Are we sure we have taken the best from clopidogrel? In the above-mentioned article, Goy et al 1 describe the outcome of 350 patients treated with a sirolimus-eluting stent. The 5-year follow-up is the longest in this clinical setting and shows a cumulative rate of stent thrombosis of 3.6%; only one patient was on clopidogrel treatment at the time of ST. Optimal chronic antiplatelet therapy is a well-known key point in patients undergoing drug-eluting stent (DES) implantation. As a matter of fact, DES thrombosis rate after dual antiplatelet therapy discontinuation is not trivial, occurring in 0.4% to 0.6% patients per year as the above mentioned study has confirmed. 2 The Food and Drug Administration recommended dual antiplatelet therapy in patients implanted with DES for up to 12 months or beyond, whenever not contraindicated. Unfortunately, long-term dual antiplatelet therapy is a treatment scarcely tolerated in “real-world” patients because of adverse effects and in case of surgery. Therefore, sooner or later, most patients treated with DES are likely to switch from dual antiplatelet regimen to the lone aspirin. If we believe that an “optimal antiplatelet regimen” should provide the best balance between thrombosis and bleeding, we must admit that neither dual antiplatelet therapy, nor aspirin alone can be considered “optimal,” being the former associated with excess bleeding and the latter with excess thrombosis. Thus, long-term prevention of DES thrombosis remains an unmet clinical need. Clopidogrel provides 40% to 50% inhibition of platelet activity. 3 In the CAPRIE trial, 4 clopidogrel has been shown to be more effective than aspirin in preventing adverse vascular events (9% relative risk reduction) with similar safety profile. In the MATCH trial, 5 clopidogrel was as effective as dual antiplatelet therapy in preventing adverse cardiovascular events, inducing significantly less life- threatening or major bleedings. Therefore, clopidogrel seems to provide a better effectiveness/safety ratio being as effective as dual antiplatelet regimen and as safe as aspirin alone. So the question is: after discontinuation of dual antiplatelet therapy for DES implantation, should we maintain aspirin or clopidogrel? In our opinion, available evidence might be enough to justify a prospective randomized trial testing this specific point. The possibility to enroll the vast cohort of patients with DES and still in dual antiplatelet therapy, whenever its discontinuation is planned, should allow for rapid recruitment of a large study population. Last but not least, clopidogrel molecule is at the near end of its trademark. The expected substantial decrease in clopidogrel market price will improve its cost-effectiveness profile in case of positive trial results. Am Heart J 2009;158:e59. 0002-8703/$ - see front matter doi:10.1016/j.ahj.2009.07.026 Bernardo Cortese, MD Andrea Picchi, MD Andrea Micheli, MD Ugo Limbruno, MD, PhD Cardiologia Interventistica Ospedale della Misericordia, Grosseto, Italy E-mail: bcortese@gmail.com References 1. Goy J, Urban P, Kaufmann U, et al. Incidence of stent thrombosis and adverse cardiac events 5 years after sirolimus stent implantation in clinical practice. Am Heart J 2009;157:883-8. 2. Daemen J, Wenaweser P, Tsuchida K, et al. 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. Lancet 2007;369:667-78. 3. Serebruany VL, Steinhubl SR, Berger PB, et al. Variability in platelet responsiveness to clopidogrel among 544 individuals. J Am Coll Cardiol 2005;45:246-51. 4. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996;348:1329-39. 5. Diener HC, Bogousslavsky J, Brass LM, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double blind, placebo-controlled trial. Lancet 2004;364:331-7. Letter to the Editor