Cardiology · Medical Literature
Diabetes does not attenuate the benefit of physiology-guided complete revascularization in older patients with myocardial infarction.
Abstract
BACKGROUND: In patients with myocardial infarction (MI) and multivessel disease, diabetes mellitus is associated with more diffuse coronary atherosclerosis and worse clinical outcomes, often influencing revascularization decisions. The Functional Assessment in Elderly MI Patients with Multivessel Disease (FIRE) trial demonstrated the superiority of physiology-guided complete revascularization in older patients with MI. Whether this benefit is preserved in patients with diabetes remains uncertain. METHODS: In FIRE, 1445 patients aged ≥ 75 years with MI and multivessel disease were randomized to culprit-only or physiology-guided complete revascularization. In this prespecified analysis, outcomes were assessed according to diabetes status. The primary endpoint was a composite of death, MI, stroke, or revascularization at 3 years. The key secondary endpoint was cardiovascular death or MI. The safety endpoint included contrast-associated acute kidney injury, stroke, or Bleeding Academic Research Consortium type 3–5 bleeding. RESULTS: Among 1445 patients, 463 (32%) had diabetes. After adjustment for baseline characteristics, diabetes was independently associated with a higher risk of the primary endpoint (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.02–1.56) and heart failure (HR 1.35, 95% CI 1.01–1.83) at 3 years. Physiology-guided complete revascularization reduced the primary outcome in both patients with diabetes (HR 0.70, 95% CI 0.50–0.97) and without diabetes (HR 0.75, 95% CI 0.58–0.97), with no evidence of effect modification by diabetes status (p for interaction = 0.712). Similar consistency was observed for the key secondary and safety endpoints. CONCLUSIONS: In older patients with MI and multivessel disease, physiology-guided complete revascularization reduces ischemic events irrespective of diabetes status, supporting its use in elderly diabetic patients. Trial registration ClinicalTrials.gov Identifier NCT03772743.
Clinical relevance
In older patients (≥75 years) with myocardial infarction and multivessel disease, does diabetes mellitus modify the clinical benefit of physiology-guided complete revascularization compared with culprit-only percutaneous coronary intervention? __SNAPSHOT__ {"studyDesign":"Prespecified subgroup analysis of a multicenter, investigator-initiated, prospective, randomized, open-label superiority trial with blinded adjudicated outcomes (PROBE design) — the FIRE trial (NCT03772743)","setting":"Multinational; academic and community cardiac catheterization centers in Italy, Spain, and Poland","sampleSize":"n=1,445 total (diabetic subgroup: n=463 [32%]; non-diabetic subgroup: n=982 [68%]); original trial: 720 randomized to complete revascularization, 725 to culprit-only","population":"Patients aged ≥75 years presenting with myocardial infarction (STEMI or NSTEMI) and angiographically confirmed multivessel coronary artery disease with a clearly identifiable culprit lesion; 32% had diabetes mellitus at baseline","intervention":"Physiology-guided complete revascularization of non-culprit lesions (guided by pressure wire or quantitative flow ratio) performed during index hospitalization","comparator":"Culprit-lesion–only percutaneous coronary intervention (no further non-culprit revascularization)","primaryOutcome":"Composite of all-cause death, myocardial infarction, stroke, or any revascularization at 3 years","followUp":"3 years (primary endpoint of the current analysis; original FIRE trial primary endpoint assessed at 1 year)","fundingSource":"Non-profit (Consorzio Futuro in Ricerca, Italian nonprofit, as trial sponsor); unrestricted funding also provided by several medical device companies (Sahajanand Medical Technologies, Medis Medical Imaging Systems, Eukon S.r.l., Siemens Healthineers, GE Healthcare, Insight Lifetech); companies had no role in design, data collection, analysis, or manuscript preparation"}
Key findings
Among 1,445 patients, 463 (32%) had diabetes. After multivariable adjustment, diabetes was independently associated with a higher risk of the primary composite endpoint at 3 years (HR 1.26, 95% CI 1.02–1.56) and of heart failure (HR 1.35, 95% CI 1.01–1.83), confirming the higher-risk phenotype conferred by diabetes in this elderly MI population. Regarding the primary treatment comparison, physiology-guided complete revascularization reduced the primary composite outcome in patients with diabetes (HR 0.70, 95% CI 0.50–0.97) and in those without diabetes (HR 0.75, 95% CI 0.58–0.97). Critically, the interaction test for diabetes status and revascularization strategy was non-significant (p for interaction = 0.712), indicating no evidence of effect modification by diabetes. Absolute risk differences by diabetes subgroup were not reported in the available abstract. NNT by diabetes status is not calculable from the available data. Safety outcomes (composite of contrast-associated acute kidney injury, stroke, or BARC type 3–5 bleeding) were not reported to differ by diabetes status, though event-level data by subgroup were not available from the abstract alone.
