Swedish Data ‘Corroborate’ FFR’s Survival Benefit Seen in RCTs

The observational analysis suggests lower all-cause mortality. A possible mechanism is FFR’s ability to pinpoint vulnerable plaque.

Swedish Data ‘Corroborate’ FFR’s Survival Benefit Seen in RCTs

More than a decade’s worth of fractional flow reserve (FFR) use to inform PCI choices in stable CAD patients has borne fruit, according to data from SCAAR (Swedish Coronary Angiography and Angioplasty Registry) that suggest a survival benefit with physiological assessment.

Now published in the Journal of the American College of Cardiology, the analysis is an expanded version of earlier numbers presented at EuroPCR 2018.

Speaking with TCTMD, senior author Elmir Omerovic, MD, PhD (Sahlgrenska University Hospital, Göteborg, Sweden), noted that “the main message is the same”—physiologic assessment is warranted in stable CAD patients undergoing PCI and may reduce hard outcomes.

Today, FFR use varies around the world, he pointed out. It has reached around 50% to 60% in Sweden, for example, and around 30% in the United States. “More and more hospitals are using it, and I think it will increase more in a couple of years,” Omerovic predicted.

While the current analysis can’t prove causation, for Omerovic, the observed link between FFR and better outcome is convincing and this latest analysis falls in line with earlier reports. “We have evidence [from the FAME trials] that FFR-led revascularization decreases the incidence of myocardial infarction,” he said. “Myocardial infarction is the single most important cause of death in Western societies, so one could argue that any intervention that decreases the incidence of myocardial infarction would eventually translate into a decrease in all-cause mortality.”

William F. Fearon, MD, and Hiroyuki Arashi, MD (both from Stanford University School of Medicine, CA), writing in an editorial, agree: “These observational, real-world data are important because they corroborate the significant reduction in death and myocardial infarction with FFR-guided PCI compared with angiography-guided PCI that was seen in the randomized, controlled FAME . . . trial and the reduction in spontaneous MI at 5 years after FFR-guided PCI compared with medical therapy alone in patients with stable CAD enrolled in the FAME 2 trial.”

What’s less clear, Omerovic and the editorialists say, is exactly how the process of measuring and applying FFR leads to better outcomes.

It takes time to introduce treatments that have been shown beyond reasonable doubt to be effective. It can take years. Elmir Omerovic

Led by Sebastian Völz, MD, PhD (Sahlgrenska University Hospital), the investigators analyzed data on 23,860 patients with stable angina who underwent PCI between January 2005 and March 2016. The use of FFR guidance rose from 8% in 2005 to 32% in 2016, an annual increase of 15.3%. On the whole, there was wide variation in FFR use among PCI centers, ranging from 3% to 37% of cases.

Periprocedural complications were similar in the FFR and no-FFR groups. With propensity score matching, physiologic testing was associated with a reduced likelihood of all-cause mortality for the FFR group (HR 0.81; 95% CI 0.73-0.89) as well as less stent thrombosis or restenosis (HR 0.74; 95% CI 0.57-0.96) over a median follow-up of 4.7 years. These differences in risk, however, only appeared after 1 year.

“Our study supports the current European and American guidelines for the use of FFR in PCI and shows that PCI with intracoronary pressure wire guidance has prognostic benefit in patients with stable angina pectoris,” Völz et al conclude.

FFR for All?

One important limitation of this analysis is that “the investigators were unable to distinguish cardiac from noncardiac death and did not have data regarding rates of MI,” Fearon and Arashi point out. Nor does the study “provide important follow-up data such as antiplatelet and statin medication usage, lipid and diabetes control, and smoking cessation in the two groups.”

Regardless, though, the study adds to a growing body of literature, they say. And an interesting question remains: how does physiologic assessment impact hard outcomes?

“Perhaps performing PCI on coronary lesions with a low FFR responsible for ischemia does prevent MI and death, whereas medically treating lesions with a high FFR limits the risk of PCI and optimizes its benefit. Emerging data suggest that hemodynamically significant lesions with a low FFR are more likely to have features of plaque vulnerability compared with similar stenoses that are not functionally significant,” the editorialists note, adding, “One could argue that measuring FFR is the most accurate invasive method for identifying vulnerable plaque.”

But what makes a 70% lesion with low FFR, they ask, different from a similarly severe lesion with high FFR? “It may be that hemodynamically significant lesions create changes in biomechanical forces on the plaque, such as wall shear stress and plaque stress, which result in downregulation of vasoprotective factors and upregulation of inflammatory, oxidative stress, and thrombogenic factors,” Fearon and Arashi suggest.Alternatively, it may be that greater inflammation results in changes in plaque morphology and vascular function that then leads to a particular stenosis having an abnormal FFR.”

Omerovic, too, said that FFR results can indicate which lesions are most apt to eventually cause trouble. “We also know that treating all lesions indiscriminately [isn’t good],” he said, adding: “As Salim Yusuf used to say, restenosis is a man-made disease. Of course, restenosis is not as benign as we initially thought 10 years ago,” when recurrent angina was the concern; instead, “10% to 15% of restenotic lesions cause infarctions.”

Although the news of a possible survival benefit is welcome, some on #CardioTwitter were careful in interpreting the observational data.

Asked why there isn’t more uptake of FFR given the evidence base, Omerovic cited several reasons. For some healthcare systems, it can be an issue of resources. Also, he said, “not all centers and groups of physicians are equally well informed about the importance of the methodology. They’re just repeating what they’ve been doing for years. It takes time to introduce treatments that have been shown beyond reasonable doubt to be effective. It can take years.”

For every stable CAD patient in whom there aren’t safety concerns, FFR should be used to guide PCI, Omerovic stressed, saying this portion could reach as high as 70% to 80%. “And then the question is, should FFR be used with equal frequency in patients with acute coronary syndromes? I think the coming years will show that even in those settings FFR will provide better guidance,” he predicted, citing Compare-Acute. In that trial, FFR-guided revascularization of all functionally significant lesions in patients with acute STEMI was better at reducing subsequent MACCE than treating only the culprit artery.

  • The study was supported by the Swedish Heart-Lung Foundation, the Swedish Research Council, and ALF Göteborg.
  • Völz and Arashi report no relevant conflicts of interest.
  • Omerovic reports having received institutional research grants from AstraZeneca.
  • Fearon reports having received institutional research support from Abbott Vascular, Medtronic, and Edwards Lifesciences; having received consulting fees from CathWorks; and holding minor stock options with HeartFlow.