed (COMPLETE OCT substudy data)
• Systemic inflammatory milieu of acute STEMI may destabilize nonculprit plaques
• Achieving complete revascularization immediately reduces the ischemic burden in the vulnerable early post-STEMI period
• Practical advantages: single arterial puncture, reduced contrast volume, reduced radiation, avoidance of a second hospitalization

Key Exclusions (Where Immediate Strategy Has NOT Been Tested)

• Cardiogenic shock: Culprit-only PCI is recommended (CULPRIT-SHOCK trial: multivessel PCI increased 30-day death/renal failure); immediate complete PCI is Class III: Harm
• Left main CAD: Excluded from MULTISTARS AMI — insufficient evidence for immediate complete PCI
• Chronic total occlusion: Excluded — CTO PCI is technically complex; timing in STEMI not established
• Prior CABG: Excluded from MULTISTARS AMI

Immediate vs Staged: iMODERN (NEJM 2026) — iFR-Guided vs MRI-Guided

• Design: 1,146 STEMI patients with multivessel CAD post-successful primary PCI, 41 sites; randomized to (a) immediate iFR-guided nonculprit PCI (iFR ≤0.89) or (b) deferred cardiac stress MRI-guided PCI within 6 weeks (sources/iFR-PPCI-iMODERN-NEJM-2026, rating: very high)
• Primary outcome: Composite of death from any cause, recurrent MI, or HF hospitalization at 3 years
• Result: 9.3% (iFR) vs 9.8% (MRI); HR 0.95 (95% CI 0.65–1.40); P=0.81 — NOT SUPERIOR (sources/iFR-PPCI-iMODERN-NEJM-2026, rating: very high)
• Revascularization rates: iFR arm treated 42.6% of patients; MRI arm treated only 18.7% — 2× difference driven by inherent modality sensitivity differences
• Notable secondary findings: HF hospitalization HR 0.24 (0.07–0.84) and stroke/TIA HR 0.36 (0.15–0.86) favoured iFR; stent thrombosis higher in iFR (1.7% vs 0.6%)
• Key distinction from MULTISTARS AMI: iMODERN excluded unplanned revascularization from the primary composite (which was the main driver of benefit in MULTISTARS AMI); comparator was physiologically-guided deferred PCI (MRI), not an untreated waiting period

FFR-Guided Complete Revascularization — FULL REVASC (NEJM 2024)

• Design: 1,542 patients with STEMI or very-high-risk NSTEMI and multivessel CAD; 1:1 FFR-guided complete revascularization (FFR ≤0.80 = significant) vs culprit-lesion-only PCI; 32 centres, 7 countries; median 4.8-year follow-up (sources/ffrpci-mi-fullrevasc-nejm-2024, rating: very high)
• Primary outcome (death/MI/unplanned revascularization): 19.0% vs 20.4%; HR 0.93 (95% CI 0.74–1.17); P=0.53 — not superior
• Death or MI: HR 1.12 (NS); Unplanned revascularization: HR 0.76 (NS)
• Any revascularization: 10.2% vs 16.5% (HR 0.59) — fewer total procedures with FFR strategy
• Stent thrombosis: 2.5% vs 0.9% (HR 2.80) — significantly higher with FFR-guided complete revascularization
• Key FFR finding: 40% of patients in the complete-revascularization arm had ALL nonculprit lesions deferred (FFR >0.80); only 47% of tested vessels had FFR ≤0.80
• Trial terminated early (1,542 vs planned 4,052) after COMPLETE trial publication — approximately 74% power
• Critical contrast with COMPLETE: COMPLETE (angiography-guided, n=4,041) showed 26% lower CV death/MI; FFR was used in <1% of COMPLETE patients; the divergence is attributed to FFR's inability to detect plaque vulnerability — it defers high-grade lesions (FFR >0.80) that may harbor rupture-prone plaques

Guideline Positioning (ACS AHA 2025)

• Complete revascularization in STEMI: Class I/A
• Single-procedure (immediate) multivessel PCI may be preferred over staged: Class IIb/B-R (based on BIOVASC and MULTISTARS AMI) (sources/ACS-AHA-2025 and sources/complete-pci-multistars-ami-nejm-2023, rating: high)
• iMODERN (2026) adds: Even with physiologic guidance, immediate strategy shows no superiority over a deferred, imaging-selected approach — the Class IIb designation appears well-calibrated (sources/iFR-PPCI-iMODERN-NEJM-2026, rating: very high)

