Long-term clopidogrel therapy in the drug-eluting stent era: beyond CREDO and PCI-CURE

T.W Koh

Cardiac Catheterisation Laboratory, Department of Cardiology, London Chest Hospital, Bonner Road, London E2 9JX, UK Tel.: +44-208-983-2457; Fax: +44-208-983-2278

E-mail address: tatkoh{at}hotmail.com

We agree with the main thrust of the argument in the recent article by Eriksson1 that long-term clopidogrel treatment (8 and 12 months) confers a small, or at most modest, advantage when compared to the standard 1-month treatment in patients undergoing percutaneous coronary intervention.

Eriksson should be commended for the critical analysis of the data from PCI-CURE and CREDO. In particular, for pointing out that the small absolute reductions in composite endpoints of death, myocardial infarction, revascularisation in the long-term clopidogrel treatment group compared to the standard 1-month treatment group, could easily be negated by the increased bleeding risk.

However, we wish to highlight that both trials were conducted before the era of drug-eluting stents. In fact, the main reason for prescribing clopidogrel beyond the standard 1 month period is not so much driven by the results of PCI-CURE or CREDO, but by the implantation of drug-eluting stents.

The theoretical concerns of delayed endothelialisation leading to stent thrombosis have not been borne out by trials comparing drug-eluting stents to bare metal stents. Nevertheless, all these trials of drug-eluting stents have used clopidogrel for beyond the standard 1 month period normally applied to bare metal stents.

In RAVEL,2 where short coronary lesions (mean length 9.58 mm) were treated with a single sirolimus-eluting stent, clopidogrel was prescribed for 2 months. The SIRIUS3 and TAXUS IV4 trials involved treating longer lesion lengths (mean length 14.4 and 13.4 mm, respectively) and more complex disease (diabetes, multiple stents and small vessels). The duration of clopidogrel treatment for SIRIUS and TAXUS IV trials was therefore longer, at 3 and 6 months respectively. None of these trials showed an increased risk of stent thrombosis in the drug-eluting stent group when clopidogrel was prescribed for between 2 and 6 months.

In fact, two recent reports of stent thrombosis in drug-eluting stents5,6 in the literature demonstrate a strong link to the discontinuation of anti-platelet therapy within the first month. Lemos et al.,7 has shown that even in unselected "real world" patients outside the strict entry criteria of trials, patients with complex disease such as multi-vessel disease, bifurcation disease requiring multiple stenting can be treated with sirolimus-eluting stents effectively without an excess of stent thrombosis with clopidogrel treatment of 3–6 months duration.

Although the optimal duration of clopidogrel treatment after drug-eluting stent implantation is not known, empirical long-term treatment (3–6 months) is here to stay because of the fear of the dreaded complication of stent thrombosis and its serious consequences. Depending on lesion complexity and adverse patient characteristics such as diabetes, some authorities even recommend 6–12 months treatment with clopidogrel.8 This prolonged use of clopidogrel has economic consequences and should be considered in any cost analysis of the use of drug-eluting stents.

References

  1. Eriksson P. Long-term clopidogrel therapy after percutaneous coronary intervention in PCI-CURE and CREDO: the "Emperor's New Clothes" revisited. Eur. Heart J. 2004;25:720–722.[Free Full Text]
  2. Morice MC, Serruys PW, Sousa JE et al. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N. Engl. J. Med. 2002;346:1773–1780.[Abstract/Free Full Text]
  3. Moses JW, Leon MB, Popma JJ et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N. Engl. J. Med. 2003;349:1315–1323.[Abstract/Free Full Text]
  4. Stone GW, Ellis SG, Cox DA et al. A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease. N. Engl. J. Med. 2004;350:221–231.[Abstract/Free Full Text]
  5. Jeremias A, Sylvia B, Bridges J et al. Stent thrombosis after successful sirolimus-eluting stent implantation. Circulation. 2004;109:1930–1932.[Abstract/Free Full Text]
  6. Kerner A, Gruberg L, Kapeliovich M et al. Late stent thrombosis after implantation of a sirolimus-eluting stent. Catheter Cardiovasc. Interv. 2003;60:505–508.[CrossRef][Medline]
  7. Lemos PA, Serruys PW, van Domburg RT 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;109:190–195.[Abstract/Free Full Text]
  8. Stone GW, Ellis SG, Russell ME. Paclitaxel-eluting coronary stents. N. Engl. J. Med. 2004;350:2099–2100.[Free Full Text]




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