Benefits of complete revascularization in elderly patients

The benefit of complete revascularization in older patients (≥75 years) with myocardial infarction and multivessel disease is still unclear. At the ESC Congress, however, the results of the FIRE study were presented, in which physiologically guided complete revascularization was compared with revascularization aimed only at correcting the cause of the STEMI in older patients [1,2].

An increasing proportion of older patients (≥75 years) are admitted to hospital with a myocardial infarction. Although increasing age is a known predictor of poor outcome after myocardial infarction, patients in this age group are often excluded or underrepresented in clinical trials, and many are treated conservatively or suboptimally [3,4]. Clinicians often face challenges in the medical and procedural management of older patients with myocardial infarction due to a lack of robust evidence, fear of complications, perceived poor outcomes and low success rates in this age group [5,6].

One of these challenges is deciding whether to aim for complete coronary artery revascularization by treating nondisease lesions with percutaneous coronary intervention (PCI) [7,8]. Although the benefits of complete revascularization in younger patients with myocardial infarction who have multivessel coronary artery disease are well established [9,10], these benefits are uncertain in older patients with myocardial infarction who are at higher risk of complications [11,12]. To address this knowledge gap, a multicenter, randomized trial in elderly patients with myocardial infarction and multivessel disease was conducted to investigate whether complete revascularization performed on the basis of coronary physiology is superior to culprit PCI alone.

After the heart attack: Hearts on FIRE!

In the FIRE study (Functional Assessment in Elderly MI Patients with Multivessel Disease) was an investigator-initiated, multicenter, prospective, randomized, superiority trial to evaluate a strategy of physiologically guided complete myocardial revascularization versus a culprit-only strategy in elderly patients (≥75 years) who had either ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI) and multivessel disease.

Patients were eligible for participation in the study if they were at least 75 years old, had been hospitalized with a STEMI or NSTEMI, had undergone successful PCI of the culprit lesion, and had multivessel disease with at least one lesion in a non-culprit coronary artery with a vessel diameter of at least 2.5 mm and a visually estimated diameter stenosis of 50 to 99%. Exclusion criteria included inability to identify a clear causal lesion (based on history, electrocardiography, echocardiography, and angiography), localization of the noncausal lesion in the left main coronary artery, planned or previous surgical revascularization, or a life expectancy of less than one year.

After successful treatment of the culprit lesion, patients were randomized either immediately or within 48 hours. Using a central randomization system, patients were assigned in a 1:1 ratio to either physiologically guided complete revascularization or Culprit-only revascularization. Randomization was concealed using a web-based system (Integrated Clinical Trial Environment, AdvicePharma), and treatment allocation was determined using a computer-generated randomization list stratified by center, sex, and clinical presentation with STEMI or NSTEMI.

Treatment and aftercare of patients

Patients randomly assigned to physiologically guided complete revascularization underwent PCI of all functionally significant nonculprit lesions [13]. Both physiologic assessment and PCI of nonculprit lesions were allowed either during the index procedure or in a staged procedure within the index hospital.

Physiological assessment was performed using wire-based methods (hyperemic or non-hyperemic) and angiography-based measurements (quantitative flow ratio) (Medis QFR, Medis Medical Imaging Systems) [13]. A functionally significant non-culprit lesion was defined as a lesion with a hyperemic, non-hyperemic, or angiography-based threshold ratio of 0.80, 0.89, or 0.80 or less, respectively. No physiologic assessment or revascularization of non-culprit lesions was performed in patients randomly assigned to culprit-only revascularization [13].

The use of ultra-thin sirolimus-eluting stents made of biodegradable polymer (Supraflex Cruz, Sahajanand Medical Technologies) was strongly recommended [13]. Guideline-based medical therapy was indicated for both treatment groups. In addition, dual antiplatelet therapy was recommended for at least one year, except in patients at high risk of bleeding [13]. Follow-up examinations took place after one and 12 months and were then scheduled annually for up to 5 years after randomization.

Primary and secondary endpoints

The primary endpoint was a composite of death, myocardial infarction, stroke or ischemia-related coronary revascularization within one year of randomization [13]. An important secondary endpoint was a composite of cardiovascular death or myocardial infarction after one year. Other secondary endpoints were the individual components of the primary endpoint [13].

The safety endpoint was a composite of contrast agent-related acute kidney injury, stroke or bleeding defined by the Academic Bleeding Research Consortium (BARC) as type 3, 4 or 5 at one year [13]. The endpoints were assessed according to the definitions of the Academic Research Consortium and the BARC consensus documents [14,15].

