Drug-eluting stents (DES) in percutaneous coronary interventions significantly reduce rates of restenosis and the need for new revascularizations compared with bare metal stents. However, as the use of DES has increased dramatically, questions have been raised about their long-term safety. Concerns about an increased risk of late stent thrombosis, particularly beyond the first year of treatment, have arisen and have been exacerbated by sparse and conflicting information, and boosted an intense debate between cardiologists. In this article, we reviewed the most recent information to clarify the conundrum of late stent thrombosis and the long-term safety of DES.
Airoldi, F., Colombo, A., Morici, N., Latib, A., Cosgrave, J., Buellesfeld, L. et al. (2007) Incidence and predictors of drug-eluting stent thrombosis during and after discontinuation of thienopyridine treatment . Circulation116: 745—754.
2.
Brunner-La Rocca, H.P., Kaiser, C., Pfisterer, M. (2007) Targeted stent use in clinical practice based on evidence from the Basel Stent Cost Effectiveness Trial (BASKET). Eur Heart J28: 719—725.
3.
Camenzind, E., Steg, P.G., Wijns, W. (2007) Stent thrombosis late after implantation of first-generation drug-eluting stents: a cause for concern. Circulation115: 1440—1455; discussion 1455.
4.
Chen, M.S., John, J.M., Chew, D.P., Lee, D.S., Ellis, S.G., Bhatt, D.L. (2006) Bare metal stent restenosis is not a benign clinical entity. Am Heart J151: 1260—1264.
5.
Cutlip, D.E., Windecker, S., Mehran, R., Boam, A., Cohen, D.J., van Es, G.A. et al. (2007) Clinical end points in coronary stent trials: a case for standardized definitions. Circulation115: 2344—2351.
6.
Daemen, J., Wenaweser, P., Tsuchida, K., Abrecht, L., Vaina, S., Morger, C. et al. (2007) Early and late coronary stent thrombosis of sirolimus-eluting and paclitaxel-eluting stents in routine clinical practice: data from a large two-institutional cohort study. Lancet369: 667—678.
7.
de Feyter, P.J., Kay, P., Disco, C., Serruys, P.W. (1999) Reference chart derived from post-stent-implantation intravascular ultrasound predictors of 6-month expected restenosis on quantitative coronary angiography. Circulation100: 1777—1783.
8.
Fajadet, J., Wijns, W., Laarman, G.J., Kuck, K.H., Ormiston, J., Munzel, T. et al. (2006) Randomized, double-blind, multicenter study of the, Endeavor zotarolimus-eluting phosphorylcholine-encapsulated stent for treatment of native coronary artery lesions: clinical and angiographic results of the ENDEAVOR II trial. Circulation114: 798—806.
9.
Farb, A., Burke, A.P., Kolodgie, F.D., Virmani, R. (2003) Pathological mechanisms of fatal late coronary stent thrombosis in humans. Circulation108: 1701—1706.
10.
Fischman, D.L., Leon, M.B., Baim, D.S., Schatz, R.A., Savage, M.P., Penn, I. et al. (1994) A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. Stent Restenosis Study Investigators. N Engl J Med331: 496—501.
11.
Jensen, L.O., Maeng, M., Kaltoft, A., Thayssen, P., Hansen, H.H., Bottcher, M. et al. (2007) Stent thrombosis, myocardial infarction, and death after drug-eluting and bare-metal stent coronary interventions. J Am Coll Cardiol50: 463—470.
12.
Joner, M., Finn, A.V., Farb, A., Mont, E.K., Kolodgie, F.D., Ladich, E. et al. (2006) Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. J Am Coll Cardiol48: 193—202.
13.
Kastrati, A., Mehilli, J., Pache, J., Kaiser, C., Valgimigli, M., Kelbaek, H. et al. (2007) Analysis of 14 trials comparing sirolimus-eluting stents with bare-metal stents. N Engl J Med356: 1030—1039.
14.
Kotani, J., Awata, M., Nanto, S., Uematsu, M., Oshima, F., Minamiguchi, H. et al. (2006) Incomplete neointimal coverage of sirolimus-eluting stents: angioscopic findings. J Am Coll Cardiol47: 2108—2111.
15.
Kuntz, RE (2007) Medtronic, Vascular: Endeavor safety analysis. http://www.fda.gov/ohrms/dockets/ac/06/slides/2006-4253oph2_17_Kuntz.pdf (Last accessed november 19th 2007).
16.
Lagerqvist, B., James, S.K., Stenestrand, U., Lindback, J., Nilsson, T., Wallentin, L. (2007) Long-term outcomes with drug-eluting stents versus bare-metal stents in Sweden. N Engl J Med356: 1009—1019.
17.
Laskey, W.K., Yancy, C.W., Maisel, W.H. (2007) Thrombosis in coronary drug-eluting stents: report from the meeting of the Circulatory System Medical Devices Advisory Panel of the Food and Drug Administration Center for Devices and Radiologic Health, December 7—8, 2006Circulation115: 2352—2357.
18.
Liistro, F., Fineschi, M., Angioli, P., Sinicropi, G., Falsini, G., Gori, T. et al. (2006) Effectiveness and safety of sirolimus stent implantation for coronary in-stent restenosis: the TRUE (Tuscany Registry of Sirolimus for Unselected In-Stent Restenosis) Registry. J Am Coll Cardiol48: 270—275.
19.
Luscher, T.F., Steffel, J., Eberli, F.R., Joner, M., Nakazawa, G., Tanner, F.C. et al. (2007) Drug-eluting stent and coronary thrombosis: biological mechanisms and clinical implications. Circulation115: 1051—1058.
