Biodegradable polymer limus-eluting stents are noninferior to permanent polymer-based stents: the ISAR-TEST-4 trial

Background & rationale Over time, it has become clear that despite their dramatic success in tackling coronary restenosis, first generation drug-eluting stents (DES) are associated with a small but significant excess of adverse events late after stent implantation (>12 months), in particular, late stent thrombosis and delayed loss of antirestenotic eff icacy [1–4]. The central process underlying these events is delayed healing of the stent segment – a process that is characterized by delayed endothelialization, persistent fibrin deposition and chronic arterial wall i nflammation [5,6]. The etiology of delayed arterial healing is undoubtedly multifactorial and at times the definitive dissociation of drug and polymer effects can be difficult [5]. A number of preclinical studies demonstrate increasing arterial wall inflammatory responses late after index intervention [7–9]. At this time point the active drug is completely eluted (at least in limus agent stents) and ongoing inflammatory response to durable polymer residue appears to be the dominant pathology [5]. The time course of adverse events in human autopsy and clinical studies also appear to indicate that polymers rather than drugs are more likely to be the trigger for persistent inflammation and subsequent stent thrombotic events [10,11]. „ ISAR stent project The Individualizable Drug-Eluting Stent System to Abrogate Restenosis (ISAR) stent project seeks to investigate novel DES coatings yielding a high antirestenotic efficacy without recourse to permanent polymer (Table 1) [12–19]. Previous experience revealed that while a completely polymer-free microporous DES platform effectively reduced restenosis [14], the constraints imposed on drug-release control by total absence of carrier polymer resulted in an antirestenotic performance that was not noninferior to currently available gold-standard DES platforms [15,20]. Options to enhance the antirestenotic efficacy of platforms devoid of permanent polymer include the addition of a second drug targeted at another element of the restenotic response cascade or the employment of a self-degrading carrier polymer.