ACC 2024: Preventive PCI Or Medical Therapy Alone For Atherosclerotic Coronary Vulnerable Plaques

Increased major adverse cardiac events are observed in vulnerable plaque (VP) identified through intracoronary imaging. Stabilizing plaque vulnerability is achieved through Optimal Medical Therapy (OMT). The safety and effectiveness of preventive percutaneous coronary intervention (PCI) for non-flow-limiting VP are uncertain. A study across 15 sites in four countries investigated whether preventive PCI for non-flow-limiting, imaging-defined VP improves outcomes compared to OMT alone. The trial involves lesions with coronary stenosis over 50%, significant angiographic stenosis with negative Fractional Flow Reserve (FFR), and two criteria for imaging-defined VP. Lesions are randomized to receive preventive PCI plus OMT or OMT alone, with the primary endpoint being target vessel failure at two years.

The study enrolled individuals aged ≥ 18 years with significant stenosis, negative FFR, or imaging-defined VP, eligible for PCI with observed bioresorbable vascular scaffold (BVS) and everolimus-eluting metallic stent (EES) or giant stent, with reference vessel diameter of 2.75-4.0 mm and lesion length ≤ 40 mm. Exclusion criteria included a preference for bypass surgery, prior stents or grafts, heavily calcified or angulated lesions, or contraindications to planned dual antiplatelet therapy (anti-DAPT). Initially using BVS, PCI later used cobalt-chromium EES. All target lesions underwent intravascular imaging, with patients receiving dual antiplatelet therapy for 6-12 months post-PCI. Follow-up occurred at 1, 6, 12, and 24 months, then annually for 2 years post-randomization. A typical case presented with 70% diameter stenosis, negative FFR, 2.11 mm², minimal lumen diameter, and 79% plaque burden. The primary endpoint was target vessel failure at 2 years, with secondary endpoints including components of the primary composite outcome, patient-oriented outcomes, procedural safety, stroke, bleeding events, and anti-anginal medication usage. 

In the study, 1,606 participants were randomly assigned in a 1:1 open-label manner to receive either preventive PCI plus OMT therapy (n = 803) or OMT alone (n = 803). The median duration of follow-up was 7 years. The baseline characteristics of the patients included a mean age of 64 years, with 25% being female and 30% having diabetes. The mean left ventricular ejection fraction was in 63% of patients. 83% of patients had stable angina or silent ischemia, while 13% had unstable angina, and 3% had non-ST elevation myocardial infarction.

The study found that after two years, target vessel failure occurred in 3.4% of patients with OMT alone and 0.4% with preventive PCI plus OMT, showing a significant difference. Over seven years, rates were 6.5% in preventive PCI plus OMT and 9.4% in OMT alone. Patient-oriented composite outcome rates at seven years were 14.4% in preventive PCI plus OMT and 19.3% in OMT alone. While differences were seen in cardiac events and target vessel-related outcomes, there was no significant disparity in ischemic-driven target vessel revascularization and hospitalization for unstable angina.

The secondary endpoint outcomes, including deaths from any cause, showed no difference. Similarly, no difference was observed in non-target vessel MI and non-target vessel revascularization. Definite stent scaffold thrombosis and stroke, as well as major bleeding events, also showed no difference between the groups. Subgroup analysis revealed no difference in interaction testing outcomes. All subsets actually favoured the preventive PCI group. However, at the seven-year follow-up, there were differences observed. Some PCI procedures on non-target vessels with a minimal lumen diameter of > 55% and using drug-reduced devices showed statistically significant differences

The trial clearly demonstrated that preventive PCI reduces the risk of death, cardiac events, target vessel Magnetic resonance imaging (MRI), ischemic-driven target-to-background ratio (TBR) and hospitalization for unstable or progressive angina at 2 years. Additionally, it reduced the composite patient-oriented outcomes of all deaths, myocardial infarction and repeated revascularization. This benefit was sustained throughout the seven-year follow-up period. In this trial, preventive PCI plus OMT resulted in a low incidence of major adverse cardiac events compared with OMT alone in patients with non-flow-limiting vulnerable plaque. These key findings might provide valuable insight into the role of preventive PCI in non-flow-limiting, high-risk VP in the future.

Panel Discussion: Preventive PCI Or Medical Therapy Alone For Atherosclerotic Coronary Vulnerable Plaques

The panel expert emphasized the high safety rates and favourable long-term outcomes achieved in the Preventive PCI or Medical Therapy Alone for Vulnerable Atherosclerotic Coronary Plaque (PREVENT) Trial. The difference in expected event rates in the trial was noted, and further clarification was sought regarding the basis of the 12 % estimated event rate and the medical therapy administered to patients, including their average or mean LDL levels. In response, the presenter, Dr Park, highlighted that there is still limited penetration of the physiologic concept in real-world practice, with less than 10 % of PCI procedures being physiologically guided. Despite this, a large number of patients exhibited negative FFR lesions, exceeding 50 % of those with significant stenosis, and imaging was primarily oriented toward identifying VP patterns. Dr Park recommended prioritizing a physiologic approach when assessing patients and lesions, followed by imaging evaluation for further patient management.

Another question was asked by a panel expert whether these were all VP or just patients with a large plaque burden because over 97% of the patients had criteria met for large plaque burden and small MLA, whereas only a smaller subset had abnormal entry criteria that were truly vulnerable as indicated by near-infrared spectroscopy (NIRS)  or Thin-cap fibroatheroma (TCFA). It was suggested that simplification for future use might be necessary as it could be unrealistic to expect every interventionalist to use multiple imaging modalities, although intravascular ultrasound (IVUS) may provide an adequate assessment. Dr. Park responded that, based on the data of trial, practical concerns primarily revolve around grayscale, which clearly indicates plaque burden and minimal luminal dimensions. These factors differ for various clinical characteristics, making it easier to identify plaque burden and minimal luminal dimensions in real practice using grayscale. However, more data on different characteristics and their influence on clinical events are needed, prompting a call for further study.

American College of Cardiology (ACC) Congress 2024, 6th April – 8th April 2024, Atlanta, Georgia, USA