No Clear Winner in Tests Between Biodegradable-Polymer DES vs. Conventional SES

PARIS, France—Two large randomized trials presented May 17 at EuroPCR 2012 showed nearly identical results for biodegradeable-polymer drug-eluting stents (DES) compared with first-generation sirolimus-eluting stents (SES) containing permanent polymers. Yet noninferiority criteria proved hard to meet, with only 1 of the newer stents reaching that goal.

EVOLUTION

For the 30-center EVOLUTION trial, Junbo Ge, MD, of Zhongshan Hospital, Fudan University (Shanghai, China), attempted to isolate the effect of the polymer by considering 2 SES: the biodegradable-polymer Excel (JW Medical Systems, Weihai, China) and the permanent-polymer Cypher Select (Cordis, Miami Lakes, FL). A total of 1,923 patients, who had de novo coronary artery lesions and clinical presentations ranging from silent ischemia to ACS, were randomized in a 2:1 ratio to Exel (n = 1,239) or Cypher Select (n = 670).

Baseline characteristics were largely similar between groups, though Excel patients were significantly older and more likely to be women and receive treatment in small vessels (≤ 2.57 mm) than Cypher patients, who had a higher prevalence of LAD disease. At 12 months, aspirin and clopidogrel use were approximately 97% and 98%, respectively.

At 12 months, Excel was noninferior to Cypher for the primary endpoint of target lesion failure (combined cardiac death, MI, and ischemia-driven TLR; P < 0.05), with the 2 stents showing equivalent rates of TLF and its components. Cases of Academic Research Consortium-defined definite/probable stent thrombosis were rare and evenly distributed (table 1).

Table 1. EVOLUTION: Adverse Outcomes

 

Excel
(n = 1,239)

Cypher Select
(n = 670)

P Value

12-Month Follow-Up

TVF

Cardiac Death

MI

Ischemia-Driven TLR

 

0.89%

0.24%

0.40%

0.24%

 

1.34%

0.30%

0.75%

0.45%

 

0.3509

1.0000

0.3346

0.4294

Definite/Probable Stent Thrombosis

Acute

Subacute

Late

Very Late

 

0

0.08%

0.24%

0

 

0

0

0.60%

0

 

-

1.000

0.2493

-

 

Though 1-year follow-up shows comparable safety and efficacy, “Longer term follow-up, especially after stopping antiplatelet therapy, will be necessary to find out the potential divergence in outcomes between the 2 different types of stents,” Dr. Ge concluded.

Panel member Bernard R. Chevalier, MD, of Institut Cardiovasculaire Paris Sud (Massy, France), expressed surprise at the low event rates documented in EVOLUTION. Dr. Ge pointed out that this is often the case in studies performed in China, Japan, and Korea. It may have to do with low resistance to antiplatelet therapy among Asian patients, he proposed.

SORT OUT V

Evald Christiasen, MD, of Skejby University Hospital (Aarhus, Denmark), and colleagues took a slightly different angle by testing a biodgradable-polymer DES—this time the biolimus A-9-eluting Nobori (Terumo, Tokyo, Japan)—against Cypher Select Plus (Cordis) in an all-comers population. The SORT OUT V trial included patients with either chronic stable CAD or ACS and did not exclude subjects based on the number or length of lesions treated.

A total of 2,648 patients were randomized to receive Nobori (n = 1,229) or Cypher Select Plus (n = 1,239). Patient and lesion characteristics all were equivalent between the 2 groups; the main exceptions were that Nobori patients had a smaller reference vessel diameter than Cypher patients (median 3.2 mm vs. 3.3 mm; P = 0.03) and a lower maximum pressure at balloon inflation (median 16.0 atm vs. 18.0 atm; P < 0.0001).

Nobori did not meet noninferiority criteria for the primary endpoint of 9-month MACE (combined cardiac death, MI, definite stent thrombosis, and clinically driven TVR). At 12-month follow-up, MACE and its components were all statistically similar between the 2 stents, although Nobori showed a trend for increased definite stent thrombosis (table 2).

Table 2. SORT OUT V: Adverse Outcomes

 

Nobori
(n = 1,229)

Cypher Select Plus
(n = 1,239)

P Value

9-Month Follow-Up

MACE

 

4.1%

 

3.2%

 

0.06a

12-Month Follow-Up

MACE

Cardiac Death

MI

Definite Stent Thrombosis

Definite/Probable Stent Thrombosis

TVR

 

5.4%

1.0%

1.5%

0.8%

0.9%

4.2%

 

4.5%

1.1%

0.9%

0.2%

0.5%

3.1%

 

0.28

0.71

0.14

0.07

0.22

0.15

a P for noninferiority.

 

However, the lack of noninferiority “may change with longer follow-up time,” as the Nobori polymer degrades, Dr. Christiansen concluded.

An audience member attending the presentation suggested that a better than average performance by Cypher may be responsible for the results, and Dr. Christiansen agreed, pointing to the low rate of definite stent thrombosis. “We cannot exclude noninferiority,” he cautioned, “but the difference was small and we compared this stent with a very potent stent.”

Dr. Chevalier questioned why more pressure was required during implantation for Cypher compared with Nobori. Noting that the same pattern was observed in SORT OUT IV, Dr. Christiansen explained “the compliance of the new stent is much better than [that of] this older, more rigid stent. Operator experience shows that the stiffer stent needs more pressure to be well expanded.”

Such a difference might bias results, Dr. Chevalier suggested.

Panel member Spencer B. King III, MD, of Saint Joseph's Heart and Vascular Institute (Atlanta, GA), said that while the extremely good results for Cypher might be a “fluke,” he wondered whether “it is worthwhile to compare [newer devices] to a stent with such a well documented track record and really fairly low stent thrombosis. I'm surprised that [your power calculation was based on] such a high event rate in the sirolimus group to start with.”

Dr. Christiansen replied that, in light of the expected low event rates, the researchers had tightened the margin of the confidence intervals. Based on the positive outcomes for both stents, “I think you should continue with the technology of a biodegradable polymer.”

Regardless, “the results of stenting seem to be pretty good right now,” Dr. King observed. “Where do we go from here? We hear about a lot of other things, totally bioabsorbable stents and so forth. But it's an interesting challenge, because if you look at stent comparisons right now, we're getting to a bit of a plateau.”

 

Sources:

  1. Ge J. Sirolimus-eluting stent with biodegradable-polymer versus sirolius-eluting stent with durable polymer for the treatment of patients with de novo coronary artery lesions (EVOLUTION): A randomised non-inferiority trial. Presented at: EuroPCR. May 17, 2012. Paris, France.
  2. Christiansen E. Randomised comparison of the sirolimus-eluting non-biodegradable polymer coated Cypher Select+ stent and the biolimus-eluting biodegradable polymer-coated Nobori stent in unselected patients treated with PCI: The SORT OUT V trial. Presented at: EuroPCR. May 17, 2012. Paris, France.

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Disclosures
  • ·        Dr. Ge reports receiving research contracts from Abbott Vascular, JW Medical, and MicroPort as well as serving as a consultant to MicroPort.
  • ·        Dr. Christiansen reports receiving research grants and speakers fees from Cordis/Johnson &amp; Johnson, speaker's fees from St. Jude Medical, and research grants from Terumo.

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