Effectiveness of Drug-Eluting Stents in Real-World Patients
Authors: Debabrata Mukherjee, David J. Moliterno
Journal: JAMA (2008)

DRUG-ELUTING STENTS ARE A MAJOR ADVANCE IN PERcutaneous coronary intervention (PCI) because they reduce the need for repeat target lesion revascularization several-fold compared with bare-metal stents. Early randomized clinical trials separately testing sirolimus-eluting stents and paclitaxel-eluting stents against their bare-metal counterparts demonstrated that rates of target lesion revascularization were reduced from approximately 10% to 15% to approximately 4% to 5%, whereas the rates of death, myocardial infarction, and stent thrombosis were similar between bare-metal and drug-eluting stents. Because these studies were performed for device regulatory approval, they enrolled patients and lesions with relatively low risk for restenosis and adverse events. Subsequent head-to-head trials of sirolimusand paclitaxel-eluting stents in cohorts with a broader risk profile have provided inconsistent results; some trials have suggested equivalent rates of target lesion revascularization for these stents, whereas others have reported superiority of sirolimus-eluting stents. Initial clinical trials in any area of medicine are primarily designed to test efficacy (ie, is the drug or device beneficial under ideal conditions?) rather than to test effectiveness or relevance (ie, is the drug or device beneficial in everyday practice?). Phase 4 (postapproval) studies are expected to be conducted to help bridge this gap while monitoring safety. The sirolimus-eluting stent was the first to become clinically available, and early postapproval data from the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry showed that the unrestricted use of sirolimus-eluting stents in the real world was safe and effective in reducing target lesion revascularization as well as major adverse cardiac events at 1 year compared with bare-metal stents—findings similar to the regulatory approval studies. Subsequently, observational data from the Taxus-Stent Evaluated At Rotterdam Cardiology Hospital (T-SEARCH) registry suggested that the unrestricted use of paclitaxel-eluting stents was safe and associated with a similar adjusted outcome when indirectly compared with sirolimus-eluting stents. There was an “inferior trend” in crude outcome observed with paclitaxel-eluting stents—although this finding was attributed to higher-risk characteristics among patients receiving such stents, since practice had become comfortable with a wider application of drug-eluting stents over time. Thereafter, a number of small, direct-comparison trials were reported, with most individually observing a similar outcome for patients receiving sirolimusvs paclitaxeleluting stents. On the other hand, a meta-analysis of 16 such randomized head-to-head trials determined sirolimuseluting stents to be superior to paclitaxel-eluting stents with regards to target lesion revascularization and stent thrombosis. Likewise, a collaborative network meta-analysis of 38 trials including 18 023 patients and having a follow-up of up to 4 years also suggested that sirolimus-eluting stents provided a clinical advantage over paclitaxel-eluting stents. The discordance in findings among some trials and subsets of patients (eg, those with diabetes) has been confusing and challenging to interpret. In this issue of JAMA, Galloe and colleagues aim to add clarity and relevance to the issue by comparing outcome among patients randomized to receive sirolimusvs paclitaxel-eluting stents in a study design reflecting everyday clinical practice by including unselected patients and by using symptom-driven clinical end points. They report in this large-scale practical randomized trial that there were no significant differences in clinical outcomes between patients receiving sirolimusand paclitaxel-eluting stents. Their preliminary data were included in the recent meta-analyses and can now be further examined. A noteworthy feature of the study by Galloe et al is that it is the largest randomized direct comparison of these drug-eluting stents; yet with low event rates and the challenges presented by enrollment of all-comers, it has several limitations that need to be considered. First, the study randomized less than a third (27.7%) of potentially eligible patients, which suggests that the cohort may not be as unselected as the authors intended. This raises some concern of selection bias and generalizability of the results and is compounded by the observation that clinical outcomes were worse among patients who were eligible for en-