Implications of the presence and length of “geographic miss” on restenosis and the edge phenomenon in the INHIBIT trial

Abstract

Restenosis after percutaneous coronary intervention is an important limitation of current interventional cardiology practice. In particular, in-stent restenosis has a high recurrence rate.1 Recently, γ and β vascular brachytherapy were demonstrated to significantly reduce clinical and angiographic recurrence of in-stent restenosis.2–5 However, it has been reported that recurrence after brachytherapy is more frequently located at the margins of the radiation source where a decrease in radiation dose occurs—the so-called “edge effect.”6 Geographic miss has been implicated as an important contributor to the edge effect after brachytherapy.6–8 The INtimal Hyperplasia Inhibition with Beta In-stent Trial (INHIBIT) showed a significant reduction in binary restenosis after β brachytherapy (52% vs 26%, p <0.0001). Restenosis rates in nonradiated patients were similar in every analyzed subsegment: stent, injured, irradiated, and analysis segments. Conversely, radiated patients had an increase in restenosis because the analysis was extended beyond the stent, creating an apparent restenosis gradient between in-stent and the proximal and distal segments. Restenosis occurred exclusively outside the stent in 11.4% of radiated patients compared with 2.4% of patients taking placebos.5 The objectives of this study were (1) to determine if the β isotope (phosphorous-32 [P-32]) used in INHIBIT has a proliferative effect at the dose decrease zones, (2) to assess the frequency and the extent of injury occurring at or beyond the radiation edges (geographic miss), and (3) to determine the contribution of geographic miss to edge recurrence.