A new meta-analysis comparing drug-eluting stents (DES) and bare-metal stents (BMS) in patients with myocardial infarction has provoked opposing take-away messages from an author of the study and an editorialist. The authors emphasize the reduction in target-vessel revascularization (TVR) associated with DES, but the editorialist focuses on several potential DES weaknesses suggested by the study.
In the paper, published in Archives of Internal Medicine, members of the Drug-Eluting Stent in Primary Angioplasty (DESERT) Cooperation pooled patient data from more than 11 clinical trials in which more than 8,600 patients were randomized to either sirolimus-eluting or paclitaxel-eluting stents or BMS. After a mean follow-up of 1201 days, DES was associated with a significant reduction in TVR but there were no significant differences in death, reinfarction, or stent thrombosis (ST):
- TVR: 12.7% for DES vs 20.1% for BMS, HR 0.57, CI 0.50-0.66, p<.001
- Mortality: 8.5% vs 10.2%, HR 0.85, CI 0.70- 1.04, p = .11
- Reinfarction: 9.4% vs 5.9%, HR 1.12, CI 0.88-1.41, p = .36
- Stent thrombosis: 5.8% vs 4.3%, HR 1.13, CI 0.86-1.47, p = .38
However, after two years there was a significant increase in the risk of stent thrombosis associated with the DES group (HR 2.81, CI 1.28-6.19, p=0.04).
The findings, write the authors,
provide strong evidence of the beneficial effects of SES and PES during primary PCI in STEMI. With follow- up as late as 6 years, a robust and sustained decrease in TVR was noted with use of these DES. Although the rates of late reinfarction and ST progressively increased, with the difference becoming statistically significant after 2 years in patients receiving SES and PES, the HR for mortality, while not significantly different between DES and BMS, favored DES.
In an accompanying editorial, James Brophy notes that the difference in TVR “may be artificially inflated by protocol-mandated, rather than clinically driven, repeated angiograms.” Brophy also states that analyzing the data with a different statistical approach leaves open the possibility that DES is associated with a two-fold increase in the risk of reinfarction. Brophy provides the follow perspective on choosing BMS versus DES for MI patients:
An informed patient with STEMI should be told that substituting DES for BMS in 100 patients likely results in no mortality differences but approximately 5 fewer repeat revascularizations at the cost of 1 additional late reinfarction with a possibility that this risk may be substantially higher.
Gregg Stone, senior author of the meta-analysis, provided CardioExchange with the following response to the editorial:
The editorialist makes valid points about the precision that can be achieved from any meta-analysis, including ours. He ignores, however, that the reduction in TVR is robust, and the trend toward a reduction in mortality (with no evidence of a late risk for death) favors the interpretation that DES should be favored in STEMI. Many MIs are small and not of prognostic importance, and very late stent thromboses may not carry the prognostic import of earlier such events. Mortality thus trumps all. Moreover, these data were generated with first generation DES, and the network meta-analysis we recently published in the Lancet suggest that newer DES, especially fluoropolymer-based everolimus-eluting stents may have lower rates of definite stent thrombosis than not only first generation DES, but also BMS. However, all meta-analyses are hypothesis-generating, and require testing in adequately powered randomized trials before being accepted as definitive. Clinical equipoise continues to be present in the clinical community regarding the utility of DES vs BMS in STEMI. Thus, later this year we will be initiating the HORIZONS-AMI II trial, in which 7,000 – 10,000 patients with STEMI will be randomized to PROMUS Element everolimus-eluting stents vs BMS, with this study powered to demonstrate not only improved clinical outcomes but a reduction in stent thrombosis with DES compared to BMS. If positive, this demonstration will truly be paradigm shifting.