Complete or Culprit-Only PCI in Older Patients with Myocardial Infarction (FIRE)

Authors, Journal, Affiliations, Type, DOI

• Authors: Simone Biscaglia, Vincenzo Guiducci, Javier Escaned, Raul Moreno, Valerio Lanzilotti, Andrea Santarelli, Enrico Cerrato, Giorgio Sacchetta, Alfonso Jurado-Roman, Alberto Menozzi, Ignacio Amat Santos, José Luis Díez Gil, Marco Ruozzi, Marco Barbierato, Luca Fileti, Andrea Picchi, Veronica Lodolini, Giuseppe Biondi-Zoccai, Elisa Maietti (deceased), Rita Pavasini, Paolo Cimaglia, Carlo Tumscitz, Andrea Erriquez, Carlo Penzo, Iginio Colaiori, Gianluca Pignatelli, Gianni Casella, Gianmarco Iannopollo, Mila Menozzi, Ferdinando Varbella, Giorgio Caretta, Dariusz Dudek, Emanuele Barbato, Matteo Tebaldi, Gianluca Campo; for the FIRE Trial Investigators
• Journal: New England Journal of Medicine 2023;389(10):889–898 (published online August 26, 2023)
• Affiliations: Multicentre — Cardiology Unit, Azienda Ospedaliero Universitaria di Ferrara, and 33 other sites in Italy, Spain and Poland
• Type: Investigator-initiated, multicentre, prospective, open-label, superiority randomised controlled trial
• DOI: 10.1056/NEJMoa2300468

Overview

FIRE asked whether physiology-guided complete revascularization beats culprit-only PCI in patients aged ≥75 years with myocardial infarction and multivessel disease — a group largely excluded from the trials that established complete revascularization. In 1,445 randomized patients (median age 80), complete revascularization reduced the 1-year composite of death, myocardial infarction, stroke or ischaemia-driven revascularization from 21.0% to 15.7% (HR 0.73; 95% CI 0.57–0.93; P=0.01), with consistent benefit across STEMI and NSTEMI. Nonculprit lesions were treated only when physiologically significant, so roughly half of assessed nonculprit vessels were left alone. The safety composite did not differ, and the result was driven by hard outcomes (death and MI), not only repeat revascularization.

Keywords

Myocardial infarction; Complete revascularization; Culprit-only PCI; Older patients; Fractional flow reserve; Quantitative flow ratio; Multivessel coronary artery disease

Key Takeaways

Background

• The proportion of patients aged ≥75 years admitted with myocardial infarction is increasing, but this group is excluded from or under-represented in trials and is often treated conservatively or suboptimally.
• Complete revascularization is established in younger patients with MI and multivessel disease, but its benefit in older patients — who have more comorbidity, frailty, complex anatomy and higher procedural risk — was uncertain.
• Physiology-guided revascularization was hypothesized to reduce the number of treated vessels and stents, limiting periprocedural complications and the duration of dual antiplatelet therapy in a population at high bleeding risk.

Methods

Design and population

• Investigator-initiated, multicentre, prospective, superiority RCT across 34 sites in Italy, Spain and Poland; 1,898 patients screened between July 2019 and October 2021; 1,445 randomized (720 complete revascularization, 725 culprit-only).
• Inclusion: age ≥75 years; STEMI or NSTEMI; successful culprit PCI; multivessel disease with ≥1 nonculprit lesion in a vessel ≥2.5 mm with 50–99% visual diameter stenosis.
• Exclusions: unclear culprit lesion; nonculprit lesion in the left main; planned or previous surgical revascularization; life expectancy <1 year.
• Randomization was 1:1, web-based and concealed, stratified by centre, sex and presentation (STEMI vs NSTEMI), performed immediately after culprit PCI or within 48 hours.

Physiology-guided strategy

• Nonculprit lesions were assessed with wire-based hyperaemic or non-hyperaemic methods and angiography-based quantitative flow ratio (QFR); a lesion was significant at a ratio ≤0.80 (hyperaemic or QFR) or ≤0.89 (non-hyperaemic).
• PCI of significant nonculprit lesions could be performed during the index procedure or as a staged procedure within the index hospitalization.
• The culprit-only arm received no physiological assessment of nonculprit lesions.
• Sirolimus-eluting, biodegradable-polymer, ultrathin stents (Supraflex Cruz) were strongly suggested; guideline-directed medical therapy and ≥1 year of DAPT were recommended.

Outcomes

• Primary: composite of death, myocardial infarction, stroke or ischaemia-driven coronary revascularization at 1 year.
• Key secondary: cardiovascular death or myocardial infarction at 1 year.
• Safety: composite of contrast-associated acute kidney injury, stroke, or BARC type 3/4/5 bleeding at 1 year.
• Events were adjudicated by an independent committee blinded to assignment; analysis was intention-to-treat; competing risk of non-cardiovascular death was handled with Fine–Gray models.

