The major finding of this study is that the frequency of ST after primary PCI for STEMI is high with both BMS and DES and continues to increase to at least 11 years with BMS and to at least 4.5 years with DES. After the first year, VLST, reinfarction, and reinfarction of the target vessel were significantly higher with DES compared with BMS. Very late stent thrombosis resulted in reinfarction in all cases with both BMS and DES, but STEMI was more common with DES.
Randomized trials comparing DES with BMS with primary PCI for STEMI have shown similar rates of ST at 1 year (9
). Data on ST rates after 1 year have been limited, but some data are becoming available. Two small trials, the SESAMI (Sirolimus-Eluting Stent Versus Bare-Metal Stent in Acute Myocardial Infarction) and TYPHOON (Trial to Assess the Use of the Cypher Stent in Acute Myocardial Infarction Treated with Balloon Angioplasty) trials, found no differences in the rates of ST between DES and BMS at 3 and 4 years (16
). Another small trial, the PASSION (Paclitaxel Eluting Stent Versus Conventional Stent in ST-segment Elevation Myocardial Infarction) trial, found higher rates of ST with DES versus BMS at 5 years (3.6% vs. 1.7%, p = 0.20), raising some concern about safety with DES (18
). The largest trial, the HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial, found no differences in rates of ST between DES and BMS at 2 years (4.3% vs. 4.3%, p = 0.98) (19
). None of these trials found any differences in mortality or reinfarction between DES and BMS at late follow-up.
Our data showing that the frequency of ST with BMS continues to increase to 11 years after stent implantation are somewhat unexpected. Previous studies after elective implantation of BMS have found that VLST is uncommon (20
). Serial angiographic studies after BMS implantation have shown that late loss is generally complete by 9 to 12 months, after which there is stabilization and often regression of late loss (22
). However, most of the late stent thromboses with BMS in our study had severe restenosis associated with thrombotic occlusion, indicating that restenosis with BMS can occur very late after implant in some patients and can result in VLST. New strategies might be needed to deal with this problem of VLST with BMS.
It is not clear whether the increased frequency of VLST with DES compared with BMS in our study is a true difference or might be related to selection bias. In most observational databases comparing DES and BMS, selection bias has favored DES. Bare-metal stents are generally implanted in patients who are sicker, are expected to have limited life expectancy, are at risk for bleeding, or who are thought to be less compliant with medical therapies. This bias seems to be true in our study, because mortality was higher in patients treated with BMS compared with DES. These differences are likely due to selection bias, because all the differences in mortality occurred in the first 30 days, when the type of stent would not be expected to affect mortality. It is possible that selection bias involving variables affecting ST might be different from those affecting mortality. Drug-eluting stents might be chosen for diabetic patients and patients with small vessels and long lesions, because of the higher risk of restenosis in these patients. This could increase the risk of VLST with DES. We adjusted for these variables in the Cox regression analyses and propensity analyses, but we might not have been able to correct for all the differences. There is also potential bias related to the historical time that these stents were implanted. The BMS were implanted from 1995 to 2009, and DES were implanted from 2003 to 2009. Differences in treatment protocols between these time periods could affect outcomes. However, one might expect that outcomes, including VLST, might be worse in the earlier time period (when most BMS were implanted) when stent deployment techniques and antiplatelet therapy were less optimal. We compared rates of VLST between DES and BMS in the DES era (2003 to 2009) when both types of stent were implanted and found similar outcomes with a higher frequency of VLST with DES. Another possibility for the differences in outcomes is that the “real world” population in our registry might be different from the patient populations enrolled in randomized trials. Differences in the use of dual antiplatelet therapy do not seem to be a likely explanation for differences in VLST rates, because most patients were not taking dual antiplatelet therapy after 1 year and the frequency of dual antiplatelet therapy use was low in both BMS and DES patients at the time of VLST.
There are previous data to support the position that the frequency of VLST is truly higher with DES than BMS, because of differences between the 2 stent types. As stated earlier, when DES are implanted for STEMI, there is an increased incidence of late malapposition and poor healing that could predispose to VLST (6
). Randomized trials with elective stenting have shown small but significant increased rates of VLST with DES compared with BMS (23
). The PASSION trial, which evaluated DES versus BMS for STEMI and had follow-up data to 5 years, showed trends for increased rates of VLST with DES (18
). The relatively short follow-up in the HORIZONS-AMI trial and the small sample sizes in the other randomized trials comparing DES with BMS with primary PCI might have so far prevented the detection of significant differences in VLST between the 2 types of stents (16
Although it is not clear whether the differences in the frequency of VLST between DES and BMS are real or are related to selection bias, it is clear that the frequency of ST and continued late occurrence of ST after stenting for STEMI in this “real world” STEMI population are disturbingly high for both BMS and DES.
Our study is a single-center observational study and, as discussed in the preceding text, has the potential for selection bias that might affect outcomes. Our study is also limited by historical time differences when DES and BMS were implanted, which could affect outcomes, although our results are similar when we analyzed the DES era when both DES and BMS were being implanted. We have data on dual antiplatelet therapy in patients who had ST but do not have data on patients without ST to assess the impact of this therapy on outcomes. The great majority of DES implanted were first-generation sirolimus-eluting or paclitaxel-eluting stents, and our results might not apply to second-generation stents.
Our results might have implications regarding the management of patients treated with primary PCI and stenting for STEMI. The high incidence of VLST after stenting for STEMI with both DES and BMS should encourage evaluation of new strategies to prevent VLST, including procedural techniques to optimize stent deployment (such as more frequent use of intravascular ultrasound, post-dilation, and thrombectomy) and longer or more intensive antiplatelet therapies. The development of newer-generation stents, including new polymers and bio-absorbable stents, might also help to reduce this complication. If VLST rates and reinfarction rates are truly higher with DES compared with BMS, the benefit of reduced restenosis with DES might not be worth the increased risk of ST and reinfarction, and BMS might be a more appropriate choice in many patients with STEMI.