Drug-eluting stents and in-stent restenosis

Stent types. A bare-metal stent (BMS) is a bare metallic scaffold that prevents acute recoil but has a high restenosis rate of 20–30%. A drug-eluting stent (DES) has three components — a metal platform, an antiproliferative drug and a polymer carrier. Current-generation DES use thin-strut cobalt-chromium or platinum-chromium platforms eluting everolimus, zotarolimus or sirolimus from biocompatible or biodegradable polymers.

Mechanism and benefit of DES. The antiproliferative drug inhibits vascular smooth muscle proliferation and neointimal hyperplasia, reducing restenosis and target-lesion revascularisation to under 5%. Current-generation DES also have lower stent thrombosis rates than BMS, so DES are now the default for virtually all patients, including the elderly and those at high bleeding risk — BMS are essentially obsolete.

In-stent restenosis (ISR) — definition and mechanism. ISR is renarrowing of ≥ 50% of the stented segment. Two mechanisms: neointimal hyperplasia (dominant with BMS, occurs early at 3–12 months) and neoatherosclerosis — new atherosclerotic plaque forming inside the stent (typical of DES, occurs late, beyond 1 year, and may rupture). Usually presents as recurrent stable angina, but up to a third present as an acute coronary syndrome.

Risk factors for ISR. Patient factors — diabetes mellitus, chronic kidney disease, continued smoking. Lesion factors — small vessel diameter (< 2.5 mm), long lesions, bifurcation and ostial lesions, heavily calcified lesions, chronic total occlusion. Procedural factors — stent under-expansion or malapposition, geographic miss, residual dissection, stent fracture. Premature discontinuation of dual antiplatelet therapy is the key modifiable factor for stent thrombosis.

Evaluation and treatment of ISR. Coronary angiography with intravascular imaging (IVUS or OCT) to define the mechanism — under-expansion needs high-pressure or cutting/scoring balloon dilatation, whereas neointimal hyperplasia needs antiproliferative therapy. Definitive options: drug-coated balloon (DCB) or implantation of a second DES; plain balloon angioplasty alone has an unacceptably high recurrence rate. CABG is considered for recurrent or diffuse multi-vessel ISR.

Antiplatelet therapy and geriatric considerations. Dual antiplatelet therapy (aspirin + a P2Y inhibitor) is 12 given for 6 months after elective PCI and 12 months after an acute coronary syndrome, shortened to 1–3 months in patients at high bleeding risk (ARC-HBR criteria — age ≥ 75, anaemia, CKD, prior bleeding, oral anticoagulation), followed by single antiplatelet therapy. Never stop DAPT prematurely — stent thrombosis carries about 40% mortality. In the very old prefer clopidogrel; prasugrel is contraindicated over 75 years, under 60 kg, or with prior stroke/TIA. If oral anticoagulation is also needed, use triple therapy for only about a week, then a DOAC plus clopidogrel.

The AGENT IDE trial (2024) showed that a paclitaxel-coated balloon was superior to conventional balloon angioplasty for coronary in-stent restenosis, reducing target-lesion failure — leading to the first FDA approval of a coronary drug-coated balloon in the United States (2024). DCB treatment avoids adding another metal layer, which is particularly attractive in older patients with recurrent ISR and high bleeding risk. In parallel, the 2023 ESC ACS guideline endorses abbreviated DAPT (1–3 months) followed by P2Y inhibitor 12 monotherapy in high-bleeding-risk patients.