Meta-analysis Finds Equivalence Between First-, Second-Generation DES

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A comparison of a first-generation sirolimus-eluting stent with a second-generation everolimus-eluting stent reveals no difference in the risk of thrombotic events or revascularization, according to a meta-analysis published online July 26, 2011, ahead of print in Circulation: Cardiovascular Interventions.

Researchers led by Adnan Kastrati, MD, of Deutsches Herzzentrum (Munich, Germany), examined 5 randomized trials that compared patients receiving Xience V everolimus-eluting stents (EES; n = 4,044; Abbott Vascular, Santa Clara, CA) with those receiving Cypher sirolimus-eluting stents (SES; n = 3,326; Cordis, Warren, NJ). The trials, with follow-up durations ranging from 9 to 36 months (median 13.3 months), were:

  • BASKET-PROVE
  • ESSENCE-DIABETES
  • EXCELLENT
  • ISAR-TEST 4
  • SORT OUT IV

In the Big Picture, Outcomes Similar

Overall, there were no significant differences between EES and SES with respect to the primary endpoint of MACE at the longest available follow-up or the secondary endpoints of cardiac death, MI, repeat revascularization, and composite of Academic Research Consortium-defined definite or probable stent thrombosis (table 1).

Table 1. Risk of Primary and Secondary Endpoints: EES vs. SES

 

HR (95% CI)

P Value

MACE

0.91 (0.77-1.08)

0.28

Cardiac Death

1.02 (0.73-1.41)

0.92

MI

0.97 (0.66-1.35)

0.76

Repeat Intervention

0.85 (0.68-1.07)

0.16

Definite or Probable Stent Thrombosis

0.97 (0.49-1.27)

0.33


The study authors also performed a separate TLR analysis without data from BASKET-PROVE, because the trial’s exclusion of lesions in vessels smaller than 3 mm in diameter might blunt differences in antirestenotic efficacy. Again, the likelihood of repeat intervention was similar with EES vs. SES (HR 0.84; 95% CI 0.65-1.09; P = 0.19).

In addition, 2 trials without scheduled follow-up angiography (BASKET-PROVE and SORT OUT IV) showed similar treatment effects, with no major differences between the 2 DES.

But Is It a Moot Point?

According to the study authors, the inability to detect an advantage with either DES “may be interpreted as a signal that any true difference is likely to be of limited relevance and highlights the great challenge in the design of future trials targeting this comparison.”

The large size of the meta-analysis along with the fact that the 5 included trials “adopted very few exclusion criteria and may well be considered as ‘all-comers’ trials,” add to the strength of the study findings, according to Dr. Kastrati and colleagues.

They also comment that, for a number of reasons, SES are the “most obvious” comparator for EES:

  • As the most effective first-generation DES, SES provide the best benchmark against which second-generation devices should be evaluated
  • As a sirolimus analog, everolimus constitutes a more intuitive target for interdevice efficacy trials

While these points may be true, one obvious factor that cannot be overlooked is the recent announcement by Cordis that it will cease making its sirolimus-eluting Cypher and Cypher Select stents by the end of 2011.

In a telephone interview with TCTMD, Robert S. Schwartz, MD, of the Minneapolis Heart Institute (Minneapolis, MN), said that factor alone may make the meta-analysis a moot point.

However, Dr. Schwartz cautioned against taking the view that the equivalency findings mean there is no need for newer-generation devices.

“It’s probably true that for the average patient, the older devices work perfectly well,” he said. “But it’s dangerous to draw global conclusions when there are niche areas for very much advanced patient care in the cath lab that clearly require newer, more advanced devices. Yes, the differences are subtle, and overall when you apply them to a large population you can’t see much difference—but when you get down to the very specific, very difficult cases there’s a huge difference and Cypher just doesn’t make it. Those are the kinds of things you are not going to see in a meta-analysis.”

The study authors suggest that future studies should focus on longer follow-up to ascertain if differences eventually will emerge between the 2 stents.

Dr. Schwartz agreed that the issue of late catch-up is important, pointing out that some animal data do indicate that SES patients will have more complications by 7 to 10 years.

Study Details

The mean age of participants in the 5 trials ranged from 63 to 67 years. Recommended duration of clopidogrel therapy was at least 6 months.


Sources:
1. de Waha A, Dibra A, Byrne RA, et al. Everolimus-eluting versus sirolimus-eluting stents: A meta-analysis of randomized trials. Circ Cardiovasc Interv. 2011;Epub ahead of print.

2. Cordis Announces Discontinuation of Nevo Sirolimus-Eluting Coronary Stent [press release]. Bridgewater, NJ: Johnson and Johnson; June 15, 2011. http://www.jnj.com/connect/news/all/cordis-announces-discontinuation-of-nevo-sirolimus-eluting-coronary-stent. Accessed August 2, 2011.

 

 

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Disclosures
  • Dr. Kastrati reports receiving lecture fees from Abbott and Cordis.
  • Dr. Schwartz reports no relevant conflicts of interest.

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