20.
Marx, S.O. and Marks, AR (2001) Bench to bedside: the development of rapamycin and its application to stent restenosis. Circulation104: 852—855.
21.
Marzocchi, A., Piovaccari, G., Manari, A., Aurier, E., Benassi, A., Saia, F. et al. (2005) Comparison of effectiveness of sirolimus-eluting stents versus bare metal stents for percutaneous coronary intervention in patients at high risk for coronary restenosis or clinical adverse events. Am J Cardiol95: 1409—1414.
22.
Marzocchi, A., Saia, F., Piovaccari, G., Manari, A., Aurier, E., Benassi, A. et al. (2007) Long-term safety and efficacy of drug-eluting stents: two-year results of the REAL (REgistro AngiopLastiche dell'Emilia Romagna) multicenter registry. Circulation115: 3181—3188.
23.
McFadden, E.P., Stabile, E., Regar, E., Cheneau, E., Ong, A.T., Kinnaird, T. et al. (2004) Late thrombosis in drug-eluting coronary stents after discontinuation of antiplatelet therapy. Lancet364: 1519—1521.
24.
Mercado, N., Boersma, E., Wijns, W., Gersh, B.J., Morillo, C.A., de Valk, V., van Es, G.A. (2001) Clinical and quantitative coronary angiographic predictors of coronary restenosis: a comparative analysis from the balloon-to-stent era. J Am Coll Cardiol38: 645—652.
25.
Moussa, I., Leon, M.B., Baim, D.S., O'Neill, W.W., Popma, J.J., Buchbinder, M. et al. (2004) Impact of sirolimus-eluting stents on outcome in diabetic patients: a SIRIUS (SIRolImUS-coated Bx Velocity balloon-expandable stent in the treatment of patients with de novo coronary artery lesions) substudy . Circulation109: 2273—2278.
26.
Nordmann, A.J., Briel, M., Bucher, H.C. (2006) Mortality in randomized controlled trials comparing drug-eluting vs. bare metal stents in coronary artery disease: a meta-analysis . Eur Heart J27: 2784—2814.
27.
Pfisterer, M., Brunner-La Rocca, H.P., Buser, P.T., Rickenbacher, P., Hunziker, P., Mueller, C. et al. (2006) Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drug-eluting versus bare-metal stents. J Am Coll Cardiol48: 2584—2591.
28.
Serruys, P.W., de Jaegere, P., Kiemeneij, F., Macaya, C., Rutsch, W., Heyndrickx, G. et al. (1994) A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. Benestent Study Group. N Engl J Med331: 489—495.
29.
Serruys, P.W., Degertekin, M., Tanabe, K., Abizaid, A., Sousa, J.E., Colombo, A. et al. (2002) Intravascular ultrasound findings in the multicenter, randomized, double-blind RAVEL (RAndomized study with the sirolimus-eluting VElocity balloon-expandable stent in the treatment of patients with de novo native coronary artery Lesions) trial. Circulation106: 798—803.
30.
Serruys, P.W., Kay, I.P., Disco, C., Deshpande, N.V., de Feyter, PJ (1999) Periprocedural quantitative coronary angiography after Palmaz-Schatz stent implantation predicts the restenosis rate at six months: results of a meta-analysis of the BElgian NEtherlands Stent study (BENESTENT) I., BENESTENT II Pilot, BENESTENT II and MUSIC trials. Multicenter Ultrasound Stent In Coronaries. J Am Coll Cardiol34: 1067—1074.
31.
Sollott, S.J., Cheng, L., Pauly, R.R., Jenkins, G.M., Monticone, R.E., Kuzuya, M., Froehlich, J.P. et al. (1995) Taxol inhibits neointimal smooth muscle cell accumulation after angioplasty in the rat. J Clin Invest95: 1869—1876.
32.
Stettler, C., Wandel, S., Allemann, S., Kastrati, A., Morice, M.C., Schomig, A. et al. (2007) Outcomes associated with drug-eluting and bare-metal stents: a collaborative network meta-analysis. Lancet370: 937—948.
33.
Stone, G.W., Ellis, S.G., Colombo, A., Dawkins, K.D., Grube, E., Cutlip, D.E. et al. (2007) Offsetting impact of thrombosis and restenosis on the occurrence of death and myocardial infarction after paclitaxel-eluting and bare metal stent implantation. Circulation115: 2842—2847.
34.
Stone, G.W., Ellis, S.G., Cox, D.A., Hermiller, J., O'Shaughnessy, C., Mann, J.T. et al. (2004) A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease. N Engl J Med350: 221—231.
35.
Stone, G.W., Moses, J.W., Ellis, S.G., Schofer, J., Dawkins, K.D., Morice, M.C. et al. (2007) Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents. N Engl J Med356: 998—1008.
36.
Tu, J.V., Bowen, J., Chiu, M., Ko, D.T., Austin, P.C., He,Y. et al. (2007) Effectiveness and safety of drug-eluting stents in Ontario. N Engl J Med357: 1393—1402.
37.
Virmani, R., Guagliumi, G., Farb, A., Musumeci, G., Grieco, N., Motta, T. et al. (2004) Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent: should we be cautious? Circulation109: 701—705.
38.
Wessely, R., Kastrati, A., Schomig, A. (2005) Late restenosis in patients receiving a polymer-coated sirolimus-eluting stent. Ann Intern Med143: 392—394.
