Treatment Recommendations for In‑Stent Restenosis

Preferred First‑Line Therapy

The 2021 ACC/AHA/SCAI guidelines give a Class I recommendation (Level B‑R evidence) for repeat percutaneous coronary intervention (PCI) with a drug‑eluting stent (DES) when anatomic conditions are suitable, making DES the preferred first‑line treatment for ISR. 1

Network meta‑analyses of all available ISR treatment modalities (DES, bare‑metal stents, vascular brachytherapy, drug‑coated balloons, conventional balloons, rotational atherectomy) consistently show that DES achieve the lowest rates of restenosis and target‑vessel revascularization. 1
Among DES, everolimus‑eluting stents provide superior efficacy compared with other DES platforms for ISR treatment. 1
In the ISAR‑DESIRE randomized trial, angiographic restenosis at follow‑up was 14.3 % with sirolimus‑eluting stents, 21.7 % with paclitaxel‑eluting stents, and 44.6 % with plain balloon angioplasty. This demonstrates a clear advantage of DES over both alternative DES and POBA. 2
The same trial reported target‑vessel revascularization rates of 8 % for sirolimus‑eluting stents, 19 % for paclitaxel‑eluting stents, and 33 % for plain balloon angioplasty, confirming the clinical benefit of the more effective DES. 2

Plain balloon angioplasty alone results in 44.6 % angiographic restenosis at 6 months, markedly higher than the 14.3 % observed with DES in the same trial, underscoring POBA’s inferior efficacy. 2

Earlier ACC/AHA guidelines (2005‑2006) noted that rotational atherectomy, excimer laser therapy, and repeat stenting lacked evidence of superiority over balloon angioplasty for ISR, reflecting the pre‑DES era of practice. 3, 4

For patients with recurrent ISR who have multiple stent layers, unfavorable anatomy for additional DES, and are not surgical candidates, vascular brachytherapy remains a reasonable option, providing a treatment strategy that avoids placing another permanent metallic scaffold. 1

The Mehran classification categorizes in-stent restenosis into four distinct patterns based on lesion length and geographic distribution, with progressively worse outcomes from Class I through Class IV 5
Target-lesion revascularization rates correlate directly with Mehran class severity, ranging from 10% for Class I to 80% for Class IV 5, 6, 7

Drug-eluting stents are the preferred treatment for focal in-stent restenosis, with sirolimus-eluting stents demonstrating superior outcomes to paclitaxel-eluting stents 5
Repeat DES implantation remains the treatment of choice for diffuse patterns, though outcomes are progressively worse with increasing lesion length 5, 6
Class IV ISR carries an 80% target-lesion revascularization rate and warrants consideration of coronary artery bypass grafting in addition to repeat PCI with DES 5, 6

Brachytherapy can be useful for ISR but has been largely superseded by DES technology, with gamma radiation reducing target-lesion revascularization from 42% to 24% in the GAMMA-1 trial 8, 9
Balloon angioplasty alone for ISR results in unacceptably high restenosis rates (44.6%) and should be avoided when DES are available 5, 6

The most common error is failing to identify and address mechanical causes of ISR before attributing it solely to neointimal hyperplasia, with stent underexpansion, fracture, and malapposition requiring high-pressure balloon dilation or additional stent coverage 7
Premature discontinuation of dual antiplatelet therapy dramatically increases thrombosis risk, particularly after brachytherapy or repeat DES implantation 8, 9