saphenous vein grafts; however, use in these bypass grafts is an example of "off-label" use of drug-eluting stents. That is, this application has not been sufficiently examined by the Food and Drug Administration for that agency to recommend the use. For "on-label" applications, the FDA "believes that coronary drug-eluting stents remain safe and effective when used for the FDA-approved indications. These devices have significantly reduced the need for a second surgery to treat restenosis for thousands of patients each year." Some concern has been expressed about the overzealous use of stents in general. Two studies found about half of patients received stents for unapproved reasons, with worse outcomes for the patients in both studies. More recent data suggest off-label use of both bare-metal stents and drug-eluting stents brings increased risks. However, drug-eluting stents seemed to have similar or improved rates of death or myocardial infarction compared with bare-metal stents, and consistently reduced the need for target vessel revascularization. Overall, the data support the use of drug-eluting stents for off-label indications. Efficacy Benefits Drug-eluting stents (DES) have been extensively studied, and are generally superior to bare-metal stents concerning the occurrence of major adverse cardiac events (generally defined as death, myocardial infarction, or the need for a repeat revascularization procedure). In a 2019 meta-analysis comparing new generation DES to BMS, 26,616 patients spanning 20 randomized clinical trials were evaluated for primary outcomes of myocardial infarction and cardiac death. Those who received DES had a significantly reduced risk of myocardial infarction and cardiac mortality at 1 year. The superiority of newer generation polymer stents, particularly the cobalt chromium everolimus-eluting stents have been well-studied. One of the major benefits of drug-eluting stents (DES) to bare-metal stents (BMS) is the prevention of in-stent restenosis (ISR). Restenosis is a gradual re-narrowing of the stented segment that occurs most commonly between 3–12 months after stent placement. High rates of restenosis associated with BMS prompted the development of DES, which resulted in a reduction of ISR incidence to around 5-10%. Continued development of newer generation DES have resulted in the near-elimination of BMS from clinical practice. Long term outcomes Data on long term effects of DES is limited. This is primarily because the technology has only been around for the last two decades, so many studies investigating long-term outcomes have yet to be concluded. However, there are a number of studies investigating intermediate-term outcomes. One particular meta-analysis looked