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Sirolimus-Eluting Stents or Vascular Brachytherapy for In-Stent Restenosis After 3-Year Follow-Up of the SISR (Sirolimus-Eluting Stent Versus Vascular Brachytherapy for In-Stent Restenosis) Trial

A Call for Caution?

We would like to raise several issues and concerns that we have with the methodology, the results, and the conclusions of this study.

First, due to slow enrollment in the vascular brachytherapy arm, historic control from the Gamma One (Localized Intracoronary Gamma Radiation Therapy to Inhibit the Recurrence of Restenosis after Stenting) study, the first pivotal trial, was used to support the VBT group. This group does not reflect the latest practice of VBT: the dose was lower, the patients in the study were treated with stents that were found to be associated with worse results when combined with VBT, and the duration of clopidogrel in that cohort was limited. These issues raise flaws in the methodology because the concurrent enrolled group and the historic group should not be pooled for the analysis.

Second, although the study was not powered to detect differences in hard clinical end points, at 3 years of follow-up, the overall cardiac mortality, Q-wave and non–Q-wave MI were higher in the SES group than in the VBT group. As detailed in Table 2 (1), the overall mortality and incidence of MI increased with SES therapy over 38% and 48%, respectively.

Third, although the TLR was lower in the SES group, major adverse cardiovascular events were similar, suggesting that the rise in major adverse cardiovascular events with SES was related to an increase of death and MI. In addition, the incidence of cumulative stent thrombosis was higher in the SES-treated group (4.2%).

Fourth, Holmes et al. (1) suggested that there is clinical evidence that coronary restenosis after BMS implantation is associated with high incidence of MI and death (2). Currently, most BMS restenoses are treated with drug-eluting stents (DES), which are associated with high rate of late stent thrombosis and perhaps lead to increase in death and MI (3).

In contrast, in the era before DES, BMS restenosis was not associated with major incidence of death or MI. In the head-to-head comparisons of BMS to coronary artery bypass graft, although BMS was associated with increase of TLR when compared with coronary artery bypass graft, this was not associated with increase of mortality or MI. In fact, in a recent meta-analysis from 4 large randomized studies (4), survival was almost identical in both BMS or coronary artery bypass graft groups in spite of repeat revascularization, which was 4 times higher in BMS patients. In addition, in the ERACI III (Argentine Randomized Trial of Coronary Stents versus Bypass Surgery) study registry (5), at 3 years of follow-up, regardless to the reduction of TLR, both DES and BMS groups had similar incidence of death and MI, including diabetic patients. In ERACI III, all BMS data was collected in the era before DES; therefore, any BMS restenoses had been treated with DES implantation.

In conclusion, the 3-year report of the SISR (Sirolimus-Eluting Stent Versus Vascular Brachytherapy for In-Stent Restenosis) study alarms us regarding the high rates of stent thrombosis and mortality and raises the question of what is the ideal therapy for BMS restenosis. Clearly when these patients are treated with SES, they should be monitored closely, perhaps with indefinite dual antiplatelet therapy, to prevent late events until we get more data from large randomized clinical trials and registries.

^_* Interventional Cardiology Unit, Otamendi Hospital/Buenos Aires School of Medicine, Azcuenaga 870 (AAC1115) Buenos Aires, Argentina (Email: rodrigueza{at}sanatorio-otamendi.com.ar).

	REFERENCES

Top REFERENCES

 

1. Holmes D, Teirstein P, Satler L, et al. Three-year follow-up of the SISR (Sirolimus-Eluting Stent Versus Vascular Brachytherapy for In-Stent Restenosis) trial J Am Coll Cardiol Intv 2008;1:439-448.[Abstract/Free Full Text]
2. Nayak AK, Kawamura A, Nesto RW, et al. Myocardial infarction as a presentation of clinical in-stent restenosis Circ J 2006;70:1026-1029.[CrossRef][Web of Science][Medline]
3. Degertekin M, Regar E, Tanabe K, et al. Sirolimus-eluting stent for treatment of complex in-stent restenosis: the first clinical experience J Am Coll Cardiol 2003;41:184-189.[Abstract/Free Full Text]
4. Daemen J, Boersma E, Flather M, et al. Long-term safety and efficacy of percutaneous coronary interventions with stenting and coronary bypass surgery for multivessel coronary artery disease: a meta-analysis with 5-year patient level data from ARTS, ERACI-II, MASS-II, and SoS trials Circulation 2008;118:1146-1154.[Abstract/Free Full Text]
5. Rodriguez AE, Maree A, Mieres J, et al. Late loss of early benefit from drug-eluting stents when compared with bare-metal stents and coronary artery bypass surgery: 3 years follow-up of the ERACI III registry Eur Heart J 2007;28:2118-2125.[Abstract/Free Full Text]

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