Attending to Links in the Safety Chain for Drug-Eluting Stents

Login or register to view PDF.
Citation
US Cardiology, 2006;3(1):1-3

Pages

An unintended consequence of the market success of drug-eluting stents has been a growing concern about their safety and safety-related costs. These devices have been so quickly and widely adopted that their market penetration already equals that of some of the most popular pharmaceutical drugs. Consequently, the absolute significance of even a low incidence of side effects becomes magnified by sheer volume.

The safety profiles of the different drug-eluting stents, however, represent just one aspect of the apprehension associated with the rapid adoption of these devices. The success and safety of stent placement depends on meticulous technique, thorough acute follow-up and then persistent long-term monitoring. Unfortunately, we have seen signs of weakness in each of these links in the safety chain.

The most catastrophic of the unwanted outcomes that have been associated with stenting is stent thrombosis. Neither drug-eluting stents nor bare metal stents have eliminated this safety concern.1 Of patients who experience stent thrombosis, 60-70% suffer myocardial infarction (MI) and 20-25% die.The overall incidence of stent thrombosis with bare metal stents is reported to be less than 1% and can be more frequent in high-risk patient/lesion subsets or multivessel procedures.2,3 Given that a total of 800,000 stents are implanted in the US annually and calculating based on a conservative stent-thrombosis rate of 0.9%, the additional economic burden in terms of healthcare costs directly associated with stent thrombosis can be estimated at more than US$80 million per year.1

A prospective study by Iakovou et al. of 2,229 consecutive real-world patients who received sirolimus-or paclitaxel-eluting stents found an overall nine-month incidence of stent thrombosis of 1.3%.4 This finding was substantially higher than the rates previously reported in the placebo-controlled randomised trials that led to the approval of drug-eluting stents (0.4% for the sirolimus-eluting stent,5 0.6% for the paclitaxel-eluting stent6).The fatality rate for patients experiencing stent thrombosis in the study by Iakovou and colleagues was 45%.Compared with patients in the pivotal placebo-controlled trials for these stents, the patients in this prospective study had a higher prevalence of diabetes, multivessel disease, small reference-vessel diameter and complex lesions.4

The single strongest independent predictor of stent thrombosis in this study was premature discontinuation of antiplatelet therapy (hazard ratio (HR) 89.78, p<0.0014), confirming the observations of several case reports.7,8 The other independent predictors of stent thrombosis were renal failure (HR 6.49, p<0.001), bifurcation lesions (HR 6.42, p<0.001), diabetes (HR 3.71, p=0.001) and a lower left ventricular ejection fraction (LVEF) (HR 1.09, p<0.001) for each 10% decrease.

Pages

References
  1. Honda Y, Fitzgerald P J, Stent thrombosis: an issue revisited in a changing world , Circulation (2003);108: pp. 2-5.
    Crossref | PubMed
  2. Leon M B, Baim D S, Popma J J et al., A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting. Stent Anticoagulation Restenosis Study Investigators , N Engl J Med (1998);339: pp. 1,665-1,671.
    Crossref | PubMed
  3. Cutlip D E, Baim D S, Ho K K et al., Stent thrombosis in the modern era: a pooled analysis of multicenter coronary stent clinical trials , Circulation (2001);103: pp. 1,967-1,971.
    Crossref | PubMed
  4. Iakovou I, Schmidt T, Bonizzoni E et al., Incidence, predictors, and outcome of thrombosis after successful implantation of drugeluting stents , JAMA (2005);293: pp. 2,126-2,130.
    Crossref | PubMed
  5. Moses J W, Leon M B, Popma J J et al., Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery , N Engl J Med (2003);349: pp. 1,315-1,323.
    Crossref | PubMed
  6. Stone G W, Ellis S T, Cox D A et al., A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease , N Engl J Med (2004);350: pp. 221-231.
    Crossref | PubMed
  7. McFadden E P, Stabile E, Regar E et al., Late thrombosis in drug-eluting coronary stents after discontinuation of antiplatelet therapy , Lancet (2004);364: pp. 1,519-1,521.
    Crossref | PubMed
  8. Jeremias A, Sylvia B, Bridges J et al., Stent thrombosis after successful sirolimus-eluting stent implantation , Circulation (2004);109: pp. 1,930-1,932.
    Crossref | PubMed
  9. Bertrand M E, Rupprecht H J, Urban P et al., Double-blind study of the safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting: the clopidogrel aspirin stent international cooperative study (CLASSICS) , Circulation (2000);102: pp. 624-629.
    Crossref | PubMed
  10. Gurbel P A, Cummings C C, Bell C R et al., Onset and extent of platelet inhibition by clopidogrel loading in patients undergoing elective coronary stenting: the Plavix Reduction Of New Thrombus Occurrence (PRONTO) trial , Am Heart J (2003);145: pp. 239-247.
    Crossref | PubMed
  11. Schofer J, Schluter M, Gershlick A H et al., Sirolimus-eluting stents for treatment of patients with long atherosclerotic lesions in small coronary arteries: double-blind, randomised controlled trial (E-SIRIUS) , Lancet (2003);362: pp. 1,093-1,099.
    Crossref | PubMed
  12. Schampaert E, Cohen E A, Schluter M et al., The Canadian study of the sirolimus-eluting stent in the treatment of patients with long de novo lesions in small native coronary arteries (C-SIRIUS) , J Am Coll Cardiol (2004);43: pp. 1,110-1,115.
    Crossref | PubMed
  13. Lemos P A, Serruys P W, van Domburg R T et al., Unrestricted utilization of sirolimus-eluting stents compared with conventional bare stent implantation in the real world : the Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry , Circulation (2004);109: pp. 190-195.
    Crossref | PubMed
  14. Colombo A, Drzewiecki J, Banning A et al., Randomized study to assess the effectiveness of slow- and moderate-release polymerbased paclitaxel-eluting stents for coronary artery lesions , Circulation (2003);108: pp. 788-794.
    Crossref | PubMed
  15. Gershlick A, De Scheerder I, Chevalier B et al., Inhibition of restenosis with a paclitaxel-eluting, polymer-free coronary stent: the European evaLUation of pacliTaxel Eluting Stent (ELUTES) trial , Circulation (2004);109: pp. 487-493.
    Crossref | PubMed
  16. Nguyen T A, Diodati J G, Pharand C, Resistance to clopidogrel: a review of the evidence , J Am Coll Cardiol (2005);45: pp. 1,157-1,164.
    Crossref | PubMed
  17. Gum P A, Kottke-Marchant K,Welsh P A,White J,Topol E J, A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease , J Am Coll Cardiol (2003);41: pp. 961-965.
    Crossref | PubMed
  18. Wenaweser P, Dorffler-Melly J, Imboden K et al., Stent thrombosis is associated with an impaired response to antiplatelet therapy , J Am Coll Cardiol (2005);45: pp. 1,748-1,752.
    Crossref | PubMed