Drug-Eluting Balloon Treatment vs. Guideline-Directed Medical Therapy for the Treatment of Lipid-Rich Plaques

Rationale:

Acute coronary syndromes (ACS) are often caused by rupture or erosion of certain high-risk vulnerable plaques. These plaques demonstrate specific features, such as a large lipid-rich necrotic core, a thin fibrous cap, and inflammation. Half of patients presenting with non-ST-segment elevation ACS have an additional vulnerable plaque, which increases their risk for non-culprit events during follow-up. Coronary intravascular ultrasound (IVUS) with the addition of near-infrared spectroscopy (NIRS) enables the identification of coronary lesions with high lipid content, quantified using the lipid-core burden index (LCBI) and is therefore able to distinguish plaques at risk to cause future non-culprit events. In addition, computed tomography coronary angiography (CCTA) is a non-invasive imaging modality that can identify high-risk plaque characteristics such as positive remodeling, low attentuation plaque, napkin-ring sign, and spotty calcification. Incorporating CCTA into this trial offers a unique opportunity to explore the potential of AI-based quantitative CT (AI-QCT) paramters by comparing them to IVUS-NIRS findings and clinical outcomes, which may support the future role of CCTA as a non-invasive tool for identifying and monitoring vulnerable plaques.

The main question remains whether local and systemic treatment of such high-risk plaques decreases the risk for adverse clinical outcome.

In our previous pilot study, DEBuT-LRP, we demonstrated that it was safe and feasible to treat vulnerable lipid-rich plaques with a drug-coated balloon (DCB) and that it was able to reduce the maximum LCBI on a 4 mm segment (maxLCBI4mm) after 9 months. In this randomized controlled trial, we intend to investigate the impact of DCB treatment on the maxLCBI4mm of lipid-rich plaques when compared to guideline-directed medical therapy alone.

Objective:

To test the hypothesis that paclitaxel-coated balloon treatment of non-obstructive non-culprit vulnerable lipid-rich plaques (LRP) leads to a greater reduction of the lipid-core burden index than guideline-directed medical therapy alone.

Study design:

A prospective two-arm randomized controlled trial.

Study population:

Patients older than 18 years with ACS who are scheduled for invasive percutaneous coronary intervention (PCI) of a native coronary artery.

Intervention:

DCB treatment of LRP in addition to guideline-directed medical therapy (GDMT).

Main study parameters:

The main study endpoint is the difference in maxLCBI4mm reduction from baseline to 9 months follow-up compared between the two randomization groups.

Secondary study endpoints are clinical safety endpoints (1. Flow-limiting dissection related to DCB-treatment necessitating bail-out stenting; 2. Periprocedural myocardial infarction; 3. Bleeding; 4. LRP lesion failure: cardiovascular death, myocardial infarction or repeat revascularization related to the index LRP, 5. Patient-oriented outcome: all-cause death, myocardial infarction or repeat revascularization) and imaging endpoints (1. IVUS-derived parameters; 2. QCA endpoints; 3. NIRS analyses of non-treated vessels; 4. CCTA-derived parameters).

Inclusion criteria

• Presenting with acute coronary syndrome (ACS);
• Successful PCI of a native coronary artery or major side branch;
• At least 2 native coronary arteries are accessible for invasive coronary imaging; i.e. not totally occluded and >2 mm and <6 mm reference vessel diameter.

Exclusion criteria

• Hemodynamically unstable (presence of cardiogenic shock, need for intubation, need for inotropes);
• Known hypersensitivity to paclitaxel;
• Procedural complications of the index PCI;
• Known renal insufficiency, i.e. eGFR <30 mL/min/1.73 m2;
• Hypersensitivity or allergy to contrast with inability to administer steroid and antihistamine premedication;
• Presence of a comorbid condition with a life expectancy of less than one year;
• Body weight >250 kg;
• Subject belonging to a vulnerable population (per investigator's judgment, e.g., subordinate hospital staff) or is unable to read or write.