Rationale: Two-thirds of intracoronary thrombi causing acute coronary syndrome (ACS) result from rupture of lipid-rich plaques (LRP). After treatment of the culprit lesion in ACS patients, additional LRPs are found in approximately 50% of patients. Near infrared spectroscopy (NIRS) combined with intracoronary ultrasound (IVUS) can identify these vulnerable plaques during coronary angiography (CAG) and is able to assess plaque characteristics and the lipid-core burden index in a 4mm segment (LCBImm4). It is currently unknown whether treatment of LRPs leads to plaque stabilization, potentially reducing the number of subsequent ACS. We hypothesize that LRPs can be treated with balloons coated with an antiproliferative drug (i.e. drug-eluting balloons; DEB) to deliver selective pharmacotherapeutic treatment to halt the local atherosclerotic process and subsequently reduce the risk for atherosclerotic events.

Objectives: To determine the change in plaque characteristics of non-culprit LRPs, as measured with IVUS/NIRS, after treatment with DEB in patients with ACS.

Study design: Prospective single-arm clinical trial

Study population: Patients with non-ST-elevation acute coronary syndromes

Intervention: If a LRP is detected with IVUS/NIRS, it will be treated with DEB. In case multiple LRPs are detected, only one will be treated.

Main study endpoints: The difference in LCBImm4 between baseline and 9 months of plaques treated with DEB.

Inclusion Criteria:

• Patient has an acute coronary syndrome without ST-segment elevation on the ECG (NSTE-ACS), including non-ST-elevation myocardial infarction and unstable angina pectoris, defined according to the Fourth Universal Definition of Myocardial Infarction.
• An invasive revascularization strategy for NSTE-ACS with PCI is chosen.

Exclusion Criteria:

- Angiographic exclusion criteria:

1. Previous coronary artery bypass-grafting;

2. Presence of a chronic total occlusion;

3. Too many (complex) coronary lesions requiring staged PCI procedure(s);

4. Procedural complication of the index PCI;

   - Clinical exclusion criteria:

5. Unstable patients (the presence of cardiogenic shock, need for intubation, need for inotropes);

6. Patients with ST-segment elevations on the ECG requiring immediate primary PCI;

7. Body weight > 250 kg;

8. Known renal insufficiency (estimated Glomerular Filtration Rate [eGFR] <30 mL/min/1.73m2 or subject on dialysis);

9. Hypersensitivity or allergy to contrast with inability to properly pre-hydrate;

10. Presence of a comorbid condition with a life expectancy of less than one year;

11. Participation in another trial;

12. Subject is belonging to a vulnerable population (per investigator's judgment, e.g., subordinate hospital staff) or is unable to read or write.