Treatment of Long, Diffuse In-Stent Restenosis with<br />
Sirolimus-Eluting Stents

ABSTRACT: Treatment of long, diffuse in-stent restenosis remains a therapeutic challenge. We report the successful use of multiple sirolimus-eluting stents (three 33-mm long stents) in a long, diffuse in-stent restenotic lesion. No major adverse cardiovascular events, including acute/subacute/delayed stent thrombosis, were noted at ten months. Angiography at six months showed widely patent stents with 19% restenosis only at the worst segment.

Key words: coronary angioplasty, in-stent restenosis, drug-eluting stents

In-stent restenosis (ISR) remains the Achilles’ heel of coronary angioplasty.¹ Brachytherapy has proven effective in the treatment of ISR, when compared with simple angioplasty.^2–4 However, it may not be feasible in very long lesions or in vessels smaller than 2.75 mm. Drug-eluting stents (DES), apart from de novo lesions, have also been used to treat ISR. However, lesions treated in the study protocols were usually limited to short lesions and there are few data on the feasibility of using multiple DESs in the treatment of long, diffuse ISR. We report a case of the successful treatment of long, diffuse ISR with the use of multiple sirolimus-eluting stents. Case Report. A 74-year-old woman with a history of diabetes mellitus and hypertension was admitted because of unstable angina. Failing medical treatment, a coronary angiogram was performed, which revealed a normal left main artery, a calcified 55% diffuse stenosis of the left anterior descending (LAD) coronary artery, a 90% stenosis of the obtuse marginal (OM) branch of the left circumflex artery and a long, diffuse 80% stenosis of the right coronary artery (RCA) that extended from near the ostium to the distal portion (Figures 1A and 1B). Percutaneous coronary intervention (PCI) was first performed on the RCA. Vessel diameters were measured using the Automated Coronary Analysis program of the Integris BH5000 Cardiovascular Imaging System (Philips Medical Systems, Leiden, The Netherlands). The distal reference diameter of the RCA was 2.36 mm and the proximal was 2.83 mm. Due to the long total length of the diseased segments (85.6 mm), three stents were deployed focally and separately to the tightest areas of the distal, mid and proximal parts of the diseased segments of RCA, i.e., a 2.5 x 18 mm Pixel stent (Guidant Corporation, Temecula, California), a 2.5 x 18 mm S660 stent (Medtronic USA, Inc., Minneapolis, Minnesota) and a 3.0 x 15 mm S7 stent (Medtronic USA, Inc.), respectively. All stents were dilated up to 14 atmospheres. There was no residual stenosis inside the stented segments (Figures 1C and 1D). The patient was discharged and later readmitted for a successful staged PCI to the OM branch. The LAD was conservatively treated. The patient was readmitted two months later because of unstable angina. Coronary angiogram revealed severe subtotal ISR throughout the entire RCA (Figures 2A and 2B). PCI was performed again, with a view for brachytherapy. However, during the procedure, the patient developed marked atrioventricular block and chest pain with balloon inflation at the proximal RCA when the balloon occlusion time exceeded 20 seconds. This, coupled with the small size of the distal vessel ( Discussion. Brachytherapy is the mainstay of transcatheter treatment of ISR, although focal lesions may be treated with simple balloon angioplasty.⁵ However, brachytherapy may not be feasible in small vessels, long lesions or in cases where prolonged occlusion of the vessel is poorly tolerated. Restenosis is not eliminated after intra-coronary radiation and the widespread use of brachytherapy is limited by logistical requirements, such as additional safety facilities and multi-disciplinary involvement. The availability of DESs introduces a new option of treatment for de novo lesions.⁶ There are few data on the feasibility and safety of their use in ISR. Small studies showed promising results and large randomized clinical trials are in progress. Initial results are promising.^7,8 However, target lesions in these studies are usually short lesions with good vessel size and multiple stents (more than two) were rarely used in the study protocols.^7,8 There are obvious advantages in treating ISR with DES, such as avoidance of exposure to radiation sources, fewer demands on medical personnel (no physicist and radiation oncologist are needed) and potentially less immediate cost. Up-front investments toward the purchase of brachytherapy equipment and additional lead shielding of the catheterization suite are also not necessary. Procedure time may also be less. In cases where restenosis occurred again after DES treatment, the patient may still be sent for brachytherapy. The results in our patient suggest that DESs may be safe and effective in treating lesions with complex in-stent restenosis. A previous study showed that geographical miss in a non-covered segment between two DESs may lead to restenosis with neointimal hyperplasia.⁷ Therefore, a continuous deployment of three overlapping stents without gaps was performed in this patient. We did not know the best duration of post-procedural antiplatelet therapy and we empirically gave a six-month course of clopidogrel similar to that of brachytherapy. The six-month angiographic result without acute/subacute thrombosis is encouraging. However, there was one report that late thrombosis occurred in a patient receiving five overlapping DESs in the treatment of ISR three weeks after discontinuation of his five-month course of clopidogrel.⁷ Conclusion. To date, there are still many uncertainties about using DES to treat ISR with regard to the best drug, safety of multiple DESs, duration of post-procedural use of clopidogrel and the restenosis rate. The successful treatment of this patient demonstrated that the use of multiple DESs to treat ISR may be feasible and safe. However, large-scale randomized trials are needed to establish its efficacy and safety, particularly when compared with brachytherapy.