Highlight
– Physiology-guided complete revascularization significantly reduces the composite risk of death, myocardial infarction (MI), stroke, and ischemia-driven revascularization at three years compared with culprit-lesion-only treatment in patients aged 75 years and older.
– Secondary outcomes, including cardiovascular death or MI and heart failure hospitalizations, are also significantly lower with physiology-guided complete revascularization.
– The benefit shown at one year in earlier studies is sustained over a longer-term follow-up, emphasizing durable clinical advantages in a vulnerable elderly population.
Study Background and Disease Burden
Myocardial infarction (MI) in older adults, particularly those with multivessel coronary artery disease (CAD), represents a major clinical challenge due to anatomical complexity, coexisting comorbidities, and heightened vulnerability to adverse outcomes. Complete revascularization—treating all significant coronary lesions—has emerged as an important therapeutic strategy to reduce recurrent ischemic events and mortality. However, many trials have primarily focused on younger or mixed-age populations, leaving uncertainty about long-term efficacy and safety in patients aged 75 years and older. Moreover, the optimal strategy for managing multivessel disease in this group remains debated, especially considering frailty, procedural risks, and life expectancy.
Earlier studies, including shorter-term follow-up analyses, have indicated that complete revascularization guided by physiological assessment (such as fractional flow reserve or similar methods) reduces cardiovascular death and MI within the first year post-MI. Yet, whether these benefits persist beyond one year is unclear due to limited data and conflicting evidence from recent studies.
The FIRE (Functional Assessment in Elderly MI Patients With Multivessel Disease) trial was designed to address this critical knowledge gap by evaluating the sustainability of benefits offered by physiology-guided complete revascularization compared to culprit-only treatment in a real-world elderly MI cohort over three years.
Study Design
FIRE was an investigator-initiated, multicenter, prospective, randomized superiority trial conducted across 34 centers in three countries from July 2019 to October 2021. It enrolled 1445 patients aged 75 years or older who had experienced ST-segment elevation MI (STEMI) or non-ST-segment elevation MI (NSTEMI) and were found to have multivessel coronary artery disease after successful treatment of the culprit lesion.
Key exclusion criteria included patients with nonculprit lesions involving the left main coronary artery and cases where the culprit lesion could not be clearly identified. This ensured a focused study population appropriate for evaluating revascularization strategies in a high-risk group.
Participants were randomized to one of two interventions:
– Culprit-only revascularization, where only the infarct-related artery was treated.
– Physiology-guided complete revascularization, where all hemodynamically significant nonculprit lesions were identified by physiological assessment and treated accordingly.
The primary outcome was a patient-oriented composite endpoint comprising death from any cause, MI, stroke, or ischemia-driven revascularization. Secondary endpoints included a composite of cardiovascular death or MI and hospitalization rates for heart failure.
Follow-up data were analyzed from March to May 2025, capturing clinical events up to three years post-procedure.
Key Findings
The median age was 80 years (IQR 77–84), with 63.5% male and 36.5% female patients. Baseline characteristics were well balanced between groups, ensuring comparability.
At three years, the primary composite outcome occurred in 22.9% of patients in the physiology-guided complete revascularization group versus 29.8% in the culprit-only group, representing a significant 28% relative risk reduction (hazard ratio [HR] 0.72; 95% CI, 0.58–0.88; P = .002).
Regarding the key secondary endpoint, cardiovascular death or MI was significantly reduced by 34% in the physiology-guided group (12.8% vs. 18.2%, HR 0.66; 95% CI, 0.50–0.88; P = .004).
Additionally, heart failure hospitalizations were less frequent among patients receiving complete revascularization (14.3%) compared with culprit-only treatment (19.7%), reflecting a 27% risk reduction (HR 0.73; 95% CI, 0.54–0.97; P = .03).
These findings demonstrate not only improved survival and reduced ischemic events but also a meaningful impact on quality of life through fewer heart failure admissions.
Safety outcomes and procedural complications were not explicitly detailed in the brief but previous related data suggest acceptable tolerability of physiology-guided interventions even in elderly populations.
The durable benefit observed at three years reinforces the clinical value of physiology-guided complete revascularization in older patients, providing stronger evidence for revising treatment strategies and guidelines.
Expert Commentary
The FIRE trial uniquely contributes to the evidence base by focusing on a geriatric MI population with multivessel disease, a subgroup often underrepresented in cardiovascular trials but with substantial clinical importance. The use of physiological assessment to guide intervention ensures that only lesions likely to cause ischemia are targeted, balancing procedural risks with benefits.
Current guideline recommendations support complete revascularization in selected patients to improve outcomes after MI; however, older patients frequently pose challenges related to frailty and comorbidities.
This study confirms not only the short-term but also the sustained long-term benefit of such an approach — a critical consideration since elderly patients often have competing risks and limited life expectancy that could negate potential intervention benefits.
Limitations include the exclusion of left main disease and ambiguous culprit lesions, which may limit generalizability. Further, detailed safety data, quality-of-life metrics, and cost-effectiveness analyses would better inform clinical decision-making.
Nonetheless, the trial’s robust design, substantial sample size, and multicenter setting strongly support physiology-guided complete revascularization as the preferred treatment in appropriate elderly patients post-MI with multivessel disease.
Conclusion
The FIRE randomized clinical trial provides compelling evidence that physiology-guided complete revascularization in patients aged 75 years and older with myocardial infarction and multivessel coronary disease offers sustained reduction in major adverse cardiovascular events, including death, MI, stroke, and heart failure hospitalizations, over a three-year period. These findings advocate for broader adoption of physiology-driven comprehensive treatment strategies in the elderly MI population, with careful patient selection and procedural planning.
Future research should emphasize personalized risk stratification, long-term safety, and integration of geriatric assessments to maximize therapeutic benefits while minimizing risks.
References
1. Biscaglia S, Erriquez A, Guiducci V, et al. Physiology-Guided Complete Revascularization in Older Patients With Myocardial Infarction: Three-Year Outcomes of a Randomized Clinical Trial. JAMA Cardiol. 2025 Aug 29:e253099. doi:10.1001/jamacardio.2025.3099. Epub ahead of print.
2. Writing Committee Members et al. 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization. Circulation. 2022;145(3):e18-e114.
3. Stone GW, Maehara A, Lansky AJ, et al. A Prospective Natural History Study of Coronary Atherosclerosis. N Engl J Med. 2011;364(3):226-235.
4. Tonino PA, De Bruyne B, Pijls NH, et al. Fractional Flow Reserve versus Angiography for Guiding Percutaneous Coronary Intervention. N Engl J Med. 2009;360(3):213-224.
