What is the management strategy for in-stent restenosis (ISR) according to the Mehran classification?

Mehran Classification of In-Stent Restenosis

Classification System

The Mehran classification categorizes in-stent restenosis (ISR) into four distinct patterns based on lesion length and geographic distribution, with progressively worse outcomes from Class I through Class IV. 1

The classification system includes:

• Pattern I (Focal): Lesions <10 mm in length, subdivided into types A-D based on location 1
• Pattern II (Diffuse Intrastent): ISR ≥10 mm confined within the stent 1
• Pattern III (Diffuse Proliferative): ISR ≥10 mm extending beyond the stent margins 1
• Pattern IV (Total Occlusion): Complete occlusion of the previously stented segment 1

Prognostic Significance

Target-lesion revascularization rates correlate directly with Mehran class severity, ranging from best to worst outcomes 1:

• Class I (Focal): 10% TLR rate 1
• Class II (Diffuse Intrastent): 25% TLR rate 1
• Class III (Diffuse Proliferative): 50% TLR rate 1
• Class IV (Total Occlusion): 80% TLR rate 1

Management Strategy by Mehran Class

For Focal ISR (Class I)

Drug-eluting stents are the preferred treatment for focal in-stent restenosis, with sirolimus-eluting stents demonstrating superior outcomes to paclitaxel-eluting stents. 1

• DES implantation reduces angiographic restenosis to 14.3% compared to 44.6% with balloon angioplasty alone 1
• The ISAR-DESIRE trial showed sirolimus-eluting stents achieved 8% target-vessel revascularization versus 19% for paclitaxel-eluting stents (P=0.02) 1
• Drug-coated balloons represent an alternative strategy, though DES show superior long-term outcomes 2, 3

For Diffuse ISR (Classes II-III)

Repeat DES implantation remains the treatment of choice for diffuse patterns, though outcomes are progressively worse with increasing lesion length. 1, 4

• Both sirolimus and paclitaxel-eluting stents significantly outperform balloon angioplasty (14.3% and 21.7% restenosis versus 44.6%) 1
• Treatment with DES is associated with reduced target vessel revascularization (subdistribution HR: 0.623,95% CI: 0.511-0.760) and mortality (HR: 0.730,95% CI: 0.641-0.830) compared to other modalities 4
• Intravascular imaging should be considered to identify mechanical causes (underexpansion, fracture, malapposition) that require specific interventions 1, 3

For Total Occlusion (Class IV)

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. 1

• The extremely high failure rate with percutaneous approaches necessitates surgical evaluation 1
• If PCI is attempted, DES implantation after successful recanalization is recommended over other modalities 4

Alternative Treatment Modalities

Vascular Brachytherapy

Brachytherapy can be useful for ISR but has been largely superseded by DES technology. 1

• Gamma radiation (Ir-192) reduced target-lesion revascularization from 42% to 24% in the GAMMA-1 trial 1
• Critical limitations include late stent thrombosis (up to 14%), edge stenoses, and requirement for 6-12 months of dual antiplatelet therapy 1
• The TROPICAL study demonstrated SES superiority over historical brachytherapy controls 1

Plain Balloon Angioplasty

Balloon angioplasty alone for ISR results in unacceptably high restenosis rates (44.6%) and should be avoided when DES are available. 1

• PTCA may be considered only for focal DES restenosis when repeat stenting is not feasible 1
• The mechanism of improvement is primarily tissue extrusion rather than addressing the underlying neointimal hyperplasia 1

Critical Pitfalls

The most common error is failing to identify and address mechanical causes of ISR before attributing it solely to neointimal hyperplasia. 1, 3

• Stent underexpansion, fracture, and malapposition require high-pressure balloon dilation or additional stent coverage rather than drug-eluting technologies alone 1, 3
• Geographic miss (inadequate lesion coverage) necessitates extension of stent coverage beyond the original segment 1
• Ostial locations, particularly left circumflex ostia in bifurcation lesions, represent particularly high-risk anatomies with focal restenosis in 85% of cases 5

Premature discontinuation of dual antiplatelet therapy dramatically increases thrombosis risk, particularly after brachytherapy or repeat DES implantation. 1