Repeated beta irradiation for recurrent coronary in-stent restenosis.

Vascular brachytherapy (VBT) is the only proven treatment option for patients with in-stent restenosis. In seven randomised trials with almost 1500 patients that evaluated {gamma} (five studies) and ß (two trials) irradiation, target vessel failure reduction ranged from 73% to 34% by VBT compared with conventional angioplasty.1 However, the reported restenosis rates with the active treatment still varied between 17% and 32%.1 We therefore postulated that repeat VBT is safe and efficacious for preventing refractory in-stent restenosis in high risk patients with failed VBT.

METHODS

Beginning in January 1999, VBT was applied for all patients with in-stent restenosis. VBT was systematically performed with intravascular ultrasound (IVUS) guidance. The repeat procedure was performed with a strontium/yttrium-90 source train (BetaCath, Novoste, Norcross, Georgia, USA). The design and application of this catheter have been described previously.2 The dosimetry was based on the manufacturer’s recommendations but taking into account not the angiographic vessel reference diameter but the external elastic membrane diameter (as determined by IVUS). The mean dose delivered at 2 mm from the source centre was 23.3 (2.2) Gy during the index procedure and 25.3 (2.2) Gy during the repeat intervention. Percutaneous coronary intervention (PCI) was performed according to standard clinical practice.

Failed VBT was defined as angina recurrence combined with target vessel failure (as documented by any repeat angiography: premature depending on early symptom recurrence or at the planned six month control). Repeat VBT was considered for patients estimated to be at high risk for refractory in-stent restenosis or if they had a prognostic risk—that is, diffuse or ostial in-stent restenosis or total occlusion, or proximal left anterior descending artery stenosis. Focal edge effect stenoses and non-prognostic lesion locations in symptomatic patients were treated by conventional PCI. Written informed consent was obtained from all patients before intervention. The study was approved by the hospital ethics committee. All VBT patients were prospectively entered in a dedicated database by a person not taking part in the interventions.

A combined antiplatelet treatment (aspirin 100 mg and clopidogrel 75 mg daily) was prescribed for at least six months after the index procedure and for one year after the second VBT. Control angiography was mandatory at six months in all VBT patients and systematic long term clinical follow up was carried out.

RESULTS

Between July 1998 and March 2003, 251 VBT interventions were performed at our institution: 22 patients were treated for primary restenosis prevention and 229 patients for in-stent restenosis. VBT failed in 34 patients (14.8%): 23 underwent conventional PCI and 11 underwent repeat VBT. The baseline clinical and angiographic demographics were comparable for both groups. Concerning the repeat VBT group, mean (SD) age was 60 (7) years, nine patients were men, and two had diabetes. All patients who underwent a repeat procedure had incapacitating angina pectoris. Angina recurred at 7 (2) months (range 4–10) after the first, failed VBT. The restenosis pattern (table 1Go) was diffuse in the majority of patients at the first presentation and remained diffuse with exacerbation to total occlusion in two patients. In the focal restenosis group, two patients had ostial in-stent restenosis. The cause of recurrent in-stent restenosis was an evident geographical miss in two patients (a focal and a diffuse pattern case). IVUS and angioplasty were successful before irradiation therapy in all patients. During repeat VBT, a 40 mm source train was used in seven patients and a pullback technique was required in two because of the length of the restenotic segment. No additional stents were implanted and no evidence of geographical miss was seen at repeat intervention. Table 1Go shows quantitative coronary angiography and IVUS data. During the index procedure, the minimum in-stent luminal area increased from mean (SD) 5.8 (1.8) to 7.5 (1.4) mm2. This area was maintained at the repeat intervention at 7.8 (2.1) mm2 and further expanded to 8.9 (1.8) mm2. All repeat interventions were technically successful and there were no adverse clinical events during the in-hospital phase.