FIRE: Complete Revascularization Best Even for Elderly Patients With MI
Complete PCI guided by functional testing was safe and reduced hard outcomes, including death and MI, in the 75-plus set.
AMSTERDAM, the Netherlands—Age is just number, at least when it comes to complete revascularization for MI patients, according to results from the FIRE trial presented today during a Hot Line session at the European Society of Cardiology Congress 2023.
The study, which was published simultaneously in the New England Journal of Medicine, showed that older patients presenting with either STEMI or NSTEMI had a lower risk of cardiovascular events at 1 year when treated with complete revascularization compared with PCI of the culprit lesion only.
“The first important key message of our study is the study population,” said lead investigator Simone Biscaglia, MD (Azienda Ospedaliero Universitaria di Ferrara, Italy), during a press conference announcing the results. This is the first randomized trial of complete revascularization in those aged 75 years and older, he noted. “[FIRE] is an impactful trial on clinical practice, because the actual management of older MI patients is often the treatment of only the culprit lesion. This is the first trial showing a benefit that seems to be higher, or at least as high, as that seen in younger patients.”
As a result, said Biscaglia, “our practice will probably shift from a minimalist approach to complete revascularization guided by physiology.”
During the press conference, Biscaglia said the global population is greying and a large percentage of these older adults—as many as 20%— will go on to have a myocardial infarction. Despite the shifting demographics, physicians had limited data on how to best manage older MI patients with multivessel disease.
[FIRE] is an impactful trial on clinical practice, because the actual management of older MI patients is often the treatment of only the culprit lesion. Simone Biscaglia
In one of the largest trials to date, COMPLETE, investigators showed that patients with STEMI and multivessel disease undergoing angiography-guided complete revascularization had a lower risk of cardiovascular death or MI compared with those in whom operators treated only the culprit lesion. The average age of patients in COMPLETE, however, was just 62 years old. FIRE was conducted to help fill a gap in the evidence for older adults.
Kevin Bainey, MD (Mazankowski Alberta Heart Institute/University of Alberta, Edmonton, Canada), one of the COMPLETE investigators, told TCTMD that while the data support complete revascularization for STEMI, the question has always been whether it makes sense for an average 80-year-old patient.
“You step back and ask, ‘Will the elderly derive a benefit in terms of hard endpoints?’” he said. “That’s why this trial is important. The COMPLETE trial is based on outcomes at 3 years, but FIRE is just 1 year yet it showed a benefit in the primary composite endpoint, as well as in deaths and MI. This will push people to say that we need to entertain complete revascularization in the elderly.”
The flip side of the conversation in older patients is always safety, said Bainey, noting they often have complex disease, with multiple comorbidities, and are predisposed to bleeding and acute kidney injury. “According to FIRE, there is no risk, so that is reassuring,” he said. “It pushes the envelope for complete revascularization.”
Edward Fry, MD (Ascension St. Vincent Hospital, Indianapolis, IN), immediate past president of the American College of Cardiology, also called FIRE a reassuring trial. “It’s important because our patient population is aging rapidly,” he told TCTMD. “This is a question clinicians face every day.”
Benefit Driven by Hard Endpoint Reductions
In FIRE, patients who were randomized to complete revascularization received a stent in all functionally significant nonculprit lesions identified via pressure wire or on angiography with quantitative flow ratio (QFR). The assessment and revascularization of nonculprit lesions was performed either during the index intervention or in a staged procedure while the patient was still in hospital. Patients randomized to culprit-only PCI did not receive any physiologic testing or treatment of other lesions.
Operators were recommended to use the sirolimus-eluting, ultra-thin DES with biodegradable polymer (Supraflex Cruz; SMT), and all patients were treated with dual antiplatelet therapy for 1 year except for those at high risk for bleeding. To TCTMD, Biscaglia said this type of stent—DES with a biodegradable polymer—was selected because it is the only type with data, from the SENIOR trial, supporting its use in patients 75 years and older. Additionally, uniform stent selection eliminates any possible differences in outcomes related to the stent, he said.
After successful PCI of the culprit lesion, 1,445 patients 75 years and older (mean age 80 years; 36.5% female; and 35.2% with STEMI) at more than 30 sites in Italy, Spain, and Poland were randomized.
