Network meta-analyses on in-stent restenosis treatment: dealing with complexity to clarify efficacy and safety

Major advances have occurred during the last decade in the prevention of in-stent restenosis (ISR). Notably, drug-eluting stents (DES) drastically reduced the incidence of ISR as compared with that seen with bare-metal stents (BMS) (1). However, DES-ISR still occur especially when these devices are used in adverse clinical and anatomic scenarios (1). In addition, BMS are frequently used in selected patient subsets, including those unable to maintain a prolonged dual antiplatelet regimen and those at high bleeding risk (1). Therefore, nowadays treatment of ISR still represents a real challenge in every day clinical practice (2-4). Although the acute results obtained by repeated interventions are largely favorable the long-term outcome of these patients is frequently shadowed by clinical recurrences (2-4). Of concern, the underlying anatomic substrate of DES-ISR appears to be particularly complex and prone to recurrent ISR (2). Furthermore, recent evidence suggest that ISR presentation, formerly considered a benign phenomenon, is frequently associated with unstable symptoms, including a significant number of patients fulfilling current criteria for myocardial infarction (2). Many randomized clinical trials have compared different therapeutic strategies in patients with ISR (2-4). These include plain balloon angioplasty (BA), cutting balloon angioplasty, BMS, ablative devices, brachytherapy, DES and drug-coated balloons (DCB). Recent clinical practice guidelines suggest that both DES and DCB are effective (recommendation/evidence IA) for patients suffering from ISR (5). Nevertheless, the therapy of choice for these patients currently remains unsettled. Indeed, most randomized trials used surrogate late angiographic parameters (including percent diameter stenosis, binary restenosis, minimal lumen diameter and late lumen loss) as a measure of efficacy (2-4). This was a reasonable strategy to ensure an adequate enrollment of the required number of patients presenting with this relatively rare condition within a short time frame. Indeed, these trials provided major evidence on relative efficacy of these interventions. However, most randomized studies eventually enrolled a limited number of patients and, therefore, additional evidence is still warranted in order to establish the relative clinical efficacy and safety of these competing interventions.