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(Circulation. 1998;98:2098-2102.)
© 1998 American Heart Association, Inc.

Correspondence

Chronology of Use of Ticlopidine to Prevent Stent Occlusion

Marie-Claude Morice, MD, FESC

Institut Cardiovascular Paris Sud Antony, France

Response

Joseph P. Carrozza, Jr, MD; ; Donald S. Baim, MD

Beth Israel Deaconess Medical Center, Boston, Mass

We thank Dr Morice for her comments. As she indicates, the replacement of prophylactic anticoagulation with antiplatelet therapy in an effort to prevent stent thrombosis was promulgated by several European groups. Indeed, the work of numerous investigators in Italy, France, and Germany led to the widespread replacement of draconian warfarin-based regimens with safer and more effective antiplatelet therapies. Antonio Columbo and colleagues at the Centro Cuore in Milan, Italy,¹ demonstrated that after low-pressure deployment, the majority of stents were underexpanded despite optimal angiographic appearance by IVUS and that suboptimal expansion increased the risk for stent thrombosis.¹ The use of adjunctive high-pressure dilatation allowed these investigators to substitute antiplatelet agents for warfarin. Concomitantly, a multiphase registry that commenced at multiple sites in France evaluated novel regimens for preventing thrombosis, including both low-molecular-weight heparin and ticlopidine.² In the initial phases, patients were treated with aspirin, ticlopidine, and low-molecular-weight heparin. Only in the fifth and final phase did patients receive just aspirin and ticlopidine. The overall incidence of proven or suspected stent thrombosis (1.8%) did not differ significantly among the cohorts treated with aspirin and ticlopidine alone versus aspirin/ticlopidine and low-molecular-weight heparin. The data in this large French registry clearly provided an important link in the chain of evidence suggesting that the incidence of stent thrombosis could be reduced to an acceptably low level with only aspirin and ticlopidine. The finding of these pioneering French and Italian investigators were subsequently corroborated in the randomized German ISAR and the US STARS randomized trials.

It was not our intent to imply primacy of the work of Dr Colombo and colleagues over Dr Morice and her team in making the transition from anticoagulation to antiplatelet-based regimens possible. In a field in which many of the breakthroughs are disseminated before publication, it is frequently difficult to ascertain which individual or groups initially proposed an idea, such as that stents could be safely deployed without any anticoagulation. But we are sure that interventionists and their patients throughout the world should be indebted to these enlightened investigators from France, Italy, and Germany for providing the data that freed us all from the burdens of anticoagulation and its associated complications.

References

1. Nakamura S, Colombo A, Gaglione S, Almagor Y, Goldberg Sl, Maieuo ML, Finci L, Tobis JM. Intracoronary ultrasound observations during stent implantation. Circulation. 1994;89:2026–2034.[Free Full Text]
   
2. Karrillon GJ, Morice MC, Benveniste E, Bunouf P, Aubry P, Cattan S, Chevalier B, Commeau P, Cribier A, Eiferman C, Grollier G, Guerin Y, Henry M, Lefebevre T, Livarek B, Louvard Y, Marco J, Makowski S, Monassier JP, Pernes JM, Rioux P, Spaulding C, Zemour G. Intracoronary stent implantation without ultrasound guidance and replacement of conventional anticoagulation by antiplatelet therapy: 30-day clinical outcome of the multicenter registry. Circulation. 1996;94:1519–1527.[Medline] [Order article via Infotrieve]
   

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