For a patient with in‑stent restenosis, which treatment is preferred—second‑generation drug‑eluting stent (DES), drug‑eluting balloon (DEB), or plain old balloon angioplasty (POBA)?

Treatment of In-Stent Restenosis: DES vs DEB vs POBA

For in-stent restenosis, drug-eluting stents (DES) and drug-coated balloons (DEB) are both superior to plain balloon angioplasty and should be your primary treatment options, with DES showing the lowest rates of target-vessel revascularization overall, particularly with everolimus-eluting stents. 1

Primary Treatment Recommendation

Drug-eluting stents represent the preferred first-line treatment for in-stent restenosis based on the most robust guideline evidence. 1 The 2021 ACC/AHA/SCAI guidelines give a Class 1 recommendation (Level of Evidence B-R) for repeat PCI with a DES when anatomic factors are appropriate 1. Network meta-analyses demonstrate that among all treatment modalities—including DES, BMS, vascular brachytherapy, drug-coated balloons, conventional balloons, and rotational atherectomy—DES consistently achieves the lowest rates of restenosis and target-vessel revascularization 1.

DES Selection Specifics

• Everolimus-eluting stents demonstrate superior efficacy compared to other DES types for treating ISR 1
• The ISAR-DESIRE trial showed angiographic restenosis rates of 14.3% with sirolimus-eluting stents versus 21.7% with paclitaxel-eluting stents, compared to 44.6% with balloon angioplasty alone 1
• Target-vessel revascularization occurred in only 8% of sirolimus-eluting stent patients versus 19% for paclitaxel-eluting stents and 33% for balloon alone 1

Drug-Coated Balloons as Alternative

Drug-coated balloons represent a reasonable alternative to DES, particularly when avoiding additional metallic layers is desirable. 1, 2 The 2021 ACC/AHA/SCAI guidelines state it is reasonable to perform repeat PCI with either a DES or DCB if anatomic factors are appropriate 2.

When to Choose DEB Over DES

• Patients who already have multiple stent layers where adding another permanent metallic layer may perpetuate the restenosis cycle 3, 4
• Recurrent ISR despite previous DES implantation, where additional metal may enhance neointimal hyperplasia and promote neoatherosclerosis 4
• Focal ISR patterns (Mehran Class I), where the mechanical scaffolding advantage of DES is less critical 3

DEB Performance Data

• Network meta-analysis shows DEB reduces target lesion revascularization with an odds ratio of 0.22 (95% CrI: 0.10-0.42) compared to POBA 5
• Direct comparison between DEB and DES shows similar TLR rates (OR: 0.92,95% CrI: 0.43-1.90), indicating non-inferiority 5
• DEB showed a trend toward lower MI rates compared to DES (63.0% probability of being ranked best treatment for MI prevention versus 1.7% for DES) 5
• The European Society of Cardiology gives drug-eluting balloons a Class IIa, Level B recommendation for ISR after prior bare metal stent implantation 2

Plain Balloon Angioplasty: Avoid as Monotherapy

Plain old balloon angioplasty (POBA) alone results in unacceptably high restenosis rates and should be avoided when DES or DEB are available. 3

• POBA produces 44.6% angiographic restenosis rates at 6 months versus 14.3% for DES 1
• Target lesion revascularization reaches 42.1% with POBA compared to 15.8-16.5% with repeat DES 6
• Multivariate analysis identifies POBA as an independent predictor of TLR with an odds ratio of 8.84 6
• Historical ACC/AHA guidelines from 2005-2006 noted that rotary ablation, excimer laser, and restenting showed no data indicating superiority over balloon angioplasty, but this was before the DES era for ISR treatment 1

Clinical Decision Algorithm

Step 1: Assess ISR Pattern and Complexity

Use the Mehran classification to stratify risk and guide treatment intensity: 3

• Class I (focal, ≤10mm): Either DES or DEB acceptable; DEB may be preferred to avoid additional metal layer 3
• Class II-III (diffuse, >10mm): DES preferred for mechanical scaffolding advantage 3
• Class IV (total occlusion): Consider CABG in addition to repeat PCI with DES due to 80% TLR rate 3

Step 2: Evaluate Stent Burden

• First episode of ISR with single stent layer: DES is preferred first-line treatment 1
• Multiple previous stent layers: DEB becomes more attractive to avoid perpetuating the metal-hyperplasia cycle 3, 4
• Recurrent ISR after DES: Consider switching to DEB or alternative DES type, though switching DES types alone does not reliably prevent recurrence 6

Step 3: Consider Anatomic Suitability for CABG

For diffuse ISR in large vessels, recurrent episodes despite repeat PCI, or complex presentations like CTO with multivessel disease, CABG may be preferred if anatomy is suitable. 1

Step 4: Identify Mechanical Causes Before Attributing to Neointimal Hyperplasia

The most common error is failing to identify mechanical causes of ISR—including stent underexpansion, fracture, and malapposition—which require high-pressure balloon dilation or additional stent coverage before drug delivery. 3 Use intravascular imaging (IVUS or OCT) to identify these correctable mechanical issues 4.

Special Considerations and Pitfalls

High-Risk Clinical Features

Independent predictors of recurrent TLR after ISR treatment include: 6

• Diabetes mellitus (OR 3.4)
• Hemodialysis (OR 7.74)
• Nonfocal ISR patterns (OR 3.35)
• Previous myocardial infarction (OR 3.26)

These patients warrant more aggressive treatment strategies and closer follow-up.

Ostial Location Considerations

Ostial left circumflex lesions represent particularly high-risk anatomy for ISR. 7 When treating ostial LCx in the context of distal left main disease:

• Single-stent approaches with provisional side branch stenting show TLR rates <5% 7
• Two-stent techniques increase ostial LCx restenosis to 25-42% without mortality benefit 7
• Avoid routine two-stent techniques unless there is a large side branch with high occlusion risk 7

Antiplatelet Therapy Duration

Premature discontinuation of dual antiplatelet therapy dramatically increases thrombosis risk, particularly after repeat DES implantation. 3 Ensure adequate DAPT duration based on current guidelines.

Vascular Brachytherapy as Last Resort

For patients with recurrent ISR who have multiple stent layers, unfavorable anatomy for additional DES, and are not CABG candidates, vascular brachytherapy remains a reasonable option. 1 This circumvents the need for another stent layer 1. However, brachytherapy has been largely superseded by DES and DEB technology in contemporary practice 3.

Outcomes Data Summary

The hierarchy of effectiveness for preventing target lesion revascularization: 5

1. DEB: 59.9% probability of being ranked best treatment
2. DES: 40.1% probability of being ranked best treatment
3. POBA: 0.1% probability of being ranked best treatment

Both DEB and DES reduce TLR by approximately 75-80% compared to POBA, with no significant difference between DEB and DES in head-to-head comparison. 8, 5