In an adult patient with coronary risk factors, does the presence of a vulnerable plaque identified by near‑infrared spectroscopy (NIRS) justify preventive percutaneous coronary intervention (PCI)?

Does Vulnerable Plaque by NIRS Justify Preventive PCI?

No, the presence of vulnerable plaque identified by NIRS alone does not currently justify preventive PCI in routine clinical practice, though emerging evidence from the 2024 PREVENT trial suggests this paradigm may be shifting for specific high-risk plaques meeting strict imaging criteria.

Current Guideline Position on Vulnerable Plaque Detection

The fundamental limitation is that coronary angiography cannot assess whether an atherosclerotic plaque is stable or "vulnerable" (i.e., likely to rupture and cause an acute coronary syndrome) 1. This represents a critical gap in traditional coronary assessment that imaging technologies like NIRS attempt to address.

Technical Capabilities and Limitations of Plaque Imaging

NIRS-IVUS enhances conventional IVUS through its ability to characterize a plaque's lipid core 1, but several technical constraints limit clinical decision-making:

• The thin fibrous cap of vulnerable plaques measures approximately 70 micrometers, which is 10 times beyond the present in-plane resolution of MDCT (750 micrometers) 2
• Current technology can identify plaque composition characteristics but cannot assess whether a plaque is truly "vulnerable" or likely to rupture 2
• Optimal diagnostic image quality cannot be obtained in approximately 15% of coronary vessels 2

What Existing Guidelines Say About Preventive Intervention

The 2014 ACC/AHA guidelines for stable ischemic heart disease make no recommendation for preventive PCI of vulnerable plaques 1. The guidelines emphasize that:

• Many stenoses considered severe (≥70% luminal narrowing) do not restrict coronary blood flow, whereas others considered "insignificant" (<70%) are hemodynamically significant 1
• Intravascular ultrasound and optical coherence tomography provide more precise information about plaque morphology than coronary angiography and can be useful adjunctive tests 1
• FFR can assess the hemodynamic significance of angiographically intermediate lesions 1

The 2010 ACC/AHA risk assessment guidelines explicitly state: "There are no published trials evaluating the impact of specific therapy on clinical outcome in patients identified as having noncalcified atheroma by CCTA" 1.

Emerging Evidence: The PREVENT Trial (2024)

The landscape changed significantly with the 2024 PREVENT trial, which represents the first large randomized trial showing potential benefit of focal treatment for vulnerable plaques 3.

PREVENT Trial Key Findings

In 1,606 patients with non-flow-limiting (FFR >0.80) vulnerable plaques identified by intracoronary imaging:

• The primary composite outcome occurred in 0.4% of PCI patients versus 3.4% of medical therapy patients at 2 years (absolute difference -3.0 percentage points; p=0.0003) 3
• Preventive PCI reduced major adverse cardiac events arising from high-risk vulnerable plaques compared with optimal medical therapy alone 3
• Safety was comparable: death occurred in 0.5% versus 1.3% and MI in 1.1% versus 1.7% (not statistically different) 3

Critical Inclusion Criteria from PREVENT

The trial enrolled patients with non-flow-limiting lesions (FFR >0.80) that met specific high-risk imaging criteria 3. This is crucial—not all vulnerable plaques qualified, only those meeting strict definitions by intracoronary imaging.

Supporting Evidence from Other Trials

PROSPECT ABSORB (2020)

This earlier trial randomized 182 patients with angiographically mild lesions (median diameter stenosis 41.6%) but large plaque burden (median 73.7%) 4:

• PCI substantially enlarged the follow-up minimum lumen area (6.9 mm² vs 3.0 mm²; p<0.0001) 4
• Target lesion failure at 24 months was similar (4.3% vs 4.5%; p=0.96) 4
• Randomized lesion-related MACE occurred in 4.3% of PCI patients versus 10.7% of medical therapy patients (not statistically significant, p=0.12) 4

2025 Meta-Analysis

A recent meta-analysis of 4 randomized trials with 1,843 participants found 5:

• No statistical difference in overall MACE (RR=0.38; 95% CI 0.10-1.45; p=0.16) 5
• Significant reduction in clinically-driven revascularization (RR=0.11; p<0.001) and hospitalization for unstable/progressive angina (RR=0.16; p=0.004) 5
• No difference in all-cause death or MI 5

Clinical Algorithm for Decision-Making

Step 1: Confirm Non-Flow-Limiting Status

• Measure FFR to document FFR >0.80 3
• Do not proceed with preventive PCI if the lesion is hemodynamically significant—this becomes standard revascularization, not preventive intervention

Step 2: Characterize Plaque with Multimodality Imaging

Vulnerable plaque criteria should include multiple high-risk features 6, 7:

• Large plaque burden (≥65-70%) 3, 4
• Small minimal luminal area (typically <3.0 mm²) 3, 4
• Thin fibrous cap 6, 7
• Large lipid/necrotic core (high NIRS signal) 6, 7, 4

Step 3: Optimize Medical Therapy First

Pharmacology, including lipid-lowering agents, and intensive risk-factor control are pivotal for management of vulnerable plaques 6. This remains the foundation regardless of imaging findings.

Step 4: Consider Patient-Specific Factors

• Prior acute coronary syndrome presentation 3, 4
• Diabetes status 3
• Ability to tolerate dual antiplatelet therapy
• Procedural risk (1.5% complication rate for diagnostic angiography) 1

Critical Caveats and Common Pitfalls

Pitfall 1: Treating Based on NIRS Alone

NIRS identifies lipid content but cannot definitively predict which plaques will rupture 1, 2. The PREVENT trial used combined intracoronary imaging (IVUS + NIRS), not NIRS in isolation 3.

Pitfall 2: Ignoring Hemodynamic Significance

FFR assessment is mandatory to confirm non-flow-limiting status 3. Treating a hemodynamically significant lesion is standard care, not preventive PCI.

Pitfall 3: Inadequate Image Quality

Do not rely on plaque characterization from suboptimal quality studies 2. Assessment of noncalcified plaque is limited to studies of very high image quality 2.

Pitfall 4: Overlooking Medical Therapy

Recurrent events tend to accrue despite intensive pharmacotherapy, but medical therapy remains foundational 6. Preventive PCI is adjunctive, not replacement therapy.

Current Clinical Recommendation

Based on the PREVENT trial results, preventive PCI may be considered for non-flow-limiting vulnerable plaques that meet strict multimodality imaging criteria (large plaque burden ≥65-70%, small MLA, high lipid content by NIRS, FFR >0.80) in patients already on optimal medical therapy 3. However, this represents an expansion of traditional PCI indications that has not yet been incorporated into formal guidelines 1.

For routine clinical practice in 2025, the safest approach is intensive medical therapy with lipid-lowering agents and risk factor modification for all vulnerable plaques, reserving preventive PCI for research protocols or highly selected cases discussed in multidisciplinary conferences 6, 7. The PREVENT findings support consideration to expand indications, but this is the first large trial showing potential effect 3, and guideline integration typically requires multiple confirmatory studies.

The presence of vulnerable plaque by NIRS alone, without comprehensive intracoronary imaging confirmation of multiple high-risk features and FFR documentation of non-flow-limiting status, does not justify preventive PCI outside of clinical trials 1, 2, 3.