Early Win for Preemptive Stents on Vulnerable Coronary Plaque

ATLANTA — The concept of using stents to seal off non-flow-limiting vulnerable plaques, before they have a chance to rupture, worked out in the first major trial testing this provocative idea.

Compared with standard medical therapy alone, focal preventive percutaneous coronary intervention (PCI) resulted in a large reduction in target vessel failure at 2 years (0.4% vs 3.4%; HR 0.11, 95% CI 0.03-0.36) — the benefit persisting out to 7 years (6.5% vs 9.4%; HR 0.54, 95% CI 0.33-0.87), reported Seung-Jung Park, MD, PhD, of University of Ulsan College of Medicine and Asan Medical Center, Seoul.

Target vessel failure was defined as a composite of cardiac death, target vessel myocardial infarction (MI), ischemia-driven target vessel revascularization, hospitalization for unstable or progressive angina — the benefit of PCI apparently driven by the latter two endpoint components.

Park presented the PREVENT trial results here at the American College of Cardiology (ACC) meeting. The study manuscript was simultaneously published in The Lancet.

“Given that PREVENT is the first large trial to show the potential effect of the focal treatment for vulnerable plaques, these findings support consideration to expand indications for [PCI] to include non-flow-limiting, high-risk vulnerable plaques,” the authors wrote.

They reported that the benefits of preventive PCI on vulnerable plaque were consistent across patient subgroups by age, sex, diabetes status, and clinical presentation.

Vulnerable plaque refers to the lipid-rich atherosclerotic coronary plaque that is not flow-limiting. Though they may look benign on angiography, these plaques show up as thin-capped fibroatheromas — with a large plaque and lipid-rich necrotic core — on intravascular imaging and are associated with major adverse cardiovascular events down the line.

“Acute rupture of vulnerable plaques was shown to be the underlying culprit in 73% of all thrombotic coronary events resulting in fatality, suggesting a great mechanistic relevance of vulnerable plaques,” according to Josip Andelo Borovac, MD, PhD, of University Hospital of Split in Croatia, in an accompanying editorial.

In the present trial, participants had to meet certain criteria for vulnerable plaque in untreated, non-culprit lesions. Vulnerable plaques were assessed largely with intravascular ultrasound (IVUS), with near-infrared spectroscopy assessments being commonly employed as well.

Clinical guidelines currently reserve PCI for coronary lesions that are hemodynamically flow-limiting or have caused an acute coronary syndrome (ACS).

“I think it is brave to challenge the paradigm that medical therapy alone is sufficient to treat vulnerable, moderate, nonobstructive plaque. And here we show that we had high rates of safety and great long-term outcomes with an interventional approach,” commented ACC session discussant Dawn Abbott, MD, of Brown University and Lifespan Cardiovascular Institute in Providence, Rhode Island.

Abbott nevertheless remarked on the questionable generalizability of taking an image-heavy approach to the real world. “I think it’s unrealistic for every interventionalist to use multiple imaging modalities,” she said, suggesting gray-scale IVUS alone may provide adequate assessment of vulnerable plaque.

Similarly, Marc Bonaca, MD, MPH, of University of Colorado School of Medicine, Anschutz in Aurora, questioned whether the right tools are in place to identify and subsequently treat vulnerable plaque. During a press conference, he suggested considering a noninvasive imaging approach such as CT angiography.

In the meantime, focal preventive PCI is not ready for primetime, he warned.

PREVENT was an open-label trial conducted in South Korea, Japan, Taiwan, and New Zealand.

Park’s group screened 5,627 people with stable coronary disease or ACS undergoing cardiac catheterization, seeking adults with coronary stenosis (>50%) with negative fractional flow reserve (FFR 0.80 or higher) and imaging evidence of vulnerable plaque.

Investigators ultimately had people randomized to optimal medical therapy with or without PCI, with 803 patients in each group.

The two study arms shared comparable baseline characteristics. Nearly three in four participants were men with a median age of 65 years. LDL cholesterol was around 90 mg/dL. Nearly 85% had presented with stable angina or silent ischemia and almost all the rest had unstable angina; fewer than 5% had a recent MI as part of their clinical presentation.

Each patient had approximately one target lesion with vulnerable plaque. Median FFR of all target lesions was 0.86 and mean diameter stenosis 54.5%.

Notably, the initial stage of PREVENT had operators perform PCI with troubled first-generation bioresorbable vascular scaffolds. Starting in 2017, operators switched to everolimus-eluting drug-eluting Xience stents as default for the last two-thirds of the PCI cohort.

Optimal medical therapy consisted of lifestyle and medical therapies such as high-intensity statins. Less than 2% of people were on PCSK9 inhibitors, the early initiation of which was previously shown to regress coronary plaque after an ACS.

Park reported no difference in serious adverse events between PCI and conservative treatment groups in PREVENT. Throughout follow-up, there were two scaffold thromboses in target lesions that underwent preemptive PCI versus three stent thromboses in non-target lesions among controls.

Besides bringing down target vessel failure, preventive PCI also reduced the patient-oriented outcome counting all-cause death, any MI, or any repeat revascularization at 2 years (0.6% vs 1.9%) and 7 years (6.2% vs 8.6%) compared with conservative treatment.

Park cautioned that 9% of the PCI arm had crossed over to optimal medical therapy alone; 1% went the other way around. Nevertheless, the trial’s main results were supported by as-treated and per-protocol analyses.

PREVENT investigators acknowledged that their open-label study design left room for placebo effect and ascertainment bias. They were also limited by lower-than-expected event rates.

As such, they pointed to multiple ongoing randomized trials — COMBINE-INTERVENE, INTERCLIMA, FAVOR V AMI, and VULNERABLE — for more answers about preventive PCI on vulnerable plaques.