PARIS -- For the treatment of stable coronary artery disease (CAD), medical therapy alone is no match for percutaneous coronary intervention (PCI) guided by physiological assessment, researchers here suggested.
Stenting guided by fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) was associated with better clinical outcomes over medical therapy alone when patients present with stable CAD or non-culprit lesions in stabilized acute coronary syndrome (ACS) in three studies presented in a late-breaking trial session at the annual EuroPCR meeting.
In turn, the PCR conference group and the sponsoring society for EuroPCR, the European Association of Percutaneous Cardiovascular Interventions (EAPCI), released a statement advocating FFR- and iFR-guided PCI as the treatment of choice for stable angina. This will officially be reflected in future European guidelines to come, Michael Haude, MD, PhD, of Germany's Städtische Kliniken Neuss, said at a press conference.
One such study supporting stenting in stable CAD with abnormal FFR in at least one stenosis was FAME-2. In a 5-year analysis presented at the session, PCI with drug-eluting stents (DES) was associated with lower odds of urgent revascularization and spontaneous MI at that point than was medical therapy alone for this population.
Randomization to receive a drug-eluting stent (DES) was associated with a lower primary combined endpoint of death, MI, and urgent revascularization versus medical therapy (13.9% versus 27%, HR 0.46, 95% CI 0.34 to 0.63) at 5 years in the 19 of 28 sites still participating in follow-up at that point.
Moreover, rates of these events in PCI recipients were low enough to be comparable to what was experienced by the 332 individuals who had normal-range FFR and were put on medical therapy from the start (15.7%, HR 0.88, 95% CI 0.55 to 1.39).
The advantage of stenting was driven by urgent revascularization (6.3% versus 21.1%, HR 0.27, 95% CI 0.18 to 0.41), along with a trend for reduced MI (8.1% versus 12%, HR 0.66, 95% CI 0.43 to 1.00) and a greater impact on spontaneous MIs (HR 0.62, 95% CI 0.39 to 0.99).
Panagiotis Xaplanteris, MD, PhD, of OLV-Clinic in Aalst, Belgium, and colleagues had their study simultaneously published online in the New England Journal of Medicine.
It's often said that PCI has no impact on hard endpoints in stable angina except for ischemia, according to session panelist Martin Leon, MD, of Columbia University Medical Center/New York-Presbyterian Hospital in New York City. A reduction in the "hard and important" endpoint of spontaneous MI "gives credence to the understanding that PCI improves not only ischemia but hard endpoints," Leon said.
However, the NEJM paper cautioned that this secondary endpoint of non-periprocedural MIs was not adjusted for multiple testing, "and any inferences drawn from the intervals as reported may not be reproducible."
All participants in the open-label FAME-2 trial got standardized medical therapy consisting of aspirin, ACE inhibitors, statins, and P2Y12 inhibitors. Most patients were highly compliant to their medications, Xaplanteris said, as 80% were still on their assigned drugs after 5 years without a significant difference in adherence between groups.
Separately, PCI was associated with better improvement in anginal frequency and quality of life even when stable CAD patients started with grey-zone FFR measurements, according to the GZ-FFR trial presented during the same session.
Outcomes of the Seattle Angina Questionnaire (SAQ) favored those who were randomized to PCI over medical therapy such that at 3 months, these patients had a lower anginal frequency (+20.58 versus +9.39 points for domain score, P=0.035) and a better quality of life (+24.04 versus +10.54 points, P=0.012).
Participants in this prospective single-center trial (n=110) all had FFR in the 0.75-0.82 range and lacked other PCI target vessels or residual ischemia, said presenter Barry Hennigan, MB BCh BAO, of the Mater Private Hospital and Cork University Hospital in Ireland.
Hennigan's group also had the study population undergo 3T perfusion MRI for the purposes of the study and showed that before randomization, rates of major ischemia and any ischemia were 17.4% and 24.4%, respectively, which fell to 7.3% and 12.2% after PCI.
Although stenting therefore only halved ischemia on repeat MRI, patients who started off with ischemia were especially likely to gain a 10-point boost in the SAQ quality of life domain (89% versus 53% for those who didn't have ischemia, P=0.046).
Finally, FFR-guided PCI was tied to lower odds of cardiac death or MI in stable CAD compared with medical therapy in pooled analysis of the FAME 2, DANAMI-3-PRIMULTI, and Compare-Acute studies (n=2,400).
Over 35 months of follow-up, there was a reduction in these hard outcomes (HR 0.72, 95% CI 0.54 to 0.96) that turned out to be driven by MI (HR 0.71, 95% CI 0.51 to 0.97), according to Frederik Zimmermann, MD, of Catharina Hospital Eindhoven in the Netherlands.
While the benefit of PCI tended to be more pronounced in those with at least one FFR-positive lesion, this wasn't a statistically significant interaction (P=0.065).
"These findings imply that appropriately-selected patients have a prognostic benefit from PCI independent of its impact on symptoms," Zimmermann told the audience.
Unlike FAME 2, the DANAMI and Compare-Acute studies enrolled patients that had a prior ST-segment elevation MI but had the culprit lesion treated and were hemodynamically stable at the time of randomization. Even so, "all trials were pointing in the same direction" in terms of the main findings, according to the author.
GZ-FFR was supported by the British Heart Foundation.
Haude disclose receiving grants/research support from Biotronik, as well as honoraria/consultation fees from Abbott, Biotronik, Cardiac Dimensions, OrbusNeich, and Philips Healthcare.
Xaplanteris and Zimmermann disclosed no relevant conflicts of interest.
Hennigan reported receiving honoraria for consulting for Philips Volcano.