Rabab Mohsin, MD
Sabate M, Cequier A, Iniguez A, 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.
Percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for patients with ST-segment elevation myocardial infarction (STEMI). The American College of Cardiology/ American Heart Association (ACC/AHA) have published several updates on the recent guidelines and summaries that help direct health care providers and health care centers through the creation of protocols and appropriate management plans for patients with STEMI. A topic of scrutiny has been the use of the bare metal stent (BMS) versus the drug-eluting stent (DES) with respect to improvement in reperfusion strategies in patients with STEMI.
The FDA has approved multiple drug-eluting stents for PCI, which are now referred to by the ACC/AHA in most of the PCI and STEMI guidelines. First-generation DESs include Cypher, a sirolimus-eluting stent, and Taxus, a paclitaxel-eluting stent. Second-generation DESs that are approved by the FDA include the Xience/Promus, or everolimus- eluting stent (EES), and the Endeavor, which is a zotarolimus-eluting stent.1 Many of these stents have undergone head-to-head comparisons in clinical trials. Target vessel revascularization data is the most frequently used clinical indicator of stent efficacy.2,3
In-stent restenosis has been shown to be reduced in the DES population; however, DESs have not shown superiority in the STEMI population compared with BMSs with respect to overall mortality. Hao et al recently described the results of a meta-analysis of 13 randomized controlled trials (RCTs) in which DESs were shown to have significant reductions in recurrent myocardial infarction (MI), better outcomes in target vessel revascularization (TVR), and reduced instent restenosis.4 Multiple drug-eluting stents have been thoroughly studied, including paclitaxel-eluting stents, sirolimus- eluting stents, and zotarolimuseluting stents. The EXAMINATION (clinical Evaluation of the Xience-V stent in Acute Myocardial INfArcTION) trial is the first multinational, multicenter study to compare the second-generation everolimus-eluting stents (EES) with a BMS in the STEMI population.
The authors of the EXAMINATION trial compared a second-generation EES with the Vision BMS in patients with STEMI. Both of the stents have the same metallic platform.
EXAMINATION was a 12-center, multinational, single-blind, randomized controlled trial carried out between December 2008 and May 2010. The authors recruited 2149 patients with STEMI but only 1504 were randomized. After 6 patients withdrew, 751 were assigned to EES and 747 were assigned to cobalt-chromium BMS. The inclusion
criteria consisted of patients with STEMI within the first 48 hours after symptom onset requiring emergent PCI. Exclusion criteria were age <18 years, pregnancy, patients with intolerance to aspirin, clopidogrel, heparin or contrast material, patients on anti-vitamin K agents, and STEMI secondary to stent thrombosis. Patients were randomized in blocks of 4 to 6 patients; each patient received procedural anticoagulation with unfractionated heparin or bivalirudin. Loading doses of aspirin and clopidogrel were given prior to PCI, and administration of glycoprotein IIb/IIIa inhibitors was left to the discretion of the investigator. Manual thrombectomy followed by direct stenting was the recommended technique used by the operators.
The primary end point was the combined end point of all-cause death, myocardial infarction (MI), or need for revascularization at 1 year. Secondary end points were the device-oriented combined end point of cardiac death, target vessel MI, or target lesion revascularization (TVR) at 1 year, all-cause and cardiac death, recurrent MI, target
lesion and TVR, stent thrombosis, device and procedure success, and major and minor bleeding. Baseline and procedural characteristics were well balanced between study groups, including the anti-platelet regimen.
Device success rate, defined as successful delivery and deployment of the study stent at the intended target with residual stenosis <50%, was similar in the 2 groups. The procedural success rate was significantly higher in the EES group and the cumulative incidence of stent thrombosis was shown to be greater in the BMS group compared with the EES group in both 30-day and 360- day follow-up. The primary end point for EES versus BMS was 11.9% and 14.2%, respectively. This did not show
significance or meet the authors’ superiority hypothesis. However, the deviceoriented secondary end point was 5.9% and 8.4% for EES versus BMS, respectively.
