Chronology of Use of Ticlopidine to Prevent Stent Occlusion
To the Editor:
We read with interest the editorial by Dr Baim, and we wish to provide a chronologically accurate summary with respect to the use of ticlopidine and aspirin after stent implantation. Dr Colombo has greatly contributed to the development of stenting by being the first to demonstrate that use of intravascular ultrasound (IVUS) could eliminate the need for anticoagulation treatment in stented patients.2 3 However, it does not seem necessary to attribute the introduction of poststenting treatment with ticlopidine and aspirin to Dr Colombo. Indeed, he does not claim credit for it.
It was Dr Barragan who asserted, as early as 1992, that ticlopidine could prevent stent occlusion.4 Pursuant to this, the French registry “Stenting without Coumadin”5 6 7 was started in December 1992, and all patients included in this registry were treated with ticlopidine and aspirin on the advice of Dr Benvéniste. More than 25 centers participated, and 2900 patients were included between 1992 and 1995. The results demonstrated to the scientific community that the combination of ticlopidine and aspirin, taking into account the molecules currently available, was the treatment of choice for stented patients. These findings were verified in an open, nonrandomized study, the MUST study, monitored by Cardialysis, and eventually validated in a randomized study of ticlopidine and aspirin versus conventional treatment conducted by Schömig et al.8 All the French results were published with some delay because of the authors’ inexperience in the publication of articles.
- Copyright © 1998 by American Heart Association
Baim DS, Carroza JP Jr. Stent thrombosis: closing in on the best preventive treatment. Circulation. 1997;95:1098–1100.
Hall P, Nakamura S, Maiello L, Ithoh A, Blengino S, Martini G, Ferraro M, Colombo A. A randomized comparison of combined ticlopidine and aspirin therapy versus aspirin therapy alone after successful intravascular ultrasound-guided stent implantation. Circulation. 1996;93:215–222.
Barragan P, Silvestri M, Sainsous J, Simeoni JB, Bayet G, Bouvier JL, Comet B. Prevention of subacute occlusion after stenting with ticlopidine regimen without intravascular ultrasound. J Am Coll Cardiol. 1995;25:182A. Abstract.
Morice MC, Bourdonnec C, Biron Y, Fajadet J, Glatt B, Royer T, Descaves C, Gaspard P, Lienhard Y, Marco J. Coronary stenting without coumadin: phase II. J Am Coll Cardiol. 1994;(suppl):335A. Abstract.
Morice MC, Zemour G, Benvéniste E, Biron Y, Bourdonnec C, Faivre R, Fajadet J Gaspard P, Glatt B, Joly P. Intracoronary stenting without coumadin: one month of a French multicenter study. Cathet Cardiovasc Diagn. 1995;35:1–7.
Karillon G, Morice MC, Benvéniste E, Bunouf P, Aubry P, Cattan S, Chevalier B, Commeau P, Cribier A, Eiferman C, Grollier G, Guérin Y, Henry M, Lefèvre T, Livarek B, Louvard Y, Makowski S, Monassier JP, Pernes JM, Rioux P, Spaulding C, Zemour G. Intracoronary stenting without coumadin without ultrasound guidance and with replacement of conventional anticoagulation by antiplatelet therapy: 30-day clinical outcome of the French Multicenter Registry. Circulation. 1996;94:1519–1527.
Schömig A, Neumann FJ, Kastrati A, Schulen H, Blasini R, Hadamitzky M, Walker H, Zitzman-Roth EM, Richard G, Alt E, Schmitt C, Ulm K. A randomized comparison of antiplatelet and anticoagulant therapy after placement of coronary artery stents. N Engl J Med. 1996;334:1084–1089.
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,R1 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.R1 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.R2 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.
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.
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.