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October 6th, 2010

The Skinny on Drug-Eluting Stents (DES)

(“All we want are the facts, ma’am.” –Joe Friday, Dragnet)

Having trouble keeping up with DES and the recent stent studies? Want a brief tutorial? To learn the top six things every cardiologist should know about DES, read on…

1. What they do. DES are superior to both bare-metal stents and angioplasty in reducing the incidence of clinical restenosis and the need for reintervention after PCI. Clinical restenosis occurs in 30% to 50% of patients after angioplasty, in 20% to 30% after bare-metal stent implantation, and in about 10% after DES implantation.

Compared with bare-metal stents, DES confer an increased risk for stent thrombosis months (and years) after placement. Therefore, patients who receive DES are placed on dual antiplatelet therapy for at least a year, which increases their risk for a bleeding complication.

2. What they don’t do. DES do not reduce the risk for death or MI in patients with stable ischemic heart disease. This is a commonly held misperception (among patients and physicians). Sorry to burst this bubble.

3. First-generation stents. Three first-generation DES are available in the U.S.: the sirolimus-eluting CYPHER stent (Cordis), the paclitaxel-eluting TAXUS stent (Boston Scientific) and the zotarolimus-eluting ENDEAVOR stent (Medtronic). Outcomes after sirolimus- and paclitaxel-eluting stent implantation appear to be similar; however, the zotarolimus-eluting stent appears to be less effective (higher all cause-mortality, MI, and target-lesion restenosis [TLR] at 18 months than the sirolimus-eluting stent in the SORT OUT III study). Hard to justify using the zotarolimus-eluting stent.

4. Second-generation stents. Second-generation DES are designed to improve stent deployment, safety, and efficacy by altering the composition and thickness of the metal struts, the copolymer, and/or the antiproliferative drug. Second-generation DES release everolimus, a semisynthetic sirolimus analogue, from a thin coating of a biocompatible fluoropolymer on a flexible cobalt–chromium stent frame with thin struts.

Figure 1. Scanning Electron Micrographs of a Paclitaxel-Eluting Stent and an Everolimus-Eluting Stent. Shown are scanning electron micrographs of a cross-section of a paclitaxel-eluting stent strut (TAXUS Express, Boston Scientific) (Panel A) and an everolimus-eluting stent strut (XIENCE V, Abbott) (Panel B). As compared with the everolimus-eluting stent, the paclitaxel-eluting stent has a thicker strut and a thicker polymer coating (arrow). Reprinted with permission from Doostzadeh et al. Recent progress in percutaneous coronary intervention: Evolution of the drug-eluting stents, focus on the XIENCE V drug-eluting stent. Coron Artery Dis 2010; 21:46-56.

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Two everolimus-eluting stents are currently available in the U.S.: the Xience V (Abbott) and the Promus (Boston-Scientific “private label”). Don’t be fooled. The Promus stent is actually the Xience V stent from Abbott (i.e., like bottling the same wine under 2 different labels…vive la différence!)

Why sell 2 second-generation stents that are identical? DES is big business, with a world market of approximately $5 billion annually and over 2 million stents implanted already. Not surprisingly, therefore, both companies want a share of the market.

The second-generation stents cost about $300 more than the first-generation stents.

5. Stent Wars: Who’s Winning? In two studies (COMPARE and SPIRIT IV) with 2-year follow-up, the second-generation everolimus-eluting stent was superior to the first generation paclitaxel-eluting stent, with fewer stent “failures” (i.e., composite cardiac death, MI, TLR and stent thrombosis).

In two studies (SORT OUT IV and ISAR 4) with 9 and 24 months of follow-up, the second-generation everolimus-eluting stent was noninferior to the first-generation sirolimus-eluting stent, with a trend towards less restenosis with the everolimus-eluting device after longer follow-up.

6. The Bottom Line. Studies have shown that the everolimus-eluting stent is comparable to the less-expensive sirolimus-eluting stent (although longer follow-up and additional studies are needed to confirm this) and superior to the paclitaxel-eluting stent.

In patients with diabetes, who comprise 20% to 30% of patients undergoing PCI, the second-generation stents do not appear to be more effective than the first-generation (less expensive) stents.

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5 Responses to “The Skinny on Drug-Eluting Stents (DES)”

  1. ISAAC MAMMEN, M.B.B.S , M.D, D.M cardiology says:
    October 9, 2010 at 12:59 pm

    Excellent review.
    Thanks

  2. Sangmesh Jabshetty, MD says:
    October 14, 2010 at 7:21 pm

    Very informative.I had a question .
    How long one needs to on anti plates if he has pacitaxel stent ,how long if he has sirolimus stent.

