CENTURY II: Bioresorbable Polymer DES Stands up to Everolimus-Eluting Device

PARIS, France—A new bioresorbable polymer drug-eluting stent (DES) has matched the safety and efficacy of a commercially available DES with a durable polymer, according to data presented in a Hot Line session on May 20, 2014, at EuroPCR and simultaneously published in the European Heart Journal.

For CENTURY II, William Wijns, MD, PhD, of Cardiovascular Center Aalst (Aalst, Belgium), and colleagues enrolled 1,119 patients slated for PCI with DES at 58 study sites in Europe, Japan, and Korea. Patients were stratified according to whether or not they fulfilled requirements for DES use in Japan then randomized to receive:

• Ultimaster (n = 562; Terumo; Tokyo, Japan), which releases sirolimus from an abluminal coating expected to resorb within 3 to 4 months
• Xience (n = 557; Abbott Vascular; Abbott Park, IL), which elutes everolimus from a permanent polymer

DAPT was recommended to continue for at least 6 months. Follow-up is planned through 5 years.

CENTURY II “is harmonization in action,” Dr. Wijns said at a press conference. “There is a lot of work being done to have global approval processes,” he continued, but this trial is unique in attempting to simultaneously provide the needed evidence for approval in the European Union and Japan. Examples of exclusion criteria for the Japanese Requirement (JR) cohort (n = 722) include age younger than 20 years, acute MI within 48 hours before baseline procedure, previous stenting within 30 days, and previous stenting of the target lesion.

Similar Safety, Efficacy at 9 Months

Baseline characteristics were largely similar between the 2 study arms in both the total population and the JR cohort. Compared with the overall group, the JR cohort had lower prevalence of high-risk ACS and higher prevalence of diabetes.

Ultimaster proved noninferior to Xience for the primary endpoint of freedom from target lesion failure (TLF; defined as cardiac death, target vessel MI, and clinically driven TLR) at 9 months, both in the total population and in the JR cohort (table 1).

Table 1. Per Protocol Analysis: Freedom from TLF at 9 Months

In the overall group, cardiac death/MI rates were 2.9% for Ultimaster and 3.8% for Xience (P = .40), and TVR rates were 4.5% and 4.2%, respectively (P = .77). Stent thrombosis occurred at a rate of 0.9% in both treatment arms.

Nine-month angiographic follow-up, available for 429 patients (484 lesions), found that in-stent late loss was higher for Ultimaster than for Xience (0.26 vs 0.18 mm; P = .003), though results for in-segment late loss and binary restenosis were similar.

“Both stents showed excellent performance and low rate of adverse events,” Dr. Wijns commented.

Designed to Streamline Regulatory Process

According to the paper, widespread adoption of the Xience stent in contemporary practice “was the major reason” for choosing it as the comparator stent when testing the novel device.

The current findings demonstrate that Ultimaster is as safe and effective as Xience in a “relatively complex patient population,” Dr. Wijns and colleagues conclude. Ongoing follow-up “is expected to provide further unambiguous assessment of the potential long-term clinical benefits of DES with a bioresorbable polymer,” they write.

Panelist Patrick W. Serruys, MD, PhD, of Erasmus Medical Center (Rotterdam, the Netherlands), who admitted to seeing the CENTURY II results early as a reviewer of the paper, described the trial design as solid. “There’s not much material to dispute or debate. I think that we have to congratulate not only the companies but also the European and Japanese investigators,” Dr. Serruys said, noting that such cooperation is “a sign of globalization.”

Mohammed Balghith, MD, of King Abdulaziz Cardiac Center (Riyadh, Saudi Arabia), another panel member, agreed that having more countries involved in research is a worthy goal. “Most trials in interventional cardiology come from Western areas such as the United States and Europe. It is very good for us in the Middle East to have other regions [participating], because they might be similar to us.”

Advantage May Develop Over Time

Long-term follow-up in CENTURY II will be crucial, Dr. Serruys said, citing the LEADERS trial, which showed that the difference between permanent and bioresorbable technologies “only emerged after 3 [to] 5 years.”

Dr. Serruys noted that it is becoming increasingly difficult to show differences between devices, given that adverse outcomes are rare. For patients with chronic disease, the main purpose of PCI “is basically to relieve angina,” he said. “So I think that in Europe and the United States, the [US Food and Drug Administration] and other regulators are talking about [a return to measuring] clinical symptoms instead of counting thrombosis and TLR, which are becoming very rare events.”

“I still think,” replied Dr. Wijns, “when developing new devices like this one, that it is important to have a very strong metric of performance, both in terms of safety and efficacy, even when we may anticipate noninferiority will be present…. It is the real-life experience with very large numbers in postmarketing that will perhaps allow us to identify smaller differences in difficult subsets or high-risk populations.”

 

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Source:
Saito S, Valdes-Chavarri M, Richardt G, et al. A randomized, prospective, intercontinental evaluation of a bioresorbable polymer sirolimus-eluting coronary stent system: the CENTURY II (Clinical Evaluation of New Terumo Drug-Eluting Coronary Stent System in the Treatment of Patients with Coronary Artery Disease) trial. Eur Heart J. 2014;Epub ahead of print.

 

 

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