The primary outcome of death, MI, stroke, or ischemia-driven revascularization at 1 year occurred in 21.0% of those undergoing culprit-only revascularization and 15.7% of those who were completely revascularized (HR 0.73; 95% CI 0.57-0.93). The number needed to treat (NNT) to prevent one primary-outcome event was 19 patients.
For the secondary endpoint of cardiovascular death or MI, complete revascularization was associated with a 36% reduction in events (HR 0.64; 95% CI 0.47-0.88) and the NNT was 22 patients. Regarding other secondary endpoints, death from any cause, death from cardiovascular causes, MI, and ischemia-driven revascularization were significantly reduced by 30%, 36%, 38%, and 37%, respectively, with complete revascularization. There did not appear to be any reduction in the risk of stroke.
Biscaglia highlighted the relatively high rate of clinical events at 1 year in this older patient population, noting that the benefit of treatment was driven by a reduction in hard clinical outcomes. With respect to safety, there were no significant differences in the composite endpoint of contrast-associated acute kidney injury, stroke, or BARC type 3, 4, or 5 bleeding (HR 1.11; 95% CI 0.89-1.37).
In an editorial accompanying the NEJM publication, Shamir Mehta, MD (McMaster University/Population Health Research Institute, Hamilton, Canada), who led COMPLETE, states that “the FIRE trial confirms the benefit of complete revascularization that has been observed in previous trials and provides additional evidence for this approach in older patients.”
For Mehta, “the reduction in mortality with complete revascularization at 1 year is particularly notable and reinforces the finding that complete revascularization should be considered in all patients presenting with acute myocardial infarction, regardless of age,” he said.
To TCTMD, Fry emphasized the importance of identifying the goals of treatment when dealing with older patients, who ranged from 77 to 84 years in FIRE. This study, he added, showed a significant reduction in all-cause and cardiovascular mortality, “which is pretty powerful.”
Differences Between FIRE and COMPLETE
Despite providing support for complete PCI older patients, FIRE differed from the COMPLETE trial in important ways. For one, the decision to revascularize nonculprit lesions was based on physiologic measures (physiologic testing was allowed in COMPLETE for moderate stenoses but infrequently used—nearly all nonculprit lesions had > 70% stenosis on angiography).
Biscaglia said use of functional testing in FIRE was a deliberate choice, emphasizing that the trial was designed so that operators would treat only flow-limiting, nonculprit coronary lesions.
“In older patients, we have a huge amount of data showing that complications are more frequent and impactful on prognosis,” he told TCTMD. “In FIRE, 50% of nonculprit lesions were deemed visually important for the operator and amenable to treatment but were negative on physiological assessment. We can’t state that [had] we used angiography-based PCI the results would have been the same. We would have overtreated patients—50% of vessels or more—and we can’t say if the safety signal would have been the same [with angiography-guided PCI].”
[FIRE] pushes the envelope for complete revascularization. Kevin Bainey
Bainey believes this is one of the limitations of FIRE, namely that the results can’t be extrapolated to complete revascularization based on angiographic stenosis severity. There is still uncertainty around the benefits of physiology-guided revascularization, he said, noting that physiologic testing may leave behind coronary lesions vulnerable to plaque rupture. He pointed out that they observed consistent benefits in both younger and older COMPLETE patients (< 65 vs ≥ 65 years) undergoing complete revascularization guided by angiography.
For his part, Bainey said he’d still consider doing complete revascularization guided by angiography as opposed to that driven by physiology. “We can’t say definitively that one approach is better than the other,” he said.
The COMPLETE-2 trial will provide further insight into the best strategy to guide treatment of the nonculprit lesions. That trial, which is expected to enroll 5,100 patients with STEMI/NSTEMI and multivessel disease, is investigating any potential differences in outcomes between physiology- and angiography-guided revascularization.
Notably, the FIRE investigators also randomized patients with STEMI and NSTEMI, while the COMPLETE trial exclusively focused on those with STEMI. FIRE, said Bainey, provides very good data to support complete revascularization for NSTEMI patients, which has been lacking. “Here it’s in the elderly, but we don’t actually have very good randomized controlled trials for NSTEMI,” he said. “FIRE sets the bar for complete revascularization in non-ST elevation MI.”
Biscaglia S, Guiducci V, Escaned J, et al. Complete or culprit-only PCI in older patients with myocardial infarction. N Engl J Med. 2023;Epub ahead of print
Mehta SR. Complete revascularization in older adults with myocardial infarction. N Engl J Med. 2023;Epub ahead of print.