How is in-stent restenosis classified and managed?

Classification and Management of In-Stent Restenosis

In-stent restenosis (ISR) is classified according to angiographic patterns, with treatment strategies tailored to the pattern type, with drug-eluting stents (DES) being the first-line therapy for clinical ISR regardless of the original stent type. 1

Classification of In-Stent Restenosis

Angiographic Classification for BMS Restenosis

• Pattern I: Focal lesions ≤10 mm in length
• Pattern II: In-stent restenosis >10 mm within the stent
• Pattern III: In-stent restenosis >10 mm extending outside the stent
• Pattern IV: Totally occluded in-stent restenosis 1

DES Restenosis

• Predominantly presents as focal (≤10 mm in length) pattern 1
• Occurs later than BMS restenosis (mean time ~12 months for DES vs. ~6 months for BMS) 2

Pathophysiology

Mechanisms of ISR

1. BMS restenosis: Primarily neointimal hyperplasia within the stent and at its edges 1
2. DES restenosis: Multiple factors including:
   • Drug resistance
   • Hypersensitivity
   • Stent underexpansion
   • Stent strut fracture
   • Nonuniform stent strut coverage
   • Gap in stent coverage 1
   • Neo-atherosclerosis (especially in late restenosis) 3

Risk Factors for Restenosis

• Diabetes mellitus
• Dyslipidemia
• Female gender
• Chronic kidney disease
• Smoking 1
• Longer lesion length (>30 mm)
• Smaller vessel diameter (<2.5 mm)
• Smaller post-treatment lumen diameter
• Residual stenosis after primary procedure 1

Diagnostic Evaluation

Clinical Presentation

• Typically presents as recurrent angina (77% of cases)
• Can present as unstable angina (5%) or non-ST-elevation myocardial infarction (10%)
• Approximately 8% may be asymptomatic 4

Diagnostic Tools

1. Coronary Angiography: Primary tool for diagnosis and classification
2. Intravascular Ultrasound (IVUS):
   • Recommended to determine the cause of ISR
   • Helps guide treatment strategy 1
   • Identifies mechanisms such as stent underexpansion, edge dissection, or geographic miss
3. Optical Coherence Tomography: Provides detailed assessment of tissue characteristics 2
4. Fractional Flow Reserve: Evaluates hemodynamic significance of ISR 2

Management Algorithm

1. For Restenosis After Balloon Angioplasty

• First-line treatment: Stent implantation
• Superior to repeat balloon angioplasty or atheroablation devices
• Target-lesion revascularization rates: 10% for stent-treated vs. 27% for balloon-treated patients 1

2. For BMS Restenosis

• First-line treatment: Drug-eluting stent
• Treatment outcomes by pattern type with balloon angioplasty, repeat BMS, or atheroablation:
  • Pattern I: 19% 1-year target-lesion revascularization
  • Pattern II: 35% 1-year target-lesion revascularization
  • Pattern III: 50% 1-year target-lesion revascularization
  • Pattern IV: 83% 1-year target-lesion revascularization 1
• DES significantly reduces recurrent restenosis compared to BMS or vascular brachytherapy 1

3. For DES Restenosis

• For focal DES restenosis:
  • Balloon angioplasty 1
  • Consider drug-coated balloon 5
• For nonfocal DES restenosis:
  • Repeat DES (preferably with a different drug if the original was a first-generation DES)
  • Consider BMS if appropriate
  • Consider CABG especially for diffuse, recurrent ISR 1
• For recurrent DES-ISR:
  • CABG is useful for symptomatic recurrent diffuse ISR 1
  • Brachytherapy may be considered to improve symptoms in patients with multiple recurrences 1, 6
  • Drug-eluting balloon angioplasty may reduce and delay in-stent re-restenosis 1

Follow-up Protocol

Post-PCI Surveillance

• Clinical and duplex ultrasound surveillance at:
  • 1 month
  • 6 months
  • Annually thereafter 1
• Include formal neurologic examination for carotid stents 1

Antiplatelet Therapy

• After treatment of ISR, dual antiplatelet therapy (DAPT) is essential
• Emphasize strict compliance with aspirin and P2Y12 inhibitor therapy 1
• Duration depends on stent type and patient risk factors

Important Caveats and Pitfalls

1. Avoid using standard velocity criteria for in-stent restenosis assessment:

   • Standard criteria lead to significant over-estimation of ISR
   • In-stent velocity thresholds for significant (≥70%) restenosis: peak-systolic velocity ≥3 m/s and end-diastolic velocity ≥1.4 m/s 1

2. Consider stent design in follow-up:

   • Braided stent design is an independent risk factor for first and recurrent in-stent restenosis 1
   • Normal in-stent velocities are affected by stent design (open-cell vs. closed-cell) 1

3. Recognize that ISR is not benign:

   • 10% of patients with DES-ISR may present with myocardial infarction 4
   • Post-CEA restenosis carries higher risk of symptoms than post-CAS restenosis 1

4. Avoid routine stress testing:

   • No proven benefit for routine periodic stress testing after PCI
   • If clinically indicated, stress imaging is preferred over exercise ECG alone 1

5. Consider IVUS for all cases of ISR:

   • IVUS helps determine the cause of ISR and guide appropriate treatment strategy 1
   • Particularly important for recurrent ISR cases