Patients with intracoronary imaging-defined vulnerable plaques (VP) have a higher risk of experiencing major adverse cardiac events.¹ While optimal medical therapy (OMT) is the standard approach to stabilize plaque vulnerability, the effectiveness and safety of focal preventive percutaneous coronary intervention (PCI) have not been established.¹  At the ACC Annual Scientific Session 2024, Professor Seung-Jung Park from the University of Ulsan College of Medicine, Seoul, South Korea, presented results from the PREVENT trial, which aimed to assess whether focal preventive PCI of non-flow-limiting imaging-defined VPs improves clinical outcomes compared to OMT alone.¹

This trial recruited adult patients who had angiographically significant stenosis (>50%) with negative fractional flow reserve (FFR) (≥0.80) who met at least 2 of the following criteria for VP: 1) minimal lumen area (MLA)<4mm², 2) plaque burden >70%, 3) thin-cap fibroatheroma (TCFA) detected by radiofrequency-based intravascular ultrasound (RF-IVUS) or optical coherence tomography (OCT), or 4) large lipid-rich plaque detected by near-infrared spectroscopy (NIRS) (maxLCBI_4mm>315).¹  Other key inclusion criteria were eligibility for PCI with a bioresorbable vascular scaffold (BVS) or everolimus-eluting stent (EES), reference vessel diameter of 2.75mm-4.0mm and lesion length of ≤40mm.¹

In total, 1,608 patients who met the imaging criteria of VP were included and randomly assigned 1:1 to receive preventive PCI + OMT (n=803) or OMT alone (n=803).¹ PCI was initially performed using BVS, but when these were withdrawn, cobalt-chromium everolimus-eluting metallic stents (CoCr-EES) were used as the default device of PCI.¹ Patients received dual antiplatelet therapy (DAPT) for at least 6 or 12 months after PCI according to clinical presentation and anatomical complexity.¹ Patients were followed up at 1, 6, 12  and 24 months and every year thereafter until the last enrolled patient reached 2 years after randomization.¹

The primary endpoint of the study was target vessel failure, which was a composite of death from cardiac causes, target vessel myocardial infarction, ischemia-driven target vessel revascularization, or hospitalization for unstable or progressive angina, at 2 years post-randomization.¹ Results of the trial showed that the cumulative incidence of target vessel failure at 2 years follow-up was significantly lower in the preventive PCI + OMT group compared to the OMT alone group (0.4% vs. 3.4%; HR=0.11; 95% CI: 0.03-0.36; log-rank p=0.0003).¹ At 7 years follow-up, the trend remained the same with a cumulative incidence of 6.5% in the PCI + OMT group compared to 9.4% in the OMT alone group (HR=0.54. 95% CI: 0.33-0.87; log-rank p=0.0097).¹

The secondary endpoints of the study were individual components of the primary composite outcome, a patient-oriented composite outcome (all-cause mortality, all myocardial infarctions, or any repeat revascularization), procedural safety outcomes, stroke, bleeding events and number of anti-anginal medications used at each time point.¹ Within the primary composite outcome, only ischemia-driven target vessel revascularization (HR=0.44; 95% CI: 0.25-0.77) and hospitalization for unstable or progressive angina (HR=0.19; 95% CI: 0.06-0.54) were significantly improved with PCI + OMT compared to OMT alone.¹ The cumulative incidence of the patient-oriented composite outcome was also significantly lower in the preventive PCI + OMT group compared to the OMT alone group at 7 years follow-up (14.4% vs. 19.3%; HR=0.69; 95% CI: 0.50-0.95; log-rank p=0.022).¹ Individual components within the patient-oriented composite outcome, as well as stroke and major bleeding events, were not significantly different between the groups.¹

Subgroup analyses of the primary outcome did not show any significant differences at 2-year follow-up, but patients who had PCI of non-target vessel, median diameter stenosis of ≥55% by quantitative coronary angiography, or who received PCI with CoCr-EES instead of BVS, experienced greater clinical benefit at 7-year follow-up with PCI + OMT compared to OMT alone.¹

In summary, the PREVENT trial is the first large-scale, randomized controlled study to compare preventive PCI + OMT with OMT alone for the treatment of non-flow limiting, imaging-defined VPs.¹ Preventive PCI + OMT resulted in a lower incidence of major adverse cardiac events and this benefit was sustained throughout the 7-year follow-up period, thus providing new insights on the role of preventive PCI for VPs in the future.