Off-Label Use and the Spectre of Drug-Eluting Stent Thrombosis

Off-label use of drug-eluting stents (DES) occurs when the implantation takes place outside the scope of the approved label. In the case of DES, the “on-label” indications are limited to short de novo lesions in coronary arteries measuring 2.5 to 3.75 mm in diameter. As anticipated, the use of paclitaxel-eluting stents (PES) has shown excellent outcomes with low rates of target lesion revascularization at long-term follow-up in on-label indications.1Article see p 285 However, generalization of these data to the general population is problematic, because most patients fall into the “off-label” indication, which is associated with higher periprocedural risk. Since its launch in March 2004, thanks to its demonstrated ability to decrease target lesion revascularization, indications for PES were rapidly extended to those who would benefit most from it, such as patients with diabetes, renal failure, very small vessels, very long lesions, chronic total occlusions, bifurcations, left main coronary artery disease, in-stent restenosis, multivessel disease, acute myocardial infarction, or saphenous vein graft disease. In general, the more complex the case is, the more likely the occurrence of adverse events. Accordingly, the US Food and Drug Administration (FDA) required manufacturers to follow-up patients in the original clinical trials for 5 years after implantation and conduct registry studies of consecutively enrolled new patients, to collect data on “real-world” use.2The emergence of the adverse events logically materialized with an increased incidence of very late stent thrombosis (ST). Concerns arose about the impact of this rare complication on cardiac mortality, and the concerns of the scientific community reached their peak at the end of 2006.The article by Lasala et al3 in this issue of Circulation: Cardiovascular Interventions was born out of this surveillance program. The first Peri-Approval Registry: A Multi-Center Safety Surveillance (ARRIVE) trial was an FDA-mandated postmarketing trial …