Pathologist and clinician weigh in on persistent risks of DES.

In a session investigating the pathogenesis of stent thrombosis after DES implantation, Renu Virmani, MD, of the CVPath Institute in Gaithersburg, Md., and Edoardo Camenzind, MD, of the University of Geneva, examined the pathological correlates and clinical profiles of ST risk and occurrence in DES patients.

Since 2005, the rates of early and late stent thrombosis in DES patients have decreased, from a high of 23% for early ST (<30 days) and 26% for late ST (>30 days) in 2005 to the more current rate of 7% and 14% for early and late ST, respectively, according to the CVPath DES Registry.

Virmani attributes this to possible improvements in antiplatelet therapy, stent technology, and implantation procedures. However, the risk remains higher for DES patients than for bare-metal stent patients. Camenzind referred to the MILAN and ERACI III registries, which showed mortality rates of 45% and 44.4%, respectively, in cases of late ST. He also cited data showing the cumulative incidence of late angiographic ST (.30 days) is, on average, 0.6% per year.

Predictors of ST

Lack of endothelialization is a “good predictor of ST,” and DES patients in previous studies have shown significantly less endothelialization after 18-month follow-up than bare-metal stent patients (55.8% of DES struts were endothelialized after 18 months compared with 89.8% of bare-metal stent struts; P = .0001). Neointimal area was smaller in DES patients, indicating DES usefulness in retarding restenosis, but fibrin score was significantly higher for DES patients, according to Virmani (Figure).

Strut coverage as a marker of endothelialization shows significant accuracy, and it is a pathological correlate that should be recognized as a predictor of ST, Virmani said. The odds ratio for late ST in lesions having a ratio of uncovered-tototal stent struts per section (RUTSS) greater than 30% is 9.0 (95% CI, 3.5-22). Other pathological predictors of ST development include fibrin accumulation on the stent, as well as inflammation score, according to a recent study she cited (Circulation 2007;115:2435-41).

Causes of ST

Particularly problematic, according to Virmani, is implanting DES in the setting of AMI. Patients with AMI showed significantly higher rates of predictors for ST compared with non-AMI patients, including strut fibrin (67.2% vs. 41.8%; P = .02), strut inflammation (54.7% vs. 17.8%; P = .03) and uncovered struts (33.6% vs. 23.8%; P = .02), according to data from the CVPath registry. Virmani attributes this risk for ST in AMI patients to the fact that in a ruptured plaque site, there is a higher likelihood of unmetabolized drug being present.

DES must be evaluated separately

Camenzind emphasized that not all DES are the same, and each one must be evaluated separately. The Cypher (Cordis, Johnson & Johnson) and Taxus (Boston Scientific) stents have been subjected to the most randomized trials (39 and 29, respectively), so most results today refer to one or both of them. In a meta-analysis of 4 randomized trials (RAVEL, SIRIUS, E-SIRIUS, C-SIRIUS), Camenzind et al found a 6.3% rate of mortality or Q-wave MI among Cypher patients (n = 878), significantly higher than the rate found among bare-metal stent patients (n = 870, 3.9%, P = .03).