This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lablanche, J.-M. Articles by Bertrand, M. E. Search for Related Content PubMed PubMed Citation Articles by Lablanche, J.-M. Articles by Bertrand, M. E.

(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

This article has been cited by other articles:

				F. Hofmann, R. Feil, T. Kleppisch, and J. Schlossmann Function of cGMP-Dependent Protein Kinases as Revealed by Gene Deletion Physiol Rev, January 1, 2006; 86(1): 1 - 23. [Abstract] [Full Text] [PDF]

				A. G. Herman and S. Moncada Therapeutic potential of nitric oxide donors in the prevention and treatment of atherosclerosis Eur. Heart J., October 1, 2005; 26(19): 1945 - 1955. [Abstract] [Full Text] [PDF]

				M. Dixit, D. Zhuang, B. Ceacareanu, and A. Hassid Treatment With Insulin Uncovers the Motogenic Capacity of Nitric Oxide in Aortic Smooth Muscle Cells: Dependence on Gab1 and Gab1-SHP2 Association Circ. Res., November 14, 2003; 93 (10): e113 - e123. [Abstract] [Full Text] [PDF]

				S. H. Baek, J. A. Hrabie, L. K. Keefer, D. Hou, N. Fineberg, R. Rhoades, and K. L. March Augmentation of Intrapericardial Nitric Oxide Level by a Prolonged-Release Nitric Oxide Donor Reduces Luminal Narrowing After Porcine Coronary Angioplasty Circulation, June 11, 2002; 105(23): 2779 - 2784. [Abstract] [Full Text] [PDF]

				P. Maffia, A. Ianaro, R. Sorrentino, L. Lippolis, F. M. Maiello, P. del Soldato, A. Ialenti, and G. Cirino Beneficial Effects of NO-Releasing Derivative of Flurbiprofen (HCT-1026) in Rat Model of Vascular Injury and Restenosis Arterioscler Thromb Vasc Biol, February 1, 2002; 22(2): 263 - 267. [Abstract] [Full Text] [PDF]

				R D Rakhit and M S Marber Nitric oxide: an emerging role in cardioprotection? Heart, October 1, 2001; 86(4): 368 - 372. [Full Text] [PDF]

				M. Kalinowski, H. Alfke, S. Bergen, K. J. Klose, J. J. Barry, and H.-J. Wagner Comparative Trial of Local Pharmacotherapy with L-Arginine, r-Hirudin, and Molsidomine to Reduce Restenosis after Balloon Angioplasty of Stenotic Rabbit Iliac Arteries Radiology, June 1, 2001; 219(3): 716 - 723. [Abstract] [Full Text] [PDF]

				A. Lafont, E. Durand, J. L. Samuel, B. Besse, F. Addad, B. I. Levy, M. Desnos, C. Guerot, and C. M. Boulanger Endothelial Dysfunction and Collagen Accumulation : Two Independent Factors for Restenosis and Constrictive Remodeling After Experimental Angioplasty Circulation, September 7, 1999; 100(10): 1109 - 1115. [Abstract] [Full Text] [PDF]

				J. Y. Jeremy, D. Rowe, A. M. Emsley, and A. C. Newby Nitric oxide and the proliferation of vascular smooth muscle cells Cardiovasc Res, August 15, 1999; 43(3): 580 - 594. [Full Text] [PDF]

				J. P Cooke The 1998 Nobel prize in Medicine: clinical implications for 1999 and beyond Vascular Medicine, May 1, 1999; 4(2): 57 - 60. [PDF]

				Y. Hattori, S. Hattori, and K. Kasai Troglitazone Upregulates Nitric Oxide Synthesis in Vascular Smooth Muscle Cells Hypertension, April 1, 1999; 33(4): 943 - 948. [Abstract] [Full Text] [PDF]

				A. Lafont and D. Faxon Why do animal models of post-angioplasty restenosis sometimes poorly predict the outcome of clinical trials? Cardiovasc Res, July 1, 1998; 39(1): 50 - 59. [Full Text] [PDF]

				S. Janssens, D. Flaherty, Z. Nong, O. Varenne, N. van Pelt, C. Haustermans, P. Zoldhelyi, R. Gerard, and D. Collen Human Endothelial Nitric Oxide Synthase Gene Transfer Inhibits Vascular Smooth Muscle Cell Proliferation and Neointima Formation After Balloon Injury in Rats Circulation, April 7, 1998; 97(13): 1274 - 1281. [Abstract] [Full Text] [PDF]