FFR-Guided Complete Revascularization Tops PCI of Culprit Artery Alone in Acute STEMI

WASHINGTON, DC—Using fractional flow reserve (FFR) to guide revascularization of all functionally significant lesions in the setting of acute STEMI appears to improve outcomes over treating only the culprit artery, the Compare-Acute trial shows.

The primary MACCE endpoint occurred in 7.8% of patients who underwent FFR-guided complete revascularization and 20.5% of those who received PCI of the infarct-related artery alone through 1 year (HR 0.35; 95% CI 0.22-0.55), Pieter Smits, MD, PhD (Maasstad Hospital, Rotterdam, the Netherlands), reported at the American College of Cardiology 2017 Scientific Session here.

The advantage was driven primarily by a reduction in repeat revascularization (6.1% vs 17.5%; HR 0.32; 95% CI 0.20-0.54), with no differences in the other components of the composite endpoint, including all-cause death, nonfatal MI, and cerebrovascular events.

Smits noted that about half of the lesions in non-infarct-related arteries that were identified as significant on angiography had FFR values above 0.8, indicating that they were not flow-limiting. A subgroup analysis confined to the complete revascularization arm of the trial showed that patients who did not have non-infarct-related arteries treated because of negative FFR findings had event rates similar to those who underwent additional interventions because of positive FFR values.

Thus, Smits concluded, “deferring treatment of angiographically significant coronary lesions in non-infarct-related arteries with an FFR of greater than 0.8 is safe and efficient.”

Serving as a discussant after Smits’ presentation, Nils Johnson, MD (University of Texas Health Science Center at Houston), said the trial is a major step forward in addressing how best to treat patients with acute STEMI and multivessel disease.

But he raised concerns regarding the benefits and costs of performing complete revascularization at the time of primary PCI, noting that if the additional interventions in the non-infarcted-related arteries are considered, the FFR-guided strategy requires additional PCIs in about half of patients. For comparison, only about 20% of patients in the culprit artery-only arm of the trial required additional interventions after the index procedure.

“If you move to an FFR-guided strategy, you need to pay for the extra wires and you probably increase the rate of additional PCI by about two- or threefold,” Johnson said. “That would be useful to do if you can show that there is a reduction in the hard endpoints of death or MI.”

He pointed out that there was a suggestion of such a benefit in Compare-Acute, although the difference did not reach statistical significance. That, he said, provides the motivation for larger clinical trials that can confirm or refute any such benefit, such as COMPLETE and FULL-REVASC, which each have enrollments of roughly 4,000 patients and have composite primary endpoints consisting solely of hard clinical outcomes.

The Compare-Acute findings were published simultaneously online in the New England Journal of Medicine.

Adding to Evidence in Favor of Complete Revascularization

Up until October 2015, guidelines contained a class III recommendation against treating non-infarct-related arteries at the time of primary PCI in patients who were hemodynamically stable. But based on the results of multiple trials—including PRAMI, CvLPRIT, and DANAMI3-PRIMULTI—that restriction was removed.

None of those trials, however, evaluated use of FFR to guide complete revascularization at the time of primary PCI.

In Compare-Acute, conducted at 24 centers in Europe and Asia, 885 patients who were stable following successful primary PCI were randomized 1:2 to treatment of all functionally significant non-infarct-related lesions identified by FFR—preferably during the index procedure—or the culprit artery only. FFR was performed in both groups, but the results were not made available to patients or physicians in the control group.

Flow-limiting lesions in non-infarct-related arteries were identified in 54.1% of patients in the FFR-guided group. Those patients, plus an additional five, underwent PCI of non-infarct-related arteries, mostly during the index procedure (83.4% of cases). The rest had staged procedures an average of 2.1 days later.

In the control group, 47.8% of patients had at least one flow-limiting lesion in a nonculprit artery. All patients in this arm of the trial were initially treated conservatively, although 59 of them—including 44 with functionally significant non-infarct-related lesions—had an elective PCI in the first 45 days. These procedures were not considered adverse outcomes.

In addition to the advantage in terms of MACCE, FFR-guided complete revascularization also showed benefits on some secondary outcomes, including the rate of hospitalization for heart failure, unstable angina, or chest pain (4.4% vs 8.0%; HR 0.54; 95% CI 0.29-0.99). Though not reaching statistical significance, there were also lower rates of nonfatal MI (2.4% vs 4.7%; P = 0.10) and death or MI (3.7% vs 6.4%; P = 0.10).

There were only two FFR-related serious adverse events identified, both in the control group.

Uncertain Impact on Hard Outcomes

Smits listed several reasons for doing FFR-guided revascularization of functionally significant nonculprit lesions at the time of primary PCI: the reductions in MACCE and readmissions for heart failure and chest pain, the ability to give patients a “one stop” procedure without requiring them to return to the cath lab, and the high likelihood that such an approach will be cost-effective. To that last point, however, he acknowledged that further studies are needed.

In a panel discussion following Smits’ presentation, Morton Kern, MD (University of California, Irvine), supported the approach, citing reductions in readmissions and revascularizations. One caveat, he said, is that interventional cardiologists should be cautious about interpreting FFR values near the infarct zone.

Others stressed the need to await the findings of the larger trials before implementing changes in practice.

To that point, Lars Køber, MD (Rigshospitalet, Copenhagen, Denmark), notes in an editorial accompanying the paper that there remains uncertainty about whether an FFR-guided approach will reduce hard outcomes.

“In one trial involving complete upfront revascularization that reported a reduction in a hard endpoint (death from cardiac causes or nonfatal myocardial infarction), annual mortality was similar to that among patients in the current study, but the patients were followed for a longer period of time; that trial did not include measurement of FFR,” he writes, noting that the Compare-Acute investigators are planning longer-term follow-up.

“Larger trials powered for hard endpoints (recurrent myocardial infarction or cardiovascular mortality) are needed to determine the effects of an FFR-guided complete revascularization strategy on these outcomes and to identify the subgroups of patients most likely to benefit (recruitment is ongoing in one trial of 3,900 patients,” he concludes, referring to the COMPLETE trial.

Photo Credit: Caitlin E. Cox