#stemi #multivessel-pci #complete-revascularization #coronary-artery-disease #pci-timing

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

Complete Revascularization in Patients Aged ≥75 — FIRE (NEJM 2023)

Design: 1,445 patients aged ≥75 with STEMI (35.2%) or NSTEMI and multivessel disease, randomized after culprit PCI to physiology-guided complete revascularization or culprit-only PCI; 34 sites in Italy, Spain and Poland; 1-year follow-up (sources/CompletePCI-Elderly-FIRE-NEJM-2023, rating: very high)
Primary composite (death/MI/stroke/ischaemia-driven revascularization): 15.7% vs 21.0%; HR 0.73 (95% CI 0.57–0.93); P=0.01; CV death/MI HR 0.64 (0.47–0.88); all-cause death HR 0.70 (0.51–0.96) (sources/CompletePCI-Elderly-FIRE-NEJM-2023, rating: very high)
Nonculprit lesions were assessed with FFR, non-hyperaemic pressure ratios or QFR; only 49.6% of patients had a significant nonculprit vessel, and 50.9% of assessed vessels were left untreated — this is a selective completion strategy, not "stent everything" (sources/CompletePCI-Elderly-FIRE-NEJM-2023, rating: very high)
Completion was performed during the index hospitalization; the trial was not designed to compare immediate versus staged timing (sources/CompletePCI-Elderly-FIRE-NEJM-2023, rating: very high)

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: the 2024–2025 inference that angiography should guide selection has been overturned for index-procedure physiology. That position rested on an indirect cross-trial comparison — angiography-guided COMPLETE reduced CV death/MI while wire-FFR-guided FULL REVASC was neutral. AIR-STEMI (2026) ran the direct head-to-head and physiology won: physiology- vs angiography-guided completion (n=1,823), primary composite of death/MI/stroke-TIA/ischaemia-driven revascularization 8.9% vs 13.7%, HR 0.62 (95% CI 0.47–0.83), P<0.001, plus a better safety composite (contrast-associated AKI or major bleeding 4.6% vs 7.1%, HR 0.63). Mortality did not differ — the gain is in MI and repeat revascularization (sources/AIR-STEMI-NEJM-2026, rating: very high)
What reconciles the trials is timing and implementation, not modality: physiology helped when applied at the index procedure and integrated into a treatment strategy (FRAME-AMI, AIR-STEMI) and did not when applied during staged procedures as a binary gate (FLOWER-MI, FULL REVASC). See contradictions
The AHA 2025 Class IIa "may be useful" position for FFR in intermediate stenoses predates AIR-STEMI
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

Physiology- vs angiography-guided completion — the indirect comparison is superseded by a direct trial, and the reconciling variable is implementation rather than modality. The old inference came from comparing angiography-guided COMPLETE (n=4,041; −26% CV death/MI vs culprit-only) with wire-FFR-guided FULL REVASC (n=1,542; neutral, HR 0.93; stent thrombosis HR 2.80), and it suggested FFR's deferral of high-grade lesions denies treatment to vulnerable plaques that flow measurement cannot detect. AIR-STEMI (2026) tested this directly and found the opposite — physiology-guided completion beat angiography-guided completion (HR 0.62 for death/MI/stroke/ischaemia-driven revascularization; HR 0.63 for the safety composite). The authors reconcile the divergence by when and how physiology was applied: FLOWER-MI used FFR predominantly in staged procedures (96%) as a binary lesion-selection tool and was neutral; FRAME-AMI integrated it into the index procedure (60%) and improved outcomes, driven by procedure-related MI; AIR-STEMI applied it during the index hospitalization for both lesion selection and PCI planning (pullback, stent length, landing zones). The trial series therefore suggests the benefit of physiological assessment lies in integration into a predefined strategy, not in using it as an isolated binary gate. Still unresolved: (1) whether the advantage belongs to angiography-derived physiology specifically or to index-procedure timing in general — AIR-STEMI cannot separate the two; (2) whether the benefit comes from lesion selection, PCI planning, or both, since the strategy bundled them; (3) whether the vulnerable-plaque argument that motivated the old inference survives — AIR-STEMI's benefit was in MI, which is consistent with either explanation (sources/AIR-STEMI-NEJM-2026, rating: very high; 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.
FIRE extends completion to patients ≥75 but does not resolve timing: FIRE found a large benefit from physiology-guided completion in older MI patients (HR 0.73 for the primary composite), but it randomized completeness (complete vs culprit-only), not immediate versus staged treatment, and completion occurred during the index hospitalization. Its result therefore supports offering completion to older patients without answering whether it should be done at the index procedure (sources/CompletePCI-Elderly-FIRE-NEJM-2023, rating: very high)

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
Related to concepts/Complete-Revascularization — completeness, lesion selection and older patients