FFR-Guided PCI Reduces Cardiac Death, MI in Stable Lesions

Neil Osterweil

May 22, 2018

PARIS — It took three studies to show it, but pooled results from phase 3 clinical trials show that for patients with stable coronary artery lesions, percutaneous coronary intervention guided by fractional flow reserve is associated with a significant decrease in risk for cardiac death or myocardial infarction (MI) compared with pharmacologic therapy.

The pooled patient-level analysis included 2400 patients with stable coronary artery disease as well as non-culprit lesions in hemodynamically stabilized acute coronary syndrome patients in the FAME 2, DANAMI-3-PRIMULTI, and COMPARE-ACUTE trials. Results showed that compared with optimal medical therapy, fractional flow reserve (FFR)–guided percutaneous coronary intervention (PCI), was associated with a hazard ratio (HR) of 0.72 (P = .024) for a composite of cardiac death and MI, reported Frederik Zimmermann, MD, from Catharina Hospital Eindhoven in the Netherlands.

This difference translated into an absolute reduction in risk of approximately 4.5% at 5 years. Secondary analysis showed the reduction in the composite endpoint was driven almost entirely by reductions in MI.

"These findings imply that appropriately selected patients have a prognostic benefit from PCI independent of its impact on symptoms," he said at Congress of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR) 2018.

In an interview with theheart.org | Medscape Cardiology, Zimmermann said that the key issue in determining in a clinical trial whether an individual patient would benefit from the invasive procedure or would do just as well with medical management hinges on lesion selection.

"A portion of patients have a FFR-negative lesion, and you can imagine if you have a FFR-negative lesion, whether you are randomized to medical therapy or FFR-guided PCI, the treatment will be exactly the same. That's a really underappreciated point, I think, because if you include patients who have FFR-negative lesions, then the treatment is the same and therefore you dilute the effect," he said.

He said the findings are generalizable to both patients with stable coronary artery disease and stabilized patients with acute coronary syndrome (ACS) after successful treatment of culprit lesions who still have clear nonculprit lesions. 

"Several studies have shown that nonculprit lesions are physiologically stable in the acute phase and during follow-up," Zimmermann said. "Our new data show that the relative benefit of FFR-guided PCI versus medical therapy is identical for both clinical situations."

Patients with ACS might have a higher risk than do patients with stable CAD, but that is true both after medical therapy and after PCI, he added. "The clinically most relevant question is whether the relative benefit is different," he said. "We now see it is identical." 

However, he cautioned that "it is a different story for hemodynamically unstable patients, patients in whom you are not sure which lesion is the culprit, or patients where the culprit cannot be opened successfully."

Three Trials

Zimmermann and colleagues sought to determine whether stable patients with coronary lesions or stabilized patients with the ACS who have clearly identified nonculprit lesions would fare better with FFR-guided PCI than with optimal medical therapy.

Although each of the three trials included in the analysis showed a clinical benefit in favor of FFR-guided PCI for clinical endpoints, such as urgent revascularization or a composite of major adverse cardiac events, none was sufficiently powered to detect potential differences in other major events, such as cardiac death or MI, he noted.

To see whether pooling patient-level data from the trials would reveal a significant difference between the two treatment modalities, Zimmermann and colleagues included in their retrospective analysis data on 2400 hemodynamically stable patients with stable coronary lesions. The analysis included 1056 patients randomly assigned to PCI and 1344 to medical therapy.

They found, as noted above, that FFR-guided PCI was associated with a 28% reduction in the primary endpoint. The relative benefit of FFR-guided PCI did not differ significantly among the three studies.

An analysis of secondary endpoints showed that the differences between the treatment groups were driven entirely by reduction in MI. For example, for the endpoint of all-cause death or MI, the HR favoring PCI was 0.77 (P = .041), and the endpoint of MI alone was associated with an HR of 0.71 (P = .030).

There were no significant differences, however, in cardiac death or all-cause death considered as separate outcomes, Zimmermann noted.

"Hopefully, these results will fill the gaps in evidence as cited by the ESC [European Society of Cardiology] guidelines on what is the real benefit of myocardial revascularization, and challenge the American guideline stating that PCI does not lower the long-term risk of MI," Zimmermann said in his presentation of the data in a late-breaking abstracts session.

"This is very thought-provoking, of course, for us to bring prognosis into the realm of stable angina," commented Andreas Baumbach, MD, from the University of Bristol, United Kingdom, an invited discussant.

"The real question here," he added, "is the use of prognosis in a combined endpoint when actually you have death and MI as an endpoint, but the only difference is MI, and there is absolutely no difference in death."

Zimmermann replied that the composite endpoint was chosen before analysis of the data, and "we think that it's fair to state also that if you have a reduction in death or MI you can say that you have a prognostic benefit. If you want to focus on only, let's say, the cardiac deaths, then you would probably need a much larger cohort, or only patients who have a fairly large ischemic detriment," he said.

Patrick W. Serruys, MD, PhD, from Imperial College London, United Kingdom, who was not involved in the study, told theheart.org | Medscape Cardiology that although there appears to be a modest benefit for intervention in patients with stable disease, medical therapies in development may soon eliminate the advantage of more invasive treatments.

"When you talk about pharmacological treatment, you have to make clear the difference between two things: the symptomatic treatment — you take your nitrate, you take your β-blocker, you take all these drugs — to treat the symptoms, you don't treat the disease," he said.

"With statins, we were able to prevent the progression; now you get the reduction of disease" with the proprotein convertase subtilisin/kexin type 9 synthesis inhibitors and with monoclonal antibodies such as canakinumab, "and these will come into the equation in the next decade," he said.

He envisions that patients with ST-elevation MI (STEMI) and non-STEMI will still require urgent interventional procedures, but for patients with stable disease that is not flow-limiting, "that's the kind of individual which would be prone to go for a long-term treatment aiming at regression," he said.

The study was internally supported. Zimmermann, Baumbach, and Serryus reported having no conflicts of interest.

Congress of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR) 2018. Late-breaking abstract. Presented May 22, 2018.

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