BIOSCIENCE: Biodegradable Polymer SES Noninferior to Durable Polymer EES in All-Comers Trial

BARCELONA, Spain—A novel biodegradable polymer sirolimus-eluting stent (SES) holds its own against a standard-of-care durable polymer everolimus-eluting stent (EES), according to results presented September 1, 2014, at the European Society of Cardiology Congress and simultaneously published in the Lancet. However, because outcomes for newer-generation stents have been so good in recent years, an editorial questions how much effort should go into developing new versions. 

The ultrathin Osiro stent (Biotronik AG; Bülach, Switzerland) is composed of cobalt-chromium covered with a biodegradable poly-L-lactic acid polymer that elutes the drug sirolimus at a dose of 1.4 μg/mm2 stent surface for up to 12-14 weeks. Its polymer fully degrades 12-24 months after implantation.

Methods
For the BIOSCIENCE trial, Thomas Pilgrim, MD, of Bern University Hospital (Bern, Switzerland), and colleagues randomized 2,129 patients with stable CAD or ACS at 9 Swiss hospitals to treatment with either the biodegradable polymer Osiro SES (n = 1,063 patients, 1,594 lesions) or the durable polymer Xience Prime/Xpedition EES (Abbott Vascular; Abbot Park, IL; n = 1,056 patients, 1,545 lesions) from February 24, 2012 to May 22, 2013. Unfractionated heparin was given during the procedure, while the use of GPIs and bivalirudin was left to the discretion of the operator. Dual antiplatelet therapy was recommended for 12 months after implantation.
One-third (35%) of patients presented with STEMI, NSTEMI, or multivessel disease necessitating treatment of more than one stenosis. More than half of all lesions were long, about 30% were in small vessels, and about 17% were bifurcated.

 
 At 12 months, there were no differences in the primary endpoint of target lesion failure (composite of cardiac death, target vessel MI, and clinically indicated TLR) and any of its individual components between the treatment groups (table 1). Moreover, noninferiority was established for the SES vs EES (absolute risk difference -0.14%; P = .0004 for noninferiority). 

Table 1. Outcomes at 12 Months

 

SES

(n = 1,063)

EES

(n = 1,056)

Rate Ratio (95% CI)

P Value

Target Lesion Failure

6.7%

6.7%

0.99 (0.71-1.38)

.950

Cardiac Death

1.9%

2.1%

0.91 (0.50-1.67)

.770

Clinically Indicated TLR

3.4%

2.4%

1.42 (0.85-2.37)

.18

Target Vessel MI

2.9%

3.0%

0.97 (0.58-1.60)

.897

Repeat Revascularization

7.6%

5.7%

1.35 (0.96-1.89)

.085

BARC Bleeding Type 3-5

3%

2.6%

1.15 (0.69-1.92)

.6

Definite/Probable Stent Thrombosis

2.8%

3.4%

0.83 (0.50-1.35)

.45

 

In the as-treated analysis, results were maintained for the primary endpoint between the study (6.2%) and control (6.7%) groups (P < .0001 for noninferiority). Findings were also consistent across the subgroups of diabetes, ACS, off-label use, small vessels, de novo lesions, long lesions, multivessel treatment, sex, age, BMI, and renal failure. However, STEMI patients treated with the biodegradable polymer SES derived more benefit than those receiving the durable polymer EES with regard to the primary endpoint (3.3% vs 8.7%; rate ratio 0.38; 95% CI 0.16-0.91; P = .024).

How Good is Good Enough? 

In an editorial accompanying the paper, Julinda Mehilli, MD, and Steffen Massberg, PhD, both of Ludwig-Maximillians University (Munich, Germany), write that though BIOSCIENCE was a “well-designed and well-performed trial,” it falls prey to the same dilemma that has affected the majority of all stent trials performed in the last 5 years. “The slightly lower-than-expected frequency of the primary endpoint… and the large margin of noninferiority chosen… affect the robustness of the results, particularly of the subgroup analyses,” they say.

“Because of the excellent performance of the newer-generations of drug-eluting stent, the reported rates of target lesion failure range between 3% and 8% in most trials,” Drs. Mehilli and Massberg comment. The results emphasize “the excellent performance of the drug-eluting stent platforms on the market and, on the other hand, [question] the necessity for newer drug-eluting stents.” 

Time to Quantify Success Rather Than Failure

Discussant Patrick W. Serruys, MD, PhD, of Erasmus Medical Center (Rotterdam, The Netherlands), said the “core of the problem” is that the Osiro stent platform differs in 4 ways from the Xience stent—passive coating, biodegradable polymer, thinner struts, and the eluted drug. “Ideally, from a scientific perspective, you would only vary one feature at a time,” he said. 

Secondly, he challenged the benefit of the biodegradable polymer stent in STEMI patients as “a little bit on thin ice…. You don’t need too much change in the data to have something that is no longer significant, so I would be careful with this subgroup.”

Lastly, he questioned the long-term nature of the polymer, which takes longer to degrade than that of any other stent in the literature. Dr. Pilgrim responded that although the issue is of concern, compared to a durable polymer EES, “it’s better to have a polymer that at least disappears within one or 2 years rather than a polymer that stays there forever.”

Speaking to clinical trials in general, Dr. Serruys said, “[T]oday we go from one noninferiority trial to [another] noninferiority trial. We keep quantifying the failure of the device—the death, the MI, and the TLR. However, we don’t [develop] these devices for failure, but to treat our patients.” 

The rate of failure will soon be below 5%, he suggested, leaving no wiggle room for future trials. “I suggest that we rethink our approach and start to quantify success by reducing angina early because it is still there,” Dr. Serruys observed. “If you look, most of these trials end up at one year with 25% of patients still having angina after PCI.”

 


Sources:
1. Pilgrim T, Heg D, Roffi M, et al. Ultrathin strut biodegradable polymer sirolimus-eluting stent versus durable polymer everolimus-eluting stent for percutaneous coronary revascularization (BIOSCIENCE): a randomized, single-blind, non-inferiority trial. Lancet. 2014;Epub ahead of print.

 

2. Mehilli J, Massberg S. Revisiting the BIOSCIENCE of drug-eluting stent technology [editorial]. Lancet. 2014;Epub ahead of print.

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Disclosures
  • BIOSCIENCE was supported by Biotronik.
  • Dr. Pilgrim reports receiving travel expenses and lecture fees from Biotronik.
  • Dr. Mehilli reports receiving speaker fees from Abbott Vascular, Biotronik, Eli Lilly/Daiichi Sankyo, and Terumo.
  • Dr. Massberg reports no relevant conflicts of interest.

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