FFR-Guided Complete or Culprit-Only PCI in Patients with Myocardial Infarction

Authors, Journal, Affiliations, Type, DOI

• Felix Böhm, Brynjölfur Mogensen, Thomas Engstrøm, Goran Stankovic, et al. for the FULL REVASC Trial Investigators
• New England Journal of Medicine, 2024;390:1481–92
• Lead centre: Karolinska Institute and Danderyd Hospital, Sweden; 32 centres across Sweden, Denmark, Serbia, Finland, Latvia, Australia, New Zealand
• Type: Multinational registry-based randomized clinical trial (open-label; integrated with SWEDEHEART registry)
• DOI: https://doi.org/10.1056/NEJMoa2314149

Overview

The FULL REVASC trial randomized 1,542 patients with STEMI or very-high-risk NSTEMI and multivessel CAD — following successful culprit-lesion PCI — to FFR-guided complete revascularization of nonculprit lesions or no further revascularization. At a median follow-up of 4.8 years, the primary composite of death from any cause, MI, or unplanned revascularization did not differ between groups (19.0% vs 20.4%; HR 0.93; P=0.53). FFR-guided revascularization reduced total revascularization burden (10.2% vs 16.5%) but was associated with higher rates of stent thrombosis (2.5% vs 0.9%; HR 2.80) and restenosis (4.2% vs 2.3%), without improvement in hard clinical outcomes. This diverges from the angiography-guided COMPLETE trial (which showed benefit) and establishes that FFR-guided and angiography-guided complete revascularization strategies may have meaningfully different outcomes in ACS.

Keywords

Fractional flow reserve; FFR; complete revascularization; multivessel coronary artery disease; STEMI; NSTEMI; nonculprit lesion; percutaneous coronary intervention; culprit-lesion-only PCI; physiology-guided PCI; stent thrombosis; FULL REVASC

Key Takeaways

Background and Rationale

• Approximately 50% of STEMI patients have multivessel CAD; prior angiography-guided trials (PRAMI, CvLPRIT, COMPLETE) showed complete revascularization reduces recurrent MI and ischemia-driven events
• Visual stenosis estimation may lead to overtreatment of hemodynamically insignificant lesions; FFR identifies truly flow-limiting nonculprit lesions
• Two prior FFR-guided STEMI trials (DANAMI-3-PRIMULTI 2015; Compare-Acute 2017) showed FFR-guided complete revascularization reduced repeat revascularization but were not powered for death or MI
• FULL REVASC was designed to test whether FFR-guided complete revascularization — with fewer stents placed than an angiography-guided approach — achieves better long-term outcomes

Trial Design

• Registry-based RCT integrated into the SWEDEHEART registry (Sweden) and separate web platforms in 6 other countries; 1:1 randomization within 6 hours of successful culprit PCI
• Complete revascularization group: FFR-guided nonculprit PCI (FFR ≤0.80 = significant; PCI recommended); could be performed during the index procedure or separately during index hospitalization
• Culprit-only group: No further revascularization during index hospitalization; subsequent elective revascularization for symptoms allowed
• For 90–99% visual stenoses: FFR recommended but not mandated
• Exclusions: prior CABG, left main CAD, cardiogenic shock; CTO allowed only if ≥1 other nonculprit vessel with 50–99% stenosis

Results — Primary and Key Secondary Outcomes (median 4.8 years)

• Primary composite (death/MI/unplanned revascularization): 19.0% vs 20.4%; HR 0.93 (95% CI 0.74–1.17); P=0.53 — not significant
• Death from any cause or MI: HR 1.12 (95% CI 0.87–1.44) — not significant
• Unplanned revascularization: HR 0.76 (95% CI 0.56–1.04) — not significant
• All-cause death: HR 1.15 (95% CI 0.83–1.58); CV death: HR 0.87 (NS); MI alone: HR 1.09 (NS)
• Any revascularization (planned + unplanned): 10.2% vs 16.5%; HR 0.59 (95% CI 0.45–0.78) — significantly lower with complete revascularization strategy
• No significant differences in stroke, major bleeding, or HF rehospitalization

Results — Safety Outcomes

• Stent thrombosis: 2.5% vs 0.9% (HR 2.80; 95% CI 1.18–6.67) — significantly higher with FFR-guided complete revascularization
• Restenosis: 4.2% vs 2.3% — higher with complete revascularization
• Target-vessel revascularization: 8.6% vs 5.5% — higher with complete revascularization
• Contrast-associated AKI, neurologic complications: no significant difference
• Contrast volume, radiation exposure, and in-hospital stay: all significantly higher in complete-revascularization group