Thus, EES showed significant reductions in target lesion revascularization. The incidence of target vessel MI secondary to stent thrombosis was found to be 5 times higher in the BMS group compared with the EES group.
1. Levine G, Bates E, Blankenship J, et al. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. JACC. 2011;58:e44-e122.
2. Alfonso F, Fernandez C. Second generation drug eluting stents: moving the field forward. JACC. 2011;58:26-29.
3. Mukherjee D, Moliterno D. Second-generation drug-eluting stents and the continuous need for rapidly available real-world data. JACC Cardiovasc Interv. 2009;2:1236-1239.
4. Hao P-P, Chen Y-G, Wang X-L, Zhang Y. Efficacy and safety of drug-eluting stents in patients with acute ST-segment elevation myocardial infarction. Texas Heart Inst J.
5. Iijima R, Byrne R, Dibra A, et al. Drugeluting stents versus bare-metal stents in diabetic patients with ST-segment elevation acute myocardial infarction: a pooled analysis of individual patient data from 7 randomized trials. Rev Esp Cardiol. 2009;62:354- 364.
6. Kastrati A, Dibra A, Spaulding C, et al. Meta-analysis of randomized trials on drugeluting stents vs. bare-metal stents in patients with acute myocardial infarction. Eur Heart J. 2007;28:2706-2713.
A Continuing Controversy
The EXAMINATION trial is one of many ongoing studies looking at DES in the STEMI population undergoing PCI. This is especially important since EXAMINATION has an all-comer protocol, which has not been successful in other trials such as Typhoon or Resolute US. It is important to understand the significance of this population because the pro-inflammatory and biochemical changes in STEMI patients impact reperfusion strategies.
The 2011 PCI guidelines discuss the efficacy considerations for DES, especially its risk-benefit profile in preventing in-stent restenosis.1 Iijima et al did a pooled analysis of 7 RCTs that showed DESs (sirolimus- and paclitaxel-eluting stents) improved clinical outcomes in diabetic patients with STEMI undergoing PCI.5 However, it is important to note that the ACC/AHA guidelines do not show that DESs are the preferred strategy over BMSs simply because of the safety considerations and the implications of dual antiplatelet therapy (DAPT).1 In EXAMINATION, the compliance with DAPT was similar in both BMS and DES groups. The major concern in the PCI and STEMI guidelines also imply that most operators determine the type of stent based on safety considerations and compliance and tolerance of the patients to DAPT.1 During STEMI, platelet activation increases and primary PCI has been shown to increase the thrombotic phenomenom.5 Thus far, the randomized controlled trials have not shown clear differences in mortality and survival benefit in DES over BMS.
Several of the EXAMINATION study’s limiting factors are important to mention. The study was not originally designed to find the differences in the rate of stent thrombosis between the 2 groups. Also, this trial was single-blinded, which leads to some operator bias, and the crossover from BMS to EES in staged procedures was a violation of the original study protocol. Finally, the results in this article were only from a 1-year follow-up, and the authors note that a longer period of follow-up is needed to rule out late hazards and identify the safety of second-generation DESs in the STEMI population.
Analyses published previously did not show a significant impact of major adverse cardiovascular events for DES over BMS. Kastrati et al in 2007 performed a meta-analysis of 8 randomized trials that showed a 62% reduction in reintervention with DES.6 Future RCTs are warranted that will have more second-generation DESs
compared head to head, as well as long-term follow-up to look at very late stent thromboses (>48 months).
The debate over DES versus BMS continues to be controversial because of the limited amount of follow-up most trials have completed. With innovative, new designs
in stents and new antithrombotic agents, the safety and efficacy of DESs may prove better in primary PCI, but only time will tell.
About the Author
Rabab Mohsin, MD, is a Cardiology Fellow at Texas Tech Medical Center in El Paso, Texas. She is board certified in Internal Medicine. Dr Mohsin received her MD from Ross University School of Medicine, Dominica, West Indies, and completed a residency in internal medicine at University of Kentucky in Lexington, where she participated in cardiac research protocols. She has published multiple abstracts on atrial fibrillation, obesity, and anticoagulation.