For Real-world ACS Patients, FFR Use in PCI Tied to Lower In-Hospital Mortality

The registry data show an “overall picture [with] positive signals” for FFR in the ACS setting, a researcher says.

For Real-world ACS Patients, FFR Use in PCI Tied to Lower In-Hospital Mortality


(UPDATED) Use of fractional flow reserve (FFR) to guide treatment in patients with acute coronary syndromes is associated with a lower risk of in-hospital mortality, as well as a lower risk of acute kidney injury and shortened hospital stay, according to an observational analysis of data on more than 300,000 patients.

In-hospital mortality was 1.1% when FFR was used to guide PCI and 3.1% without FFR (P < 0.01). Hospital length of stay was 0.7 days shorter in the FFR-treated patients (mean 4.6 vs 5.3 days; P < 0.01).

“Overall, I do think there is a role for FFR in acute coronary syndrome, specifically for evaluating the nonculprit vessel and potentially improving patient outcomes, for lowering the amount of contrast, and at the same time decreasing the unnecessary complications of PCI,” lead investigator Jad Omran, MD (University of California, San Diego), told TCTMD. “When a patient comes in with an acute coronary syndrome, we know they have worse outcomes compared with the patient with stable angina, and efforts should be taken to decrease the risk of major adverse events. FFR is one way.”

Omran emphasized their retrospective, registry-based analysis has several limitations, but said FFR should be utilized more, noting that their results line up with other data suggesting FFR can benefit patients presenting with ACS. The FAME trial, he said, included roughly 30% of patients with NSTEMI/unstable angina who underwent physiologic testing with FFR and had a significant reduction in the risk of cardiovascular outcomes. In the FAMOUS-NSTEMI trial, which included 350 patients presenting with NSTE ACS, the use of FFR during PCI reduced the rate of revascularization in the subsequent 12 months.  

In the setting of STEMI, where roughly 40% of patients present with multivessel disease, studies have also shown that FFR for evaluating non-infarct-related lesions of intermediate stenosis could lead to improved clinical outcomes, said Omran. For example, the use of FFR led to a reduction in the composite endpoint of all-cause mortality, nonfatal MI, and ischemia-driven revascularization in DANAMI3-PRIMULTI and a reduction in the composite of all-cause mortality, nonfatal MI, revascularization, and cerebrovascular events in Compare-Acute. These results were primarily driven by a decrease in the need for ischemia-driven revascularization.  

“We wanted to look at real-world utilization of FFR during the setting of patients with acute coronary syndrome, including patients with STEMI, NSTEMI, and unstable angina,” said Omran.

Just 2.6% Had FFR-Guided PCI

The new study, published online November 29, 2019, ahead of print in Catheterization and Cardiovascular Interventions, includes patients enrolled in the Nationwide Readmissions Database that is part of the Healthcare Cost and Utilization Project. Using data from 2014, the researchers extracted ICD codes and identified 304,548 discharged patients with an ACS diagnosis who were treated with PCI during the index hospitalization (average age 65 years; 64% men). Of these, just 7,832 (2.6%) had PCI guided with FFR. Control patients had a diagnosis of transmural MI more often than did the FFR group (25.9% vs 9.3%), while unstable angina was more common in those undergoing PCI with FFR (43.5% vs 25.1%; P < 0.01 for both).

In addition to reduced in-hospital mortality and length of stay, FFR use was associated with a lower incidence of acute kidney injury (12.5% vs 14.6%), less bleeding (7.0% vs 8.5%), and reduced hospital charges ($99,805 vs $105,736; P < 0.01 for all). There were no significant differences in coronary dissection, stroke, or the number of stents used during PCI. FFR was associated with a lower risk of in-hospital mortality across ACS types.

Arnold Seto, MD (Long Beach VA Medical Center, CA), who was not involved in the analysis, said that ACS constitutes approximately 80% of PCIs performed today, partly because of small NSTEMIs. Like Omran, he noted the 2009 FAME trial included patients with unstable angina (STEMI patients were included if the MI occurred 5 days prior to PCI or, if occurring within the 5-day window was considered small).

“The suggestion which I agree with is that so long as you don't have a large MI (CK > 1,000 IU/L), then the FFR was valid,” said Seto in an email. “Now with troponins being so sensitive, pretty much most patients are labeled as NSTEMI- ACS because they will have a mildly abnormal troponin. There is a small theoretical concern that ACS in this form would cause a problem with the FFR measurement, but overall the microvasculature is not likely to be significantly dysfunctional with small MIs and FFR is likely to be accurate in these cases."

The major exclusion for FFR is in the culprit lesion of STEMI cases, where the FFR can be falsely normal due to microvascular dysfunction. However, even in STEMI, the benefit of FFR in nonculprit lesions has been tested, such as in the DANAMI3-PRIMULTI and Compare-Acute trials, noted Seto.

“I'm not surprised by the findings in this paper, but it would be extremely hard from an observational, charge-based study to discern why there might be an association with FFR use and reduced length of stay or mortality,” he said. “One could easily presume that FFR was used when there wasn't a clear culprit, or there was nothing to stent, or in patients who were just not as sick.”

Omran stressed that the results should be interpreted with caution given the limitations of the retrospective analysis. Unmeasured confounding might impact the results, he said, noting the researchers have no data available on the use of medical therapy, the type of acute MI, cardiac markers, or the number of arteries involved.

Despite these limitations, “the overall picture is that there are positive signals” for the use of FFR in the ACS setting, said Omran. At present, the 2016 appropriate use criteria for coronary revascularization in ACS patients state that PCI is “appropriate therapy” in asymptomatic nonculprit lesions of intermediate severity, provided the FFR is ≤ 0.80.

Omran, like Seto, said there has been some concern about the accuracy of FFR in ACS because “there is a lot going on in these patients,” including increased platelet activation, coronary vasospasm, and endothelial dysfunction.” However, FFR evaluations of nonculprit lesions performed at the time of ACS, as well those done 5 weeks after the event, have shown the measurements to be no different, suggesting that FFR is accurate even at the time of ACS.

“A lot of times when patients come in and we’re not sure if the lesions are hemodynamically significant, it’s really better to use a physiological assessment,” said Omran. “As practitioners, our main thing is treating acute coronary syndrome. They represent the major bulk of our patient population. A lot of times, if we have the chance to improve our outcomes, our mortality, we should be able to take it.”   

Michael O’Riordan is the Associate Managing Editor for TCTMD and a Senior Journalist. He completed his undergraduate degrees at Queen’s…

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  • Omran and Seto report no relevant conflicts of interest.