Second-generation drug-eluting stents (DES) are working better, but they are not perfect, especially in sicker patients. Therefore, a variety of models are being developed and tested, but most likely, it won't result in a one-size-fits-all solution.
What's missing now?
"Deliverability has improved with the second-generation DES with respect to the ability to cross a lesion. But there is a movement toward even thinner struts and more flexible designs, which could allow stent delivery to be more similar to that of balloons," explains Jeffrey J. Popma, MD, director of interventional cardiology at Beth Israel Deaconess Medical Center in Boston.
Currently, the deliverability of a stent changes proportionately and inversely to lesion length. "Deploying stents in more difficult, longer lesions requires the implantation of multiple stents," Popma says.
To assess DES in these complex cases, the FDA is "actively engaging" trial sponsors and investigators to broaden inclusion criteria to treat a wider spectrum of more complex patients and lesions, says Andrew Farb, MD, medical officer and senior reviewer at the Office of Device Evaluation at the FDA's Division of Cardiovascular Devices.
However, in terms of stent design, Patrick W. Serruys, MD, PhD, an interventional cardiologist at Thoraxcenter, Erasmus Medical Center in Rotterdam, the Netherlands, suggests a metallic scaffold is a "transient need, only required for approximately six months to prevent restenosis. The permanence of metal in coronary arteries is detrimental, and once the metallic cage is implanted, the patient has permanent boundaries of the vessel."
Restenosis is an ongoing clinical concern that newer stent profiles need to address. "Restenosis with second-generation stents has improved, but it still occurs, particularly in complex lesions," says Popma. Restenosis rates are between 5 and 8 percent with the current second-generation stents—an improvement over bare-metal stents (BMS), but "we'd still like to see improvements in efficacy," he adds.
Soon, there may be fiscal incentives to reduce restenosis if the healthcare reform debate continues to push providers toward bundled payments. "Under the current fee-for-service model, restenosis results in another treatment for the patient, but the hospital collects reimbursement on the second procedure," Popma says. "However, the potential plan for a managed care model may create a financial incentive—in addition to a clinical benefit—to lower restenosis rates over the lifetime of the patient. Health plans may eventually be responsible for the entire cost of the patient over a multi-year period, so payors are going to expect a very durable effect from DES."
For safety considerations, patients who receive DES are required to be on dual-antiplatelet therapy (DAPT) for up to one year following PCI. "While Plavix [Bristol-Myers Squibb/Sanofi-Aventis] will be cheaper when it goes off-patent in the U.S. in 2012, there will always be an adherence problem," Popma says. "Therefore, our newer stent designs must release the shackled dependence on DAPT, a therapy which is currently keeping the patient safe."
The rates of stent thrombosis have improved with the second-generation stents, especially with SPIRIT IV that showed a 0.17 percent rate with the everolimus-eluting stent (Xience V, Abbott Vascular) at one year (N Engl J Med 2010;362:1663-1674). Serruys says that these second-generation DES have "set the bar quite high because of the low stent thrombosis rates."
"We've been encouraged by the overall clinical event rates in recent trials with newer-generation DES, but we need to see adequate long-term follow-up that demonstrates continued safety and effectiveness," says Farb. "With such low event rates, we acknowledge that there are significant challenges to conducting studies that require large numbers of patients to show differences in safety and/or effectiveness between competing DES platforms."
However, Popma had been hoping that the very late stent thrombosis rates would have been closer to zero. "While the rates of stent thrombosis were promising in SPIRIT IV in the first year, all the patients were on DAPT, and new solutions need to present a way to suspend this dependence," he says.
BVS paves the way; questions abound
In January, the bioresorbable vascular scaffold