Optimizing outcomes in high-risk cardiac patients: lessons from the FIRE trial on complete revascularization

Dear Editor, Cardiovascular disease remains the leading cause of death globally, with myocardial infarction (MI) a significant contributor1–5. The management of MI in patients with multivessel coronary artery disease (CAD) presents a complex challenge, particularly in older patients who are often at high bleeding risk (HBR). The Functional Assessment in Elderly MI Patients With Multivessel Disease (FIRE) trial provides critical insights into this dilemma, particularly regarding the benefits of physiology-guided complete revascularization versus a culprit-only strategy6. The FIRE trial’s major contribution is demonstrating that physiology-guided complete revascularization significantly reduces the primary endpoint of death, MI, stroke, or ischemia-driven revascularization at 1 year compared with a culprit-only strategy in older patients with MI and multivessel disease who are at HBR. Notably, the trial found a hazard ratio of 0.73 (95% CI: 0.55–0.96) for the primary endpoint in the HBR group under complete revascularization, highlighting a substantial reduction in adverse outcomes without an increase in major bleeding. These results are pivotal for several reasons. First, the trial robustly supports the strategy of complete revascularization in reducing ischemic events in a high-risk population. This finding is crucial as it extends the benefits of complete revascularization observed in younger and lower-risk populations to older, more vulnerable patients. Second, by utilizing coronary physiology to guide revascularization, the FIRE trial emphasizes a precision medicine approach. This strategy ensures that only functionally significant lesions are treated, potentially reducing unnecessary interventions that could increase procedural risks. Third, the significant findings for patients with HBR are particularly noteworthy. In these patients, the approach of complete revascularization addresses the complex interplay between ischemic risk and the potential for bleeding, a balance that is critical in this group due to their frailty and multiple comorbidities. The implications of the FIRE trial for everyday clinical practice are significant. First, cardiologists should consider complete revascularization for older patients with MI and multivessel disease, particularly those at HBR. This approach could become part of standard practice, reflecting a shift from the more conservative culprit-only strategy. Second, the trial’s outcomes suggest that patient selection for complete revascularization can be effectively guided by physiological assessments rather than relying solely on anatomical indications. This could lead to more tailored and effective interventions. Third, the findings underscore the importance of balancing ischemic and bleeding risks, especially in HBR patients. Cardiologists must integrate these results with other clinical information to optimize treatment decisions, potentially adjusting antiplatelet therapy durations based on individual patient risk profiles. Fourth, the trial’s results should be incorporated into educational programs and guidelines to train cardiologists in the nuanced care of older, high-risk patients. Understanding when and how to apply complete revascularization in this context is crucial for improving outcomes. While the FIRE trial advances our understanding significantly, several limitations must be acknowledged. First, the study population was European, mostly White, and older than 75 years with MI and multivessel disease. Whether these findings can be fully extrapolated to other ethnicities, younger patients, or those with different clinical profiles (e.g. stable CAD) remains to be determined. Second, as a prespecified analysis of a larger trial, the study was not originally powered specifically to explore all the secondary outcomes in the HBR subgroup. This could affect the strength of conclusions for some of the less prominent outcomes. Third, the trial predominantly used sirolimus-eluting biodegradable-polymer ultrathin stents. The applicability of findings to other stent types or newer generations of drug-eluting stents could differ. Fourth, the trial reported outcomes at 1 year. Longer-term results are necessary to understand the sustained benefits and potential late complications of the strategies compared. Future research should aim to fill the gaps left by the FIRE trial and expand our knowledge in several key areas. First, studies with longer follow-up periods are needed to assess the durability of the benefits from complete revascularization in this patient population and to monitor for late adverse effects. Second, conducting similar trials in more diverse populations, including different ethnic groups and patients with varying comorbidities, would help validate the universality of the FIRE trial’s findings. Third, future trials should compare physiology-guided complete revascularization with other treatment modalities, such as newer antiplatelet strategies or different stent technologies. Fourth, analyzing the cost-effectiveness of complete versus culprit-only revascularization in high-risk older patients could influence healthcare policy and practice, particularly in resource-constrained settings. Fifth, incorporating quality of life and functional status assessments into future research could provide a more comprehensive understanding of the real-world benefits of different revascularization strategies. In conclusion, the FIRE trial represents a significant step forward in the management of older patients with MI and multivessel disease, especially those at HBR. By demonstrating the efficacy of physiology-guided complete revascularization, the trial offers a pathway to optimize outcomes in this vulnerable population. Cardiologists should integrate these findings into their clinical practice, enhancing patient care through informed, evidence-based strategies. Future research should build on these results, expanding our understanding and refining our approaches to treating high-risk cardiac patients. Ethical approval Ethical approval is not applicable for this correspondence article. Consent Informed consent is not applicable for this correspondence article. Sources of funding Not applicable. Author contribution Y.A.: conceptualization, project administration, writing – original draft, and writing –review and editing; A.V. and B.C.S.: project administration, validation, writing – original draft, and writing –review and editing; E.B.M.: project administration, writing – original draft, and writing –review and editing; P.S., R.K.S., M.N.K., S.G., Q.S.Z., and S.R.: supervision, validation, and writing – review and editing. Conflicts of interest disclosure The authors declare no conflicts of interests. Research registration unique identifying number (UIN) Not applicable. Guarantor Endalkachew Belayneh Melese. Data availability statement Not applicable. Provenance and peer review Not commissioned, externally peer-reviewed.