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At 5 years, patients with ST-segment elevation myocardial infarction (STEMI) who received first-generation drug-eluting stents (DES) have higher rates of cardiac death—but not stent thrombosis—than those treated with bare-metal stents (BMS), according to long-term follow-up of a randomized trial published in the June 2013 issue of JACC: Cardiovascular Interventions. In keeping with earlier results, however, DES patients were less likely to need repeat revascularization.

The DEDICATION trial randomized 626 STEMI patients referred to 2 Danish centers within 12 hours of symptom onset to various DES (46% sirolimus, 41% paclitaxel, 13% zotarolimus; n = 313) or BMS (n = 313), with or without distal protection. In initial 8-month results, published in Circulation in 2008, DES improved angiographic outcomes and reduced the need for revascularization with no increased risk of short-term stent thrombosis but a trend toward more cardiac death.

For the current analysis, a team led by Henning Kelbæk, MD, of the University of Copenhagen (Copenhagen, Denmark), looked at 5-year outcomes of 623 of the DEDICATION patients (median follow-up of 2,095 days).

Five-Year Follow-up

At 5 years, the rate of MACE (cardiac death, recurrent MI, and TLR), the primary endpoint, tended to be lower in the DES group, driven mainly by a higher need for repeat revascularization among BMS patients. Although mortality rates were similar between the DES and BMS arms, the DES group experienced more cardiac death. Rates of stent thrombosis, including very late definite events, were similar between the groups (table 1).

Table 1. Five-Year Outcomes

 
None of the early cardiac deaths were clearly related to stent thrombosis, whereas 78% of deaths occurring after 1 month were attributed to stent thrombosis.

No interaction was found between use of distal protection and the type of stent implanted. 

The authors observe that while revascularization rates favored DES at 8 months, the finding may have been influenced by protocol-driven angiographic follow-up at that time point. Between 8 months and 5 years, the difference between DES and BMS lost statistical significance such that TVR rates were 4.2% and 5.1%, respectively (P = 0.70). 

Low BMS Mortality an Explanation?

Results of the large randomized HORIZONS-AMI trial (Stone GW, et al. Lancet. 2011;377:2193-2204) comparing PES and BMS for STEMI are broadly similar to those of the current study, except for the similarity in mortality rates between the stent groups, Dr. Kelbæk and colleagues note. They add that although BMS mortality in HORIZONS-AMI is considered very low (3.8% in the BMS group at 3 years), the rate in the current study is even lower (1.9% over the same follow-up).

The discrepancy may be explained in part by differences in patient selection for the trials, with lower prevalence of diabetes, hypertension, and hyperlipidemia in DEDICATION. In addition, while only 63% of BMS patients in HORIZONS-AMI were on a thienopyridine at 1-year follow-up, in the current study all patients were prescribed clopidogrel for 12 months. 

In a telephone interview with TCTMD, Jeffrey W. Moses, MD, of Columbia University Medical Center/Weill Cornell Medical Center (New York, NY), said it is difficult to explain the difference in cardiac mortality favoring BMS when there is no difference in stent thrombosis and when the other parameters favor DES, either statistically or directionally.

One possibility is that DES thrombosis was more often fatal than BMS thrombosis, he said, although that is “a little far-fetched.” The simpler explanation, he suggested, is the “unusually low” cardiac mortality in the BMS group, especially in the first 8 months.

First-Generation DES No Longer in Play

Overall, though, the results are “old news,” Dr. Moses said, noting that the reduced need for repeat revascularization with DES is consistent with earlier studies. They also “confirm the lack of problems with MI in the first-generation DES, which was a big red flag” in the European Society of Cardiology ‘firestorm’ of 2006, he added.

However, PES and SES should not be lumped together in the same class, Dr. Moses observed. “If you look at adverse outcomes such as thrombosis and restenosis [associated with first-generation DES in studies of the general PCI population], there is no doubt that Taxus drove a lot of them. And that is certainly true in the STEMI population as well.”

That said, first-generation DES are no longer used in primary PCI, so these data are not very relevant to contemporary practice, Dr. Moses concluded, noting that in a recent meta-analysis second-generation cobalt-chromium EES were superior to BMS.

Study Details

Baseline demographic and lesion characteristics were similar between the DES and BMS groups. All patients were treated with aspirin, clopidogrel, unfractionated heparin, and, if no contraindication, a glycoprotein IIb/IIIa inhibitor.

Holmvang L, Kelbæk H, Kaltoft A, et al. Long-term outcome after drug-eluting versus bare-metal stent implantation in patients with ST-segment elevation myocardial infarction: 5 years follow-up from the randomized DEDICATION trial (Drug Elution and Distal Protection in Acute Myocardial Infarction). J Am Coll Cardiol Intv. 2013;6:548-553.

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• DES, BMS Equally Effective for STEMI, Revascularization Edge Goes to DES