Bare-Metal or Everolimus-Eluting Stents in STEMI?
Abstract & Commentary
By Andrew J. Boyle, MBBS, PhD, Assistant Professor of Medicine, Interventional Cardiology, University of California, San Francisco. Dr. Boyle reports no financial relationships relevant to this field of study.
Source: Sabate M, et al. Everolimus-eluting stent versus bare-metal stent in ST-segment elevation myocardial infarction (EXAMINATION): 1 year results of a randomised controlled trial. Lancet 2012;380:1482-1490.
Drug-eluting stents (DES) reduce the rate of in-stent restenosis (ISR) compared to bare-metal stents (BMS). However, the first-generation DES had higher rates of late stent thrombosis than BMS, and this was more evident after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). However, second-generation DES show substantial benefit over their first-generation counterparts. A large recent meta-analysis of everolimus-eluting stents (EES) showed lower ISR and lower stent thrombosis than BMS. The effectiveness of EES had not been directly compared to BMS in patients presenting with STEMI. Therefore, Sabate and colleagues performed a randomized controlled trial of EES vs BMS in STEMI. Patients presenting within 48 hours of symptom onset who had ST-segment elevation or a new left bundle branch block were enrolled. Exclusion criteria were age younger than 18 years, pregnancy, patients with known intolerance to aspirin, clopidogrel, heparin, stainless steel, everolimus or contrast material, patients on chronic treatment with vitamin K antagonists, and STEMI secondary to stent thrombosis. They were randomized to receive either EES or BMS and the primary endpoint was a combination of all-cause death, myocardial infarction, or any revascularization at 1 year.
A total of 1498 patients in three countries were randomly assigned to receive either an EES (n = 751) or a BMS (n = 747). They were prescribed loading doses of aspirin and clopidogrel and then maintenance doses of 100 mg and 75 mg daily, respectively. The baseline characteristics were similar between groups; mean age was 61 years, 83% were male, and 17% were diabetic. Primary PCI was performed within 12 hours of symptom onset in 85% while the others were rescue PCI, PCI after lysis, or late presenters (12-48 hours after symptom onset). unfractionated heparin was used in 80% of cases, with few receiving bivalirudin or low molecular weight heparins. Glycoprotein IIb/IIIa inhibitors were used in 51%. The primary combined endpoint of all-cause death, any myocardial infarction, or any revascularization occurred in 11.9% and 14.2% of the EES and BMS groups, respectively (P = 0.19). There was no difference in the rate of death (3.5% in both groups; P = 1.0), myocardial infarction (1.3% vs 2.0%; P = 0.32), or total revascularization (8.0% vs 10.6%; P = 0.09). The EES group had lower rates of target lesion revascularization (2.1% vs 5.0%; P = 0.003) and target vessel revascularization (3.7% vs 6.8%; P = 0.0077) than the BMS group. In addition, the EES group had lower rates of definite (0.5% vs 1.9%; P = 0.018) and definite or probable stent thrombosis (0.9% vs 2.5%; P = 0.02). Bleeding rates were similar between groups. The authors conclude that the use of EES compared with BMS in the setting of STEMI did not lower the patient-oriented combined endpoint of death, MI, or revascularization. However, at the stent level, both rates of target lesion revascularization and stent thrombosis were reduced in recipients of EES.
Second-generation DES demonstrate clear benefits over first-generation DES and BMS. While the first-generation DES reduced ISR compared to BMS, there was a slightly higher risk of late stent thrombosis. Now, however, the second-generation EES show lower ISR and lower stent thrombosis. This is a win-win situation. This study is important because it extends the benefits of EES from the stable coronary artery disease and non-ST-elevation acute coronary syndrome populations to now also include the population of patients presenting with STEMI.
This is a large, randomized, controlled trial and the conclusions are strengthened by the rigorous trial design. However, a few methodological considerations warrant mention when interpreting these data. First, this was a single-blind study. The patients and the clinical events committee were blinded to the treatment allocation, but the operators could not be blinded. Second, 13% of BMS-treated patients and 16% of EES-treated patients had staged PCI for other non-culprit lesions. During the staged procedure, one-third of BMS patients crossed over and had EES implanted; none of the EES patients crossed over to BMS. This may have altered the outcome in favor of those BMS patients who crossed over. Third, follow-up is only for 1 year. Longer-term follow-up is needed to definitively exclude late complications. The precise mechanism by which second-generation DES result in significant clinical benefit over previous generations is not clear. It may relate to the thin strut cobalt-chromium design of the stent platform. Alternatively, it may relate to the second-generation polymer or to the eluted drug (everolimus). It may be a combination of all three factors. Regardless of the reason, this stent performs better than its predecessors and is now considered the standard against which other technologies should be judged. Both patients and payors will surely welcome a stent with a lower risk of stent thrombosis and lower need for repeat revascularization.