Results of the FIRE study

From 2019 to 2021, a total of 1898 patients were selected for the study at 34 locations in Italy, Spain and Poland. Of these patients, 1445 were randomly assigned to either physiologically guided complete revascularization (720 patients) or culprit lesion-only revascularization (725 patients). Randomization occurred in 877 patients (60.7%) at the time of the index procedure and in 568 patients (39.3%) within 48 hours of the index procedure.

The median age of the patients was 80 years, 528 patients (36.5%) were women, and 509 (35.2%) were admitted for STEMI. The assigned treatment was performed in 693 patients (96.2%) in the complete revascularization group and in 706 patients (97.4%) in the culprit lesion revascularization alone group. In the complete revascularization group, a physiological assessment of at least one non-culprit vessel was performed in 700 patients (97.2%); this assessment identified 357 patients (49.6%) with at least one functionally significant non-culprit vessel. Revascularization of at least one non-culprit vessel was performed in 361 patients (50.1%); of these patients, 346 had a functionally significant non-culprit vessel, four had a negative physiological assessment, and 11 did not receive a physiological assessment prior to PCI. The median length of hospital stay was five days and appeared to be longer in the group with complete revascularization than in the group with culprit lesion revascularization alone (6 days and 5 days, respectively).

One-year follow-up data were complete in 1444 of 1445 patients (99.9%). A primary event occurred in 113 patients (15.7%) in the group with complete revascularization and in 152 patients (21.0%) in the group with culprit lesion revascularization alone (hazard ratio, 0.73; 95% confidence interval [CI], 0.57 to 0.93; p=0.01) (Fig. 1A) [2]. The number of patients who required treatment to prevent the occurrence of a primary outcome event was 19, and the incidence of the composite outcome of cardiovascular death or myocardial infarction appeared to be lower in the complete revascularization group (hazard ratio, 0.64; 95% CI, 0.47 to 0.88) (Fig. 1B) [2]. The number of patients who had to be treated to prevent one patient from suffering a cardiovascular death or myocardial infarction was 22.

With the exception of stroke, the incidence of each component of the primary outcome appeared to be lower in the fully revascularized group, including death from any cause (hazard ratio, 0.70; 95% CI, 0.51 to 0.96); the number of patients who required treatment to prevent the occurrence of death was 27. Subgroup analyses showed that the effect of complete revascularization on the primary outcome appeared to be consistent across the prespecified subgroups.

There was no apparent difference between the two treatment groups in the incidence of the composite safety outcome consisting of contrast-associated acute kidney injury, stroke, or hemorrhage (defined as BARC type 3, 4, or 5), with 22.5% in the complete revascularization group and 20.4% in the culprit lesion revascularization alone group (hazard ratio, 1.11; 95% CI, 0.89 to 1.37; p=0.37).

Closing a knowledge gap

One limitation of the study is the open-label design. Due to comorbidities, cognitive impairment and post-bypass surgery in elderly patients, the results will probably not be fully transferable to a general patient population. In addition, it is unclear whether conventional angiography-based complete revascularization would have led to similar results. “Physiology-guided complete revascularization in patients over 75 years of age with myocardial infarction and coronary multi-vessel disease is safe and effective,” said Dr. Simone Biscaglia from the University Hospital Santa Anna in Ferrara, Italy, summarizing the results of the FIRE trial at the ESC Congress in Amsterdam. However, it will be interesting to see the results of the long-term follow-up and whether these effects persist.

According to the results of the study, complete revascularization is also associated with a reduction in cardiovascular events, including death, in heart attack patients in this age group. The results of the FIRE study point the way towards more comprehensive revascularization in everyday clinical practice, even in the elderly. It remains to be seen whether the study will find its way into the guidelines. Further studies with this special patient population (≥75 years) would certainly be desirable.

In summary, the FIRE study confirms the results of the COMPLETE study. However, there are major differences between the two studies. The average age of the participants in the FIRE study was higher than in the COMPLETE study (80 versus 62 years). In contrast to the COMPLETE study, many patients with NSTEMI were also included in the FIRE study. In addition, revascularization of non-infarct arteries in the FIRE study was only performed in the case of coronary stenoses identified as hemodynamically relevant by physiological testing (pressure wire or angiography-based FFR measurement). The FIRE study thus closes the existing knowledge gap on the benefit of complete revascularization in older patients (≥75 years) with acute myocardial infarction (STEMI/NSTEMI) and coronary multi-vessel disease.

Congress: ESC 2023

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