FFR-Specific Findings

• Mean FFR value for most severe nonculprit lesion per patient: 0.76 ± 0.14
• 40% of patients assigned to complete revascularization had ALL nonculprit lesions deferred (FFR >0.80) — FFR prevented nonculprit stenting in a large proportion of patients
• Only 47% of FFR-tested nonculprit coronary arteries had FFR ≤0.80
• 17.1% received FFR-guided PCI during the primary PCI procedure; 78.8% underwent a separate staged procedure (median 2 days after index PCI)
• Protocol adherence: 95.9% in complete-revascularization arm; 99.6% in culprit-only arm

Comparison with Other Trials

• COMPLETE trial (NEJM 2019; n=4,041): Angiography-guided complete revascularization → 26% lower risk of CV death or MI vs culprit-only; FFR used in <1% of patients; benefit driven by stenoses ≥80% (visual) or ≥60% (QCA); longer follow-up (3 years)
• FIRE trial (NEJM 2023; n=1,445; age ≥75): Physiology-guided (multiple tools) complete revascularization → 36% lower risk of composite death/CV death/MI/revascularization at 1 year vs culprit-only
• DANAMI-3-PRIMULTI (Lancet 2015); Compare-Acute (NEJM 2017): FFR-guided complete revascularization → fewer repeat revascularizations; not powered for death/MI; consistent with FULL REVASC
• Key mechanistic hypothesis for divergence from COMPLETE: Angiography-guided approach treats high-grade stenoses (≥60–80%) that likely include vulnerable plaques; FFR defers some of these lesions (FFR >0.80 despite high angiographic grade) — FFR cannot detect plaque vulnerability, only flow limitation

Interpretation

• In the absence of reduction in irreversible outcomes (death or MI), performing routine FFR-guided nonculprit PCI to prevent later revascularization in a minority of patients is clinically debatable
• FFR's limitation: cannot identify vulnerable nonculprit plaques that may cause future spontaneous MI — a critical gap in the ACS context where plaque instability is ubiquitous
• Higher stent thrombosis (HR 2.80) suggests significant harm potential from additional stents placed in ACS patients, even when guided by FFR
• Premature termination (74% power) cannot exclude a moderate benefit — but the signal is clearly null and the safety signal is adverse

Limitations of the Document

• Trial terminated prematurely (1,542 of planned 4,052 patients) after COMPLETE publication for feasibility and ethical reasons — underpowered (~74% power for primary endpoint)
• Selection bias: insufficient enrollment of patients with high-grade nonculprit lesions and three-vessel disease who may derive the greatest benefit from complete revascularization
• No race or ethnicity data collected; generalizability limited to participating countries (Scandinavia, Serbia, Australia, New Zealand, Latvia)
• Strict definition of "unplanned revascularization" (requires hospital admission) more stringent than COMPLETE/FIRE (ischemia-driven), creating cross-trial comparison difficulties
• Open-label design — operators and patients aware of treatment assignment
• FFR not mandated for 90–99% stenoses; 3 culprit-only patients underwent FFR (protocol deviations)
• 40% of complete-revascularization patients had no nonculprit intervention — dilutes ITT treatment effect toward null

Key Concepts Mentioned

• concepts/Fractional-Flow-Reserve — primary physiologic guidance strategy evaluated
• concepts/Multivessel-PCI-STEMI-Timing — FFR vs angiography guidance for nonculprit revascularization in STEMI; timing context
• concepts/Instantaneous-Wave-Free-Ratio — related physiologic index validated equivalent to FFR in stable CAD

Key Entities Mentioned

• entities/Acute-Coronary-Syndrome — patient population (STEMI and very-high-risk NSTEMI)

Wiki Pages Updated

• Created wiki/sources/ffrpci-mi-fullrevasc-nejm-2024.md
• Created wiki/concepts/Fractional-Flow-Reserve.md
• Updated wiki/concepts/Multivessel-PCI-STEMI-Timing.md
• Updated wiki/concepts/Instantaneous-Wave-Free-Ratio.md
• Updated wiki/sourceindex.md
• Updated wiki/wikiindex.md
• Appended log.md