Sirolimus-eluting Stents for Restenosis of Bare-metal Stents
Abstract & Commentary
By Andrew J. Boyle, MBBS, PhD
Source: Liistro F, et al. Long-term effectiveness and safety of sirolimus stent implantation for coronary in-stent restenosis. Results of the TRUE (Tuscany Registry of Sirolimus for Unselected In-Stent Restenosis) Registry at 4 years. J Am Coll Cardiol 2010;55:613-616.
In-stent restenosis (ISR) is the Achilles' heel of bare-metal stents (BMS). The advent of drug-eluting stents (DES) brought a safe and effective treatment for ISR of BMS, by placing a DES inside the area of ISR. However, recent autopsy studies showing incomplete endothelialization of DES raise questions about the long-term safety of DES for BMS ISR, in particular, the risk of stent thrombosis. Prior studies have shown short-term safety of using DES to treat ISR of BMS, but long-term safety data have been lacking. Here, Liistro et al present the four-year follow-up of the TRUE registry, a two-center study performed in Italy, in patients with BMS restenosis treated with sirolimus-eluting stents (SES). They report major adverse cardiac events (MACE), defined as death, myocardial infarction (MI), and ischemia-driven target lesion revascularization (IDTLR), as well as stent thrombosis defined by the academic research consortium definition.
Results: There were 244 patients treated with SES implantation for BMS ISR that were followed clinically for four years. All patients were prescribed dual anti-platelet therapy (DAT) with aspirin, at least 100 mg, and either ticlopidine 500 mg daily or clopidogrel 75 mg daily, starting at least 48 hours prior to the stenting procedure and continued for at least six months. The mean duration of adherence to DAT was 341 ± 112 days. Over four years, MACE occurred in 20%, death in 9.8%, and IDTLR in 11.1%. Regression analysis showed that independent predictors of MACE were diabetes (Odds Ratio 0.38; p = 0.002), ejection fraction < 50% (OR 0.32; p = 0.01), creatinine > 1.5 mg/dL (OR 0.23; p = 0.0001).
Stent thrombosis was uncommon, occurring in 2.8% over four years (2.0% definite, 0% probable, and 0.8% possible). Importantly, the occurrence of stent thrombosis did not appear to be time-dependent: In the five patients with definite stent thrombosis, this occurred at 261, 614, 621, 631, and 847 days from the index procedure. Furthermore, this occurred in one patient taking DAT; the other four were taking aspirin alone. In the two cases of possible stent thrombosis, they occurred at 60 and 538 days post-procedure; both were taking DAT at the time. The authors conclude that the clinical benefit of SES implantation for BMS restenosis is maintained at four years, with a low TLR rate and an overall incidence of stent thrombosis of 0.7% per year.
Despite the observational nature of this study with no control group and the inherent limitation of such studies, the results are very reassuring. The use of SES for ISR in BMS appears safe out to four years, with a low rate of stent thrombosis. In fact, the authors included possible, not just definite and probable, stent thrombosis, as many studies do, so their definition of stent thrombosis was generous, and may even over-estimate the true incidence. This rate of late and very late stent thrombosis (0.7% per year) is comparable to emerging data on the rates of late and very late stent thrombosis after DES implantation for de novo coronary artery lesions. Thus, the theoretical risk of higher stent thrombosis rates using DES for BMS ISR, based on incomplete endothelialization, may be unwarranted, but further long-term studies are needed to confirm this. It is interesting to note that continued DAT did not appear to be completely protective against stent thrombosis. Whether it affects the overall incidence of late or very late stent thrombosis remains to be tested in prospective, randomized, controlled trials.
In addition to safety, in terms of stent thrombosis, the efficacy of this approach is also reassuring, with only 11.1% requiring ischemia-driven TLR in four years. Unlike other treatments, such as brachytherapy, there was no late "catch-up" phenomenon of ISR observed in this study.