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(Circulation. 1997;95:83-89.)
© 1997 American Heart Association, Inc.

Articles

Effect of the Direct Nitric Oxide Donors Linsidomine and Molsidomine on Angiographic Restenosis After Coronary Balloon Angioplasty

The ACCORD Study

Jean-Marc Lablanche, MD; Gilles Grollier, MD; Jean-Rene Lusson, MD; Jean-Pierre Bassand, MD; Gerard Drobinski, MD; Bernard Bertrand, MD; Salvatore Battaglia, MD; Bernard Desveaux, MD; Yves Juilliere, MD; Jean-Michel Juliard, MD; Jean-Philippe Metzger, MD; Pierre Coste, MD; Jean-Claude Quiret, MD; Jean-Luc Dubois-Rande, MD; Pierre Dominique Crochet, MD; Brice Letac, MD; Jacques Boschat, MD; Patrice Virot, MD; Gerard Finet, MD; Herve Le Breton, MD; Bernard Livarek, MD; Florence Leclercq, MD; Thierry Beard, MD; Thierry Giraud, MD; Eugene P. McFadden, MRCPI; Michel E. Bertrand, MD

the Centre Hospitalier Regional et Universitaire, Hopital Cardiologique, Lille, France (J.-M.L., E.P.M., M.E.B.); Hopital Cote de Nacre, Caen (G.G.); Hopital Gabriel Montpied, Clermont Ferrand (J.-R.L.); Hopital Saint-Jacques, Besancon (J.-P.B.); Groupe Hospitalier Pitie-Salpetriere, Paris (G.D.); Centre Hospitalier Regional et Universitaire, Grenoble (B.B.); Hopital Broussais, Paris (S.B.); Hopital Trousseau, Tours (B.D.); Hopital de Brabois, Vandoeuvre (Y.J.); Hopital Bichat, Paris (J.-M.J.); Groupe Hospitalier Necker-Enfants Malades, Paris (J.-P.M.); Hopitaux de Haut Leveque, Pessac (P.C.); Groupe Hospitalier Sud, Amiens (J.-C.Q.); Centre Hospitalier Henri Mondor, Creteil (J.-L.D.-R.); Hopital Nord, Nantes (P.D.C.); Hopital Charles Nicolle, Rouen (B.L.); Hopital Morvan, Brest (J.B.); Hopital Universitaire Dupuytren, Limoges (P.V.); Hopital Louis Pradel, Lyon (G.F.); Hopital Hotel-Dieu, Rennes (H.L.B.); Hopital Andre Mignot, Le Chesnay (B.L.); Hopital Arnaud de Villeneuve, Montpellier (F.L.); Hopital Purpan, Toulouse (T.B.); and Laboratoires Hoechst, Paris La Defense (T.G.).

Background Nitric oxide (NO) donors, in addition to their vasodilator effect, decrease platelet aggregation and inhibit vascular smooth muscle cell proliferation. These actions could have beneficial effects on restenosis after coronary balloon angioplasty.

Methods and Results In a prospective multicenter, randomized trial, 700 stable coronary patients scheduled for angioplasty received direct NO donors (infusion of linsidomine followed by oral molsidomine) or oral diltiazem. Treatment was started before angioplasty and continued until 12 to 24 hours before follow-up angiography at 6 months. The primary study end point was minimal lumen diameter, assessed by quantitative coronary angiography, 6 months after balloon angioplasty. Clinical variables were well matched in both groups. However, despite intracoronary administration of isosorbide dinitrate, the reference diameter in the NO donor group was significantly greater than in the diltiazem group on the preangioplasty, postangioplasty, and follow-up angiograms. Pretreatment with an NO donor was associated with a modest improvement in the immediate angiographic result compared with pretreatment with diltiazem (minimum luminal diameter, 1.94 versus 1.81 mm; P=.001); this improvement was maintained at the 6-month angiographic follow-up (minimal lumen diameter, 1.54 versus 1.38 mm; P=.007). The extent of late luminal narrowing did not differ significantly between groups (loss index in the NO donor and diltiazam groups, 0.35±0.78 and 0.46±0.74, respectively; P=.103). Restenosis, defined as a binary variable (50% stenosis), occurred less often in the NO donor group (38.0% versus 46.5%; P=.026). Combined major clinical events (death, nonfatal myocardial infarction, and coronary revascularization) were similar in the two groups (32.2% versus 32.4%).

Conclusions Treatment with linsidomine and molsidomine was associated with a modest improvement in the long-term angiographic result after angioplasty but had no effect on clinical outcome. The improved angiographic result related predominantly to a better immediate procedural result, because late luminal loss did not differ significantly between groups.

Key Words: endothelium-derived factors • sydnonimines • angioplasty • restenosis

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