  3. Richard A. Lange, MD, MBA says:
    October 19, 2010 at 7:51 am

    After DES (of any type), patients should receive clopidogrel for at least 12 months and aspirin life-long. Some physicians recommend continuing the clopidogrel longer than a year because late stent thrombosis may occur after it is discontinued. Fortunately, late stent thrombosis is a rare event (<1% per year)…unfortunately, we can't predict who will experience it

  4. Jeff Jaeger, MD says:
    November 1, 2010 at 4:38 pm

    From a primary care / non cardiologist: What is the practical difference between TLR and stent thrombosis? I am having trouble understanding how the DES can reduce stenosis but have a higher incidence of thrombosis.

    Competing interests pertaining specifically to this post, comment, or both:
    No COI

    • Rahul Bhardwaj, MD says:
      November 2, 2010 at 5:20 am

      Dr. Jaeger,

      I’ll try to answer your questions about thrombosis and stenosis, and why DES are thought to be better than BMS in reducing rates of in-stent stenosis.

      There are three components of restenosis after angioplasty: elastic recoil, intimal proliferation, and arterial remodeling. Intimal hyperplasia is the predominant mechanism of renarrowing after stent implantation. It occurs because after endothelialization of the foreign stent, scar tissue continues to be produced and narrow (and perhaps even occlude) the artery. It has been shown to occur in 35-50% of patients after angioplasty, 20-25% (range of 10-60% in various studies) of patients after BMS implantation. Four patterns of in-stent restenosis
      were defined: I focal (10 mm in length), II in-stent
      restenosis >10 mm within the stent, III in-stent restenosis
      >10 mm extending outside the stent and IV totally
      occluded in-stent restenosis. TLR increased with increasing ISR class; it was 19%, 35%, 50%, and 83% in classes I to IV. DES elute drugs that prevent endothelialization / intimal hyperplasia. Basically, this means that they inhibit intimal hyperplasia of the arterial wall that is induced by the trauma associated with stent deployment and angioplasty. In-stent restenosis is typically seen 3 to 6 months after the procedure. DES have been shown in several trials (SIRIUS, TAXUS, etc) to reduce the risk of stenosis though there is some controversy about whether their benefit is overstated (See: Narrative Review: Tung et al. Drug-Eluting Stents for the Management of Restenosis: A Critical Appraisal of the Evidence, Annals of Internal Medicine June 2006 vol. 144 no. 12 913-919). Angiographic narrowing seen on follow-up in patients with stents prompted target lesion revascularization. In addition to the type of stent used, the three most important factors associated with stenosis are 1) lesion length and/or stented length, 2) inverse relationship to vessel diameter and 3) presence or absence of diabetes. The most common consequence of restenosis is reduced quality of life from recurrence of symptoms.

      Stent thrombosis is a different beast altogether, and is basically a thrombus forming in the stent. It is caused through the typical mechanism of thrombosis; thrombosis is induced by vascular injury from stent implantation through the mechanism of platelet adhesion, aggregation and activation. BMS are endothelialized much quicker than DES, and are at lower risk for in-stent thrombosis and absolutely require dual therapy for a shorter duration than DES, which (as mentioned above) do not get endothelialized as rapidly because the eluted drug. Some studies have also contended that the eluted drug itself or the polymer used in the DES have a pro-thrombotic effect that increased risk for thrombosis. Stent thrombosis is usually more serious than in-stent stenosis because it is associated with high risk of MI and death. Overall, though, thrombosis is fairly uncommon (in one metaanalysis DES 0.6% vs BMS 0.05% in one metaanalysis).

      From a practical point of view, the bottom line (as far as I understand it), is that BMS have a lower risk of thrombosis but higher risk of stenosis. Overall, thrombosis is pretty rare and stenosis can occur frequently (more in BMS vs DES). DES are associated with decreased need for revascularlization compared to BMS, but there is no change in mortality (though I’ll add that new studies suggest there is improvement in long-term mortality with DES compared with BMS).

      Other good papers to read:
      – Anstrom et al. Long-term Clinical Outcomes Following Coronary Stenting; Arch Intern Med. 2008;168(15):1647-1655
      – Kastrati et al.; Analysis of 14 Trials Comparing Sirolimus-Eluting Stents with Bare-Metal Stents; NEJM 2007; 356:1030-1039
      – Malenka et al; Outcomes Following Coronary Stenting in the Era of Bare-Metal vs the Era of Drug-Eluting Stents; JAMA. 2008;299(24):2868-2876.
      – Spaulding et al.; A Pooled Analysis of Data Comparing Sirolimus-Eluting Stents with Bare-Metal Stents; NEJM 2007; 356:989-997

      Competing interests pertaining specifically to this post, comment, or both:
      None