Results

Population

• Median age 80 years (IQR 77–84), 36.5% women, 35.2% STEMI, 60.7% randomized at the index procedure and 39.3% within 48 hours.
• Assigned treatment was performed in 96.2% (complete) and 97.4% (culprit-only).
• In the complete arm, physiological assessment was performed in 97.2%; 49.6% had ≥1 functionally significant nonculprit vessel; 50.1% underwent nonculprit PCI (346 of these had a positive physiological assessment, 4 were negative and 11 were not assessed before PCI).
• 483 nonculprit vessels (50.9%) were not treated because physiology did not indicate revascularization.
• Median hospital stay was longer with complete revascularization (6 vs 5 days).

Primary and secondary outcomes

• Primary composite: 15.7% vs 21.0%; HR 0.73 (95% CI 0.57–0.93); P=0.01; number needed to treat 19.
• CV death or MI: 8.9% vs 13.5%; HR 0.64 (95% CI 0.47–0.88); NNT 22.
• All-cause death: HR 0.70 (95% CI 0.51–0.96); NNT to prevent one death 27.
• Individual components other than stroke were lower with complete revascularization; the benefit appeared consistent across prespecified subgroups (including STEMI vs NSTEMI, sex, age, diabetes and renal function).
• Safety composite: 22.5% vs 20.4%; HR 1.11 (95% CI 0.89–1.37); P=0.37 — no significant difference, though the individual components were numerically higher with complete revascularization.

Discussion

• The authors interpret the result as showing that older patients derive the same relative benefit from physiology-guided complete revascularization as younger patients, with an absolute benefit that is larger because baseline risk is higher.
• The rationale for physiology in this population is selectivity: treating only prognostically relevant nonculprit vessels limits stent number, DAPT duration and bleeding risk — age ≥75 is itself a minor ARC-HBR criterion.
• The benefit accrued over the first year with continued separation of the Kaplan–Meier curves, rather than being confined to the periprocedural period.
• Enrolling both STEMI and NSTEMI was a deliberate contrast with prior complete-revascularization trials; the authors argue physiology-guided completion is safe in either presentation provided the culprit lesion is clearly identifiable.
• The authors note that half of nonculprit vessels were left untreated on physiological grounds, so the trial tests a selective complete strategy, not "stent everything".

Limitations (as stated)

• Open-label design: knowledge of the angiographic findings could bias patients and physicians toward subsequent revascularization in the culprit-only arm. The authors counter that ischaemia-driven revascularization was a small part of the primary outcome, while death and MI dominated.
• Results apply to physiology-guided completion and should be transferred cautiously to angiography-guided completion.
• Completion was performed during the index hospitalization with a specific ultrathin biodegradable-polymer stent platform, so applicability to other strategies and stents is unknown.

Limitations of the document

• Open-label, superiority trial with a composite primary endpoint that includes ischaemia-driven revascularization — an outcome susceptible to ascertainment bias, although the key secondary (CV death/MI) and all-cause death also favoured complete revascularization.
• The comparator is not "no further revascularization ever" — 24.2% of the culprit-only arm in SENIOR-RITA-like populations undergo later angiography, and crossover/dropout is not fully reported here; the trial also excluded patients with unclear culprits, left main disease and prior CABG, limiting generalizability.
• Physiology was a mixture of FFR, non-hyperaemic pressure ratios and QFR, so the trial cannot attribute the result to a single index or threshold.
• The 1-year horizon is short for a population with limited life expectancy; whether the benefit persists, attenuates or reverses beyond 1 year is unknown (follow-up is planned to 5 years).
• No sham or blinded adjudication of revascularization; event adjudication was blinded, but the decision to revascularize was not.
• The trial was conducted in high-volume European centres with physiology expertise; the 97.2% assessment rate may not be reproducible elsewhere.
• Cost and resource use are not reported, despite longer hospital stays in the complete arm.

Key Concepts Mentioned

• concepts/Complete-Revascularization — the strategy under test; the trial extends it to patients ≥75 years
• concepts/Fractional-Flow-Reserve — wire-based physiological reference standard used for nonculprit assessment
• concepts/Angiography-Based-Coronary-Physiology — QFR was one of the permitted physiology tools
• concepts/NSTEMI-Elderly-Invasive-Strategy — the broader question of invasive management in older patients
• concepts/Multivessel-PCI-STEMI-Timing — complete revascularization and its timing in STEMI
• entities/Acute-Coronary-Syndrome — clinical context

Key Entities Mentioned

• FIRE Trial Investigators — sponsor-investigator group
• Consorzio Futuro in Ricerca — trial sponsor
• Sahajanand Medical Technologies — supplier of Supraflex Cruz stents and unrestricted funding
• Medis Medical Imaging Systems — QFR software
• Academic Research Consortium (ARC-2) and Bleeding Academic Research Consortium (BARC) — endpoint definitions

Wiki Pages Updated

• Created: wiki/sources/CompletePCI-Elderly-FIRE-NEJM-2023.md
• Created: wiki/concepts/Complete-Revascularization.md
• Updated: wiki/concepts/Fractional-Flow-Reserve.md
• Updated: wiki/concepts/NSTEMI-Elderly-Invasive-Strategy.md
• Updated: wiki/concepts/Multivessel-PCI-STEMI-Timing.md
• Updated: wiki/concepts/Angiography-Based-Coronary-Physiology.md
• Updated: wiki/sourceindex.md
• Updated: wiki/wikiindex.md
• Updated: log.md