By Jeffrey Zimmet, MD, PhD

Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center

SYNOPSIS: In this proof-of-concept trial, treatment of non-flow limiting vulnerable plaque by PCI with bioabsorbable stents resulted in no significant difference in lesion-related events compared with optimal medical therapy.

SOURCE: Stone GW, Maehara A, Ali ZA, et al. Percutaneous coronary intervention for vulnerable coronary atherosclerotic plaque. J Am Coll Cardiol 2020; Sep 22;S0735-1097(20)37240-5. doi: 10.1016/j.jacc.2020.09.547. [Online ahead of print].

Plaque rupture events leading to myocardial infarction (MI) do not necessarily occur in areas with significant stenosis and flow limitation. Instead, the theory goes, areas of significant plaque burden containing a necrotic lipid core and covered with a thin cap of tissue represent “vulnerable” plaques that lead to acute coronary syndromes. The study of vulnerable plaque has been hampered by the dual problems of how to identify them and what to do about them once identified. First, intravascular imaging with a combination of intravascular ultrasound (IVUS) and near infrared spectroscopy (NIRS) has demonstrated a track record of recognizing and categorizing such plaque, with the obvious caveat that it requires an invasive procedure to do so. Indeed, the 2019 Lipid Rich Plaque study showed this technology can help identify both patients and plaques that are at significantly elevated risk for subsequent events.1

The PROSPECT ABSORB trial was designed to examine the results of treating such vulnerable plaques by stenting, specifically with the Absorb bioresorbable vascular scaffold (BVS). To this end, patients who presented with MI and had undergone successful percutaneous coronary intervention (PCI) of all ischemic lesions underwent imaging with a combined NIRS-IVUS catheter (Infraredx, Bedford, MA). Those who met a prespecified threshold for vulnerable plaque in angiographically non-obstructive lesions were eligible for participation. The authors examined 902 patients with MI, leading to the identification of 182 patients at 15 sites who were randomized to treatment with Absorb BVS or to medical therapy alone. Of 93 patients randomized to treatment with the Absorb, 92 underwent successful BVS implantation. One patient was found to have a vessel larger than the Absorb allows and was treated with a metallic drug-eluting stent. All patients were treated with guideline-directed medical therapy, including dual antiplatelet therapy, for six to 12 months and high-intensity statins. Overall adherence rates were high.

All but one patient had clinical follow-up available at 24 months, and 167 underwent follow-up angiography and IVUS at a median of 25 months. Unsurprisingly, minimum lumen area measured by IVUS was significantly wider in patients treated with the scaffold compared with those treated with medical therapy alone (6.9 ± 2.6 mm2 in BVS-treated lesions compared to 3.0 ± 1.0 mm2 in medical therapy alone-treated lesions). Binary restenosis, defined as diameter stenosis > 50% within the scaffolded segment, was present at follow-up in four of 86 BVS-treated lesions. Stenoses > 50% were seen in 12 of 80 lesions in the medical therapy arm (P = 0.02). Regarding clinical outcomes, the primary safety outcome of target lesion failure was not different between the two groups (4.3% vs. 4.5%). A nonsignificant trend was seen toward fewer “lesion-related MACE” in the BVS-treated arm (4.3% vs. 10.7%; OR, 0.38; 95% CI, 0.11-1.28; P = 0.12). The absolute difference here was caused primarily by fewer episodes of angina-driven revascularization, not by MI. The authors concluded interventional treatment of non-flow-limiting lesions with high plaque burden was safe and resulted in larger lumen size at follow-up. They argued this justifies a larger randomized trial powered to detect clinical outcomes.


Can stenting of non-obstructive coronary lesions, identified by intravascular imaging as vulnerable plaques, prevent downstream events such as MI? Or, alternatively, does the risk of the stenting procedure itself, or that of restenosis, outweigh the potential benefits of mechanical stabilization? How reliable is the combination of IVUS and NIRS at identifying troublesome lesions? From a scientific standpoint, these are interesting questions. For the most part, answers remain elusive.

To these points, this trial provided some valuable insight. Among patients who had recently suffered an MI, identification of nonobstructive vulnerable plaque by the study definition was made in only one in five patients. The primary safety endpoint, target-lesion failure at two years, occurred in fewer than 5% of patients, regardless of treatment assignment. Although the more inclusive endpoint of lesion-related MACE appeared to show a trend favoring the scaffold group, even this trend was driven primarily by angina requiring revascularization, not by MI or cardiac death. Even if this trend were borne out to be statistically significant in a larger trial, the benefit would be of treating the lesion now rather than treating it later, at a cost of unnecessarily scaffolding many more vessels. A larger trial is, by all accounts, in the works. For now, identification and interventional treatment of vulnerable plaque remains a goal.


  1. Waksman R, Di Mario C, Torguson R, et al. Identification of patients and plaques vulnerable to future coronary events with near-infrared spectroscopy intravascular ultrasound imaging: A prospective, cohort study. Lancet 2019;394:1629-1637.