Practice implications
This prespecified subgroup analysis of the FIRE trial establishes that the relative benefit of physiology-guided complete revascularization over culprit-only PCI is preserved in elderly patients with diabetes, with no statistically detectable interaction between diabetes status and treatment effect. The finding that diabetes independently confers a roughly 26% higher adjusted risk of the primary endpoint underscores the high-risk nature of this population, and yet the relative risk reduction with complete revascularization appears consistent (HR ~0.70–0.75) regardless of diabetic status. These results apply specifically to patients aged ≥75 years with either STEMI or NSTEMI and multivessel disease who were eligible for and underwent culprit PCI. Patients excluded from FIRE (e.g., those with cardiogenic shock, left main disease as the culprit, or extreme frailty precluding multi-vessel intervention) are not represented. The analysis does not provide data on type of diabetes (type 1 vs. type 2), glycemic control (HbA1c), diabetes duration, insulin use, or the presence of diabetic microvascular or macrovascular complications — all of which may clinically matter. Absolute risk reductions and NNT by diabetes status were not available from the abstract, limiting precise quantification of absolute benefit. Whether these findings should lead to immediate practice change is reinforced by the prespecified nature of the subgroup analysis, but confirmatory data from sufficiently powered dedicated diabetic elderly ACS trials would further strengthen confidence. Note: this summary is based on the published abstract only; full-text review is required for complete data on event rates, safety endpoints by diabetes subgroup, and covariate details. __LIMITATIONS__ Subgroup analysis: although prespecified, the diabetic subgroup (n=463) represents only 32% of the total cohort, limiting statistical power to detect treatment interactions or differences in safety outcomes within the diabetic stratum,No characterization of diabetes type, duration, HbA1c, insulin use, or antidiabetic medications — important confounders for both coronary anatomy complexity and procedural outcomes,Open-label trial design (PROBE) with potential for performance bias in procedural decisions and non-blinded caregivers, though outcomes were adjudicated blindly,Geographic restriction to Italy, Spain, and Poland may limit generalizability to health systems with different baseline diabetes prevalence, pharmacologic management norms, or PCI infrastructure,The primary composite endpoint includes revascularization — a soft, operator-influenced component that may inflate the apparent treatment benefit and complicate cross-trial comparisons,Safety endpoint data by diabetes subgroup were not reported in the abstract; the potential for excess contrast-associated AKI in diabetic patients with reduced GFR remains unquantified in this subgroup,Median age of 80 years and predominantly European population limits generalizability to younger elderly patients and non-European populations,Absolute risk differences and NNT by diabetes status not reported — clinicians cannot estimate individual absolute benefit without these values,Unrestricted industry funding (multiple device companies), although sponsors are reported to have had no role in the study; no competing interests declared by authors __BOTTOM_LINE_CATEGORY__ potentially_practice_informing __BOTTOM_LINE__ In patients aged ≥75 years with myocardial infarction and multivessel disease, physiology-guided complete revascularization reduces ischemic events equally in patients with and without diabetes, with no evidence of effect modification by diabetic status (p for interaction = 0.712). While diabetes independently increases 3-year event risk by approximately 26%, it should not be used as a reason to withhold complete revascularization in otherwise eligible older MI patients. These findings, drawn from a prespecified subgroup of the FIRE trial, are consistent and clinically coherent, supporting the extension of the FIRE trial's practice-informing strategy to elderly diabetic patients.