Biodegradable-Polymer DES Perform Well But Appear No Safer than Their Durable-Polymer Counterparts

CHICAGO, IL—Two recent trials of biodegradable-polymer drug-eluting stents (DES) have failed to support the concept that eliminating a key substrate for ongoing inflammation could promote endothelial healing, reduce neoatherosclerosis, and above all minimize the risk of very late stent thrombosis. Results were presented on November 19, 2014, at the American Heart Association Scientific Sessions.

Head-to-Head vs Conventional DES, BMS

For the BASKET-PROVE II trial, Christoph A. Kaiser, MD, of University Hospital Basel (Basel, Switzerland), and colleagues at 8 centers randomized 2,291 patients with acute or stable CAD needing stents larger than 3 mm in diameter to receive:

 

  • Biolimus-eluting biodegradable-polymer DES (Nobori; Terumo; n = 765),
  • Second-generation everolimus-eluting durable-polymer DES (Xience Prime; Abbott Vascular; n = 765)
  • Thin-strut, silicon-carbide-coated BMS (Pro-Kinetik; Biotronik; n = 761).

 

All patients were treated with aspirin and dose-adjusted prasugrel (Effient; Eli Lilly)—DES and ACS patients for 12 months and BMS patients for 1 month.

At 2 years, rates of cardiac death, MI, or clinically indicated TVR (primary endpoint) were similar between the biodegradable- and durable-polymer DES groups, while the biodegradable-polymer stent group fared better than the BMS group, driven by a lower incidence of TVR. However, in a landmark analysis, the superior efficacy did not last beyond 1 year.)

Table 1. Outcomes at 2 Years

 

Bioabsorbable-Polymer DES

(n = 765)

Durable-Polymer DES

(n = 765)

BMS

(n = 761)

Primary Endpoint

7.6%

6.8%a

12.7%

Cardiac Death

1.3%

0.9%

1.8%

Nonfatal MI

2.4%

2.7%

3.2%

TVR

5.0%

4.7%

10.4%

Primary Safety Endpoint

3.7%

3.8%

5.0%

Definite/Probable Stent Thrombosis

0.4%

0.7%

0.8%

aP = .001 for biodegradable-polymer DES vs BMS.

In the intention-to-treat analysis, the biodegradable-polymer DES was noninferior to the durable-polymer DES for the primary composite, with an absolute risk difference of 0.78% (P for noninferiority = .042). However, the per-protocol analysis showed only a trend toward noninferiority (P = .09).

The combined safety endpoint of cardiac death, MI, and definite or probable stent thrombosis as well as its individual components did not differ among the 3 stent groups. In landmark analysis, this similarity held true both overall and during the second year.

Another Entrant in the Drive for Greater Safety

The performance of another contender in the field of DES with disappearing polymers was reported by Dean J. Kereiakes, MD, of The Christ Hospital Heart and Vascular Center (Cincinnati, OH).

For the pivotal EVOLVE II trial, investigators randomized 1,684 patients to the everolimus-eluting Promus Element Plus (n = 838) or the everolimus-eluting Synergy (n = 846; both Boston Scientific). The Synergy stent consists of a thin-strut, platinum-chromium alloy platform with an ultrathin bioabsorbable PLGA abluminal polymer. Drug release and polymer absorption are 90% complete within 90 days.

At 12 months, rates of the primary endpoint of target lesion failure (cardiac death, target vessel-related MI, or ischemia-driven TLR) were similar between Promus Element Plus and Synergy, as were the component endpoints and definite or probable stent thrombosis (table 2).

Table 2. Outcomes at 12 Months

 

Promus Element Plus

(n = 838)

Synergy

(n = 846)

P Value

Primary Endpoint

6.5%

6.7%

.83

Cardiac Death

0.9%

0.5%

.34

Target Vessel-Related MI

4.7%

4.3%

.71

Clinically Indicated TLR

1.7%

2.6%

.21

Definite/Probable Stent Thrombosis

0.6%

0.4%

.50

No definite or probable stent thrombosis was observed in the Synergy arm after day 6, and no definite stent thrombosis occurred beyond 24 hours.

Commenting on the trials, Roxana Mehran, MD, of Mount Sinai Medical Center (New York, NY), said a strength of both is that they evaluated a new technology in a real-world population. But, she cautioned, interpretation of BASKET-PROVE II is complicated by the inconsistency between the intention-to-treat and per-protocol findings, the different durations of DAPT for the DES and BMS groups, and the lack of data on bleeding, especially in light of use of the more potent antiplatelet prasugrel.

Safety Issue Remains Unresolved

Most important, both trials were underpowered to evaluate safety endpoints, Dr. Mehran said, adding that the ultimate potential of biodegradable DES for improved safety can only be determined by trials with larger sample sizes and longer follow-up.

In reply to a question about possible differences among the various biodegradable devices, Dr. Kaiser replied that they are similar in terms of polymer absorption but some offer better design and deliverability.

Asked if the current results weaken the rationale for biodegradable DES, Dr. Kereiakes offered a broader perspective. “I believe it is possible to build a better mousetrap, to reduce the durable hazard of a device,” he said. “But there’s also the durable hazard of the patient. We saw that clearly in the DAPT trial where 55% of the infarcts had nothing to do with the stent.

As for the potential impact of biodegradable devices on the duration of DAPT—an issue not directly addressed in these trials—Dr. Mehran said, “It is important to distinguish between mandatory therapy for protection against a stent-related complication and a judicious use of DAPT in patient populations who may need it for secondary prevention. We need to continue to evolve these platforms to enhance our ability to reduce the mandatory DAPT duration in the first year post stent implantation. And I think these are the steps in the right direction.”

 


Sources:
1. Kaiser C, Galatius S, Jeger R, et al. Long-term efficacy and safety of biodegradable-polymer biolimus-eluting stents: main results of the Basel stent kosten-effecktivitäts trial-PROspective Validation Examination II (BASKET-PROVE II), a randomized, controlled noninferiority 2-year outcome trial. Circulation. 2014;Epub ahead of print.

 

2. Kereiakes DJ. Primary outcomes of the EVOLVE II trial: a prospective randomized investigation of a novel bioabsorbable polymer-coated, everolimus-eluting coronary stent. Presented at: American Heart Association Scientific Sessions; November 19, 2014; Chicago, IL.

Disclosures:

 

  • Dr. Kaiser reports receiving research grants from the Basel Cardiovascular Research Foundation, Biotronik Switzerland, and Stentys and serving as a speaker, consultant, or advisory board member for multiple device and pharmaceutical companies.
  • Dr. Kereiakes reports serving as a consultant or advisory board member for Abbott Vascular, Ablative Solution, Boston Scientific, Harvard Clinical Research Institute, and REVA Medical.
  • Dr. Mehran reports receiving research grants from Daiichi Sankyo/Eli Lilly, Regado Biosciences, and The Medicines Company and honoraria from Abbott Vascular, AstraZeneca, Boston Scientific, Covidien, CSL Behring, Janssen, Maya Medical, Merck, Regado Biosciences, and Sanofi.

 

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