Practical Considerations

• Nonculprit lesion selection should be based on angiographic severity; FFR guidance for intermediate lesions is now questioned in the ACS setting — FULL REVASC showed FFR-guided strategy is neutral while angiography-guided COMPLETE showed benefit; current AHA guideline positions FFR as "may be useful" (Class IIa) for intermediate stenoses only
• Intravascular imaging guidance (IVUS/OCT) was low in MULTISTARS AMI but is increasingly recommended in contemporary practice to optimize stent implantation
• DAPT, statin, and secondary prevention should follow standard post-ACS protocols regardless of revascularization strategy

Contradictions / Open Questions

• FFR-guided vs angiography-guided complete revascularization — fundamentally different outcomes: COMPLETE (angiography-guided; n=4,041) reduced CV death/MI by 26%; FULL REVASC (FFR-guided; n=1,542) was neutral (HR 0.93, P=0.53) with higher stent thrombosis (HR 2.80). The divergence suggests that FFR's deferral of high-grade lesions (FFR >0.80) may deny treatment to vulnerable plaques that drive future MI — plaques that FFR cannot detect by measuring flow alone. 40% of FULL REVASC patients had all nonculprit lesions deferred yet outcomes were no better. The ongoing COMPLETE-2 trial will directly compare physiology-guided vs angiography-guided strategies (sources/ffrpci-mi-fullrevasc-nejm-2024, rating: very high)
• iMODERN vs MULTISTARS AMI — conflicting signals: MULTISTARS AMI showed superiority of immediate strategy (RR 0.52, P<0.001), whereas iMODERN shows no superiority (HR 0.95, P=0.81). Key methodological differences explain much of this: (1) MULTISTARS AMI included unplanned revascularization in the primary endpoint (which drove most of the 45-day benefit and is a partly subjective/ascertainment-prone outcome); (2) iMODERN's deferred arm used MRI-guided selective PCI — a more active comparator than simple waiting; (3) different physiologic guidance tools (iFR vs visual assessment); (4) different staging windows. Neither trial directly answers whether immediate angiography-guided PCI is better than staged angiography-guided PCI using only hard outcomes. (sources/complete-pci-multistars-ami-nejm-2023, sources/iFR-PPCI-iMODERN-NEJM-2026, both rating: high/very high)
• iFR overdetection problem: iFR guided PCI of 42.6% of patients vs MRI-guided PCI of only 18.7% — yet no superiority in hard outcomes. This raises the possibility that iFR systematically over-identifies hemodynamically significant nonculprit lesions in the STEMI context (elevated resting flow → false-positive iFR in ~11% of lesions). Over-stenting exposes patients to procedure risk (higher stent thrombosis 1.7% vs 0.6%) without commensurate benefit. (sources/iFR-PPCI-iMODERN-NEJM-2026, rating: very high)
• Immediate superiority vs guidelines class IIb discordance: MULTISTARS AMI demonstrated p<0.001 superiority for immediate strategy, yet the ACS AHA 2025 guideline only elevated immediate PCI to Class IIb/B-R. iMODERN now reinforces this caution — even a physiologically-guided immediate strategy with higher revascularization rates does not outperform a deferred imaging-guided approach. (sources/complete-pci-multistars-ami-nejm-2023, sources/iFR-PPCI-iMODERN-NEJM-2026)
• Optimal staging window: MULTISTARS AMI used a 19–45-day window; iMODERN deferred within 6 weeks (median 40 days). Whether very early staged PCI (days 3–7, same admission) achieves similar results is tested by OPTION-STEMI (which showed non-inferiority NOT demonstrated for immediate vs in-hospital staged), suggesting same-admission staging may not be clearly better either.
• Long-term equivalence after crossover: In MULTISTARS AMI, after day 45, outcomes were identical — the immediate benefit was entirely from the waiting period, not a true biological advantage. iMODERN's 3-year follow-up with no significant difference supports this: physiologically-guided complete revascularization at either timing achieves similar long-term outcomes.

Connections

• Related to entities/Acute-Coronary-Syndrome — complete revascularization is integral to STEMI management
• Related to concepts/Intracoronary-Imaging-Guided-PCI — imaging guidance during PCI of nonculprit lesions
• Related to concepts/DAPT-Strategies — antithrombotic therapy post-complete revascularization

Sources

• sources/complete-pci-multistars-ami-nejm-2023
• sources/iFR-PPCI-iMODERN-NEJM-2026
• sources/ffrpci-mi-fullrevasc-nejm-2024