AHA session examines late stent thrombosis, future of non-polymeric solutions

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Two interventional cardiologists analyzed late stent thrombosis (ST) related to drug-eluting stents (DES), which accompanied an overall evaluation of DES and a prediction that non-polymeric solutions could become the future of DES. They presented their findings at the American Heart Association conference this week in Orlando, Fla.

Albert Raizner, MD, an interventional cardiologist in Houston, presented on “Late Thrombosis and DES: What Do We Really Know,” while Alexandre Abizaid, MD, chief of coronary interventions at Institute Dante Pazzanese de Cardiologia in São Paulo, Brazil, and visiting professor of medicine at Columbia University in New York City, presented on “Next Generation DES,” which were followed by a panel discussion.

Raizner examined the cumulative Bern-Rotterdam Registry trials, which included 8,146 patients, and followed up with 981 patients. Of the 981 patients, 24 percent with thrombosis were on a dual-anti-platelet therapy of clopidogrel and aspirin.

From the trials, he surmised that most ST with DES occurs early, like with bare metal stents. Late thrombosis only occurs 0.6 to 0.4 percent of the time, which he deemed “a recurrent theme” in various trials.

Raizner conceded that the industry is only able to track “a follow-up of four to five years. So, we just don’t know yet if the pattern of in-stent thrombosis will continue.”

Raizner cited the network meta-analysis of DES randomized controlled trials (RCTs). He examined 16 RCTs, consisting of 8,695 patients with a follow-up of four years. They produced reduced risks of reintervention with a hazard ratio of 0.74. The ST was 0.46 to 0.94 with a hazard ratio of 0.66.

He reiterated the problems with ST, stating “it’s very bad.” Statistically with ST, 7 percent die and 70 percent endure myocardial infarctions. He also said that ST is “tough to predict,” especially for complex or off-label cases. With these difficult cases, there is much higher, clinically significant, chance of ST, according to Raizner.

For Abizaid’s presentation on the future of the DES industry, he reviewed the development of Biolimus A9 DES of Biomatrix from BioSensors International; Everolimus DES of Xience V from Abbott Laboratories and of Promus from Boston Scientific; Zotarolimus DES of Endeavor Resolute from Medtronic; Novolimus of eXella from Boston Scientific; and non-polymeric solutions.

Though Abizaid reviewed some of the ongoing European and South American clinical studies of the DES, he focused on “the third-generation DES” of non-polymeric solutions, and said they presented the most promising potential to replace the current DES.

Abizaid highlighted two of these non-polymeric technologies: EPC Capture Technologies from Orbus and nanotextured surfaces from Medtronic.

Abizaid’s predictions for the future of DES are:

  • Drugs will have a wider therapeutic window, which will have a safer profile, lower dose and combination therapy (such as anti-proliferation and thrombo-resistant DES).
  • Polymeric solutions will reduce the use or mass of polymer for modulating drug release.
  • Platforms will target specific anomalies to emerge with increasing acute and long-term safety.

During the panel discussion, an FDA representative said that despite the current statistics of ST with DES, “the sun is not setting” on DES. However, he cautioned against the excited reaction concerning DES that followed the Transcatheter Cardiovascular Therapeutics conference held in Washington, D.C., two weeks ago.
Abizaid concurred, “After TCT, the sky is brighter because it presented the most optimistic data from the SCAAR trial” for consistently low statistics of MI and death with DES usage. On the other hand, Raizner said the outcome was hard to determine “when technologies are consistently changing.”

Abizaid added that whether it is the drug or the polymer “that’s causing ST, it’s still a question.” He mentioned the industry is trying to reduce the dosage, but he reiterated that he believes “the non-polymeric solution will be the future.” Abizaid added that late ST is often related to late lumen loss.

The FDA representative said that very late ST is quite rare, and 0.2 percent is currently predicted for DES mortality after stent implantation which, in his opinion, “doesn’t seem too problematic.”

The panel members polled the audience to gauge how many out of approximately 100 cardiologists used DES in more than 50 percent of their cardiac cases. More than 80 percent of the audience