ABSTRACT & COMMENTARY
Are Newer Drug-Eluting Stents Really Safer? Swedish Registry Data Says Yes
By Jeffrey Zimmet, MD, PhD
Associate Professor of Medicine, University of California, San Francisco, Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center
Dr. Zimmet reports no financial relationships relevant to this field of study.
SOURCE: Sarno G, et al. Stent thrombosis in new-generation drug-eluting stents in patients with STEMI undergoing primary PCI:
A report from SCAAR. J Am Coll Cardiol 2014;64:16-24.
Coronary artery stents are implanted in the vast majority of coronary revascularization procedures, owing to improvements in both restenosis and acute vessel occlusion vs balloon angioplasty alone. Drug-eluting stents (DES), by virtue of their well-demonstrated ability to reduce clinical restenosis and target lesion revascularization compared with bare metal stents (BMS), have captured a large proportion of the market since their introduction in Europe in 2002 and in the United States in 2003. The same drug and polymer combination in DES that staves off restenosis also delays endothelialization and vessel healing, however. And while dual antiplatelet therapy has reduced the rate of stent thrombosis (ST) to relatively low levels, late (after 1 month) and very late (after 1 year) ST remains a significant concern with these devices. Patients presenting with acute coronary syndrome, particularly those with ST elevation myocardial infarction (STEMI), are known to be at increased risk of ST. This has led to significant uncertainty regarding DES use in STEMI. Randomized trials comparing DES and BMS in acute MI generally involve the older first-generation DES and are relatively underpowered for rare events such as ST. Newer DES, with thinner struts, reduced or more-biocompatible polymers, and in some cases novel drugs, have the potential to both endothelialize more quickly and to cause less inflammation compared with earlier devices.
The Swedish Coronary Angiography and Angioplasty Registry (SCAAR) reports on ST rates out to 3 years in patients with STEMI treated with primary PCI between January 2007 and January 2013. Patients were treated with a mix of stent types and, for the purposes of the study, DES were subdivided into older first-generation models and newer second-generation stents. Among the 34,147 patients with STEMI tracked in the national registry, 25,065 were treated with BMS, 4811 with newer DES, and 4271 with older, first-generation DES. When looking at events out to 1 year ("early" + "late" ST) using adjustment by propensity scoring, both first- and second-generation DES showed significantly lower rates of ST compared with BMS. (See Table.)
When looking at events beyond 1 year in the category known as very late ST, the only significant difference was a higher risk of ST in the older DES group compared with BMS. There was no significant difference between BMS and newer DES, nor did the two DES groups differ significantly. The authors concluded that patients treated with DES have a lower risk of early/late ST than patients treated with BMS. The risk of very late ST is low and comparable between the newer DES and BMS, whereas the older DES are associated with an increased risk of very late ST.
The authors propose several major findings from this study: 1) a higher risk of ST in the first year in patients receiving BMS compared with both older and newer DES; 2) a higher risk of very late ST in patients receiving first-generation DES compared with BMS; and 3) a similar risk of very late ST in BMS vs second-generation DES patients. Are these results plausible, and what do they mean?
We should first note that procedural characteristics were not strictly similar among groups. This is to be expected in such an "all-comers" registry analysis. For example, bivalirudin was used more frequently in DES groups compared with BMS, whereas glycoprotein IIb/IIIa inhibitor use was more common among patients receiving BMS. Ticagrelor, which in ACS patients has on its own demonstrated a lower event rate (including ST) compared with clopidogrel, was used more frequently in first-generation DES patients. More importantly, the SCAAR database lacks information regarding the duration and dose of dual antiplatelet therapy in the three groups. Given the known associations between antiplatelet drugs and ST, this is a significant shortcoming.
In addition, while we are provided with common baseline characteristics of the patients in each group and that these appear to be similar, we have to remember that these patients were not randomly assigned. No mention is made of the fact that patients may be treated with BMS rather than DES for a variety of reasons including greater comorbidities, propensity for bleeding, and the need to limit the duration of dual antiplatelet therapy. Clearly this may have an effect on downstream ST in at least a subgroup of BMS patients.
The idea that the polymer in DES might have opposite, time-dependent effects on ST is not new and is supported by other data. This hypothesis suggests that the polymer has a protective effect early on, but that this is later overtaken by a proinflammatory effect that increases the risk for very late ST. The results of this study support the idea that the newer DES have at least partially overcome this late detrimental effect. DES with fully biodegradable polymers, which are already available in many parts of the world outside the United States, take this idea to the next level. For now, these data provide reassurance that the newer, durable polymer stents are relatively safe for use in the STEMI arena.