Percutaneous Coronary Intervention vs Medical Therapy for Coronary Lesions With Positive Fractional Flow Reserve (FFR) but Preserved Pressure-Bounded Coronary Flow Reserve (CFR): A Substudy of the Randomized Compare-Acute Trial

Objectives: Performing percutaneous coronary intervention (PCI) for fractional flow reserve (FFR) positive coronary lesions improves clinical outcomes and is recommended by international guidelines. It has been hypothesized that lesions with a positive FFR but a preserved coronary flow reserve (CFR) are less likely to be flow limiting and might best be treated medically. We investigated the association of CFR in FFR-positive lesions with clinical outcomes when treated medically, as well as the treatment effect of PCI vs medical therapy in FFR-positive lesions and a preserved CFR.

Methods: We performed a substudy of the randomized, multicenter Compare-Acute trial, in which stabilized ST-segment elevation myocardial infarction (STEMI) patients with non-culprit lesions were randomized to either FFR-guided PCI or medical therapy. Based on baseline and hyperemic pressure gradients, we computed physiologic limits of CFR, the so-called pressure-bounded CFR (pb-CFR), and classified lesions as low (<2) or preserved (≥2). The primary endpoint was 12-month major adverse cardiac and cerebrovascular event (MACCE) rate, defined as a composite of death from any cause, non-fatal myocardial infarction, revascularization, or cerebrovascular events.

Results: A total of 980 lesions from 885 patients were included in this substudy. In lesions with FFR ≤0.80, a total of 249 patients had a pb-CFR <2 and 29 patients had a preserved CFR (pb-CFR ≥2). The rate of MACCE at 1 year was not significantly different between patients with FFR ≤0.80 and pb-CFR <2 vs patients with FFR ≤0.80 and pb-CFR ≥2 (25% vs 17%, respectively; P=.39). Because of randomization, baseline characteristics were well balanced between patients with FFR ≤0.80 and pb-CFR ≥2 treated by either by PCI or medical therapy. Importantly, in patients with FFR ≤0.80 and pb-CFR ≥2, MACCE occurred more frequently in patients treated medically vs patients treated by PCI (44% vs 0%, respectively; P=.01).

Conclusions: Preserved or low pb-CFR did not alter clinical outcomes in patients with a positive FFR. Patients with FFR-positive coronary lesions but a preserved CFR had more clinical events when treated medically vs those treated with PCI.