DES: Risk of Delayed Healing, Late-Stent Thrombosis
Drug-eluting stents were found to cause inflammation, allergic reaction and lack of endothelialization.
Drug-eluting stents reduce restenosis but also delay or prevent vascular healing, according to a presentation by William Wijns, MD, from the Cardiovascular Center Aalst in Aalst, Belgium.
Wijns’ presentation, which was an overview of safety concerns with drug-eluting stents, also addressed the timeline and predictive factors for stent thrombosis.
According to Wijns, animal data have shown that drug-eluting stents lead to inflammation, allergic reactions and lack of endothelialization. He said in vivo invasive coronary imaging with either optical coherence tomography or angioscopy up to one-year post-implantation shows delayed healing (absent or incomplete strut coverage and mural thrombosis) with drug-eluting stents.
In addition, sequential IVUS virtual histology has shown changes in plaque size behind stent struts up to two years after implantation, Wijns said.
Wijns also noted the differences in healing between drug-eluting and bare-metal stents. He cited functional studies of endothelium-dependent vasomotion, which showed abnormal vasoconstriction with drug-eluting stents but not with bare-metal stents.
“Bare-metal stents and drug-eluting stents appear to induce different responses,” he said.
Thrombosis time frame
Wijns looked at the time frame for incidence of stent thrombosis in drug-eluting stents.
“From the outset, the Achilles’ heel of stenting has been stent thrombosis,” he said. “These events tend to cluster classically with bare-metal stents early on in the first month.”
The majority of early stent thrombosis events occur within the first 11 days with drug-eluting stents. Wijns said there is no statistically significant difference between bare-metal and drug-eluting stents at this stage.
The incidence of early stent thrombosis appears to be related to procedural technique and may also be affected by insufficient antiplatelet therapy.
There is also no proven difference in late stent thrombosis rates between drug-eluting stents (0.53%) and bare metal stents (0.53%) up to one year. “The incidence of stent thrombosis is in the expected range in real-world experience with drug-eluting stents,” he said.
Wijns cited a head-to-head study between sirolimus-eluting stents and paclitaxel-eluting stents. The study found no clear difference in the incidence of late stent thrombosis between the two.
However, very late stent thrombosis is more frequent with drug-eluting stents than with bare-metal stents, Wijns said (Figure).
Wijns cited one study that assessed the univariate predictors of cumulative stent thrombosis. Among these predictors were premature antiplatelet therapy discontinuation (29%), prior brachytherapy (8.7%), renal failure (6.2%), bifurcation with two stents (3.9%), bifurcation lesion (3.6%), unprotected left main coronary artery (3.3%) and diabetes (2.5%).
Adequate trials needed
Wijns discussed the need to better understand any safety concerns presented by drug-eluting stents.
He called for a consensus on endpoints and common definitions, as well as an independent analysis of accumulated patient data from randomized trials and registries.
He recommended the implementation of adequately sized trials that would focus on efficacy and safety endpoints, as well as on quality of life.
Wijns emphasized the need for greater research and development in the area of drug-eluting stents, as well as the need to improve on “modifiable” risk factors. He recommended optimization of the implantation technique in order to reduce early stent thrombosis. Patient compliance with dual antiplatelet therapy is also crucial to the safety and efficacy of drug-eluting stents.